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Sample records for arsenite inhibits cytokine-induced

  1. Distinctive subcellular inhibition of cytokine-induced SRC by salubrinal and fluid flow.

    Science.gov (United States)

    Wan, Qiaoqiao; Xu, Wenxiao; Yan, Jing-long; Yokota, Hiroki; Na, Sungsoo

    2014-01-01

    A non-receptor protein kinase Src plays a crucial role in fundamental cell functions such as proliferation, migration, and differentiation. While inhibition of Src is reported to contribute to chondrocyte homeostasis, its regulation at a subcellular level by chemical inhibitors and mechanical stimulation has not been fully understood. In response to inflammatory cytokines and stress to the endoplasmic reticulum (ER) that increase proteolytic activities in chondrocytes, we addressed two questions: Do cytokines such as interleukin 1 beta (IL1β) and tumor necrosis factor alpha (TNFα) induce location-dependent Src activation? Can cytokine-induced Src activation be suppressed by chemically alleviating ER stress or by applying fluid flow? Using live cell imaging with two Src biosensors (i.e., cytosolic, and plasma membrane-bound biosensors) for a fluorescence resonance energy transfer (FRET) technique, we determined cytosolic Src activity as well as membrane-bound Src activity in C28/I2 human chondrocytes. In response to TNFα and IL1β, both cytosolic and plasma membrane-bound Src proteins were activated, but activation in the cytosol occurred earlier than that in the plasma membrane. Treatment with salubrinal or guanabenz, two chemical agents that attenuate ER stress, significantly decreased cytokine-induced Src activities in the cytosol, but not in the plasma membrane. In contrast, fluid flow reduced Src activities in the plasma membrane, but not in the cytosol. Collectively, the results demonstrate that Src activity is differentially regulated by salubrinal/guanabenz and fluid flow in the cytosol and plasma membrane. PMID:25157407

  2. Distinctive subcellular inhibition of cytokine-induced SRC by salubrinal and fluid flow.

    Directory of Open Access Journals (Sweden)

    Qiaoqiao Wan

    Full Text Available A non-receptor protein kinase Src plays a crucial role in fundamental cell functions such as proliferation, migration, and differentiation. While inhibition of Src is reported to contribute to chondrocyte homeostasis, its regulation at a subcellular level by chemical inhibitors and mechanical stimulation has not been fully understood. In response to inflammatory cytokines and stress to the endoplasmic reticulum (ER that increase proteolytic activities in chondrocytes, we addressed two questions: Do cytokines such as interleukin 1 beta (IL1β and tumor necrosis factor alpha (TNFα induce location-dependent Src activation? Can cytokine-induced Src activation be suppressed by chemically alleviating ER stress or by applying fluid flow? Using live cell imaging with two Src biosensors (i.e., cytosolic, and plasma membrane-bound biosensors for a fluorescence resonance energy transfer (FRET technique, we determined cytosolic Src activity as well as membrane-bound Src activity in C28/I2 human chondrocytes. In response to TNFα and IL1β, both cytosolic and plasma membrane-bound Src proteins were activated, but activation in the cytosol occurred earlier than that in the plasma membrane. Treatment with salubrinal or guanabenz, two chemical agents that attenuate ER stress, significantly decreased cytokine-induced Src activities in the cytosol, but not in the plasma membrane. In contrast, fluid flow reduced Src activities in the plasma membrane, but not in the cytosol. Collectively, the results demonstrate that Src activity is differentially regulated by salubrinal/guanabenz and fluid flow in the cytosol and plasma membrane.

  3. Transduced Tat-DJ-1 protein inhibits cytokines-induced pancreatic RINm5F cell death

    Science.gov (United States)

    Jo, Hyo Sang; Yeo, Hyeon Ji; Cha, Hyun Ju; Kim, Sang Jin; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Yeo, Eun Ji; Choi, Yeon Joo; Eum, Won Sik; Choi, Soo Young

    2016-01-01

    Loss of pancreatic β-cells by oxidative stress or cytokines is associated with diabetes mellitus (DM). DJ-1 is known to as a multifunctional protein, which plays an important role in cell survival. We prepared cell permeable wild type (WT) and mutant type (M26I) Tat-DJ-1 proteins to investigate the effects of DJ-1 against combined cytokines (IL-1β, IFN-γ and TNF-α)-induced RINm5F cell death. Both Tat-DJ-1 proteins were transduced into RINm5F cells. WT Tat-DJ-1 proteins significantly protected against cell death from cytokines by reducing intracellular toxicities. Also, WT Tat-DJ-1 proteins markedly regulated cytokines-induced pro- and anti-apoptosis proteins. However, M26I Tat-DJ-1 protein showed relatively low protective effects, as compared to WT Tat-DJ-1 protein. Our experiments demonstrated that WT Tat-DJ-1 protein protects against cytokine-induced RINm5F cell death by suppressing intracellular toxicities and regulating apoptosisrelated protein expression. Thus, WT Tat-DJ-1 protein could potentially serve as a therapeutic agent for DM and cytokine related diseases. [BMB Reports 2016; 49(5): 297-302] PMID:26996344

  4. Inhibition of mitotic-specific histone phophorylation by sodium arsenite

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    Cobo, J.M. [Universidad de Alcala de Henares, Madrid (Spain); Valdez, J.G.; Gurley, L.R. [Los Alamos National Lab., NM (United States)

    1994-10-01

    Synchronized cultures of Chinese hamster cells (line CHO) were used to measure the effects of 10{mu}M sodium arsenite on histone phosphorylation. This treatment caused cell proliferation to be temporarily arrested, after which the cells spontaneously resumed cell proliferation in a radiomimetric manner. Immediately following treatment, it was found that sodium arsenite affected only mitotic-specific HI and H3 phosphorylations. Neither interphase, nor mitotic, H2A and H4 phosphorylations were affected, nor was interphase HI Phosphorylation affected. The phosphorylation of HI was inhibited only in mitosis, reducing HI phosphorylation to 38.1% of control levels, which was the level of interphase HI phosphorylation. The phosphorylation of both H3 variants was inhibited in mitosis, the less hydrophobic H3 to 19% and the more hydrophobic H3 to 24% of control levels. These results suggest that sodium arsenite may inhibite cell proliferation by interfering with the cyclin B/p34{sup cdc2} histone kinase activity which is thought to play a key role in regulating the cell cycle. It has been proposed by our laboratory that HI and H3 phosphorylations play a role in restructuring interphase chromatin into metaphase chromosomes. Interference of this process by sodium arsenite may lead to structurally damaged chromosomes resulting in the increased cancer risks known to be produced by arsenic exposure from the environment.

  5. Viscum album exerts anti-inflammatory effect by selectively inhibiting cytokine-induced expression of cyclooxygenase-2.

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    Pushpa Hegde

    Full Text Available Viscum album (VA preparations are extensively used as complementary therapy in cancer and are shown to exert anti-tumor activities which involve the cytotoxic properties, induction of apoptosis, inhibition of angiogenesis and several other immunomodulatory mechanisms. In addition to their application in cancer therapy, VA preparations have also been successfully utilized in the treatment of several inflammatory pathologies. Owing to the intricate association of inflammation and cancer and in view of the fact that several anti-tumor phytotherapeutics also exert a potent anti-inflammatory effect, we hypothesized that VA exerts an anti-inflammatory effect that is responsible for its therapeutic benefit. Since, inflammatory cytokine-induced cyclo-oxygenase-2 (COX-2 and prostaglandin E2 (PGE2 play a critical role in the pathogenesis of inflammatory diseases, we investigated the anti-inflammatory effect of VA on regulation of cyclo-oxygenase expression and PGE2 biosynthesis by using human lung adenocarcinoma cells (A549 cells as a model. A549 cells were stimulated with IL-1β and treated with VA preparation (VA Qu Spez for 18 hours. PGE2 was analysed in the culture supernatants by enzyme immunoassay. Expression of COX-2 and COX-1 proteins was analyzed by immunoblotting and the expression of COX-2 mRNA was assessed by semi-quantitative RT-PCR. We found that VA Qu Spez inhibit the secretion of IL-1β-induced PGE2 in a dose-dependent manner. Further, we also show that this inhibitory action was associated with a reduced expression of COX-2 without modulating the COX-1 expression. Together these results demonstrate a novel anti-inflammatory mechanism of action of VA preparations wherein VA exerts an anti-inflammatory effect by inhibiting cytokine-induced PGE2 via selective inhibition of COX-2.

  6. IGFBP-3 inhibits cytokine-induced insulin resistance and early manifestations of atherosclerosis.

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    Lathika Mohanraj

    Full Text Available Metabolic syndrome is associated with visceral obesity, insulin resistance and an increased risk of cardiovascular diseases. Visceral fat tissue primarily consists of adipocytes that secrete cytokines leading to a state of systemic inflammation in obese conditions. One of the IGF-independent functions of IGFBP-3 is its role as an anti-inflammatory molecule. Our study in obese adolescents show a decrease in total IGFBP-3 levels and increase in proteolyzed IGFBP-3 in circulation when compared to their normal counterparts and establishes a positive correlation between IGFBP-3 proteolysis and adiposity parameters as well as insulin resistance. In human adipocytes, we show that IGFBP-3 inhibits TNF-α-induced NF-κB activity in an IGF-independent manner, thereby restoring the deregulated insulin signaling and negating TNF-α-induced inhibition of glucose uptake. IGFBP-3 further inhibits TNF-α, CRP and high glucose-induced NF-κB activity in human aortic endothelial cells (HAECs and subsequently suppresses monocyte adhesion to HAEC through the IGFBP-3 receptor. In conclusion, these findings suggest that reduced levels of IGFBP-3 in circulation and reduced expression of IGFBP-3 in macrophages in obesity may result in suppression of its anti-inflammatory functions and therefore IGFBP-3 may present itself as a therapeutic for obesity-induced insulin resistance and for events occurring in the early stages of atherosclerosis.

  7. Nitric oxide contributes to cytokine-induced apoptosis in pancreatic beta cells via potentiation of JNK activity and inhibition of Akt

    DEFF Research Database (Denmark)

    Størling, J; Binzer, J; Andersson, Annica;

    2005-01-01

    Pro-inflammatory cytokines cause beta cell secretory dysfunction and apoptosis--a process implicated in the pathogenesis of type 1 diabetes. Cytokines induce the expression of inducible nitric oxide (NO) synthase (iNOS) leading to NO production. NO contributes to cytokine-induced apoptosis, but t...

  8. Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin*

    Science.gov (United States)

    Chen, Jiong-huang; Xiang, Jian-yang; Ding, Guo-ping; Cao, Li-ping

    2016-01-01

    Objective: The aim of our study is to observe the impact of cholangiocarcinoma-derived exosomes on the antitumor activities of cytokine-induced killer (CIK) cells and then demonstrate the appropriate mechanism. Methods: Tumor-derived exosomes (TEXs), which are derived from RBE cells (human cholangiocarcinoma line), were collected by ultracentrifugation. CIK cells induced from peripheral blood were stimulated by TEXs. Fluorescence-activated cell sorting (FACS) was performed to determine the phenotypes of TEX-CIK and N-CIK (normal CIK) cells. The concentrations of tumor necrosis factor-α (TNF-α) and perforin in the culture medium supernatant were examined by using an enzyme-linked immunosorbent assay (ELISA) kit. A CCK-8 kit was used to evaluate the cytotoxic activity of the CIK cells to the RBE cell line. Results: The concentrations of TNF-α and perforin of the group TEX-CIK were 138.61 pg/ml and 2.41 ng/ml, respectively, lower than those of the group N-CIK 194.08 pg/ml (Pexosomes inhibit the antitumor activity of CIK cells by down-regulating the population of CD3+, CD8+, NK (CD56+), and CD3+CD56+ cells and the secretion of TNF-α and perforin. TEX may play an important role in cholangiocarcinoma immune escape. PMID:27381730

  9. Cortex cinnamomi extract prevents streptozotocin- and cytokine-induced β-cell damage by inhibiting NF-κB

    Institute of Scientific and Technical Information of China (English)

    Kang-Beom Kwon; Eun-Kyung Kim; Eun-Sil Jeong; Young-Hoon Lee; Young-Rae Lee; Jin-Woo Park; Do-Gon Ryu; Byung-Hyun Park

    2006-01-01

    AIM: To clarify the mechanism underlying the antidiabetic activities of cortex cinnamomi extract (CCE).METHODS: To induce in vivo diabetes, mice were injected with streptozotocin (STZ) via a tail vein (100 mg STZ/kg body weight). To determine the effects of CCE,mice were administered CCE twice daily for 7 d by oral gavage starting 1 wk before the STZ injection. Blood glucose and plasma insulin concentration were measured as an index of diabetes. Also, to induce cytotoxicity of RINm5F cells, we treated with cytokines (IL-1β (2.0 ng/mL) and IFN-γ (100 U/mL)). Cell viability and nitric oxide production were measured colorimetrically.Inducible nitric oxide synthase (iNOS) mRNA and protein expression were determined by RT-PCR and Western blotting, respectively. The activation of NF-KB was assayed by using gel mobility shift assays of nuclear extracts.RESULTS: Treatment of mice with STZ resulted in hyperglycemia and hypoinsulinemia, which was further evidenced by immunohistochemical staining of islets. However, the diabetogenic effects of STZ were completely prevented when mice were pretreated with CCE. The inhibitory effect of CCE on STZ-induced hyperglycemia was mediated through the suppression of iNOS expression. In rat insulinoma RINm5F cells,CCE completely protected against interleukin-1β and interferon-y-mediated cytotoxicity. Moreover, RINm5F cells incubated with CCE showed significant reductions in interleukin-1β and interferon-y-induced nitric oxide production and in iNOS mRNA and protein expression,and these findings correlated well with in vivo observations.CONCLUSION: The molecular mechanism by which CCE inhibits iNOS gene expression appears to involve the inhibition of NF-κB activation. These results reveal the possible therapeutic value of CCE for the prevention of diabetes mellitus progression.

  10. Sodium arsenite-induced inhibition of cell proliferation is related to inhibition of IL-2 mRNA expression in mouse activated T cells

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    Conde, Patricia; Acosta-Saavedra, Leonor C.; Calderon-Aranda, Emma S. [Centro de Investigacion y de Estudios Avanzados, CINVESTAV, Seccion Toxicologia, P.O. Box 14-740, Mexico, D.F. (Mexico); Goytia-Acevedo, Raquel C. [Universidad Juarez del Estado de Durango, Facultad de Medicina, Gomez Palacio, Durango (Mexico)

    2007-04-15

    A proposed mechanism for the As-induced inhibition of cell proliferation is the inhibition of IL-2 secretion. However, the effects of arsenite on IL-2 mRNA expression or on the ERK pathway in activated-T cells have not yet been described. We examined the effect of arsenite on IL-2 mRNA expression, cell activation and proliferation in PHA-stimulated murine lymphocytes. Arsenite (1 and 10 {mu}M) decreased IL-2 mRNA expression, IL-2 secretion and cell proliferation. Arsenite (10 {mu}M) strongly inhibited ERK-phosphorylation. However, the partial inhibition (50%) of IL-2 mRNA produced by 1 {mu}M, consistent with the effects on IL-2 secretion and cell proliferation, could not be explained by the inhibition of ERK-phosphorylation, which was not affected at this concentration. The inhibition of IL-2 mRNA expression caused by 1 {mu}M could be associated to effects on pathways located downstream or parallel to ERK. Arsenite also decreased early activation (surface CD69{sup +} expression) in both CD4{sup +} and CD8{sup +}, and decreased total CD8{sup +} count without significantly affecting CD4{sup +}, supporting that the cellular immune response mediated by cytotoxic T cells is an arsenic target. Thus, our results suggest that arsenite decreases IL-2 mRNA levels and T-cell activation and proliferation. However, further studies on the effects of arsenite on IL-2 gene transcription and IL-2 mRNA stability are needed. (orig.)

  11. Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair

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    Sun, Xi; Zhou, Xixi [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Du, Libo [Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Liu, Wenlan [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Liu, Yang [Center for Molecular Science, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Hudson, Laurie G. [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States); Liu, Ke Jian, E-mail: kliu@salud.unm.edu [Department of Pharmaceutical Sciences, College of Pharmacy, University of New Mexico Health Sciences Center, Albuquerque, NM 87131 (United States)

    2014-01-15

    Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects of arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure. - Highlights: • Arsenite binding is equivalent to zinc deficiency in reducing PARP-1 function. • Zinc reverses arsenic inhibition of PARP-1 activity and enhancement of DNA damage. • Arsenite binding and zinc loss alter the conformation of zinc finger

  12. Arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair

    International Nuclear Information System (INIS)

    Inhibition of DNA repair is a recognized mechanism for arsenic enhancement of ultraviolet radiation-induced DNA damage and carcinogenesis. Poly(ADP-ribose) polymerase-1 (PARP-1), a zinc finger DNA repair protein, has been identified as a sensitive molecular target for arsenic. The zinc finger domains of PARP-1 protein function as a critical structure in DNA recognition and binding. Since cellular poly(ADP-ribosyl)ation capacity has been positively correlated with zinc status in cells, we hypothesize that arsenite binding-induced zinc loss from PARP-1 is equivalent to zinc deficiency in reducing PARP-1 activity, leading to inhibition of DNA repair. To test this hypothesis, we compared the effects of arsenite exposure with zinc deficiency, created by using the membrane-permeable zinc chelator TPEN, on 8-OHdG formation, PARP-1 activity and zinc binding to PARP-1 in HaCat cells. Our results show that arsenite exposure and zinc deficiency had similar effects on PARP-1 protein, whereas supplemental zinc reversed these effects. To investigate the molecular mechanism of zinc loss induced by arsenite, ICP-AES, near UV spectroscopy, fluorescence, and circular dichroism spectroscopy were utilized to examine arsenite binding and occupation of a peptide representing the first zinc finger of PARP-1. We found that arsenite binding as well as zinc loss altered the conformation of zinc finger structure which functionally leads to PARP-1 inhibition. These findings suggest that arsenite binding to PARP-1 protein created similar adverse biological effects as zinc deficiency, which establishes the molecular mechanism for zinc supplementation as a potentially effective treatment to reverse the detrimental outcomes of arsenic exposure. - Highlights: • Arsenite binding is equivalent to zinc deficiency in reducing PARP-1 function. • Zinc reverses arsenic inhibition of PARP-1 activity and enhancement of DNA damage. • Arsenite binding and zinc loss alter the conformation of zinc finger

  13. Arsenite-loaded nanoparticles inhibit PARP-1 to overcome multidrug resistance in hepatocellular carcinoma cells.

    Science.gov (United States)

    Liu, Hanyu; Zhang, Zongjun; Chi, Xiaoqin; Zhao, Zhenghuan; Huang, Dengtong; Jin, Jianbin; Gao, Jinhao

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the highest incidences in cancers; however, traditional chemotherapy often suffers from low efficiency caused by drug resistance. Herein, we report an arsenite-loaded dual-drug (doxorubicin and arsenic trioxide, i.e., DOX and ATO) nanomedicine system (FeAsOx@SiO2-DOX, Combo NP) with significant drug synergy and pH-triggered drug release for effective treatment of DOX resistant HCC cells (HuH-7/ADM). This nano-formulation Combo NP exhibits the synergistic effect of DNA damage by DOX along with DNA repair interference by ATO, which results in unprecedented killing efficiency on DOX resistant cancer cells. More importantly, we explored the possible mechanism is that the activity of PARP-1 is inhibited by ATO during the treatment of Combo NP, which finally induces apoptosis of HuH-7/ADM cells by poly (ADP-ribosyl) ation suppression and DNA lesions accumulation. This study provides a smart drug delivery strategy to develop a novel synergistic combination therapy for effectively overcome drug- resistant cancer cells. PMID:27484730

  14. Arsenite-loaded nanoparticles inhibit PARP-1 to overcome multidrug resistance in hepatocellular carcinoma cells

    Science.gov (United States)

    Liu, Hanyu; Zhang, Zongjun; Chi, Xiaoqin; Zhao, Zhenghuan; Huang, Dengtong; Jin, Jianbin; Gao, Jinhao

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the highest incidences in cancers; however, traditional chemotherapy often suffers from low efficiency caused by drug resistance. Herein, we report an arsenite-loaded dual-drug (doxorubicin and arsenic trioxide, i.e., DOX and ATO) nanomedicine system (FeAsOx@SiO2-DOX, Combo NP) with significant drug synergy and pH-triggered drug release for effective treatment of DOX resistant HCC cells (HuH-7/ADM). This nano-formulation Combo NP exhibits the synergistic effect of DNA damage by DOX along with DNA repair interference by ATO, which results in unprecedented killing efficiency on DOX resistant cancer cells. More importantly, we explored the possible mechanism is that the activity of PARP-1 is inhibited by ATO during the treatment of Combo NP, which finally induces apoptosis of HuH-7/ADM cells by poly (ADP-ribosyl) ation suppression and DNA lesions accumulation. This study provides a smart drug delivery strategy to develop a novel synergistic combination therapy for effectively overcome drug- resistant cancer cells. PMID:27484730

  15. Curcumin Inhibits The Adverse Effects of Sodium Arsenite in Mouse Epididymal Sperm

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    Momeni Hamid Reza

    2016-07-01

    Full Text Available Background The aim of this study was to investigate the effects of curcumin on epididy- mal sperm parameters in adult male Navel Medical Research Institute (NMRI mice ex- posed to sodium arsenite. Materials and Methods In this experimental study, we divided the animals into four groups: control, sodium arsenite (5 mg/kg, curcumin (100 mg/kg and curcumin+sodium arsenite. Exposures were performed by intraperitoneal injections for a 5-week period. After the exposure period, we recorded the animals’ body and left testes weights. The left caudal epididymis was used to count the sperm number and analyze motility, viability, morphological abnormalities, acrosome reaction, DNA integrity, and histone-protamine replacement in the spermatozoa. One-way analysis of variance (ANOVA followed by the Tukey’s test was used to assess the statistical significance of the data with SPSS 16.0. P<0.05 was considered significant. Results Mice exposed to sodium arsenite showed a significant decrease in the num- ber, motility, viability, normal sperm morphology and acrosome integrity of spermato- zoa compared to the control group. In the curcumin+sodium arsenite group, curcumin significantly reversed these adverse effects to the point where they approximated the control. In addition, the application of curcumin alone had no significant difference in these parameters compared to the control and curcumin+sodium arsenite groups. However, we observed no significant differences in the body and the testis weight as well as the DNA integrity and histone-protamine replacement in the spermatozoa of the four groups. Conclusion Curcumin compensated for the toxic effects of sodium arsenite on a number of sperm parameters in adult mice.

  16. Acanthopanax koreanum roots inhibit the expression of pro-inflammatory cytokines, inducible nitric oxide synthase, and cyclooxygenase-2 in RAW 264.7 macrophages

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    Eun-Jin Yang

    2016-03-01

    Full Text Available Acanthopanax koreanum is a popular plant found on Jeju Island, Korea and is commonly used to prevent the side effects of consumption of alcoholic beverages. However, this plant has not been properly utilized as a medicinal material. In this study, we investigated the anti-inflammatory effects of the 70% ethanol extract of A. koreanum roots (AKR-E. The results indicated that the AKR-E (200 μg/mL inhibited the lipopolysaccharide (LPS-induced production of nitric oxide (NO and prostaglandin E2 (PGE2 in RAW 264.7 macrophages by 41.2% and 78.9%, respectively. These effects were accompanied by concentration-dependent decreases in the expression levels of inducible NO synthase (iNOS and cyclooxygenase-2 (COX-2 proteins. Additionally, the AKR-E inhibited the expression of pro-inflammatory cytokines, including interleukin (IL-6 (22.7% and IL-1β (74%. These data showed that the AKR-E had protective effects against the induction of LPS-induced inflammation in RAW 264.7 macrophages.

  17. X-ray Crystal Structure of Arsenite-Inhibited Xanthine Oxidase:[mu]-Sulfido,[mu]-Oxo Double Bridge between Molybdenum and Arsenic in the Active Site

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    Cao, Hongnan; Hall, James; Hille, Russ (UCR)

    2012-10-23

    Xanthine oxidoreductase is a molybdenum-containing enzyme that catalyzes the hydroxylation reaction of sp{sup 2}-hybridized carbon centers of a variety of substrates, including purines, aldehydes, and other heterocyclic compounds. The complex of arsenite-inhibited xanthine oxidase has been characterized previously by UV-vis, electron paramagnetic resonance, and X-ray absorption spectroscopy (XAS), and the catalytically essential sulfido ligand of the square-pyrimidal molybdenum center has been suggested to be involved in arsenite binding through either a {mu}-sulfido,{mu}-oxo double bridge or a single {mu}-sulfido bridge. However, this is contrary to the crystallographically observed single {mu}-oxo bridge between molybdenum and arsenic in the desulfo form of aldehyde oxidoreductase from Desulfovibrio gigas (an enzyme closely related to xanthine oxidase), whose molybdenum center has an oxo ligand replacing the catalytically essential sulfur, as seen in the functional form of xanthine oxidase. Here we use X-ray crystallography to characterize the molybdenum center of arsenite-inhibited xanthine oxidase and solve the structures of the oxidized and reduced inhibition complexes at 1.82 and 2.11 {angstrom} resolution, respectively. We observe {mu}-sulfido,{mu}-oxo double bridges between molybdenum and arsenic in the active sites of both complexes. Arsenic is four-coordinate with a distorted trigonal-pyramidal geometry in the oxidized complex and three-coordinate with a distorted trigonal-planar geometry in the reduced complex. The doubly bridged binding mode is in agreement with previous XAS data indicating that the catalytically essential sulfur is also essential for the high affinity of reduced xanthine oxidoreductase for arsenite.

  18. The inhibition of tissue respiration and alcoholic fermentation at different catabolic levels by ethyl carbamate (urethan) and arsenite

    NARCIS (Netherlands)

    Florijn, E.; Gruber, M.; Leijnse, B.; Huisman, T.H.J.

    1950-01-01

    1. A hypothesis is given concerning the action of urethan and arsenite on malignant growth. Two assumptionsares made:- (a) the enzyme system responsible for energy production in malignant tumours is working at maximal rate, contrary to the corresponding enzyme system in normal tissues. (b) a give

  19. Embryotoxicity of arsenite and arsenate

    International Nuclear Information System (INIS)

    The distribution of 74As-labelled and arsenite in pregnant mice and a monkey has been studied by autoradiography and gamma counting of isolated tissues, and their in vitro toxicity to a chondrogenic system has been investigated. With both arsenic forms, given as single intravenous injections to the mother, the 74As-arsenic appeared to pass the mouse placenta relatively freely and approximately to the same extent. The retention time in material tissues including the placenta was, however, around three times longer with arsenite than with arsenate. In early gestation, high activity was registered in the embryonic neuroepithelium, which correlates well with reported CNS malformations in rodents. In late gestation, the distribution pattern was more like that in the adults. Accumulation in skin and squamous epithelia of the upper gastrointestinal tract (oral cavity, oesophagus and oesophageal region of stomach) dominated the distribution pucture, especially at a long survival interval. Arsenate, but not arsenite, showed affinity for the calcified areas of the skeleton. A marmoset monkey in late gestation receiving arsenite showed a somewhat lower rate of placental transfer than the mice. Skin and liver had the highest concentrations (at 8 hrs), both in mother and foetuses. This species is known not to methylate arsenic, resulting in stronger binding and longer retention times of arsenic as compared with other species. The stronger binding in maternal tissues may possibly explain the lower rate of placental transfer. Arsenite was shown to inhibit cartilage formation in a chick limb bud mesenchymal spot culture system (ED50 approximately 5-10μM) while arsenate seemed to be without effect at concentrations up to 200 μM (highest tested). Arsenate, however, showed a potential of the arsenite toxicity. (author)

  20. Sodium Meta-Arsenite Ameliorates Hyperglycemia in Obese Diabetic db/db Mice by Inhibition of Hepatic Gluconeogenesis

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    Young-Sun Lee

    2014-01-01

    Full Text Available Sodium meta-arsenite (SA is implicated in the regulation of hepatic gluconeogenesis-related genes in vitro; however, the effects in vivo have not been studied. We investigated whether SA has antidiabetic effects in a type 2 diabetic mouse model. Diabetic db/db mice were orally intubated with SA (10 mg kg−1 body weight/day for 8 weeks. We examined hemoglobin A1c (HbA1c, blood glucose levels, food intake, and body weight. We performed glucose, insulin, and pyruvate tolerance tests and analyzed glucose production and the expression of gluconeogenesis-related genes in hepatocytes. We analyzed energy metabolism using a comprehensive animal metabolic monitoring system. SA-treated diabetic db/db mice had reduced concentrations of HbA1c and blood glucose levels. Exogenous glucose was quickly cleared in glucose tolerance tests. The mRNA expressions of genes for gluconeogenesis-related enzymes, glucose 6-phosphatase (G6Pase, and phosphoenolpyruvate carboxykinase (PEPCK were significantly reduced in the liver of SA-treated diabetic db/db mice. In primary hepatocytes, SA treatment decreased glucose production and the expression of G6Pase, PEPCK, and hepatocyte nuclear factor 4 alpha (HNF-4α mRNA. Small heterodimer partner (SHP mRNA expression was increased in hepatocytes dependent upon the SA concentration. The expression of Sirt1 mRNA and protein was reduced, and acetylated forkhead box protein O1 (FoxO1 was induced by SA treatment in hepatocytes. In addition, SA-treated diabetic db/db mice showed reduced energy expenditure. Oral intubation of SA ameliorates hyperglycemia in db/db mice by reducing hepatic gluconeogenesis through the decrease of Sirt1 expression and increase in acetylated FoxO1.

  1. Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast.

    Science.gov (United States)

    Jacobson, Therese; Navarrete, Clara; Sharma, Sandeep K; Sideri, Theodora C; Ibstedt, Sebastian; Priya, Smriti; Grant, Chris M; Christen, Philipp; Goloubinoff, Pierre; Tamás, Markus J

    2012-11-01

    Several metals and metalloids profoundly affect biological systems, but their impact on the proteome and mechanisms of toxicity are not fully understood. Here, we demonstrate that arsenite causes protein aggregation in Saccharomyces cerevisiae. Various molecular chaperones were found to be associated with arsenite-induced aggregates indicating that this metalloid promotes protein misfolding. Using in vivo and in vitro assays, we show that proteins in the process of synthesis/folding are particularly sensitive to arsenite-induced aggregation, that arsenite interferes with protein folding by acting on unfolded polypeptides, and that arsenite directly inhibits chaperone activity. Thus, folding inhibition contributes to arsenite toxicity in two ways: by aggregate formation and by chaperone inhibition. Importantly, arsenite-induced protein aggregates can act as seeds committing other, labile proteins to misfold and aggregate. Our findings describe a novel mechanism of toxicity that may explain the suggested role of this metalloid in the etiology and pathogenesis of protein folding disorders associated with arsenic poisoning.

  2. Neuroglobin Plays a Protective Role in Arsenite-Induced Cytotoxicity by Inhibition of Cdc42 and Rac1GTPases in Rat Cerebellar Granule Neurons

    Directory of Open Access Journals (Sweden)

    Xiaona Liu

    2015-07-01

    Full Text Available Background and Aims: We have previously shown that neuroglobin (Ngb expression can be regulated by sodium arsenite (NaAsO2 exposure in rat cerebellar granule neurons (CGNs. However, the precise molecular mechanisms of Ngb action are largely unknown. Ras homolog (Rho guanosine triphosphatases (Rho GTPases are involved in the regulation of a number of cellular processes, including cell cytotoxicity. It has been reported that Ngb can act as a guanine nucleotide dissociation inhibitior (GDI role to inactivate Rho GTPases. Therefore, we investigated Rho GTPases activation induced by NaAsO2 exposure in rat CGNs and effects of Rho GTPases activation on the cells. We also investigated the role of Ngb in this process. Methods: Primary cultures of CGNs were prepared from 7-day-old Wistar rat pups. The cytotoxic effects of NaAsO2 on CGNs were evaluated using the Cell Counting Kit-8 assay and TUNEL staining. RNA interference technology was used to silence Ngb, and the subsequent effects were evaluated by quantitative RT-PCR and Western blot. Cdc42 and Rac1 activation were measured by pull-down assay and Western blot. Results: NaAsO2 induced cytotoxicity in rat CGNs, increased GTP-bound form of Cdc42 and Rac1 GTPases in the cells. Furthermore, inhibition of Cdc42 or Rac1 activity using the inhibitor ZCL278 or NSC23766 decreased apoptosis and increased cell viability in the cells exposed to NaAsO2. Using siRNA-mediated knockdown, we show that NaAsO2-induced cytotoxicity was exacerbated, activation of Cdc42 (GTP-Cdc42 and Rac1 (GTP-Rac1 was increased in Ngb RNA silencing cells. Conclusions: cytotoxic effects of NaAsO2 on rat CGNs is induced at least partly by Cdc42 and Rac1 activation, and Ngb can inhibit Cdc42 and Rac1 activation to play protective role in rat CGNs exposed to NaAsO2.

  3. Spontaneous and cytokine induced basophil adhesion evaluated by microtiter assay

    DEFF Research Database (Denmark)

    Quan, Sha; Poulsen, Lars K; Reimert, Claus Michael;

    2002-01-01

    We have developed a microtiter assay for evaluating basophil spontaneous adhesion to extracellular matrix (ECM) proteins exemplified by fibronectin and cytokine induced basophil adhesion to bovine serum albumin (BSA). The percentage of basophils adhering to either ECM or BSA was quantified...... by the histamine content of the adhering basophils. The spontaneous adhesion to fibronectin was higher than to laminin and collagen type I. Both spontaneous adhesion to fibronectin and interleukin-3 (IL-3), interleukin-5 (IL-5), granulocyte/macrophage colony stimulating factor (GM-CSF) induced adhesion to BSA...

  4. Spontaneous and cytokine induced basophil adhesion evaluated by microtiter assay

    DEFF Research Database (Denmark)

    Quan, Sha; Poulsen, Lars K; Reimert, Claus Michael;

    2002-01-01

    We have developed a microtiter assay for evaluating basophil spontaneous adhesion to extracellular matrix (ECM) proteins exemplified by fibronectin and cytokine induced basophil adhesion to bovine serum albumin (BSA). The percentage of basophils adhering to either ECM or BSA was quantified by the...... increased with time between 5 and 45 min. The histamine release in both spontaneous and induced basophil adhesion was lower than 3.1%. This microtiter assay is simple and reproducible and can be applied for basic and clinical studies using a limited number of partially purified basophils....

  5. Evidence for the presence of R250G mutation at the ATPase domain of topoisomerase II in an arsenite-resistant Leishmania donovani exhibiting a differential drug inhibition profile.

    Science.gov (United States)

    Singh, Gaganmeet; Thakur, Meghna; Chakraborti, Pradip K; Dey, Chinmoy S

    2009-01-01

    Resistance to operational drugs is a major barrier to successful antileishmanial chemotherapy that demands development of novel drug intervention strategies based on rational approaches. Model drug resistance phenotypes, such as arsenite resistance used in the current study, facilitate our understanding of the mechanism of drug resistance and assist in identifying new drug target(s). The current study was undertaken to investigate the sensitivity of topoisomerase II (topo II) of arsenite-sensitive (Ld-Wt) and -resistant (Ld-As20) Leishmania donovani to antileishmanial/anti-topo II agents. The effect of antileishmanial/anti-topo II drugs on partially purified topo II enzyme from Ld-Wt and Ld-As20 revealed differential inhibition of topo II decatenation activity for the two strains, with a lower amount of drug required to inhibit activity by 50% in Ld-Wt compared with Ld-As20. Comparison of topo II sequences from both strains indicated a point mutation, R250G, in the ATPase domain of the resistant strain. Furthermore, the Arg-250 of the ATPase domain of topo II was observed to be conserved throughout different species of Leishmania. Variation in the topo II gene sequence between Ld-Wt and Ld-As20 is envisaged to be responsible for the differential behaviour of the enzymes from the two sources. PMID:18805675

  6. Arsenite transport in plants.

    Science.gov (United States)

    Ali, Waqar; Isayenkov, Stanislav V; Zhao, Fang-Jie; Maathuis, Frans J M

    2009-07-01

    Arsenic is a metalloid which is toxic to living organisms. Natural occurrence of arsenic and human activities have led to widespread contamination in many areas of the world, exposing a large section of the human population to potential arsenic poisoning. Arsenic intake can occur through consumption of contaminated crops and it is therefore important to understand the mechanisms of transport, metabolism and tolerance that plants display in response to arsenic. Plants are mainly exposed to the inorganic forms of arsenic, arsenate and arsenite. Recently, significant progress has been made in the identification and characterisation of proteins responsible for movement of arsenite into and within plants. Aquaporins of the NIP (nodulin26-like intrinsic protein) subfamily were shown to transport arsenite in planta and in heterologous systems. In this review, we will evaluate the implications of these new findings and assess how this may help in developing safer and more tolerant crops.

  7. Arsenite suppression of BMP signaling in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, Marjorie A.; Qin, Qin [Department of Environmental Toxicology, University of California, Davis, CA 95616-8588 (United States); Hu, Qin; Zhao, Bin [State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085 (China); Rice, Robert H., E-mail: rhrice@ucdavis.edu [Department of Environmental Toxicology, University of California, Davis, CA 95616-8588 (United States)

    2013-06-15

    Arsenic, a human skin carcinogen, suppresses differentiation of cultured keratinocytes. Exploring the mechanism of this suppression revealed that BMP-6 greatly increased levels of mRNA for keratins 1 and 10, two of the earliest differentiation markers expressed, a process prevented by co-treatment with arsenite. BMP also stimulated, and arsenite suppressed, mRNA for FOXN1, an important transcription factor driving early keratinocyte differentiation. Keratin mRNAs increased slowly after BMP-6 addition, suggesting they are indirect transcriptional targets. Inhibition of Notch1 activation blocked BMP induction of keratins 1 and 10, while FOXN1 induction was largely unaffected. Supporting a requirement for Notch1 signaling in keratin induction, BMP increased levels of activated Notch1, which was blocked by arsenite. BMP also greatly decreased active ERK, while co-treatment with arsenite maintained active ERK. Inhibition of ERK signaling mimicked BMP by inducing keratin and FOXN1 mRNAs and by increasing active Notch1, effects blocked by arsenite. Of 6 dual-specificity phosphatases (DUSPs) targeting ERK, two were induced by BMP unless prevented by simultaneous exposure to arsenite and EGF. Knockdown of DUSP2 or DUSP14 using shRNAs greatly reduced FOXN1 and keratins 1 and 10 mRNA levels and their induction by BMP. Knockdown also decreased activated Notch1, keratin 1 and keratin 10 protein levels, both in the presence and absence of BMP. Thus, one of the earliest effects of BMP is induction of DUSPs, which increases FOXN1 transcription factor and activates Notch1, both required for keratin gene expression. Arsenite prevents this cascade by maintaining ERK signaling, at least in part by suppressing DUSP expression. - Highlights: • BMP induces FOXN1 transcription. • BMP induces DUSP2 and DUSP14, suppressing ERK activation. • Arsenite suppresses levels of phosphorylated Smad1/5 and FOXN1 and DUSP mRNA. • These actions rationalize arsenite suppression of keratinocyte

  8. Diclofenac enhances proinflammatory cytokine-induced phagocytosis of cultured microglia via nitric oxide production

    Energy Technology Data Exchange (ETDEWEB)

    Kakita, Hiroki [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Aoyama, Mineyoshi, E-mail: ao.mine@med.nagoya-cu.ac.jp [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Nagaya, Yoshiaki; Asai, Hayato [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Hussein, Mohamed Hamed [Neonatal Intensive Care Unit, Pediatric Hospital, Cairo University, Cairo 11559 (Egypt); Maternal and Child Health Department, VACSERA, 51 Wizaret El-Zeraa-Agouza, Giza 22311 (Egypt); Suzuki, Mieko [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Kato, Shin [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Saitoh, Shinji [Department of Pediatrics and Neonatology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan); Asai, Kiyofumi [Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601 (Japan)

    2013-04-15

    Influenza-associated encephalopathy (IAE) is a central nervous system complication with a high mortality rate, which is increased significantly by the non-steroidal anti-inflammatory drug diclofenac sodium (DCF). In the present study, we investigated the effects of DCF on brain immune cells (i.e. microglia) stimulated with three proinflammatory cytokines, namely tumor necrosis factor-α, interleukin-1β, and interferon-γ. Similar to previous findings in astrocytes, all three cytokines induced the expression of inducible NO synthase (iNOS), as well as NO production, in microglia. The addition of DCF to the culture system augmented iNOS expression and NO production. Immunocytochemical analysis and the phagocytosis assay revealed that cytokine treatment induced morphological changes to and phagocytosis by the microglia. The addition of DCF to the culture system enhanced microglial activation, as well as the phagocytic activity of cytokine-stimulated microglia. Inhibitors of nuclear factor (NF)-κB inhibited iNOS gene expression in cytokine-stimulated microglia with or without DCF, suggesting that the NF-κB pathway is one of the main signaling pathways involved. The iNOS inhibitor N{sup G}-monomethyl-L-arginine (L-NMMA) reduced both cytokine-induced phagocytosis and phagocytosis induced by the combination of cytokines plus DCF. Furthermore, the NO donor sodium nitroprusside induced phagocytosis, indicating that NO production is a key regulator of microglial phagocytosis. In conclusion, DCF acts synergistically with proinflammatory cytokines to increase the production of NO in microglia, leading to phagocytic activity of the activated microglia. These findings, together with previous observations regarding astrocytes, may explain the significant increase in mortality of IAE patients treated with DCF. - Highlights: ► Influenza-associated encephalopathy (IAE) is associated with a high mortality rate. ► Hyperimmunization in the brain is believed to be responsible for

  9. Induction of apoptotic death and retardation of neuronal differentiation of human neural stem cells by sodium arsenite treatment

    International Nuclear Information System (INIS)

    Chronic arsenic toxicity is a global health problem that affects more than 100 million people worldwide. Long-term health effects of inorganic sodium arsenite in drinking water may result in skin, lung and liver cancers and in severe neurological abnormalities. We investigated in the present study whether sodium arsenite affects signaling pathways that control cell survival, proliferation and neuronal differentiation of human neural stem cells (NSC). We demonstrated that the critical signaling pathway, which was suppressed by sodium arsenite in NSC, was the protective PI3K–AKT pathway. Sodium arsenite (2–4 μM) also caused down-regulation of Nanog, one of the key transcription factors that control pluripotency and self-renewal of stem cells. Mitochondrial damage and cytochrome-c release induced by sodium arsenite exposure was followed by initiation of the mitochondrial apoptotic pathway in NSC. Beside caspase-9 and caspase-3 inhibitors, suppression of JNK activity decreased levels of arsenite-induced apoptosis in NSC. Neuronal differentiation of NSC was substantially inhibited by sodium arsenite exposure. Overactivation of JNK1 and ERK1/2 and down-regulation of PI3K–AKT activity induced by sodium arsenite were critical factors that strongly affected neuronal differentiation. In conclusion, sodium arsenite exposure of human NSC induces the mitochondrial apoptotic pathway, which is substantially accelerated due to the simultaneous suppression of PI3K–AKT. Sodium arsenite also negatively affects neuronal differentiation of NSC through overactivation of MEK–ERK and suppression of PI3K–AKT. - Highlights: ► Arsenite induces the mitochondrial apoptotic pathway in human neural stem cells. ► Arsenite-induced apoptosis is strongly upregulated by suppression of PI3K–AKT. ► Arsenite-induced apoptosis is strongly down-regulated by inhibition of JNK–cJun. ► Arsenite negatively affects neuronal differentiation by inhibition of PI3K–AKT

  10. Induction of apoptotic death and retardation of neuronal differentiation of human neural stem cells by sodium arsenite treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ivanov, Vladimir N., E-mail: vni3@columbia.edu [Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, NY 10032 (United States); Hei, Tom K. [Center for Radiological Research, Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, NY 10032 (United States)

    2013-04-01

    Chronic arsenic toxicity is a global health problem that affects more than 100 million people worldwide. Long-term health effects of inorganic sodium arsenite in drinking water may result in skin, lung and liver cancers and in severe neurological abnormalities. We investigated in the present study whether sodium arsenite affects signaling pathways that control cell survival, proliferation and neuronal differentiation of human neural stem cells (NSC). We demonstrated that the critical signaling pathway, which was suppressed by sodium arsenite in NSC, was the protective PI3K–AKT pathway. Sodium arsenite (2–4 μM) also caused down-regulation of Nanog, one of the key transcription factors that control pluripotency and self-renewal of stem cells. Mitochondrial damage and cytochrome-c release induced by sodium arsenite exposure was followed by initiation of the mitochondrial apoptotic pathway in NSC. Beside caspase-9 and caspase-3 inhibitors, suppression of JNK activity decreased levels of arsenite-induced apoptosis in NSC. Neuronal differentiation of NSC was substantially inhibited by sodium arsenite exposure. Overactivation of JNK1 and ERK1/2 and down-regulation of PI3K–AKT activity induced by sodium arsenite were critical factors that strongly affected neuronal differentiation. In conclusion, sodium arsenite exposure of human NSC induces the mitochondrial apoptotic pathway, which is substantially accelerated due to the simultaneous suppression of PI3K–AKT. Sodium arsenite also negatively affects neuronal differentiation of NSC through overactivation of MEK–ERK and suppression of PI3K–AKT. - Highlights: ► Arsenite induces the mitochondrial apoptotic pathway in human neural stem cells. ► Arsenite-induced apoptosis is strongly upregulated by suppression of PI3K–AKT. ► Arsenite-induced apoptosis is strongly down-regulated by inhibition of JNK–cJun. ► Arsenite negatively affects neuronal differentiation by inhibition of PI3K–AKT.

  11. Effects of icariin on cytokine-induced ankylosing spondylitis with fibroblastic osteogenesis and its molecular mechanism.

    Science.gov (United States)

    Jia, Chunrong; Liu, Hongxiao; Li, Min; Wu, Zhikui; Feng, Xinghua

    2014-01-01

    The aim of this study is to explore the effects of icariin on cytokine induced ankylosing spondylitis fibroblast osteogenesis type expression and its molecular mechanism. The normal fibroblasts were collected as normal control group, and the fibroblasts of hip joint capsule of AS patients were collected, which were respectively added in fetal bovine serum (group AS), fetal bovine serum and cytokines (BMP-2+TGF-beta 1) (group AS), and cell factor solution (icariin group), and observed of the osteogenic expression of fibroblast, to evaluate the impact of Icariin on it. The ALP activity, the content of collagen, osteocalcin content and cbfa1mRNA and OCmRNA of fibroblast of AS group increased compared to the normal control group and AS control group (P < 0.01), indicating that icariin can significantly inhibit the above changes (P < 0.01). Icariin can inhibit fibroblast further osteogenic differentiation through inhibiting the effect of cytokines on the fibroblast osteogenesis type markers and osteogenic gene expression and osteogenic differentiation.

  12. Angiopoietin-2 is critical for cytokine-induced vascular leakage.

    Science.gov (United States)

    Benest, Andrew V; Kruse, Karoline; Savant, Soniya; Thomas, Markus; Laib, Anna M; Loos, Elias K; Fiedler, Ulrike; Augustin, Hellmut G

    2013-01-01

    Genetic experiments (loss-of-function and gain-of-function) have established the role of Angiopoietin/Tie ligand/receptor tyrosine kinase system as a regulator of vessel maturation and quiescence. Angiopoietin-2 (Ang-2) acts on Tie2-expressing resting endothelial cells as an antagonistic ligand to negatively interfere with the vessel stabilizing effects of constitutive Ang-1/Tie-2 signaling. Ang-2 thereby controls the vascular response to inflammation-inducing as well as angiogenesis-inducing cytokines. This study was aimed at assessing the role of Ang-2 as an autocrine (i.e. endothelial-derived) regulator of rapid vascular responses (within minutes) caused by permeability-inducing agents. Employing two independent in vivo assays to quantitatively assess vascular leakage (tracheal microsphere assay, 1-5 min and Miles assay, 20 min), the immediate vascular response to histamine, bradykinin and VEGF was analyzed in Ang-2-deficient (Ang-2(-/-)) mice. In comparison to the wild type control mice, the Ang2(-/-) mice demonstrated a significantly attenuated response. The Ang-2(-/-) phenotype was rescued by systemic administration (paracrine) of an adenovirus encoding Ang-2. Furthermore, cytokine-induced intracellular calcium influx was impaired in Ang-2(-/-) endothelioma cells, consistent with reduced phospholipase activation in vivo. Additionally, recombinant human Ang-2 (rhAng-2) alone was unable to induce vascular leakage. In summary, we report here in a definite genetic setting that Ang-2 is critical for multiple vascular permeability-inducing cytokines. PMID:23940579

  13. Angiopoietin-2 is critical for cytokine-induced vascular leakage.

    Directory of Open Access Journals (Sweden)

    Andrew V Benest

    Full Text Available Genetic experiments (loss-of-function and gain-of-function have established the role of Angiopoietin/Tie ligand/receptor tyrosine kinase system as a regulator of vessel maturation and quiescence. Angiopoietin-2 (Ang-2 acts on Tie2-expressing resting endothelial cells as an antagonistic ligand to negatively interfere with the vessel stabilizing effects of constitutive Ang-1/Tie-2 signaling. Ang-2 thereby controls the vascular response to inflammation-inducing as well as angiogenesis-inducing cytokines. This study was aimed at assessing the role of Ang-2 as an autocrine (i.e. endothelial-derived regulator of rapid vascular responses (within minutes caused by permeability-inducing agents. Employing two independent in vivo assays to quantitatively assess vascular leakage (tracheal microsphere assay, 1-5 min and Miles assay, 20 min, the immediate vascular response to histamine, bradykinin and VEGF was analyzed in Ang-2-deficient (Ang-2(-/- mice. In comparison to the wild type control mice, the Ang2(-/- mice demonstrated a significantly attenuated response. The Ang-2(-/- phenotype was rescued by systemic administration (paracrine of an adenovirus encoding Ang-2. Furthermore, cytokine-induced intracellular calcium influx was impaired in Ang-2(-/- endothelioma cells, consistent with reduced phospholipase activation in vivo. Additionally, recombinant human Ang-2 (rhAng-2 alone was unable to induce vascular leakage. In summary, we report here in a definite genetic setting that Ang-2 is critical for multiple vascular permeability-inducing cytokines.

  14. Clinical Studies Applying Cytokine-Induced Killer Cells for the Treatment of Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Clara E. Jäkel

    2012-01-01

    Full Text Available Metastatic renal cell carcinoma (RCC seems to be resistant to conventional chemo- and radiotherapy and the general treatment regimen of cytokine therapy produces only modest responses while inducing severe side effects. Nowadays standard of care is the treatment with VEGF-inhibiting agents or mTOR inhibition; nevertheless, immunotherapy can induce complete remissions and long-term survival in selected patients. Among different adoptive lymphocyte therapies, cytokine-induced killer (CIK cells have a particularly advantageous profile as these cells are easily available, have a high proliferative rate, and exhibit a high antitumor activity. Here, we reviewed clinical studies applying CIK cells, either alone or with standard therapies, for the treatment of RCC. The adverse events in all studies were mild, transient, and easily controllable. In vitro studies revealed an increased antitumor activity of peripheral lymphocytes of participants after CIK cell treatment and CIK cell therapy was able to induce complete clinical responses in RCC patients. The combination of CIK cell therapy and standard therapy was superior to standard therapy alone. These studies suggest that CIK cell immunotherapy is a safe and competent treatment strategy for RCC patients and further studies should investigate different treatment combinations and schedules for optimal application of CIK cells.

  15. Effects of arsenite and UVA-1 radiation on calcineurin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Musson, Ruben E.A., E-mail: rm@ream.nl [Department of Clinical Chemistry, Leiden University Medical Center (Netherlands); Department of Toxicogenetics, Leiden University Medical Center (Netherlands); Mullenders, Leon H.F. [Department of Toxicogenetics, Leiden University Medical Center (Netherlands); Smit, Nico P.M. [Department of Clinical Chemistry, Leiden University Medical Center (Netherlands)

    2012-07-01

    Calcineurin is a Ca{sup 2+}-dependent serine/threonine phosphatase and the target of the immunosuppressive drugs cyclosporin and tacrolimus, which are used in transplant recipients to prevent rejection. Unfortunately, the therapeutic use of this drugs is complicated by a high incidence of skin malignancy, which has set off a number of studies into the role of calcineurin signaling in skin, particularly with respect to cell cycle control and DNA repair. Both UVA1 radiation and arsenic species are known to promote skin cancer development via production of reactive oxygen species. In light of the well-documented sensitivity of calcineurin to oxidative stress, we examined and compared the effects of UVA1 and arsenite on calcineurin signaling. In this paper, we show that physiologically relevant doses of UVA1 radiation and low micromolar concentrations of arsenite strongly inhibit calcineurin phosphatase activity in Jurkat and skin cells and decrease NFAT nuclear translocation in Jurkat cells. The effects on calcineurin signaling could be partly prevented by inhibition of NADPH oxidase in Jurkat cells or increased dismutation of superoxide in Jurkat and skin cells. In addition, both UVA1 and arsenite decreased NF-{kappa}B activity, although at lower concentrations, arsenite enhanced NF-{kappa}B activity. These data indicate that UVA1 and arsenite affect a signal transduction route of growingly acknowledged importance in skin and that calcineurin may serve as a potential link between ROS exposure and impaired tumor suppression.

  16. Reduction of arsenite-enhanced ultraviolet radiation-induced DNA damage by supplemental zinc

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Karen L.; King, Brenee S.; Sandoval, Monica M.; Liu, Ke Jian; Hudson, Laurie G., E-mail: lhudson@salud.unm.edu

    2013-06-01

    Arsenic is a recognized human carcinogen and there is evidence that arsenic augments the carcinogenicity of DNA damaging agents such as ultraviolet radiation (UVR) thereby acting as a co-carcinogen. Inhibition of DNA repair is one proposed mechanism to account for the co-carcinogenic actions of arsenic. We and others find that arsenite interferes with the function of certain zinc finger DNA repair proteins. Furthermore, we reported that zinc reverses the effects of arsenite in cultured cells and a DNA repair target protein, poly (ADP-ribose) polymerase-1. In order to determine whether zinc ameliorates the effects of arsenite on UVR-induced DNA damage in human keratinocytes and in an in vivo model, normal human epidermal keratinocytes and SKH-1 hairless mice were exposed to arsenite, zinc or both before solar-simulated (ss) UVR exposure. Poly (ADP-ribose) polymerase activity, DNA damage and mutation frequencies at the Hprt locus were measured in each treatment group in normal human keratinocytes. DNA damage was assessed in vivo by immunohistochemical staining of skin sections isolated from SKH-1 hairless mice. Cell-based findings demonstrate that ssUVR-induced DNA damage and mutagenesis are enhanced by arsenite, and supplemental zinc partially reverses the arsenite effect. In vivo studies confirm that zinc supplementation decreases arsenite-enhanced DNA damage in response to ssUVR exposure. From these data we can conclude that zinc offsets the impact of arsenic on ssUVR-stimulated DNA damage in cells and in vivo suggesting that zinc supplementation may provide a strategy to improve DNA repair capacity in arsenic exposed human populations. - Highlights: • Low levels of arsenite enhance UV-induced DNA damage in human keratinocytes. • UV-initiated HPRT mutation frequency is enhanced by arsenite. • Zinc supplementation offsets DNA damage and mutation frequency enhanced by arsenite. • Zinc-dependent reduction of arsenite enhanced DNA damage is confirmed in vivo.

  17. Transduction of PEP-1-heme oxygenase-1 into insulin-producing INS-1 cells protects them against cytokine-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Su Jin; Kang, Hyung Kyung [Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Song, Dong Keun [Department of Pharmacology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of); Eum, Won Sik; Park, Jinseu [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Choi, Soo Young, E-mail: sychoi@hallym.ac.kr [Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702 (Korea, Republic of); Kwon, Hyeok Yil, E-mail: hykwon@hallym.ac.kr [Department of Physiology, College of Medicine, Hallym University, Chunchon 200-702 (Korea, Republic of)

    2015-06-05

    Pro-inflammatory cytokines play a crucial role in the destruction of pancreatic β-cells, thereby triggering the development of autoimmune diabetes mellitus. We recently developed a cell-permeable fusion protein, PEP-1-heme oxygenase-1 (PEP-1-HO-1) and investigated the anti-inflammatory effects in macrophage cells. In this study, we transduced PEP-1-HO-1 into INS-1 insulinoma cells and examined its protective effect against cytokine-induced cell death. PEP-1-HO-1 was successfully delivered into INS-1 cells in time- and dose-dependent manner and was maintained within the cells for at least 48 h. Pre-treatment with PEP-1-HO-1 increased the survival of INS-1 cells exposed to cytokine mixture (IL-1β, IFN-γ, and TNF-α) in a dose-dependent manner. PEP-1-HO-1 markedly decreased cytokine-induced production of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA). These protective effects of PEP-1-HO-1 against cytokines were correlated with the changes in the levels of signaling mediators of inflammation (iNOS and COX-2) and cell apoptosis/survival (Bcl-2, Bax, caspase-3, PARP, JNK, and Akt). These results showed that the transduced PEP-1-HO-1 efficiently prevented cytokine-induced cell death of INS-1 cells by alleviating oxidative/nitrosative stresses and inflammation. Further, these results suggested that PEP-1-mediated HO-1 transduction may be a potential therapeutic strategy to prevent β-cell destruction in patients with autoimmune diabetes mellitus. - Highlights: • We showed that PEP-1-HO-1 was efficiently delivered into INS-1 cells. • Transduced PEP-1-HO-1 exerted a protective effect against cytokine-induced cell death. • Transduced PEP-1-HO-1 inhibited cytokine-induced ROS and NO accumulation. • PEP-1-HO-1 suppressed cytokine-induced expression of iNOS, COX-2, and Bax. • PEP-1-HO-1 transduction may be an efficient tool to prevent β-cell destruction.

  18. The accumulations of HIF-1α and HIF-2α by JNK and ERK are involved in biphasic effects induced by different levels of arsenite in human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan; Li, Yuan [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); Li, Huiqiao [Qujing Center for Disease Control and Prevention, Qujing 655000, Yunnan (China); Pang, Ying; Zhao, Yue; Jiang, Rongrong; Shen, Lu [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); Zhou, Jianwei; Wang, Xinru [The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); Liu, Qizhan, E-mail: drqzliu@hotmail.com [Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, Jiangsu (China)

    2013-01-15

    The biphasic effects of arsenite, in which low levels of arsenite induce cell proliferation and high levels of arsenite induce DNA damage and apoptosis, apparently contribute to arsenite-induced carcinogenesis. However, the mechanisms underlying this phenomenon are not well understood. In this study, we investigated the effects of different levels of arsenite on cell proliferation, DNA damage and apoptosis as well as on signal transduction pathways in human bronchial epithelial (HBE) cells. Our results show that a low level of arsenite activates extracellular signal-regulated kinases (ERK), which probably mediate arsenite-inhibited degradation of ubiquitinated hypoxia-inducible factor-2α (HIF-2α) in HBE cells. ERK inhibition blocks cell proliferation induced by a low level of arsenite, in part via HIF-2α. In contrast, a high level of arsenite activates c-Jun N-terminal kinases (JNK), which provoke a response to suppress ubiquitinated HIF-1α degradation. Down-regulation of HIF-1α by inhibiting JNK, however, increases the DNA damage but decreases the apoptosis induced by a high level of arsenite. Thus, data in the present study suggest that the accumulations of HIF-1α and HIF-2α by JNK and ERK are involved in different levels of arsenite-induced biphasic effects, with low levels of arsenite inducing cell proliferation and high levels of arsenite inducing DNA damage and apoptosis in HBE cells. -- Highlights: ► Biphasic effects induced by different concentrations of arsenite. ► Different regulation of ERK or JNK signal pathway by arsenite. ► Different regulation of HIF1α or HIF 2α by arsenite.

  19. 亚砷酸钠抑制肝癌细胞增殖与PML蛋白表达%Sodium arsenite inhibiting proliferation of hepatoceullar carcinoma cells and expression of promyelocytic leukemia protein

    Institute of Scientific and Technical Information of China (English)

    王伟; 杨俊涛; 刘宏鸣; 袁涛; 刘孟刚; 金世龙

    2016-01-01

    目的:研究亚砷酸钠抑制肝癌(HCC)细胞增殖是否与早幼粒细胞白血病(PML)蛋白表达有关。方法免疫组织化学法、免疫荧光、蛋白免疫印迹法(Western blot)和荧光定量PCR检测HCC组织PML蛋白及基因表达。结果免疫组织化学分析显示随机选择15例高分化、中度分化和低分化HCC组织和细胞均不同程度表达PML蛋白。Western blot 分析发现24例HCC组织、HuH7、HepG2、Hep3B、SMMC‐7721和 L02细胞均表达 PML 蛋白。免疫荧光提示 HuH7、HepG2、Hep3B、SMMC‐7721细胞核均有PML蛋白颗粒,其中 HuH7和 Hep3B细胞表达PML蛋白较 HepG2、SMMC‐7721细胞多。24例 HCC组织, Hep3B、HepG2、SMCC‐7721和HuH7细胞都表达PML基因。亚砷酸钠不仅可下调HuH7和原代 HCC细胞表达PML蛋白,而且亚砷酸钠抑制HuH7,HepG2,Hep3B和SMMC‐7721细胞生长,随着暴露时间延长亚砷酸钠对HCC细胞抑制作用增强。结论HCC 组织和细胞系普遍表达PML 基因和蛋白,PML 蛋白可能是砷剂直接靶向作用的分子基础。%Objective To investigate whether the sodium arsenite inhibiting proliferation of hepatocellar carcinoma(HCC) cells and having a relation with the expression of promyelocytic leukemia (PML) protein .Methods The immunohistochemistry , Western blot analysis ,immunofluorescence assay and quantitative PCR were used to examine the PML gene and protein expression in HCC tissue and cells .Results The immunohis to chemical staining showed that the PML protein was expressed in nucleus of well‐differentiated ,moderately differentiated and poorly differentiated HCC tissues randomly selected from 15 cases of HCC under‐going hepatic resection .Western blot analysis showed that PML protein was expressed at varying levels in all 24 HCC tissue sam‐ples ,HuH7 ,HepG2 ,Hep3B ,SMMC‐7721 and L02 cells .The immunofluorescence assay demonstrated that PML protein grains were found in the nucleis of the HuH7

  20. Retention of cytokine-inducing substances inside high-flux dialyzers.

    Science.gov (United States)

    Lufft, V; Mahiout, A; Shaldon, S; Koch, K M; Schindler, R

    1996-01-01

    Reprocessing of dialyzers is often performed with nonsterile solutions possibly contaminated with bacterial-derived cytokine-inducing substances. We investigated the retention of cytokine-inducing substances inside the dialyzer during reprocessing in a closed loop in vitro hemodialysis system using a polyamide high flux membrane. After the first in vitro circulation of human whole blood, rinse of the blood compartment (BC) and reverse ultrafiltration (RUF) was performed with either cytokine-inducing substance-free saline or saline contaminated with filtrates from Pseudomonas cultures (6 ng/ml LAL-reactive material); subsequently, dialyzers were stored in 2% formaldehyde. Dialyzers were rinsed with approximately 15 liters pyrogen-free saline before the second circulation using blood from the same donor; the effluates were free of cytokine-inducing substances and formaldehyde. Before and after the blood circulations, peripheral blood mononuclear cells (PBMC) were separated and total production of IL-1 alpha and IL-1 beta was determined after overnight incubation. In noncirculated PBMC as well as in PBMC separated after whole blood circulation with pyrogen-free processed dialyzers, production of IL-1 beta was not detectable. After contaminated rinse of the BC, production of IL-1 beta could be observed (1,600 +/- 1,100 pg/ml, mean +/- SEM). When pyrogen-free RUF was performed after contaminated BC rinse, IL-1 beta production averaged 163 +/- 92 pg/ml when using reused dialyzers, but 1,820 +/- 880 pg/ml when using new dialyzers. After reuse with pyrogen-free BC-rinse and contaminated RUF no IL-1 beta synthesis was observed; however, when pyrogen-free BC-rinse and contaminated RUF was applied to new dialyzers, IL-1 beta synthesis averaged 1,620 +/- 1,200 pg/ml. We conclude that cytokine-inducing substances are retained inside the dialyzer, probably by adsorption to the membrane as well as to the protein layer covering the membrane and are still biologically active after

  1. Synergistic effect of radon and sodium arsenite on DNA damage in HBE cells.

    Science.gov (United States)

    Liu, Xing; Sun, Bin; Wang, Xiaojuan; Nie, Jihua; Chen, Zhihai; An, Yan; Tong, Jian

    2016-01-01

    Human epidemiological studies showed that radon and arsenic exposures are major risk factors for lung cancer in Yunnan tin miners. However, biological evidence for this phenomenon is absent. In this study, HBE cells were exposed to different concentrations of sodium arsenite, different radon exposure times, or a combination of these two factors. The results showed a synergistic effect of radon and sodium arsenite in cell cytotoxicity as determined by cell viability. Elevated intracellular ROS levels and increased DNA damage indexed by comet assay and γ-H2AX were detected. Moreover, DNA HR repair in terms of Rad51 declined when the cells were exposed to both radon and sodium arsenite. The synergistic effect of radon and sodium arsenite in HBE cells may be attributed to the enhanced DSBs and inhibited HR pathway upon co-exposure.

  2. A cytokine-inducing hemagglutinin from small taros.

    Science.gov (United States)

    Chan, Yau Sang; Wong, Jack Ho; Ng, Tzi Bun

    2010-07-01

    A 22.4-kDa dimeric hemagglutinin was isolated from tubers of Colocasia esculenta cv. 'Small Taro' by employing a purification protocol that involved ion exchange chromatography on Q-Sepharose, fast protein liquid chromatography (FPLC)-ion exchange chromatography on Mono Q, and FPLC-gel filtration on Superdex 75. The hemagglutinin was isolated from the fraction of the taro extract adsorbed on Q-Sepharose and subsequently adsorbed on Mono Q. The major absorbance peak from the Superdex 75 column constituted purified hemagglutinin. Its hemagglutinating activity could not be inhibited by simple sugars, and was stable after exposure for 30 minutes to temperatures up to 40 degrees C and to ambient pH in the range of pH 2 to pH 13. The activity decreased progressively when the ambient temperature was raised from 40 degrees C to 100 degrees C. Negligible activity was detected at 100 degrees C. The activity plummeted, with about 40% and 10% remaining, 4 minutes and 20 minutes after exposure to 100 degrees C, respectively. About half of the activity remained at pH 0 and pH 1 whereas the activity was completely abolished at pH 14. The hemagglutinin exhibited slight anti-tumor activity toward hepatoma HepG2 cells, and weak mitogenic activity toward murine splenocytes. It induced expression of the cytokines interleukin-1 beta, interleukin-2, interferon-gamma and tumor necrosis factor-alpha. However, it was devoid of anti-fungal activity toward a number of fungal species. PMID:19807671

  3. Removal of arsenite by simultaneous electro-oxidation and electro-coagulation process

    International Nuclear Information System (INIS)

    An electrochemical reactor was built and used to remove arsenite from water. In this reactor, arsenite can be oxidized into arsenate, which was removed by electro-coagulation process simultaneously. The reactor mainly included dimension stable anode (DSA) and iron plate electrode. Oxidation of arsenite will occur at the DSA electrode in the electrochemical process. Meantime, the iron ions can be generated by the electro-induced process and iron oxides will form. Thus, the arsenic was removed by coagulation process. Influencing factors on the removal of arsenite were investigated. It is found that Ca2+ and Mg2+ ions promoted the removal of arsenite. However, Cl-, CO32-, SiO32-, and PO43- ions inhibited the arsenic removal. And, it is observed that the inhibition effect was the largest in the presence of PO43-. Furthermore, it is observed that the removal efficiency of arsenate is the largest in the pH value of 8. Increase or decrease of pH value did not benefit to the arsenite removal. Fourier transform infrared spectra were used to analyze the floc particles, it is suggested that the removal mechanism of As(III) in this system seems to be oxidative of As(III) to As(V) and to be removed by adsorption/complexation with metal hydroxides generated in the process.

  4. Cytokine-induced killer cell therapy-associated idiopathic thrombocytopenic purpura: rare but noteworthy.

    Science.gov (United States)

    Fu, Xiaomin; Zhang, Yong; Gao, Quanli; Lin, Jizhen; Zhang, Qinxian; Xu, Benling; Song, Yongping

    2016-09-01

    Idiopathic thrombocytopenic purpura (ITP) is characterized by a diminished platelet count, an autoimmune condition with antibodies against platelets and an increased tendency to bleed. The association between ITP and solid tumors is uncommon. Cytokine-induced killer (CIK) cell therapy is a well tolerated and promising cancer treatment with minimal toxicity. For the first time, CIK cell therapy was reported to be followed by ITP. The mechanism through which CIK induces ITP remains unclear. Imbalanced ratio of Th cells, decreased numbers or impaired function of Treg cells and excessive secretion of cytokines inducing abnormal activation of B cells may be among the possible reasons. Therefore, a better understanding of this rare condition will require further investigation of these cases. PMID:27485074

  5. Cytokine-induced killer (CIK cell therapy for patients with hepatocellular carcinoma: efficacy and safety

    Directory of Open Access Journals (Sweden)

    Ma Yue

    2012-04-01

    Full Text Available Abstract Purpose To evaluate the efficacy of cytokine-induced killer (CIK cell therapy in the treatment of hepatocellular carcinoma. Materials and methods Randomized phase II and III trials on CIK cell-based therapy were identified by electronic searches using a combination of "hepatocellular carcinoma" and "cytokine-induced killer cells". Results The analysis showed significant survival benefit (one-year survival, p p p p p p +, CD4+, CD4+CD8+ and CD3+CD4+ T cells significantly increased in the CIK group, compared with the non-CIK group (p Conclusions CIK cell therapy demonstrated a significant superiority in prolonging the median overall survival, PFS, DCR, ORR and QoL of HCC patients. These results support further larger scale randomized controlled trials for HCC patients with or without the combination of other therapeutic methods.

  6. Sodium arsenite down-regulates the expression of X-linked inhibitor of apoptosis protein via translational and post-translational mechanisms in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Hong; Hao, Yuqing; Wang, Lijing; Jia, Dongwei [Gene Research Center, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Ruan, Yuanyuan, E-mail: yuanyuanruan@fudan.edu.cn [Gene Research Center, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Gene Research Center, Shanghai Medical College, Fudan University, Shanghai 200032 (China)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Sodium arsenite down-regulates the protein expression level of XIAP in HCC. Black-Right-Pointing-Pointer Sodium arsenite inhibits the de novo XIAP synthesis and its IRES activity. Black-Right-Pointing-Pointer Sodium arsenite decreases XIAP stability and promotes its proteasomal degradation. Black-Right-Pointing-Pointer Overexpression of XIAP attenuates the pro-apoptotic effect of sodium arsenite. -- Abstract: X-linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitors of apoptosis protein (IAP) family, and has been reported to exhibit elevated expression levels in hepatocellular carcinoma (HCC) and promote cell survival, metastasis and tumor recurrence. Targeting XIAP has proven effective for the inhibition of cancer cell proliferation and restoration of cancer cell chemosensitivity. Arsenic (or sodium arsenite) is a potent anti-tumor agent used to treat patients with acute promyelocytic leukemia (APL). Additionally, arsenic induces cell growth inhibition, cell cycle arrest and apoptosis in human HCC cells. In this study, we identified XIAP as a target for sodium arsenite-induced cytotoxicity in HCC. The exposure of HCC cell lines to sodium arsenite resulted in inhibition of XIAP expression in both a dose- and time-dependent manner. Sodium arsenite blocked the de novo XIAP synthesis and the activity of its internal ribosome entry site (IRES) element. Moreover, treatment with sodium arsenite decreased the protein stability of XIAP and induced its ubiquitin-proteasomal degradation. Overexpression of XIAP attenuated the pro-apoptotic effect of sodium arsenite in HCC. Taken together, our data demonstrate that sodium arsenite suppresses XIAP expression via translational and post-translational mechanisms in HCC.

  7. The Genotoxicity of Sodium Arsenite in Human Lymphocyte Culture

    International Nuclear Information System (INIS)

    Sodium arsenite was tested for its clastogenic effect alone and on isolated lymphocyte culture. The results showed a significant difference in the yield of chromosome aberrations induced with respect to the culture time 48 h. Whole blood culture showed significant increase in gaps and breaks whereas isolated lymphocyte culture showed significant inhibition of cell cycle and 75% of the lymphocytes were in their first cell cycle at 72 hr. Arsenite showed co-mutagenicity with different doses of x-ray delivered immediately or few hours after treatment of the culture with S A. The results suggest that S A is also mutagenic at the dose level used and provide support for the indispensability of whole blood culture for evaluation of the in vivo effect of any suspected mustagen using isolated lymphocytes appear to have problems leading to extensive cell cycle delay

  8. From the Cover: Arsenite Uncouples Mitochondrial Respiration and Induces a Warburg-like Effect in Caenorhabditis elegans.

    Science.gov (United States)

    Luz, Anthony L; Godebo, Tewodros R; Bhatt, Dhaval P; Ilkayeva, Olga R; Maurer, Laura L; Hirschey, Matthew D; Meyer, Joel N

    2016-08-01

    Millions of people worldwide are chronically exposed to arsenic through contaminated drinking water. Despite decades of research studying the carcinogenic potential of arsenic, the mechanisms by which arsenic causes cancer and other diseases remain poorly understood. Mitochondria appear to be an important target of arsenic toxicity. The trivalent arsenical, arsenite, can induce mitochondrial reactive oxygen species production, inhibit enzymes involved in energy metabolism, and induce aerobic glycolysis in vitro, suggesting that metabolic dysfunction may be important in arsenic-induced disease. Here, using the model organism Caenorhabditis elegans and a novel metabolic inhibition assay, we report an in vivo induction of aerobic glycolysis following arsenite exposure. Furthermore, arsenite exposure induced severe mitochondrial dysfunction, including altered pyruvate metabolism; reduced steady-state ATP levels, ATP-linked respiration and spare respiratory capacity; and increased proton leak. We also found evidence that induction of autophagy is an important protective response to arsenite exposure. Because these results demonstrate that mitochondria are an important in vivo target of arsenite toxicity, we hypothesized that deficiencies in mitochondrial electron transport chain genes, which cause mitochondrial disease in humans, would sensitize nematodes to arsenite. In agreement with this, nematodes deficient in electron transport chain complexes I, II, and III, but not ATP synthase, were sensitive to arsenite exposure, thus identifying a novel class of gene-environment interactions that warrant further investigation in the human populace.

  9. Efficient lysis of rhabdomyosarcoma cells by cytokine-induced killer cells: implications for adoptive immunotherapy after allogeneic stem cell transplantation

    OpenAIRE

    Kuçi, Selim; Rettinger, Eva; Voß, Bernhard; Weber, Gerrit; Stais, Miriam; Kreyenberg, Hermann; Willasch, Andre; Kuçi, Zyrafete; Koscielniak, Ewa; Klöss, Stephan; Laer, Dorothee von; Klingebiel, Thomas; Bader, Peter

    2010-01-01

    Background: Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and has a poor prognosis. Here we assessed the capability of ex vivo expanded cytokine-induced killer cells to lyse both alveolar and embryonic rhabdomyosarcoma cell lines and investigated the mechanisms involved. Design and Methods: Peripheral blood mononuclear cells from six healthy donors were used to generate and expand cytokine-induced killer cells. The phenotype and composition of these cells were deter...

  10. Sorption of Arsenite onto Mackinawite Coated Sand

    Science.gov (United States)

    Gallegos, T. J.; Hayes, K. F.; Abriola, L. M.

    2004-05-01

    Arsenic contamination of groundwater is a widespread problem affecting aquifers in the United States as well as abroad. Recent strengthening of the US EPA MCL for arsenic has prompted the need for technology capable of removing both arsenite and arsenate from solution. Arsenite, the more toxic form of arsenic, is more difficult to remove from anoxic zones in the subsurface. Studies by others have demonstrated the affinity of some types of iron sulfides for arsenite, such as troilite, pyrite, amorphous iron sulfide and mackinawite. However, these studies have not provided a comprehensive investigation of the macroscopic behavior of arsenite in the presence of crystalline mackinawite in a form that can be readily applied to real-world treatment technologies. This study examines the behavior of arsenite in the presence of mackinawite coated sand. PH edge results demonstrate that arsenite sorption onto mackinawite coated sand increases with increasing pH, reaching maximum removal at pH 10. Arsenite removal, albeit slight, occurring below pH 5 is independent of pH indicative of a different removal mechanism. Isotherm studies show that at low concentrations, removal is Langmuirian in nature. Arsenite sorption abruptly converts to linear behavior at high concentrations, possibly attributed to the saturation of the monolayer. Ionic strength effects were assessed by comparing pH edge data developed for three different concentrations of NaCl background electrolyte solution. Increases in ionic strength enhance the removal of arsenite from solution, suggesting possible inner-sphere surface complexation removal mechanisms. Information gathered in this study can be used to further develop surface complexation models to describe and predict reactivity of arsenite in the presence of mackinawite coated sands in anoxic regions. Mackinawite coated sands investigated here may provide a feasible reactive medium for implementation in above-ground sorption reactors or subsurface

  11. Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression.

    OpenAIRE

    Gerritsen, M. E.; Carley, W. W.; Ranges, G. E.; Shen, C. P.; Phan, S. A.; Ligon, G. F.; Perry, C. A.

    1995-01-01

    Treatment of human endothelial cells with cytokines such as interleukin-1, tumor necrosis factor-alpha (TNF-alpha) or interferon-gamma induces the expression of specific leukocyte adhesion molecules on the endothelial cell surface. Interfering with either leukocyte adhesion or adhesion protein upregulation is an important therapeutic target as evidenced by the potent anti-inflammatory actions of neutralizing antibodies to these ligands in various animal models and in patients. In the present ...

  12. IGFBP-3 Inhibits Cytokine-Induced Insulin Resistance and Early Manifestations of Atherosclerosis

    OpenAIRE

    Lathika Mohanraj; Ho-Seong Kim; Wei Li; Qing Cai; Ki Eun Kim; Hye-Jung Shin; Yong-Jae Lee; Woo Jung Lee; Jung Hyun Kim; Youngman Oh

    2013-01-01

    Metabolic syndrome is associated with visceral obesity, insulin resistance and an increased risk of cardiovascular diseases. Visceral fat tissue primarily consists of adipocytes that secrete cytokines leading to a state of systemic inflammation in obese conditions. One of the IGF-independent functions of IGFBP-3 is its role as an anti-inflammatory molecule. Our study in obese adolescents show a decrease in total IGFBP-3 levels and increase in proteolyzed IGFBP-3 in circulation when compared t...

  13. Inhibition of histone deacetylases prevents cytokine-induced toxicity in beta cells

    DEFF Research Database (Denmark)

    Larsen, L; Tonnesen, M; Ronn, S G;

    2007-01-01

    B (NFkappaB) is a critical signalling molecule in inflammation and is required for expression of the gene encoding inducible NO synthase (iNOS) and of pro-apoptotic genes. NFkappaB has recently been shown to associate with chromatin-modifying enzymes histone acetyltransferases and histone...... by immunoblotting and by immunoblotting combined with electrophoretic mobility shift assay, respectively. Viability was analysed by 3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and apoptosis by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay and histone...

  14. Apolipoprotein CIII Reduces Proinflammatory Cytokine-Induced Apoptosis in Rat Pancreatic Islets via the Akt Prosurvival Pathway

    DEFF Research Database (Denmark)

    Størling, Joachim; Juntti-Berggren, Lisa; Olivecrona, Gunilla;

    2011-01-01

    Apolipoprotein CIII (ApoCIII) is mainly synthesized in the liver and is important for triglyceride metabolism. The plasma concentration of ApoCIII is elevated in patients with type 1 diabetes (T1D), and in vitro ApoCIII causes apoptosis in pancreatic ß-cells in the absence of inflammatory stress...... µg/ml) did not cause apoptosis. In the presence of the islet-cytotoxic cytokines IL-1ß + interferon-¿, ApoCIII reduced cytokine-mediated islet cell death and impairment of ß-cell function. ApoCIII had no effects on mitogen-activated protein kinases (c-Jun N-terminal kinase, p38, and ERK) and had...... of the survival serine-threonine kinase Akt. Inhibition of the Akt signaling pathway by the phosphatidylinositol 3 kinase inhibitor LY294002 counteracted the antiapoptotic effect of ApoCIII on cytokine-induced apoptosis. We conclude that ApoCIII in the presence of T1D-relevant proinflammatory cytokines reduces...

  15. A Comparative Study on Rat Intestinal Epithelial Cells and Resident Gut Bacteria (ii) Effect of Arsenite

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to use facultative gut bacteria as an alternate to animals for the initial gastrointestinal toxicity screening of heavy metals, a comparative study on rat intestinal epithelial cells and resident gut bacteria was undertaken.Methods in vitro growth rate of four gut bacteria, dehydrogenase (DHA) and esterase (EA) activity test, intestinal epithelial and bacterial cell membrane enzymes and in situ effect of arsenite were analysed. Results Growth profile of mixed resident population of gut bacteria and pure isolates of Escherichia coli, Pseudomonas sp., Lactobacillus sp., and Staphylococcus sp.revealed an arsenite (2-20 ppm) concentration-dependent inhibition. The viability pattern of epithelial cells also showed similar changes. DHA and EA tests revealed significant inhibition (40%-72%) with arsenite exposure of 5 and 10 ppm in isolated gut bacteria and epithelial cells. Decrease in membrane alkaline phosphatase and Ca2+-Mg2+-ATPase activities was in the range of 33%-55% in four bacteria at the arsenite exposure of 10 ppm, whereas it was 60%-65% in intestinal epithelial villus cells. in situ incubation of arsenite using intestinal loops also showed more or less similar changes in membrane enzymes of resident gut bacterial population and epithelial cells. Conclusion The results indicate that facultative gut bacteria can be used as suitable in vitro model for the preliminary screening of arsenical gastrointestinal cytotoxic effects.

  16. Cytokine-Induced NK-Like T Cells: From Bench to Bedside

    Directory of Open Access Journals (Sweden)

    Yeh Ching Linn

    2010-01-01

    Full Text Available Cytokine-induced killer (CIK cells are polyclonal T effector cells generated when cultured under cytokine stimulation. CIK cells exhibit potent, non-MHC-restricted cytolytic activities against susceptible tumor cells of both autologous and allogeneic origins. Over the past 20 years, CIK cells have evolved from experimental observations into early clinical studies with encouraging preliminary efficacy towards susceptible autologous and allogeneic tumor cells in both therapeutic and adjuvant settings. This paper is our attempt to summarize the available published literature related to CIK cells. Looking into the future, we anticipate that the continuous therapeutic application of CIK cells will likely be developed along two major directions: overcoming the challenge to organize large prospective randomized clinical trials to define the roles of CIK cells in cancer immunotherapy and expanding its spectrum of cytotoxicity towards resistant tumor cells through experimental manipulations.

  17. Cytokine induced killer cell immunotherapy in cancer treatment: from bench to bedside

    Directory of Open Access Journals (Sweden)

    Arashar Arafar

    2014-02-01

    Full Text Available Cytokine-induced killer (CIK cells are T effector cells generated by monocytes cultured and stimulated by cytokines. CIK cells were studied for more than 20 years ago. They can cause lysis of tumor cells that of both autologous and allogeneic origins, so that they were used in cancer treatment. This review aimed to summarize advancements of CIK cells and their current clinical applications in cancer treatment. In general, CIK cells were widely clinically used for recent 5 years. They gave promising results in hepatocellular carcinoma, lung cancer, breast cancer, renal cancer, and treatment. Looking into the future, CIK cell based immunotherapy will become an important tool in cancer treatment. [Biomed Res Ther 2014; 1(2.000: 71-77

  18. ARSENITE INDUCTION OF HEME OXYGENASE AS A BIOMARKER

    Science.gov (United States)

    ARSENITE INDUCTION OF HEME OXYGENASE AS A BIOMARKER Useful biomarkers of arsenic effects in both experimental animals and humans are needed. Arsenate and arsenite are good inducers of rat hepatic and renal heme oxygenase (HO); monomethylarsonic acid (MMA) and dimethylarsi...

  19. Roles of oxidative stress and the ERK1/2, PTEN and p70S6K signaling pathways in arsenite-induced autophagy.

    Science.gov (United States)

    Huang, Ya-Chun; Yu, Hsin-Su; Chai, Chee-Yin

    2015-12-15

    Studies show that arsenite induces oxidative stress and modifies cellular function via phosphorylation of proteins and inhibition of DNA repair enzymes. Autophagy, which has multiple physiological and pathological roles in cellular function, is initiated by oxidative stress and is regulated by the signaling pathways of phosphatidylinositol 3-phosphate kinase (PI3K)/mammalian target of rapamycin (mTOR)/p70S6 kinase (p70S6K) and extracellular signaling-regulated protein kinase 1/2 (ERK1/2) that play important roles in oncogenesis. However, the effects of arsenite-induced oxidative stress on autophagy and on expression of related proteins are not fully understood. This study found that cells treated with sodium arsenite had reduced 8-oxoguanine DNA glycosylase 1 (OGG1) and increased 8-hydroxy-2'-deoxyguanosine (8-OHdG) and activating transcription factor (ATF) 3 in SV-40 immortalized human uroepithelial (SV-HUC-1) cells. Arsenite also increased the number of autophagosomes and increased levels of the autophagy markers Beclin-1 and microtubule-associated protein 1 light chain 3B. Reactive oxygen species scavenger decreased arsenite-induced autophagy in SV-HUC-1 cells. Our previous work showed that arsenite induced phosphorylation of the ERK1/2 signaling pathway. The current study further showed that arsenite decreased phosphatase and tensin homologue (PTEN) levels and increased phospho-p70S6 kinase (p-p70S6K) in SV-HUC-1 cells. However, both kinase inhibitor U0126 and the DNA (cytosine-5-)-methyltransferase 1 (DNMT1) inhibitor 5-aza-deoxycytidine abolished the effect of arsenite on expressions of PTEN and p-p70S6K. These results show that autophagy induced by arsenite exposure is mediated by oxidative stress, which regulates activation of the PTEN, p70S6K and ERK1/2 signaling pathways. Thus, this study clarifies the role of autophagy in arsenite-induced urothelial carcinogenesis. PMID:26432159

  20. Arsenite toxicity and uptake rate of rice (Oryza sativa L.) in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, Holger, E-mail: hoffmann@bgt.uni-hannover.de [Institute of Plant Nutrition, Leibniz University of Hannover, Herrenhaeuser Strasse 2, D-30419 Hannover (Germany); Schenk, Manfred K., E-mail: schenk@pflern.uni-hannover.de [Institute of Plant Nutrition, Leibniz University of Hannover, Herrenhaeuser Strasse 2, D-30419 Hannover (Germany)

    2011-10-15

    Toxicity threshold of arsenite on intact rice seedlings was determined and arsenite uptake characteristics were investigated using non-toxic concentrations of arsenite. The arsenite toxicity threshold was 2.4 {mu}M arsenite which reduced growth by 10% (EC{sub 10}). The two highest arsenite levels induced wilting of seedlings and reduced both, transpiration rate and net photosynthetic rate. Arsenic content in plant tissue increased up to 10.7 {mu}M arsenite and then declined with increasing arsenite concentration in the treatment solution. The contents of Si, P, K, and of micronutrients Cu, Fe, Mn and Zn in shoot d.m. were reduced by arsenite levels {>=} 5.3 {mu}M. In the non-toxic range, arsenite uptake rate was linearly related to arsenite concentration. High arsenite levels reduced growth without being taken up which might be due to increasing binding of arsenite to proteins at the outer side of the plasmalemma. - Highlights: > Arsenite toxicity and uptake rate were investigated with intact rice plants. > Arsenite toxicity threshold was 2.4 {mu}M arsenite. > Uptake rate was linearly related to arsenite concentration in the non-toxic range. > Arsenite concentrations above 10.6 {mu}M decreased arsenic content in plant matter. > Arsenite impaired uptake of arsenite, water and Si, P, K, Cu, Fe, Mn and Zn. - Uptake of arsenite, water, and nutrients by rice seedlings was impaired by arsenite concentrations higher than the toxicity threshold of 2.4 {mu}M.

  1. Arsenite evokes IL-6 secretion, autocrine regulation of STAT3 signaling, and miR-21 expression, processes involved in the EMT and malignant transformation of human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Fei; Xu, Yuan [Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China); Ling, Min [Jiangsu Center for Disease Control and Prevention, Nanjing 211166, Jiangsu (China); Zhao, Yue; Xu, Wenchao [Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China); Liang, Xiao [Mental Health Center of Xuhui-CDC, Shanghai 200232 (China); Jiang, Rongrong; Wang, Bairu [Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China); Bian, Qian [Jiangsu Center for Disease Control and Prevention, Nanjing 211166, Jiangsu (China); Liu, Qizhan, E-mail: drqzliu@hotmail.com [Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China); The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University (China)

    2013-11-15

    Arsenite is an established human carcinogen, and arsenite-induced inflammation contributes to malignant transformation of cells, but the molecular mechanisms by which cancers are produced remain to be established. The present results showed that, evoked by arsenite, secretion of interleukin-6 (IL-6), a pro-inflammatory cytokine, led to the activation of STAT3, a transcription activator, and to increased levels of a microRNA, miR-21. Blocking IL-6 with anti-IL-6 antibody and inhibiting STAT3 activation reduced miR-21 expression. For human bronchial epithelial cells, cultured in the presence of anti-IL-6 antibody for 3 days, the arsenite-induced EMT and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates miR-21in an autocrine manner, contributes to the EMT induced by arsenite. These data define a link from inflammation to EMT in the arsenite-induced malignant transformation of HBE cells. This link, mediated through miRNAs, establishes a mechanism for arsenite-induced lung carcinogenesis. - Highlights: • Arsenite evokes IL-6 secretion. • IL-6 autocrine mediates STAT3 signaling and up-regulates miR-21expression. • Inflammation is involved in arsenite-induced EMT.

  2. Arsenite evokes IL-6 secretion, autocrine regulation of STAT3 signaling, and miR-21 expression, processes involved in the EMT and malignant transformation of human bronchial epithelial cells

    International Nuclear Information System (INIS)

    Arsenite is an established human carcinogen, and arsenite-induced inflammation contributes to malignant transformation of cells, but the molecular mechanisms by which cancers are produced remain to be established. The present results showed that, evoked by arsenite, secretion of interleukin-6 (IL-6), a pro-inflammatory cytokine, led to the activation of STAT3, a transcription activator, and to increased levels of a microRNA, miR-21. Blocking IL-6 with anti-IL-6 antibody and inhibiting STAT3 activation reduced miR-21 expression. For human bronchial epithelial cells, cultured in the presence of anti-IL-6 antibody for 3 days, the arsenite-induced EMT and malignant transformation were reversed. Thus, IL-6, acting on STAT3 signaling, which up-regulates miR-21in an autocrine manner, contributes to the EMT induced by arsenite. These data define a link from inflammation to EMT in the arsenite-induced malignant transformation of HBE cells. This link, mediated through miRNAs, establishes a mechanism for arsenite-induced lung carcinogenesis. - Highlights: • Arsenite evokes IL-6 secretion. • IL-6 autocrine mediates STAT3 signaling and up-regulates miR-21expression. • Inflammation is involved in arsenite-induced EMT

  3. Corticosteroids reverse cytokine-induced block of survival and differentiation of oligodendrocyte progenitor cells from rats

    Directory of Open Access Journals (Sweden)

    Marx Romy

    2008-09-01

    Full Text Available Abstract Background Periventricular leukomalacia (PVL is a frequent complication of preterm delivery. Proinflammatory cytokines, such as interferon-γ (IFN-γ and tumor necrosis factor α (TNF-α released from astrocytes and microglia activated by infection or ischemia have previously been shown to impair survival and maturation of oligodendrocyte progenitors and could thus be considered as potential factors contributing to the generation of this disease. The first goal of the present study was to investigate whether exposure of oligodendrocyte precursors to these cytokines arrests the maturation of ion currents in parallel to its effects on myelin proteins and morphological maturation. Secondly, in the search for agents, that can protect differentiating oligodendrocyte precursor cells from cytokine-induced damage we investigated effects of coapplications of corticosteroids with proinflammatory cytokines on the subsequent survival and differentiation of oligodendrocyte progenitor cells. Methods To exclude influences from factors released from other cell types purified cultures of oligodendrocyte precursors were exposed to cytokines and/or steroids and allowed to differentiate for further 6 days in culture. Changes in membrane surface were investigated with capacitance recordings and Scanning Ion Conductance Microscopy. Na+- and K+- currents were investigated using whole cell patch clamp recordings. The expression of myelin specific proteins was investigated using western blots and the precursor cells were identified using immunostaining with A2B5 antibodies. Results Surviving IFN-γ and TNF-α treated cells continued to maintain voltage-activated Na+- and K+ currents characteristic for the immature cells after 6 days in differentiation medium. Corticosterone, dihydrocorticosterone and, most prominently dexamethasone, counteracted the deleterious effects of IFN-γ and TNF-α on cell survival, A2B5-immunostaining and expression of myelin basic

  4. Second-order modeling of arsenite transport in soils

    Science.gov (United States)

    Zhang, Hua; Magdi Selim, H.

    2011-11-01

    Rate limited processes including kinetic adsorption-desorption can greatly impact the fate and behavior of toxic arsenic compounds in heterogeneous soils. In this study, miscible displacement column experiments were carried out to investigate the extent of reactivity during transport of arsenite in soils. Arsenite breakthrough curves (BTCs) of Olivier and Windsor soils exhibited strong retardation with diffusive effluent fronts followed by slow release or tailing during leaching. Such behavior is indicative of the dominance of kinetic retention reactions for arsenite transport in the soil columns. Sharp decrease or increase in arsenite concentration in response to flow interruptions (stop-flow) further verified that non-equilibrium conditions are dominant. After some 40-60 pore volumes of continued leaching, 30-70% of the applied arsenite was retained by the soil in the columns. Furthermore, continued arsenite slow release for months was evident by the high levels of residual arsenite concentrations observed during leaching. In contrast, arsenite transport in a reference sand material exhibited no retention where complete mass recovery in the effluent solution was attained. A second-order model (SOM) which accounts for equilibrium, reversible, and irreversible retention mechanisms was utilized to describe arsenite transport results from the soil columns. Based on inverse and predictive modeling results, the SOM model successfully depicted arsenite BTCs from several soil columns. Based on inverse and predictive modeling results, a second-order model which accounts for kinetic reversible and irreversible reactions is recommended for describing arsenite transport in soils.

  5. Cytokine-induced killer (CIK) cells:from basic research to clinical translation

    Institute of Scientific and Technical Information of China (English)

    Yelei Guo; Weidong Han

    2015-01-01

    The accumulation of basic researches and clinical studies related to cytokine-induced killer (CIK) cells has confirmed their safety and feasibility in treating malignant diseases. This review summarizes the available published literature related to the biological characteristics and clinical applications of CIK cells in recent years. A number of clinical trials with CIK cells have been implemented during the progressive phases of cancer, presenting potential widespread applications of CIK cells for the future. Furthermore, this review briefly compares clinical applications of CIK cells with those of other adoptive immunotherapeutic cells. However, at present, there are no uniform criteria or large-scale preparations of CIK cells. The overall clinical response is difficult to evaluate because of the use of autologous CIK cells. Based on these observations, several suggestions regarding uniform criteria and universal sources for CIK cell preparations and the use of CIK cells either combined with chemotherapy or alone as a primary strategy are briefly proposed in this review. Large-scale, controlled, grouped, and multi-center clinical trials on CIK cell-based immunotherapy should be conducted under strict supervision. These interventions might help to improve future clinical applications and increase the clinical curative effects of CIK cells for a broad range of malignancies in the future.

  6. Effect of chaetocin on renal cell carcinoma cells and cytokine-induced killer cells

    Directory of Open Access Journals (Sweden)

    Rombo, Roman

    2016-04-01

    Full Text Available We examined the cytotoxic effects of chaetocin on clear cell renal cell carcinoma (ccRCC cells and the possibility to combine the effects of chaetocin with the effects of cytokine-induced killer cells (CIK assayed by MTT assay and FACS analysis. Chaetocin is a thiodioxopiperazine produced by fungi belonging to the chaetomiaceae family. In 2007, it was first reported that chaetocin shows potent and selectiveanti-cancer activity by inducing reactive oxygen species. CIK cells are generated from CD3+/CD56- T lymphocytes with double negative phenotype that are isolated from human blood. The addition of distinct interleukins and antibodies results in the generation of CIK cells that are able to specifically target and destroy renal carcinoma cells. The results of this research state that the anti-ccRCC activity of chaetocin is weak and does not show a high grade of selectivity on clear cell renal cell carcinoma cells. Although the CIK cells show a high grade of selective anti-ccRCC activity, this effect could not be improved by the addition of chaetocin. So chaetocin seems to be no suitable agent for specific targeting ccRCC cells or for the combination therapy with CIK cells in renal cancer.

  7. Opposed arsenite-mediated regulation of p53-survivin is involved in neoplastic transformation, DNA damage, or apoptosis in human keratinocytes

    International Nuclear Information System (INIS)

    Highlights: ► Different concentrations of arsenite cause biphasic effects in HaCaT cells. ► p53-survivin signal pathway plays a role in arsenite-induced biphasic effects. ► ERKs inactivate p53, but improve survivin expression by NF-κB/mot-2. ► JNKs block survivin expression by preventing p53 from mdm2-mediated degradation. ► ERKs and JNKs play roles in arsenite-induced biphasic effects. -- Abstract: Biphasic dose–response relationship induced by environmental agents is often characterized with the effect of low-dose stimulation and high dose inhibition. Some studies showed that arsenite may induce cell proliferation and apoptosis via biphasic dose–response relationship in human cells; however, mechanisms underlying this phenomenon are not well understood. Our present study shows that, for human keratinocytes (HaCaT) cells, a low concentration of arsenite activates extracellular signal-regulated kinases (ERKs), which leads to up-regulation of nuclear factor κB (NF-κB) binding to DNA and to elevated, NF-κB-dependent expression of mot-2 (a p53 inhibitor) and survivin (an inhibitor of apoptosis). Activation of p53 is blocked, and neoplastic transformation is enhanced. Inhibition of ERKs reduces cell proliferation and neoplastic transformation. In contrast, a high concentration of arsenite activates c-Jun N-terminal kinases (JNKs), positive regulators of p53, by binding to p53 and preventing its murine double minute 2 (mdm2)-mediated degradation. The elevated levels of p53 lead to repair of DNA damage and apoptosis. Inhibition of JNKs increases DNA damage but decreases apoptosis. By identifying a mechanism whereby ERKs and JNKs-mediated regulation of the p53-survivin signal pathway is involved in the biphasic effects of arsenite on human keratinocytes, our data expand understanding of arsenite-induced cell proliferation, neoplastic transformation, DNA damage, and apoptosis.

  8. A Nomogram for Predicting the Benefit of Adjuvant Cytokine-Induced Killer Cell Immunotherapy in Patients with Hepatocellular Carcinoma

    OpenAIRE

    Qiu-Zhong Pan; Qi-Jing Wang; Jia-Qiang Dan; Ke Pan; Yong-Qiang Li; Yao-Jun Zhang; Jing-Jing Zhao; De-Sheng Weng; Yan Tang; Li-Xi Huang; Jia He; Shi-Ping Chen; Miao-La Ke; Min-Shan Chen; Wicha, Max S.

    2015-01-01

    The benefits of adjuvant cytokine-induced killer (CIK) cell immunotherapy for hepatocellular carcinoma (HCC) remain mixed among patients. Here, we constructed a prognostic nomogram to enable individualized predictions of survival benefit of adjuvant CIK cell treatment for HCC patients. Survival analysis showed that the median overall survival (OS) and progression-free survival (PFS) for patients in the hepatectomy/CIK combination group were 41 and 16 months, respectively, compared to 28 and 1...

  9. Production of dendritic cells and cytokine-induced killer cells from banked umbilical cord blood samples

    Directory of Open Access Journals (Sweden)

    Phuc Van Pham

    2015-11-01

    Full Text Available Umbilical cord blood (UCB is considered to be a source of hematopoietic stem cells (HSCs. All UCB banks have recently become interested in the isolation and storage of HSCs for the treatment of hematological diseases. However, UCB was also recently confirmed as a source of immune cells for immunotherapy such as dendritic cells (DCs and cytokine-induced killer cells (CIKs. This study aimed to exploit this source of immune cells in banked UCB samples. After collection of UCB samples, mononuclear cells (MNCs containing stem cells, progenitor cells, and mature cells were isolated by Ficoll-Hypaque-based centrifugation. The MNCs were subjected to freezing and thawing according to a previously published protocol. The banked MNCs were used to produce DCs and CIKs. To produce DCs, MNCs were induced in RPMI 1640 medium supplemented with GM-CSF (50 ng/ml and IL-4 (40 ng/ml for 14 days. To produce CIKs, MNCs were induced in RPMI 1640 medium supplemented an anti-CD3 monoclonal antibody, IL-3, and GMC-SF for 21 and ndash;28 days. Both DCs and CIKs were evaluated for their phenotypes and functions according to previously published protocols. The results showed that banked UCB samples can be successfully used to produce functional DCs and CIKs. These samples are valuable sources of immune cells for immunotherapy. The present results suggest that banked UCB samples are useful not only for stem cell isolation, but also for immune cell production. [Biomed Res Ther 2015; 2(11.000: 402-408

  10. Influenza Vaccination Generates Cytokine-Induced Memory-like NK Cells: Impact of Human Cytomegalovirus Infection.

    Science.gov (United States)

    Goodier, Martin R; Rodriguez-Galan, Ana; Lusa, Chiara; Nielsen, Carolyn M; Darboe, Alansana; Moldoveanu, Ana L; White, Matthew J; Behrens, Ron; Riley, Eleanor M

    2016-07-01

    Human NK cells are activated by cytokines, immune complexes, and signals transduced via activating ligands on other host cells. After vaccination, or during secondary infection, adaptive immune responses can enhance both cytokine-driven and Ab-dependent NK cell responses. However, induction of NK cells for enhanced function after in vitro exposure to innate inflammatory cytokines has also been reported and may synergize with adaptive signals to potentiate NK cell activity during infection or vaccination. To test this hypothesis, we examined the effect of seasonal influenza vaccination on NK cell function and phenotype in 52 previously unvaccinated individuals. Enhanced, IL-2-dependent, NK cell IFN-γ responses to Influenza A/California/7/2009 virus were detected up to 4 wk postvaccination and higher in human CMV (HCMV)-seronegative (HCMV(-)) individuals than in HCMV-seropositive (HCMV(+)) individuals. By comparison, robust NK cell degranulation responses were observed both before and after vaccination, due to high titers of naturally occurring anti-influenza Abs in human plasma, and did not differ between HCMV(+) and HCMV(-) subjects. In addition to these IL-2-dependent and Ab-dependent responses, NK cell responses to innate cytokines were also enhanced after influenza vaccination; this was associated with proliferation of CD57(-) NK cells and was most evident in HCMV(+) subjects. Similar enhancement of cytokine responsiveness was observed when NK cells were cocultured in vitro with Influenza A/California/7/2009 virus, and this was at least partially dependent upon IFN-αβR2. In summary, our data indicate that attenuated or live viral vaccines promote cytokine-induced memory-like NK cells and that this process is influenced by HCMV infection. PMID:27233958

  11. The role of plasma coating on the permeation of cytokine-inducing substances through dialyser membranes.

    Science.gov (United States)

    Lonnemann, G; Schindler, R; Lufft, V; Mahiout, A; Shaldon, S; Koch, K M

    1995-01-01

    We studied the effects of coating of dialyser membranes with plasma proteins on the permeation of bacteria-derived cytokine-inducing substances (CIS). An in vitro dialysis circuit using polysulphone (PS) or modified cellulose triacetate (mCT) dialysers was used. Precoating of the dialysers was performed by recirculation of 10% normal human plasma for 30 min in the blood compartment and subsequent rinse with pyrogen-free saline. Samples from the blood compartment were tested for induction of interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF alpha) at various time points after challenging the dialysate with sterile culture supernatants from Pseudomonas aeruginosa. Contamination of the dialysate resulted in the appearance of CIS in the blood compartment of both polysuphone modified cellulose triacetate (IL-1 alpha: PS, time 0: 81 +/- 11 pg/ml, time 60 min: 4747 +/- 1822 pg/ml, P < 0.05; mCT, time 0: 235 +/- 141 pg/ml, time 60 min: 1632 +/- 531 pg/ml, P < 0.05). The plasma protein layer reduced the penetration of CIS significantly only for polysulphone (IL-1 alpha: PS, time 60: 4747 +/- 1822 versus 880 +/- 525 pg/ml, P < 0.05; modified cellulose triacetate, time 60 min: 1632 +/- 531 pg/ml versus 930 +/- 326 pg/ml). Samples from the blood compartment contained < 6 pg/ml LAL-reactive material at all time points. We conclude that plasma coating of polysulphone dialysers reduces the permeability for CIS derived from Pseudomonas, either by reducing the effective pore size or by adsorption of proteins that bind CIS.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Revving up natural killer cells and cytokine-induced killer cells against hematological malignancies

    Directory of Open Access Journals (Sweden)

    Gianfranco ePittari

    2015-05-01

    Full Text Available Natural killer (NK cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors (KIR, NK Group 2 member D (NKG2D, NKG2A/CD94, NKp46 and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells. In this respect, interleukin (IL-15 and IL-21 are instrumental in driving NK-cell differentiation and maturation, and hold great promise for the design of optimal NK-cell culture protocols.Cytokine-induced killer (CIK cells possess phenotypic and functional hallmarks of both T cells and NK cells. Similar to T cells, they express CD3 and are expandable in culture, while not requiring functional priming for in vivo activity, like NK cells. CIK cells may offer some advantages over other cell therapy products, including ease of in vitro propagation and no need for exogenous administration of IL-2 for in vivo priming.NK cells and CIK cells can be expanded using a variety of clinical-grade approaches, before their infusion into patients with cancer. Herein, we discuss GMP-compliant strategies to isolate and expand human NK and CIK cells for immunotherapy purposes, focusing on clinical trials of adoptive transfer to patients with hematological malignancies.

  13. Quantitative analysis of cytokine-induced vascular toxicity and vascular leak in the mouse brain.

    Science.gov (United States)

    Irwan, Yetty Y; Feng, Yi; Gach, H Michael; Symanowski, James T; McGregor, John R; Veni, Gopalkrishna; Schabel, Matthias; Samlowski, Wolfram E

    2009-09-30

    A storm of inflammatory cytokines is released during treatment with pro-inflammatory cytokines, such as interleukin-2 (IL-2), closely approximating changes initially observed during sepsis. These signals induce profound changes in neurologic function and cognition. Little is known about the mechanisms involved. We evaluated a number of experimental methods to quantify changes in brain blood vessel integrity in a well-characterized IL-2 treatment mouse model. Measurement of wet versus dry weight and direct measurement of small molecule accumulation (e.g. [(3)H]-H(2)O, sodium fluorescein) were not sensitive or reliable enough to detect small changes in mouse brain vascular permeability. Estimation of brain water content using proton density magnetic resonance imaging (MRI) measurements using a 7T mouse MRI system was sensitive to 1-2% changes in brain water content, but was difficult to reproduce in replicate experiments. Successful techniques included use of immunohistochemistry using specific endothelial markers to identify vasodilation in carefully matched regions of brain parenchyma and dynamic contrast enhanced (DCE) MRI. Both techniques indicated that IL-2 treatment induced vasodilation of the brain blood vessels. DCE MRI further showed a 2-fold increase in the brain blood vessel permeability to gadolinium in IL-2 treated mice compared to controls. Both immunohistochemistry and DCE MRI data suggested that IL-2 induced toxicity in the brain results from vasodilation of the brain blood vessels and increased microvascular permeability, resulting in perivascular edema. These experimental techniques provide us with the tools to further characterize the mechanism responsible for cytokine-induced neuropsychiatric toxicity.

  14. Influenza Vaccination Generates Cytokine-Induced Memory-like NK Cells: Impact of Human Cytomegalovirus Infection

    Science.gov (United States)

    Goodier, Martin R.; Rodriguez-Galan, Ana; Lusa, Chiara; Nielsen, Carolyn M.; Darboe, Alansana; Moldoveanu, Ana L.; White, Matthew J.; Behrens, Ron

    2016-01-01

    Human NK cells are activated by cytokines, immune complexes, and signals transduced via activating ligands on other host cells. After vaccination, or during secondary infection, adaptive immune responses can enhance both cytokine-driven and Ab-dependent NK cell responses. However, induction of NK cells for enhanced function after in vitro exposure to innate inflammatory cytokines has also been reported and may synergize with adaptive signals to potentiate NK cell activity during infection or vaccination. To test this hypothesis, we examined the effect of seasonal influenza vaccination on NK cell function and phenotype in 52 previously unvaccinated individuals. Enhanced, IL-2–dependent, NK cell IFN-γ responses to Influenza A/California/7/2009 virus were detected up to 4 wk postvaccination and higher in human CMV (HCMV)-seronegative (HCMV−) individuals than in HCMV-seropositive (HCMV+) individuals. By comparison, robust NK cell degranulation responses were observed both before and after vaccination, due to high titers of naturally occurring anti-influenza Abs in human plasma, and did not differ between HCMV+ and HCMV− subjects. In addition to these IL-2–dependent and Ab-dependent responses, NK cell responses to innate cytokines were also enhanced after influenza vaccination; this was associated with proliferation of CD57− NK cells and was most evident in HCMV+ subjects. Similar enhancement of cytokine responsiveness was observed when NK cells were cocultured in vitro with Influenza A/California/7/2009 virus, and this was at least partially dependent upon IFN-αβR2. In summary, our data indicate that attenuated or live viral vaccines promote cytokine-induced memory-like NK cells and that this process is influenced by HCMV infection. PMID:27233958

  15. Establishment of Adoptive Immunotherapy Transfusion Time of Cytokine-induced Killer Cells

    Institute of Scientific and Technical Information of China (English)

    Wu Changping; Deng Haifeng; Jiang Jingting

    2013-01-01

    Objective:To investigate the variation of immunophenotype and cytotoxic activity of autologous cytokine-induced killer (CIK) cells in patients with malignant tumors, and explore the best time of adoptive immunotherapy infusion of CIK cells. Methods:Peripheral blood mononuclear cells (PBMC) in 40 patients with malignant tumors were collected and cultivated into CIK cells in vitro by biotechnology under induction of several kinds of cytokines including interferon γ (IFN-γ), recombinant human interleukin 1α (rhIL-1α), CD3 monoclonal antibody (CD3McAb) and recombinant human interleukin 2 (rhIL-2). Immunophenotypes were dynamically monitored by lfow cytometry (FCM), and cytotoxic activity was analyzed by methyl thiazolyl tetrazolium (MTT) method. Results:After induction and expansion at different time, CD3+, CD3+CD8+and CD3+CD56+in mononuclear cells (MNC) had an up-regulated tendency. CD3+CD4+reached the peak on day 7, and then decreased slowly;CD25 reached the peak in earlier period of cultivation (3-7 days), and decreased slowly in 7-14 days, and then decreased rapidly in 14-21 days. Human leukocyte antigen DR (HLA-DR) was on the rise in 0-14 days, and decreased rapidly after reaching the peak on day 14. The cytotoxic activity of mature CIK cells was signiifcantly higher than that of non-activated PBMC, and the difference was statistically signiifcant (P Conclusion:PBMC can be induced into typical CIK cells for about 14 days when CD3+CD56+cells are at the logarithmic phase. The best time of CIK cell adoptive immunotherapy transfusion for the patients with malignant tumors is on day 14.

  16. Establishment of Adoptive Immunotherapy Transfusion Time of Cytokine-induced Killer Cells

    Directory of Open Access Journals (Sweden)

    Changping Wu

    2013-09-01

    Full Text Available Objective: To investigate the variation of immunophenotype and cytotoxic activity of autologous cytokine-induced killer (CIK cells in patients with malignant tumors, and explore the best time of adoptive immunotherapy infusion of CIK cells. Methods: Peripheral blood mononuclear cells (PBMC in 40 patients with malignant tumors were collected and cultivated into CIK cells in vitro by biotechnology under induction of several kinds of cytokines including interferon γ (IFN-γ, recombinant human interleukin 1α (rhIL- 1α, CD3 monoclonal antibody (CD3McAb and recombinant human interleukin 2 (rhIL-2. Immunophenotypes were dynamically monitored by flow cytometry (FCM, and cytotoxic activity was analyzed by methyl thiazolyl tetrazolium (MTT method. Results: After induction and expansion at different time, CD3+, CD3+CD8+ and CD3+CD56+ in mononuclear cells (MNC had an up-regulated tendency. CD3+CD4+ reached the peak on day 7, and then decreased slowly; CD25 reached the peak in earlier period of cultivation (3-7 days, and decreased slowly in 7-14 days, and then decreased rapidly in 14-21 days. Human leukocyte antigen DR (HLA-DR was on the rise in 0-14 days, and decreased rapidly after reaching the peak on day 14. The cytotoxic activity of mature CIK cells was significantly higher than that of non-activated PBMC, and the difference was statistically significant (P < 0.01. Conclusion: PBMC can be induced into typical CIK cells for about 14 days when CD3+CD56+ cells are at the logarithmic phase. The best time of CIK cell adoptive immunotherapy transfusion for the patients with malignant tumors is on day 14.

  17. Rapid response of advanced squamous non-small cell lung cancer with thrombocytopenia after first-line treatment with pembrolizumab plus autologous cytokine-induced killer cells

    Directory of Open Access Journals (Sweden)

    Zhenzhen eHui

    2015-12-01

    Full Text Available We present the first clinical evidence of advanced squamous non-small cell lung cancer with severe thrombocytopenia showing dramatic improvement after first-line treatment with pembrolizumab plus cytokine-induced killer cells.

  18. Preliminary Study of Local Immunotherapy with Autologous Cytokine-Induced Killer Cells for Glioma Patients

    Institute of Scientific and Technical Information of China (English)

    Li Lin; Yonggao Mu; Zhongping Chen

    2008-01-01

    OBJECTIVE Cytokine-induced killer (CIK) cells are T-cells that display effective anti-tumor activity. In this study, we investigated the anti-tumor activity of CIK cells in vitro, and conducted a preliminary investigation using autologous CIK cells to treat glioma patients through local administration.METHODS The CIK cells were derived from peripheral blood monocytes (PBMCs) of the glioma patients. The anti-tumor activity of the CIK cells against human T98-G glioma cell was tested In vitro. In addition, the autologous CIK cells were locally administrated into the tumor cavity in the malignant glioma patients through an Ommaya reservoir which was pre-inserted during tumor resection. The 4×108 CIK cells in a 5 ml suspension were injected once a week 2 times per cycle. Five hundreds KU of IL-2 was injected every other day.RESULTS (I) With incubation, the CIK cells showed dual staining of CD3+CD56+ with a positive rate of 3.45% on day 10 and 55.2% on day 30. In vitro anti-tumor activity (againstT98-G cells) of the CIK cells reached the highest level after 18 days of incubation with different effector/target (E:T) ratios. (ii)Six patients received autologous CIK cell treatment (10 cycles).Two patients showed no recurrence and are still alive (24 and 10 months), while 4 cases had a recurrence 3 of which have died. The mean survival time from the first CIK cell treatment to the end of follow-up was 12.5 months. The main side-effects of the local CIK cell treatment was brain edema, which was controlled by mannitol in most of the cases. However for one patient injection of CIK cells and IL-2 had to be discontinued.CONCLUSION In vitro CIK cells are effective anti-glioma T-cells. Local therapy with CIK cells has potential anti-glioma efficacy and tolerable side-effects.

  19. Lubricin/Proteoglycan 4 Binding to CD44 Receptor: A Mechanism of Lubricin’s suppression of Pro-inflammatory Cytokine Induced Synoviocyte Proliferation

    Science.gov (United States)

    Al-Sharif, Afnan; Jamal, Maha; Zhang, Ling; Larson, Katherine; Schmidt, Tannin; Jay, Gregory; Elsaid, Khaled

    2015-01-01

    Objective To evaluate recombinant human proteoglycan 4 (rhPRG4) binding to CD44 receptor and its consequence on cytokine induced synoviocyte proliferation. Methods rhPRG4 binding to CD44 and competition with high molecular weight hyaluronic acid (HMW HA) was evaluated using a direct enzyme linked immunosorbent assay (ELISA) and surface plasmon resonance. Sialidase-A and O-glycosidase digestion of rhPRG4 was performed and CD44 binding was evaluated using ELISA. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) were stimulated with interleukin-1 beta (IL-1β) or tumor necrosis factor alpha (TNF-α) for 48 hours in the presence or absence of rhPRG4 or HMW HA at 20, 40 and 80μg/ml and cell proliferation was measured. CD44 contribution was assessed by co-incubation with a CD44 antibody (IM7). The anti-proliferative effect of rhPRG4 was investigated following treatment of Prg4−/− synoviocytes with IL-1β or TNF-α in the presence or absence of IM7. Results rhPRG4 binds CD44 and interferes with HMW HA CD44 binding. Removal of sialic acid and O-glycosylations significantly increased CD44 binding by rhPRG4 (p<0.001). rhPRG4 and HMW HA at 40 and 80μg/ml significantly suppressed IL-1β induced RA-FLS proliferation (p<0.05). rhPRG4 at 20, 40 and 80μg/ml significantly suppressed TNF-α induced RA-FLS proliferation (p<0.05). CD44 neutralization reversed the effect of rhPRG4 on IL-1β and TNF-α stimulated RA-FLS and the effect of HMW HA on IL-1β stimulated RA-FLS. rhPRG4 inhibited cytokine-induced proliferation of Prg4−/− synoviocytes which could be prevented by blocking CD44. Conclusion Lubricin is a novel putative ligand for CD44 and may control synoviocyte overgrowth in inflammatory arthropathies via a CD44-mediated mechanism. PMID:25708025

  20. Dendritic cells decreased the concomitant expanded Tregs and Tregs related IL-35 in cytokine-induced killer cells and increased their cytotoxicity against leukemia cells.

    Science.gov (United States)

    Pan, Ying; Tao, Qianshan; Wang, Huiping; Xiong, Shudao; Zhang, Rui; Chen, Tianping; Tao, Lili; Zhai, Zhimin

    2014-01-01

    Regulatory T cells (Tregs) are potent immunosuppressive cells and essential for inducing immune tolerance. Recent studies have reported that Tregs and Tregs related cytokines can inhibit the antitumor activity of cytokine-induced killer (CIK) cells, but dendritic cells co-cultured CIK (DC-CIK) cells can be used for induction of a specific immune response by blocking of Tregs and TGF-β, IL-10. As a novel identified cytokine, IL-35 is specially produced by Tregs and plays an essential role in immune regulation. However, it remains unknown whether IL-35 roles in tumor immunotherapy mediated by CIK and DC-CIK cells. In this study, we cultured CIK and DC-CIK cells from the same healthy adult samples, and investigated their phenotype, proliferation, cytotoxic activity against leukemia cell lines K562 and NB4 by FCM and CCK-8, measured IL-35, TGF-β and IL-10 protein by ELISA, detected Foxp3, IL-35 and IL-35 receptor mRNA by Real-time PCR, respectively. We found Tregs and IL-35 concomitantly expanded by a time-dependent way during the generation of CIK cells, but DC significantly down-regulated the expression of them and simultaneously up-regulated the proliferation ability as well as cytotoxic activity of CIK cells against leukemia cell lines. Therefore, our data suggested that DC decreased concomitant expanded Tregs and Tregs related IL-35 in CIK cells and might contribute to improve their cytotoxicity against leukemia cells in vitro.

  1. The glycolipid sulfatide protects insulin-producing cells against cytokine-induced apoptosis, a possible role in diabetes

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp; Roeske-Nielsen, Allan; Månsson, Jan-Eric;

    2010-01-01

    Cytokine-induced apoptosis is recognised as a major cause of the decline in β-cell mass that ultimately leads to type 1 diabetes mellitus. Interleukin-1β, interferon-γ and tumour necrosis factor-α in conjunction initiate a series of events that lead to β-cell apoptosis; important among these is NO...... production. The glycosphingolipid sulfatide is present in β-cells in the secretory granules in varying amounts and is secreted together with insulin. We now investigate whether sulfatide is able to protect insulin-producing cells against the pro-apoptotic effect of interleukin-1β, interferon-γ and tumour...

  2. Le schisme Arsenite (1265-1310: Entre akribeia et oikonomia

    Directory of Open Access Journals (Sweden)

    Tudorie Ionuс-Alexandru

    2011-01-01

    Full Text Available By analyzing the Byzantine sources, the author presents a thorough picture of the Arsenite faction and the internal schism occurred in the Byzantine society as a result of their actions. Beside their uncompromising position towards emperor Michael VIII Palaiologos, always supported with spiritual arguments, the Arsenites also had concrete political-religious interests, making them an authentic political party.

  3. Whole-cell arsenite biosensor using photosynthetic bacterium Rhodovulum sulfidophilum. Rhodovulum sulfidophilum as an arsenite biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, Hiroyuki; Wakabayashi, Masato; Yamashiro, Hidenori; Isoda, Katsuhiro; Kondoh, Masuo; Kawase, Masaya; Yagi, Kiyohito [Osaka Univ., Suita, Osaka (Japan). Graduate School of Pharmaceutical Sciences; Maeda, Isamu [Utsunomiya Univ. (Japan). Faculty of Agriculture; Miyasaka, Hitoshi [Kansai Electric Power Co., Sourakugun, Kyoto (Japan). Environmental Research Center

    2006-11-15

    An arsenite biosensor plasmid was constructed in Escherichia coli by inserting the operator/promoter region of the ars operon and the arsR gene from E. coli and the crtA gene, which is responsible for carotenoid synthesis in the photosynthetic bacterium, Rhodovulum sulfidophilum, into the broad-host-range plasmid vector, pRK415. The biosensor plasmid, pSENSE-As, was introduced into a crtA-deleted mutant strain of R. sulfidophilum (CDM2), which is yellow in culture due to its content of spheroiden (SE) and demethylspheroidene (DMSE). CDM2 containing pSENSE-As changed from yellow to red by the addition of arsenite, which caused enzymatic transformation of SE and DMSE to spheroidenone (SO) and demethylspheroidenone (DMSO). Reverse transcriptase PCR analysis showed that the color change depended on transcription of the crtA gene in pSENSE-As. The color change could be clearly recognized with the naked eye at 5 {mu}g/l arsenite. The biosensor strain did not respond to other metals except for bismuth and antimony, which caused significant accumulation of SO and DMSO in the cells at 60 and 600 {mu}g/l, respectively. This biosensor indicates the presence of arsenite with a bacterial color change without the need to add a special reagent or substrate for color development, enabling this pollutant to be monitored in samples by the naked eye in sunlight, even where electricity is not available. (orig.)

  4. Bioaccumulation and oxidative stress in Daphnia magna exposed to arsenite and arsenate.

    Science.gov (United States)

    Fan, Wenhong; Ren, Jinqian; Li, Xiaomin; Wei, Chaoyang; Xue, Feng; Zhang, Nan

    2015-11-01

    Arsenic pollution and its toxicity to aquatic organisms have attracted worldwide attention. The bioavailability and toxicity of arsenic are highly related to its speciation. The present study investigated the differences in bioaccumulation and oxidative stress responses in an aquatic organism, Daphnia magna, induced by 2 inorganic arsenic species (As(III) and As(V)). The bioaccumulation of arsenic, Na(+) /K(+) -adenosine triphosphatase (ATPase) activity, reactive oxygen species (ROS) content, total superoxide dismutase (SOD) activity, total antioxidative capability, and malondialdehyde content in D. magna were determined after exposure to 500 µg/L of arsenite and arsenate for 48 h. The results showed that the oxidative stress and antioxidative process in D. magna exposed to arsenite and arsenate could be divided into 3 phases, which were antioxidative response, oxidation inhibition, and antioxidative recovery. In addition, differences in bioaccumulation, Na(+) /K(+) -ATPase activity, and total SOD activity were also found in D. magna exposed to As(III) and As(V). These differences might have been the result of the high affinity of As(III) with sulfhydryl groups in enzymes and the structural similarity of As(V) to phosphate. Therefore, arsenate could be taken up by organisms through phosphate transporters, could substitute for phosphate in biochemical reactions, and could lead to a change in the bioaccumulation of arsenic and activity of enzymes. These characteristics were the possible reasons for the different toxicity mechanisms in the oxidative stress process of arsenite and arsenate. PMID:26084717

  5. Cytokines induce tight junction disassembly in airway cells via an EGFR-dependent MAPK/ERK1/2-pathway.

    Science.gov (United States)

    Petecchia, Loredana; Sabatini, Federica; Usai, Cesare; Caci, Emanuela; Varesio, Luigi; Rossi, Giovanni A

    2012-08-01

    Epithelial barrier permeability is altered in inflammatory respiratory disorders by a variety of noxious agents through modifications of the epithelial cell structure that possibly involve tight junction (TJ) organization. To evaluate in vitro whether pro-inflammatory cytokines involved in the pathogenesis of respiratory disorders could alter TJ organization and epithelial barrier integrity, and to characterize the signal transduction pathway involved Calu-3 airway epithelial cells were exposed to TNF-a, IL-4 and IFN-g to assess changes in: (a) TJ assembly, that is, occludin and zonula occludens (ZO)-1 expression and localization, evaluated by confocal microscopy; (b) apoptotic activity, quantified using terminal transferase deoxyuridine triphosphate nick-end labeling staining; (c) epithelial barrier integrity, detected as transmembrane electrical resistance and expressed as G(T) values; (d) epidermal growth factor receptor (EGFR)-dependent mitogenactivated protein (MAP) kinase (MAPK)/extracellular signal-regulated kinases (ERK)1/2 phosphorylation, assessed by western blotting. Exposure to cytokines for 48 h induced a noticeable downregulation of the TJ transmembrane proteins. The degree ZO-1 and occludin colocalization was 62±2% in control cultures and significantly decreased in the presence of TNF-a (47±3%), IL-4 (43±1%) and INF-g (35±3%). Although no apoptosis induction was detected following exposure to cytokines, changes in the epithelial barrier integrity were observed, with a significant enhancement in paracellular conductance. G(T) values were, respectively, 1.030±0.0, 1.300±0.04, 1.260±0.020 and 2.220±0.015 (mS/cm²)1000 in control cultures and in those exposed to TNF-a, IFN-g and IL-4. The involvement of EGFR-dependent MAPK/ERK1/2 signaling pathway in cytokine-induced damage was demonstrated by a significant increase in threonine/tyrosine phosphorylation of ERK1/2, already detectable after 5 min incubation. All these cytokine-induced changes were

  6. Synergism between arsenite and proteasome inhibitor MG132 over cell death in myeloid leukaemic cells U937 and the induction of low levels of intracellular superoxide anion

    Energy Technology Data Exchange (ETDEWEB)

    Lombardo, Tomás [Laboratorio de Immunotoxicologia (LaITO), IDEHU-CONICET, Hospital de Clínicas, José de San Martín, Universidad de Buenos Aires (UBA), Buenos Aires (Argentina); Cavaliere, Victoria; Costantino, Susana N. [Laboratorio de Inmunología Tumoral (LIT), IDEHU-CONICET, Facultad de Farmacia y Bioquímica, UBA, Buenos Aires (Argentina); Kornblihtt, Laura [Servicio de Hematología, Hospital de Clínicas, José de San Martín (UBA), Buenos Aires (Argentina); Alvarez, Elida M. [Laboratorio de Inmunología Tumoral (LIT), IDEHU-CONICET, Facultad de Farmacia y Bioquímica, UBA, Buenos Aires (Argentina); Blanco, Guillermo A., E-mail: gblanco@ffyb.uba.ar [Laboratorio de Immunotoxicologia (LaITO), IDEHU-CONICET, Hospital de Clínicas, José de San Martín, Universidad de Buenos Aires (UBA), Buenos Aires (Argentina)

    2012-02-01

    Increased oxygen species production has often been cited as a mechanism determining synergism on cell death and growth inhibition effects of arsenic-combined drugs. However the net effect of drug combination may not be easily anticipated solely from available knowledge of drug-induced death mechanisms. We evaluated the combined effect of sodium arsenite with the proteasome inhibitor MG132, and the anti-leukaemic agent CAPE, on growth-inhibition and cell death effect in acute myeloid leukaemic cells U937 and Burkitt's lymphoma-derived Raji cells, by the Chou–Talalay method. In addition we explored the association of cytotoxic effect of drugs with changes in intracellular superoxide anion (O{sub 2}{sup −}) levels. Our results showed that combined arsenite + MG132 produced low levels of O{sub 2}{sup −} at 6 h and 24 h after exposure and were synergic on cell death induction in U937 cells over the whole dose range, although the combination was antagonistic on growth inhibition effect. Exposure to a constant non-cytotoxic dose of 80 μM hydrogen peroxide together with arsenite + MG132 changed synergism on cell death to antagonism at all effect levels while increasing O{sub 2}{sup −} levels. Arsenite + hydrogen peroxide also resulted in antagonism with increased O{sub 2}{sup −} levels in U937 cells. In Raji cells, arsenite + MG132 also produced low levels of O{sub 2}{sup −} at 6 h and 24 h but resulted in antagonism on cell death and growth inhibition. By contrast, the combination arsenite + CAPE showed high levels of O{sub 2}{sup −} production at 6 h and 24 h post exposure but resulted in antagonism over cell death and growth inhibition effects in U937 and Raji cells. We conclude that synergism between arsenite and MG132 in U937 cells is negatively associated to O{sub 2}{sup −} levels at early time points after exposure. -- Highlights: ► Arsenic combined cytotoxic and anti-proliferative effects by Chou–Talalay method. ► Cytotoxic effect

  7. Synergism between arsenite and proteasome inhibitor MG132 over cell death in myeloid leukaemic cells U937 and the induction of low levels of intracellular superoxide anion

    International Nuclear Information System (INIS)

    Increased oxygen species production has often been cited as a mechanism determining synergism on cell death and growth inhibition effects of arsenic-combined drugs. However the net effect of drug combination may not be easily anticipated solely from available knowledge of drug-induced death mechanisms. We evaluated the combined effect of sodium arsenite with the proteasome inhibitor MG132, and the anti-leukaemic agent CAPE, on growth-inhibition and cell death effect in acute myeloid leukaemic cells U937 and Burkitt's lymphoma-derived Raji cells, by the Chou–Talalay method. In addition we explored the association of cytotoxic effect of drugs with changes in intracellular superoxide anion (O2−) levels. Our results showed that combined arsenite + MG132 produced low levels of O2− at 6 h and 24 h after exposure and were synergic on cell death induction in U937 cells over the whole dose range, although the combination was antagonistic on growth inhibition effect. Exposure to a constant non-cytotoxic dose of 80 μM hydrogen peroxide together with arsenite + MG132 changed synergism on cell death to antagonism at all effect levels while increasing O2− levels. Arsenite + hydrogen peroxide also resulted in antagonism with increased O2− levels in U937 cells. In Raji cells, arsenite + MG132 also produced low levels of O2− at 6 h and 24 h but resulted in antagonism on cell death and growth inhibition. By contrast, the combination arsenite + CAPE showed high levels of O2− production at 6 h and 24 h post exposure but resulted in antagonism over cell death and growth inhibition effects in U937 and Raji cells. We conclude that synergism between arsenite and MG132 in U937 cells is negatively associated to O2− levels at early time points after exposure. -- Highlights: ► Arsenic combined cytotoxic and anti-proliferative effects by Chou–Talalay method. ► Cytotoxic effect associated with superoxide levels as assessed by flow cytometry. ► Synergism between arsenite

  8. Arsenite adsorption on goethite at elevated temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Kersten, Michael [Environmental Geochemistry Group, Institute of Geosciences, Johannes Gutenberg-University, Mainz 55099 (Germany)], E-mail: kersten@uni-mainz.de; Vlasova, Nataliya [Environmental Geochemistry Group, Institute of Geosciences, Johannes Gutenberg-University, Mainz 55099 (Germany)

    2009-01-15

    Experimental closed-system {delta}T acid-base titrations between 10 deg. C and 75 deg. C were used to constrain a temperature-dependent 1-pK basic Stern model of the goethite surface complexation reactions. Experimental data for the temperature dependence of pH{sub PZC} determined by the one-term Van't Hoff extrapolation yield a value for goethite surface protonation enthalpy of -49.6 kJ mol{sup -1} in good agreement with literature data. Batch titration data between 10 deg. C and 75 deg. C with arsenite concentrations between 10 {mu}M and 100 {mu}M yield adsorption curves, which increases with pH, peak at a pH of 9, and decrease at higher pH values. The slope of this bend becomes steeper with increasing temperature. A 1-pK charge distribution model in combination with a basic Stern layer option could be established for the pH-dependent arsenite adsorption. Formation of two inner-sphere bidentate surface complexes best matched the experimental data in agreement with published EXAFS spectroscopic information. The temperature behaviour of the thus derived intrinsic equilibrium constants can be well represented by the linear Van't Hoff logK{sub T}{sup int} vs. 1/T plot. Adsorption of arsenite on the goethite surface is exothermic (negative {delta}{sub r}H{sub 298} values) and therefore becomes weaker with increasing temperature. Application of the new constants with the aqueous speciation code VMINTEQ predicts that the As(III) concentration in presence of goethite sorbent decreases by 10 times once the hydrothermal solution is cooled from 99 deg. C to 1 deg. C. The model curve matches data from a natural thermal water spring system. The increase of adsorption efficiency for As along the temperature gradient may well serve as an additional process to prevent ecosystem contamination by As-rich water seepage from geothermal energy generation facilities.

  9. Unique proliferation response in odontoblastic cells derived from human skeletal muscle stem cells by cytokine-induced matrix metalloproteinase-3

    International Nuclear Information System (INIS)

    A pro-inflammatory cytokine mixture (CM: interleukin (IL)-1β, tumor necrosis factor-α and interferon-γ) and IL-1β-induced matrix metalloproteinase (MMP)-3 activity have been shown to increase the proliferation of rat dental pulp cells and murine stem cell-derived odontoblast-like cells. This suggests that MMP-3 may regulate wound healing and regeneration in the odontoblast-rich dental pulp. Here, we determined whether these results can be extrapolated to human dental pulp by investigating the effects of CM-induced MMP-3 up-regulation on the proliferation and apoptosis of purified odontoblast-like cells derived from human skeletal muscle stem cells. We used siRNA to specifically reduce MMP-3 expression. We found that CM treatment increased MMP-3 mRNA and protein levels as well as MMP-3 activity. Cell proliferation was also markedly increased, with no changes in apoptosis, upon treatment with CM and following the application of exogenous MMP-3. Endogenous tissue inhibitors of metalloproteinases were constitutively expressed during all experiments and unaffected by MMP-3. Although treatment with MMP-3 siRNA suppressed cell proliferation, it also unexpectedly increased apoptosis. This siRNA-mediated increase in apoptosis could be reversed by exogenous MMP-3. These results demonstrate that cytokine-induced MMP-3 activity regulates cell proliferation and suppresses apoptosis in human odontoblast-like cells. - Highlights: • Pro-inflammatory cytokines induce MMP-3 activity in human odontoblast-like cells. • Increased MMP-3 activity can promote cell proliferation in odontoblasts. • Specific loss of MMP-3 increases apoptosis in odontoblasts. • MMP-3 has potential as a promising new target for pupal repair and regeneration

  10. Unique proliferation response in odontoblastic cells derived from human skeletal muscle stem cells by cytokine-induced matrix metalloproteinase-3

    Energy Technology Data Exchange (ETDEWEB)

    Ozeki, Nobuaki; Hase, Naoko; Kawai, Rie; Yamaguchi, Hideyuki; Hiyama, Taiki [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Aichi (Japan); Kondo, Ayami [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650 (Japan); Nakata, Kazuhiko [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya 464-8651, Aichi (Japan); Mogi, Makio, E-mail: makio@dpc.agu.ac.jp [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650 (Japan)

    2015-02-01

    A pro-inflammatory cytokine mixture (CM: interleukin (IL)-1β, tumor necrosis factor-α and interferon-γ) and IL-1β-induced matrix metalloproteinase (MMP)-3 activity have been shown to increase the proliferation of rat dental pulp cells and murine stem cell-derived odontoblast-like cells. This suggests that MMP-3 may regulate wound healing and regeneration in the odontoblast-rich dental pulp. Here, we determined whether these results can be extrapolated to human dental pulp by investigating the effects of CM-induced MMP-3 up-regulation on the proliferation and apoptosis of purified odontoblast-like cells derived from human skeletal muscle stem cells. We used siRNA to specifically reduce MMP-3 expression. We found that CM treatment increased MMP-3 mRNA and protein levels as well as MMP-3 activity. Cell proliferation was also markedly increased, with no changes in apoptosis, upon treatment with CM and following the application of exogenous MMP-3. Endogenous tissue inhibitors of metalloproteinases were constitutively expressed during all experiments and unaffected by MMP-3. Although treatment with MMP-3 siRNA suppressed cell proliferation, it also unexpectedly increased apoptosis. This siRNA-mediated increase in apoptosis could be reversed by exogenous MMP-3. These results demonstrate that cytokine-induced MMP-3 activity regulates cell proliferation and suppresses apoptosis in human odontoblast-like cells. - Highlights: • Pro-inflammatory cytokines induce MMP-3 activity in human odontoblast-like cells. • Increased MMP-3 activity can promote cell proliferation in odontoblasts. • Specific loss of MMP-3 increases apoptosis in odontoblasts. • MMP-3 has potential as a promising new target for pupal repair and regeneration.

  11. Clinical research of genetically modified dendritic cells in combination with cytokine-induced killer cell treatment in advanced renal cancer

    International Nuclear Information System (INIS)

    Renal cell carcinoma (RCC) is a malignant disease that demonstrates resistance to standard chemotherapeutic agents. Yet Active immunization using genetically modified dendritic cells holds promise for the adjuvant treatment of malignancies to eradicate or control residual disease. Cytokine-induced killer (CIK) cells are a heterogeneous population of effector CD8+ T cells with diverse TCR specificities, possessing non-MHC-restricted cytolytic activities against tumor cells. Clinical studies have confirmed benefit and safety of CIK cell-based therapy for patients with malignancies. This clinical trial was conducted to evaluate efficacy and safety of genetically modified dendritic cells in combination with Cytokine-Induced Killer Cell (gmDCs-CIK) treatment of patients with RCC. 28 patients with advanced renal cancer were admitted to Affiliated Hospital of Academy of Military Medical Sciences from December 2010 to March 2012 and treated by gmDCs-CIK. Clinical efficacy and safety between pre- and post-treatment were compared. This analysis showed an objective response rate (ORR) of 39% and a disease control rate (DCR) of as 75%. There is no significant relationship between clinical efficacy and whether metastasis occurred or not (P > 0.05). There is no significant relationship between ORR and cycles of treatment (P > 0.05), but DCR was significantly related with cycles of treatment (P < 0.05). No clinically significant side effects were observed. There were no significant changes of T cell subsets including CD3+, CD4+, CD8+, CD4+ CD25+ Treg cells except Th1 in peripheral blood between day 30 after immunotherapy and 1 day before immunotherapy in 11 patients. DC-CIK is feasible and effective in treating advanced renal cancer and thus provides a new approach. ClinicalTrials.gov Identifier: http://clinicaltrials.gov/ct2/show/NCT01924156. Registration date: August 14, 2013

  12. The molecular pathway of low concentration of sodium arsenite in inducing differentiation of liver cancer stem cells by down-regulating promyelocytic leukemia protein expression

    Directory of Open Access Journals (Sweden)

    Shi-long JIN

    2016-01-01

    Full Text Available Objective  To study the molecular pathway of low concentration of sodium arsenite in inducing differentiation of liver cancer stem cells. Methods  Western blotting analysis, immunofluorescence assay and quantitative PCR were used to examine the gene and protein expression of promyelocytic leukemia (PML, Oct4 and Sox2 in HCC tissue and cell lines, and the molecule pathway of low concentration of sodium arsenite inducing differentiation of liver cancer stem cells was confirmed by comparing the changes in the gene and protein expression of PML,Oct4 and Sox2 in HCC cells and biological function of LCSCs after the treatment with low concentration of sodium arsenite. Results  0.5μg/ml of sodium arsenite was shown to alter the biological characteristics of LCSCs in HuH7 and primary HCC cells, including the ability to form tumor spheres, resistance to pirarubicin (P<0.01, and the capability of forming tumors after allogeneic transplantation (P<0.05. Both HCC cells and tissues expressed the gene and protein of PML,Oct4 and Sox2, and 0.5μg/ml of sodium arsenite not only downregulated the gene and protein expression of Oct4 (P<0.05 and Sox2 in HCC cells (P<0.05, but also downregulated the protein expression of PML (P<0.05. In contrast, sodium arsenite did not inhibit the gene expression of PML in Hep3B, HepG2, SMCC-7721, HuH7 and primary HCC cells. Furthermore, through down-regulated PML protein expression with arsenite, the biological characteristics of HuH7 and primary HCC cells containing LCSCs was simultaneously altered, and the expression of stem gene Oct4 and Sox2 was downregulated (P<0.05, while HCC cells proliferation was inhibited as well. Conclusions  Both HCC tissues and cells can express the PML gene and PML protein. Low concentrations of sodium arsenite would directly bind to PML protein in HCC cells, resulting in degradation of the PML protein, followed by collapse of PML-NBs, inhibition of transcription of the proliferation

  13. Industrial experiment of copper electrolyte purification by copper arsenite

    Institute of Scientific and Technical Information of China (English)

    ZHENG Ya-jie; XIAO Fa-xin; WANG Yong; LI Chun-hua; XU Wei; JIAN Hong-sheng; MA Yut-ian

    2008-01-01

    Copper electrolyte was purified by copper arsenite that was prepared with As2O3. And electrolysis experiments of purified electrolyte were carried out at 235 and 305 A/m2, respectively. The results show that the yield of copper arsenite is up to 98.64% when the molar ratio of Cu to As is 1.5 in the preparation of copper arsenite. The removal rates of Sb and Bi reach 74.11% and 65.60% respectively after copper arsenite is added in electrolyte. The concentrations of As, Sb and Bi in electrolyte nearly remain constant during electrolysis of 13 d. The appearances of cathode copper obtained at 235 and 305 A/m2 are slippery and even, and the qualification rate is 100% according to the Chinese standard of high-pure cathode copper(GB/T467-97).

  14. Accumulation of heme oxygenase-1 (HSP32) in Xenopus laevis A6 kidney epithelial cells treated with sodium arsenite, cadmium chloride or proteasomal inhibitors.

    Science.gov (United States)

    Music, Ena; Khan, Saad; Khamis, Imran; Heikkila, John J

    2014-11-01

    The present study examined the effect of sodium arsenite, cadmium chloride, heat shock and the proteasomal inhibitors MG132, withaferin A and celastrol on heme oxygenase-1 (HO-1; also known as HSP32) accumulation in Xenopus laevis A6 kidney epithelial cells. Immunoblot analysis revealed that HO-1 accumulation was not induced by heat shock but was enhanced by sodium arsenite and cadmium chloride in a dose- and time-dependent fashion. Immunocytochemistry revealed that these metals induced HO-1 accumulation in a granular pattern primarily in the cytoplasm. Additionally, in 20% of the cells arsenite induced the formation of large HO-1-containing perinuclear structures. In cells recovering from sodium arsenite or cadmium chloride treatment, HO-1 accumulation initially increased to a maximum at 12h followed by a 50% reduction at 48 h. This initial increase in HO-1 levels was likely the result of new synthesis as it was inhibited by cycloheximide. Interestingly, treatment of cells with a mild heat shock enhanced HO-1 accumulation induced by low concentrations of sodium arsenite and cadmium chloride. Finally, we determined that HO-1 accumulation was induced in A6 cells by the proteasomal inhibitors, MG132, withaferin A and celastrol. An examination of heavy metal and proteasomal inhibitor-induced HO-1 accumulation in amphibians is of importance given the presence of toxic heavy metals in aquatic habitats. PMID:25064141

  15. Photoinduced Oxidation of Arsenite to Arsenate on Ferrihydrite

    Energy Technology Data Exchange (ETDEWEB)

    N Bhandari; R Reeder; D Strongin

    2011-12-31

    The photochemistry of an aqueous suspension of the iron oxyhydroxide, ferrihydrite, in the presence of arsenite has been investigated using attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), X-ray absorption near edge structure (XANES), and solution phase analysis. Both ATR-FTIR and XANES show that the exposure of ferrihydrite to arsenite in the dark leads to no change in the As oxidation state, but the exposure of this arsenite-bearing surface, which is in contact with pH 5 water, to light leads to the conversion of the majority of the adsorbed arsenite to the As(V) bearing species, arsenate. Analysis of the solution phase shows that ferrous iron is released into solution during the oxidation of arsenite. The photochemical reaction, however, shows the characteristics of a self-terminating reaction in that there is a significant suppression of this redox chemistry before 10% of the total iron making up the ferrihydrite partitions into solution as ferrous iron. The self-terminating behavior exhibited by this photochemical arsenite/ferrihydrite system is likely due to the passivation of the ferrihydrite surface by the strongly bound arsenate product.

  16. Inorganic arsenite alters macrophage generation from human peripheral blood monocytes.

    Science.gov (United States)

    Sakurai, Teruaki; Ohta, Takami; Fujiwara, Kitao

    2005-03-01

    Inorganic arsenite has caused severe inflammatory chronic poisoning in humans through the consumption of contaminated well water. In this study, we examined the effects of arsenite at nanomolar concentrations on the in vitro differentiation of human macrophages from peripheral blood monocytes. While arsenite was found to induce cell death in a culture system containing macrophage colony stimulating factor (M-CSF), macrophages induced by granulocyte-macrophage CSF (GM-CSF) survived the treatment, but were morphologically, phenotypically, and functionally altered. In particular, arsenite-induced cells expressed higher levels of a major histocompatibility complex (MHC) class II antigen, HLA-DR, and CD14. They were more effective at inducing allogeneic or autologous T cell responses and responded more strongly to bacterial lipopolysaccharide (LPS) by inflammatory cytokine release as compared to cells induced by GM-CSF alone. On the other hand, arsenite-induced cells expressed lower levels of CD11b and CD54 and phagocytosed latex beads or zymosan particles less efficiently. We also demonstrated that the optimum amount of cellular reactive oxygen species (ROS) induced by nM arsenite might play an important role in this abnormal monocyte differentiation. This work may have implications in chronic arsenic poisoning because the total peripheral blood arsenic concentrations of these patients are at nM levels.

  17. Clinical efficacy of immunotherapy of dendritic cell and cytokine-induced killer cell combined with chemotherapy for treatment of multiple myeloma

    Institute of Scientific and Technical Information of China (English)

    钟国成

    2013-01-01

    Objective This research was aimed to evaluate the immune mechanism and clinical effect of immunotherapy of dendritic cells(DC) and cytokine-induced killer cell(CIK) combined with chemotherapy on multiple myeloma(MM). Methods 60 patients with MM were randomly

  18. Cytokine-induced proapoptotic gene expression in insulin-producing cells is related to rapid, sustained, and nonoscillatory nuclear factor-kappaB activation

    DEFF Research Database (Denmark)

    Ortis, Fernanda; Cardozo, Alessandra K; Crispim, Daisy;

    2006-01-01

    Cytokines, such as IL-1beta and TNF-alpha, contribute to pancreatic beta-cell death in type 1 diabetes mellitus. The transcription factor nuclear factor-kappaB (NF-kappaB) mediates cytokine-induced beta-cell apoptosis. Paradoxically, NF-kappaB has mostly antiapoptotic effects in other cell types....

  19. Feedback regulations of miR-21 and MAPKs via Pdcd4 and Spry1 are involved in arsenite-induced cell malignant transformation.

    Directory of Open Access Journals (Sweden)

    Lu Shen

    Full Text Available OBJECTIVE: To establish the functions of miR-21 and the roles of two feedback regulation loops, miR-21-Spry1-ERK/NF-κB and miR-21-Pdcd4-JNK/c-Jun, in arsenite-transformed human embryo lung fibroblast (HELF cells. METHODS: For arsenite-transformed HELF cells, apoptosis, clonogenicity, and capacity for migration were determined by Hoechst staining, assessment of their capacity for anchorage-independent growth, and wound-healing, respectively, after blockage, with inhibitors or with siRNAs, of signal pathways for JNK/c-Jun or ERK/NF-κB. Decreases of miR-21 levels were determined with anti-miR-21, and the up-regulation of Pdcd4 and Spry1 was assessed in transfected cells; these cells were molecularly characterized by RT-PCR, qRT-PCR, Western blots, and immunofluorescence assays. RESULTS: MiR-21 was highly expressed in arsenite-transformed HELF cells and normal HELF cells acutely treated with arsenite, an effect that was concomitant with activation of JNK/c-Jun and ERK/NF-κB and down-regulation of Pdcd4 and Spry1 protein levels. However, there were no significant changes in mRNA levels for Pdcd4 and Spry1, which suggested that miR-21 regulates the expressions of Pdcd4 and Spry1 through translational repression. In arsenite-transformed HELF cells, blockages of JNK/c-Jun or ERK/NF-κB with inhibitors or with siRNAs prevented the increases of miR-21and the decreases of the protein levels but not the mRNA levels of Pdcd4 and Spry1. Down-regulation of miR-21 and up-regulations of Pdcd44 or Spry1 blocked the arsenite-induced activations of JNK/c-Jun or ERK/NF-κB, indicating that knockdown of miR-21 inhibits feedback of ERK activation and JNK activation via increases of Pdcd4 and Spry1 protein levels, respectively. Moreover, in arsenite-transformed HELF cells, inhibition of miR-21 promoted cell apoptosis, inhibited clonogenicity, and reduced migration. CONCLUSION: The results indicate that miR-21 is both a target and a regulator of ERK/NF-κB and JNK

  20. Spontaneous and cytokine induced expression and activity of matrix metalloproteinases in human colonic epithelium

    DEFF Research Database (Denmark)

    Pedersen, G; Saermark, T; Kirkegaard, T;

    2009-01-01

    Matrix metalloproteinases (MMPs) have been implicated in tissue damage associated with inflammatory bowel disease (IBD).As the role of the intestinal epithelium in this process is unknown, we determined MMP expression and enzyme activity in human colonic epithelial cells (CEC). MMP mRNA expression...... was assessed by reverse transcription-polymerase chain reaction in HT-29 and DLD-1 cells and in CEC isolated from biopsies from IBD and control patients. Total MMP activity in the cells was measured by a functional assay, based on degradation of a fluorescent synthetic peptide containing the specific bond...... levels in cells from inflamed IBD mucosa. MMP-2 and -8 mRNA were expressed inconsistently and MMP-11, -13 and -14 mRNA undetectable. Proteolytic MMP activity was detected in CEC supernatants and the level was increased significantly in inflamed IBD epithelium. The enzyme activity was inhibited strongly...

  1. Vitamin D attenuates cytokine-induced remodeling in human fetal airway smooth muscle cells.

    Science.gov (United States)

    Britt, Rodney D; Faksh, Arij; Vogel, Elizabeth R; Thompson, Michael A; Chu, Vivian; Pandya, Hitesh C; Amrani, Yassine; Martin, Richard J; Pabelick, Christina M; Prakash, Y S

    2015-06-01

    Asthma in the pediatric population remains a significant contributor to morbidity and increasing healthcare costs. Vitamin D3 insufficiency and deficiency have been associated with development of asthma. Recent studies in models of adult airway diseases suggest that the bioactive Vitamin D3 metabolite, calcitriol (1,25-dihydroxyvitamin D3 ; 1,25(OH)2 D3 ), modulates responses to inflammation; however, this concept has not been explored in developing airways in the context of pediatric asthma. We used human fetal airway smooth muscle (ASM) cells as a model of the early postnatal airway to explore how calcitriol modulates remodeling induced by pro-inflammatory cytokines. Cells were pre-treated with calcitriol and then exposed to TNFα or TGFβ for up to 72 h. Matrix metalloproteinase (MMP) activity, production of extracellular matrix (ECM), and cell proliferation were assessed. Calcitriol attenuated TNFα enhancement of MMP-9 expression and activity. Additionally, calcitriol attenuated TNFα and TGFβ-induced collagen III expression and deposition, and separately, inhibited proliferation of fetal ASM cells induced by either inflammatory mediator. Analysis of signaling pathways suggested that calcitriol effects in fetal ASM involve ERK signaling, but not other major inflammatory pathways. Overall, our data demonstrate that calcitriol can blunt multiple effects of TNFα and TGFβ in developing airway, and point to a potentially novel approach to alleviating structural changes in inflammatory airway diseases of childhood. PMID:25204635

  2. Inhibitory Effects of Sodium Arsenite and Acacia Honey on Acetylcholinesterase in Rats

    OpenAIRE

    Aliyu Muhammad; Oyeronke A Odunola; Michael A. Gbadegesin; Sallau, Abdullahi B.; Ndidi, Uche S.; Ibrahim, Mohammed A.

    2015-01-01

    This study was conducted to investigate the effect of sodium arsenite and Acacia honey on acetylcholinesterase (AChE) activity and electrolytes in the brain and serum of Wistar rats. Male Wistar albino rats in four groups of five rats each were treated with distilled water, sodium arsenite (5 mg/kg body weight), Acacia honey (20% v/v), and sodium arsenite and Acacia honey, daily for one week. The sodium arsenite and Acacia honey significantly P

  3. Increased Efficacy of Brentuximab Vedotin (SGN-35) in Combination with Cytokine-Induced Killer Cells in Lymphoma

    Science.gov (United States)

    Esser, Laura; Weiher, Hans; Schmidt-Wolf, Ingo

    2016-01-01

    Brentuximab vedotin (SGN-35) is an antibody–drug conjugate with a high selectivity against CD30+ cell lines and more than 300-fold less activity against antigen-negative cells. In the last years, the results of many in vitro and in vivo studies have led to the fast approval of this drug to treat lymphoma patients. Another innovative method to treat tumor cells including lymphoma cells is the use cytokine-induced killer (CIK) cells, which have also been approved and proven to be a safe treatment with only minor adverse events. In this study, a possible additive effect when combining SGN-35 with CIK cells was investigated. The combinational treatment showed that it reduces the viability of CD30+ cell lines significantly in vitro. Additionally, the amount of lymphoma cells was significantly reduced when exposed to CIK cells as well as when exposed to SGN-35. A significant negative effect of SGN-35 on the function of CIK cells could be excluded. These results lead to the assumption that SGN-35 and CIK cells in combination might achieve better results in an in vitro setting compared to the single use of SGN-35 and CIK cells. Further investigations in in vivo models must be conducted to obtain a better understanding of the exact mechanisms of both treatments when applied in combination. PMID:27376285

  4. HSF-1 is involved in attenuating the release of inflammatory cytokines induced by LPS through regulating autophagy.

    Science.gov (United States)

    Tong, Zhongyi; Jiang, Bimei; Zhang, Lingli; Liu, Yanjuan; Gao, Min; Jiang, Yu; Li, Yuanbin; Lu, Qinglan; Yao, Yongming; Xiao, Xianzhong

    2014-05-01

    Autophagy plays a protective role in endotoxemic mice. Heat shock factor 1 (HSF-1) also plays a crucial protective role in endotoxemic mice by decreasing inflammatory cytokines. The purpose of this study was to determine whether HSF-1 is involved in attenuating the release of inflammatory cytokines in lipopolysaccharide (LPS)-stimulated mice and peritoneal macrophages (PMs) through regulating autophagy activity. Autophagosome formation in HSF-1(+/+) and HSF-1(-/-) mice and PMs stimulated by LPS was examined by Western blotting and immunofluorescence. Lipopolysaccharide-induced autophagy and inflammatory cytokines were examined in HSF-1(+/+) and HSF-1(-/-) PMs treated with 3-methyladenine (3-MA) or rapamycin. Results showed that LPS-induced autophagy was elevated transiently at 12 h but declined at 24 h in the livers and lungs of mice. Higher levels of inflammatory cytokines and lower autophagy activity were detected in HSF-1(-/-) mice and PMs compared with HSF-1(+/+) mice and PMs. Interestingly, LPS-induced release of inflammatory cytokines did not further increase in HSF-1(-/-) PMs treated with 3-MA but aggravated in HSF-1(+/+) PMs. Lipopolysaccharide-induced autophagy did not decrease in HSF-1(-/-) PMs treated with 3-MA but decreased in HSF-1 PMs(+/+). Taken together, our results suggested that HSF-1 attenuated the release of inflammatory cytokines induced by LPS by regulating autophagy activity.

  5. Cytokine-induced killer cells interact with tumor lysate-pulsed dendritic cells via CCR5 signaling.

    Science.gov (United States)

    Lee, Hong Kyung; Kim, Yong Guk; Kim, Ji Sung; Park, Eun Jae; Kim, Boyeong; Park, Ki Hwan; Kang, Jong Soon; Hong, Jin Tae; Kim, Youngsoo; Han, Sang-Bae

    2016-08-10

    The antitumor activity of cytokine-induced killer (CIK) cells can be increased by co-culturing them with tumor lysate-pulsed dendritic cells (tDCs); this phenomenon has been studied mainly at the population level. Using time-lapse imaging, we examined how CIK cells gather information from tDCs at the single-cell level. tDCs highly expressed CCL5, which bound CCR5 expressed on CIK cells. tDCs strongly induced migration of Ccr5(+/+) CIK cells, but not that of Ccr5(-/-) CIK cells or Ccr5(+/+) CIK cells treated with the CCR5 antagonist Maraviroc. Individual tDCs contacted Ccr5(+/+) CIK cells more frequently and lengthily than with Ccr5(-/-) CIK cells. Consequently, tDCs increased the antitumor activity of Ccr5(+/+) CIK cells in vitro and in vivo, but did not increase that of Ccr5(-/-) CIK cells. Taken together, our data provide insight into the mechanism of CIK cell activation by tDCs at the single-cell level.

  6. Improved Activation toward Primary Colorectal Cancer Cells by Antigen-Specific Targeting Autologous Cytokine-Induced Killer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Schlimper

    2012-01-01

    Full Text Available Adoptive therapy of malignant diseases with cytokine-induced killer (CIK cells showed promise in a number of trials; the activation of CIK cells from cancer patients towards their autologous cancer cells still needs to be improved. Here, we generated CIK cells ex vivo from blood lymphocytes of colorectal cancer patients and engineered those cells with a chimeric antigen receptor (CAR with an antibody-defined specificity for carcinoembryonic antigen (CEA. CIK cells thereby gained a new specificity as defined by the CAR and showed increase in activation towards CEA+ colon carcinoma cells, but less in presence of CEA− cells, indicated by increased secretion of proinflammatory cytokines. Redirected CIK activation was superior by CAR-mediated CD28-CD3ζ than CD3ζ signaling only. CAR-engineered CIK cells from colon carcinoma patients showed improved activation against their autologous, primary carcinoma cells from biopsies resulting in more efficient tumour cell lysis. We assume that adoptive therapy with CAR-modified CIK cells shows improved selectivity in targeting autologous tumour lesions.

  7. [Curative effect of decitabine combined with cytokine-induced killer cells in two elderly patients with acute myeloid leukemia].

    Science.gov (United States)

    Chang, Cheng; Yang, Bo; Zhang, Lin; Zhu, Hong-Li; Lu, Xue-Chun; Guo, Bo; Cai, Li-Li; Han, Wei-Dong; Wang, Yao; Fan, Hui; Li, Su-Xia; Liu, Yang; Yang, Yang; Zhai, Bing; Ran, Hai-Hong; Lin, Jie; Zhang, Feng

    2013-02-01

    This study was aimed to evaluate the effectiveness and safety of low methylation drug decitabine combined with autologous cytokine induced killer cells (CIK) to treat the elderly patients with acute myeloid leukemia (AML). Two AML patients aged over 80 years old were diagnosed and treated in our department from 2006 to 2012; both company with MDS history, and one case was M4-type, another case was M6-type according to FAB classification. The changes in lymphocyte subsets, hematologic response, transfusion frequency, leukemic gene expression, obtaining CR or PR, quality of life and survival time of the patients with different treatment regimen (decitabine alone; CIK alone; decitabine combined with CIK) were systematically observed. The results showed that therapy of decitabine combined with CIK cells could reduce bone marrow suppression extent, decrease the frequency and volume of blood transfusion, and prolong the duration of partial remission, compared with the single use of CIK cell infusion and single use of decitabine treatment. Meanwhile, the kinds of expressed genes associated with leukemia decreased and the survival time was prolonged obviously. The patients' life quality significantly improved. It is concluded that decitabine combined with CIK for treatment of elderly patients with AML is safe and effective.

  8. Arsenite Oxidation and Arsenite Resistance by Bacillus sp. PNKP-S2

    Directory of Open Access Journals (Sweden)

    Pranee Pattanapipitpaisal

    2015-01-01

    Full Text Available Arsenic causes human health problems after accumulate in the body for 10-15 years and arsenite [As(III] is generally regarded as being more mobile and toxic than other oxidation states. In this study, two-hundred and three bacterial strains were isolated from groundwater and soil samples collecting in Ubon Ratchathani Province, Thailand. All strains were screened for arsenic tolerant efficiency at 1-10 mM of sodium arsenite. Eighteen selected strains which had the highest resistance to 10 mM of As(III were further studied for their As(III-oxidizing activity and growth in enrichment and growth medium (EG medium supplemented with 0.58 mM of As(III. It was found that strain PNKP-S2 was able to grow in the medium with As(III as a sole energy source and had 89.11% As(III removal within 48 h. The PCR-based 16S rDNA sequencing analysis revealed that the strain PNKP-S2 was closed relative to Bacillus sp. This is the first report on Bacillus sp. chemolithoautotrophic As(III-oxidizer and this strain could be a potential candidate for application in arsenic remediation of contaminated water.

  9. Cytokine-induced loss of glucocorticoid function: effect of kinase inhibitors, long-acting β(2-adrenoceptor [corrected] agonist and glucocorticoid receptor ligands.

    Directory of Open Access Journals (Sweden)

    Christopher F Rider

    Full Text Available Acting on the glucocorticoid receptor (NR3C1, glucocorticoids are widely used to treat inflammatory diseases. However, glucocorticoid resistance often leads to suboptimal asthma control. Since glucocorticoid-induced gene expression contributes to glucocorticoid activity, the aim of this study was to use a 2 × glucocorticoid response element (GRE reporter and glucocorticoid-induced gene expression to investigate approaches to combat cytokine-induced glucocorticoid resistance. Pre-treatment with tumor necrosis factor-α (TNF or interleukin-1β inhibited dexamethasone-induced mRNA expression of the putative anti-inflammatory genes RGS2 and TSC22D3, or just TSC22D3, in primary human airway epithelial and smooth muscle cells, respectively. Dexamethasone-induced DUSP1 mRNA was unaffected. In human bronchial epithelial BEAS-2B cells, dexamethasone-induced TSC22D3 and CDKN1C expression (at 6 h was reduced by TNF pre-treatment, whereas DUSP1 and RGS2 mRNAs were unaffected. TNF pre-treatment also reduced dexamethasone-dependent 2×GRE reporter activation. This was partially reversed by PS-1145 and c-jun N-terminal kinase (JNK inhibitor VIII, inhibitors of IKK2 and JNK, respectively. However, neither inhibitor affected TNF-dependent loss of dexamethasone-induced CDKN1C or TSC22D3 mRNA. Similarly, inhibitors of the extracellular signal-regulated kinase, p38, phosphoinositide 3-kinase or protein kinase C pathways failed to attenuate TNF-dependent repression of the 2×GRE reporter. Fluticasone furoate, fluticasone propionate and budesonide were full agonists relative to dexamethasone, while GSK9027, RU24858, des-ciclesonide and GW870086X were partial agonists on the 2×GRE reporter. TNF reduced reporter activity in proportion with agonist efficacy. Full and partial agonists showed various degrees of agonism on RGS2 and TSC22D3 expression, but were equally effective at inducing CDKN1C and DUSP1, and did not affect the repression of CDKN1C or TSC22D3

  10. Cytoprotective Activity of Glycyrrhizae radix Extract against Arsenite-Induced Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Sang Chan Kim

    2008-01-01

    Full Text Available Licorice, Glycyrrhizae radix, is one of the herbal medicines in East Asia that has been commonly used for treating various diseases, including stomach disorders. This study investigated the effect of licorice on arsenite (As-induced cytotoxicity in H4IIE cells, a rat hepatocyte-derived cell line. Cell viability was significantly diminished in As-treated H4IIE cells in a time and concentration-dependent manner. Furthermore, results from flow cytometric assay and DNA laddering in H4IIE cells showed that As treatment induced apoptotic cell death by activating caspase-3. Licorice (0.1 and 1.0 mg ml−1 treatment significantly inhibited cell death and the activity of caspase-3 in response to As exposure. These results demonstrate that licorice induced a cytoprotective effect against As-induced cell death by inhibition of caspase-3.

  11. Sorption and desorption of arsenate and arsenite on calcite

    DEFF Research Database (Denmark)

    Sø, Helle Ugilt; Postma, Diederik Jan; Jakobsen, Rasmus;

    2008-01-01

    The adsorption and desorption of arsenate (As(V)) and arsenite (As(111)) oil calcite was investigated in a series of batch experiments in calcite-equilibrated solutions. The solutions covered a broad range of pH, alkalinity, calcium concentration and ionic strength. The initial arsenic concentrat......The adsorption and desorption of arsenate (As(V)) and arsenite (As(111)) oil calcite was investigated in a series of batch experiments in calcite-equilibrated solutions. The solutions covered a broad range of pH, alkalinity, calcium concentration and ionic strength. The initial arsenic...

  12. Autologous cytokine-induced killer cells therapy on the quality of life of patients with breast cancer after adjuvant chemotherapy: A prospective study

    Institute of Scientific and Technical Information of China (English)

    梁雪峰

    2013-01-01

    Objective To explore the effect of autologous cytokine-induced killer cells on the quality of life in patient with breast cancer who have already finished the adjuvant chemotherapy.Methods One hundred and twenty-eight postoperative patients with breast cancer who underwent anthracycline-based adjuvant chemotherapy were enrolled in this prospective study,and they were randomized into2 groups,i.e.,treatment group,which received the therapy of CIK cells transfusion,and control group,

  13. Cytotoxic capacity of IL-15-stimulated cytokine-induced killer cells against human acute myeloid leukemia and rhabdomyosarcoma in humanized preclinical mouse models

    OpenAIRE

    Eva eRettinger; Vida eMeyer; Hermann eKreyenberg; Andreas eVolk; Selim eKuci; Andre eWillasch; Ewa eKoscielniak; Simone eFulda; Winfried eWels; Halvard eBoenig; Thomas eKlingebiel; Peter eBader

    2012-01-01

    Allogeneic stem cell transplantation (allo-SCT) has become an important treatment modality for patients with high-risk acute myeloid leukemia (AML) and is also under investigation for soft tissue sarcomas. The therapeutic success is still limited by minimal residual disease (MRD) status ultimately leading to patients’ relapse. Adoptive donor lymphocyte infusions based on MRD status using IL-15-expanded cytokine-induced killer (CIK) cells may prevent relapse without causing graft-versus-host-d...

  14. Suppressor of cytokine signaling 1 protects rat pancreatic islets from cytokine-induced apoptosis through Janus kinase/signal transducers and activators of transcription pathway

    Institute of Scientific and Technical Information of China (English)

    SUN Qi; XIANG Ruo-lan; YANG Yan-li; FENG Kai; ZHANG Kui; DING Wen-yi

    2013-01-01

    Background Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathway involved in negative feedback loops.Although SOCS1 is an important intracellular suppressor of apoptosis in a variety of cell types,its role in cytokine-induced pancreatic β-cell apoptosis remains unclear.The present study investigated potential effects of SOCS1 on the cytokine-induced pancreatic β-cell apoptosis.Methods After successfully transfected with SOCS1/pEGFP-C1 or pEGFP-C1 plasmids to overexpress SOCS1,RINm5F (rat insulinoma cell line) cells were exposed to cytokines,interferon (IFN)-γ alone,IFN-γ+interleukin (IL)-1β,IFN-y+IL-1β+tumor necrosis factor (TNF)-α respectively.Pancreatic β-cell apoptosis was assessed by using MTT,FACS,and caspase-3 activity assays.Protein phosphorylation of Janus kinase 2 (JAK2) and signal transducers and activators of transcription 1 (STAT1) were verified by Western blotting and mRNA expression of inducible nitric oxide synthase (iNOS),NF-κB and Fas were analyzed by RT-PCR.Results Overexpression of SOCS1 in RINm5F cells was shown to attenuate IFN-γ alone,IFN-γ+IL-1β and IFN-γ+TNF-α+IL-1β mediated apoptosis.Phosphorylation of JAK2 and STAT1 significantly decreased in RINm5F cells which overexpressed SOCS1 protein.Overexpression of SOCS1 significantly suppressed cytokine-induced iNOS mRNA levels.Conclusion Overexpression of SOCS1 protects pancreatic islets from cytokine-induced cell apoptosis via the JAK2/STAT1 pathway.

  15. Increasing the immune activity of exosomes: the effect of miRNA-depleted exosome proteins on activating dendritic cell/cytokine-induced killer cells against pancreatic cancer* #

    OpenAIRE

    Que, Ri-sheng; Lin, Cheng; Ding, Guo-ping; WU, ZHENG-RONG; Cao, Li-ping

    2016-01-01

    Background: Tumor-derived exosomes were considered to be potential candidates for tumor vaccines because they are abundant in immune-regulating proteins, whereas tumor exosomal miRNAs may induce immune tolerance, thereby having an opposite immune function. Objective: This study was designed to separate exosomal protein and depleted exosomal microRNAs (miRNAs), increasing the immune activity of exosomes for activating dendritic cell/cytokine-induced killer cells (DC/CIKs) against pancreatic ca...

  16. Synergistic effect of chimeric antigen receptors and cytokine-induced killer cells: An innovative combination for cancer therapy

    Directory of Open Access Journals (Sweden)

    Binh Thanh Vu

    2016-06-01

    Full Text Available In recent years, the combination of gene and immunotherapy for cancer treatment has been regarded as innovative and promising; together, both therapies can help overcome limitations associated with conventional treatments. In order to augment anti-cancer efficacy and to maintain the specificity of antibody therapy, chimeric antigen receptor (CAR-modified T cells, directed toward tumor-specific antigens, have emerged as a novel and promising therapeutic platform. CARs consist of a B cell receptor (BCR-derived extracellular domain and T cell receptor (TCR-associated signaling elements. Cytokine-induced killer (CIK cells are the effector immune cells that can be activated ex vivo and possess both the anti-tumor potency of T lymphocytes and the non-major histocompatibility complex-restricted elimination of natural killer cells. With their pre-eminent ability for robust proliferation, CIK cells may overcome the main limitations of adoptive immunotherapy strategies. CIK cells have strong tumor cell killing capacity; they are effective against a wide variety of malignant tumors and have been shown to be safe in cancer patients. This review summarizes the characteristics of CARs which make them attractive for in cancer treatment strategies. In addition, the role of CIK cells and the advantages of combining CIK cells with CAR-based therapy will be discussed. Scientific evidence to support their combined therapeutic application will be highlighted, with a focus on how their innovative combination may be translated into cancer clinical trials. [Biomed Res Ther 2016; 3(6.000: 653-665

  17. In Vitro Protective Potentials of Annona muricata Leaf Extracts Against Sodium Arsenite-induced Toxicity.

    Science.gov (United States)

    George, Vazhappilly Cijo; Kumar, Devanga Ragupathi Naveen; Suresh, Palamadai Krishnan; Kumar, Rangasamy Ashok

    2015-01-01

    Sodium arsenite (NaAsO2) is a metalloid which is present widely in the environment and its chronic exposure can contribute to the induction of oxidative stress, resulting in disturbances in various metabolic functions including liver cell death. Hence, there is a need to develop drugs from natural sources, which can reduce arsenic toxicity. While there have been reports regarding the antioxidant and protective potentials of Annona muricataleaf extracts, our study is the first ofits kind to extend these findings by specifically evaluating its ability to render protection against sodium arsenite (NaAsO2) induced toxicity (10 μM) in WRL-68 (human hepatic cells) and human erythrocytes by employing XTT and haemolysis inhibition assays respectively. The methanolic extract exhibited higher activity than the aqueous extract in both assays. The results showed a dose-dependent decrease in arsenic toxicity in both WRL-68 cells and erythrocytes, suggesting the protective nature of Annona muricatato mitigate arsenic toxicity. Hence the bioactive extracts can further be scrutinized for the identification and characterization of their principal contributors.

  18. The role of the rice aquaporin Lsi1 in arsenite efflux from roots.

    Science.gov (United States)

    Zhao, Fang-Jie; Ago, Yukiko; Mitani, Namiki; Li, Ren-Ying; Su, Yu-Hong; Yamaji, Naoki; McGrath, Steve P; Ma, Jian Feng

    2010-04-01

    *When supplied with arsenate (As(V)), plant roots extrude a substantial amount of arsenite (As(III)) to the external medium through as yet unidentified pathways. The rice (Oryza sativa) silicon transporter Lsi1 (OsNIP2;1, an aquaporin channel) is the major entry route of arsenite into rice roots. Whether Lsi1 also mediates arsenite efflux was investigated. *Expression of Lsi1 in Xenopus laevis oocytes enhanced arsenite efflux, indicating that Lsi1 facilitates arsenite transport bidirectionally. *Arsenite was the predominant arsenic species in arsenate-exposed rice plants. During 24-h exposure to 5 mum arsenate, rice roots extruded arsenite to the external medium rapidly, accounting for 60-90% of the arsenate uptake. A rice mutant defective in Lsi1 (lsi1) extruded significantly less arsenite than the wild-type rice and, as a result, accumulated more arsenite in the roots. By contrast, Lsi2 mutation had little effect on arsenite efflux to the external medium. *We conclude that Lsi1 plays a role in arsenite efflux in rice roots exposed to arsenate. However, this pathway accounts for only 15-20% of the total efflux, suggesting the existence of other efflux transporters.

  19. The genetic basis of anoxygenic photosynthetic arsenite oxidation

    Science.gov (United States)

    Hernandez-Maldonado, Jamie; Sanchez-Sedillo, Benjamin; Stoneburner, Brendon; Boren, Alison; Miller, Laurence G.; McCann, Shelley; Rosen, Michael R.; Oremland, Ronald S.; Saltikov, Chad W.

    2016-01-01

    “Photoarsenotrophy”, the use of arsenite as an electron donor for anoxygenic photosynthesis, is thought to be an ancient form of phototrophy along with the photosynthetic oxidation of Fe(II), H2S, H2, and NO2-. Photoarsenotrophy was recently identified from Paoha Island's (Mono Lake, CA) arsenic-rich hot springs. The genomes of several photoarsenotrophs revealed a gene cluster, arxB2AB1CD, where arxA is predicted to encode for the sole arsenite oxidase. The role of arxA in photosynthetic arsenite oxidation was confirmed by disrupting the gene in a representative photoarsenotrophic bacterium, resulting in the loss of light-dependent arsenite oxidation. In situ evidence of active photoarsenotrophic microbes was supported by arxA mRNA detection for the first time, in red-pigmented microbial mats within the hot springs of Paoha Island. This work expands on the genetics for photosynthesis coupled to new electron donors and elaborates on known mechanisms for arsenic metabolism, thereby highlighting the complexities of arsenic biogeochemical cycling.

  20. Multiple controls affect arsenite oxidase gene expression in Herminiimonas arsenicoxydans

    Directory of Open Access Journals (Sweden)

    Coppée Jean-Yves

    2010-02-01

    Full Text Available Abstract Background Both the speciation and toxicity of arsenic are affected by bacterial transformations, i.e. oxidation, reduction or methylation. These transformations have a major impact on environmental contamination and more particularly on arsenic contamination of drinking water. Herminiimonas arsenicoxydans has been isolated from an arsenic- contaminated environment and has developed various mechanisms for coping with arsenic, including the oxidation of As(III to As(V as a detoxification mechanism. Results In the present study, a differential transcriptome analysis was used to identify genes, including arsenite oxidase encoding genes, involved in the response of H. arsenicoxydans to As(III. To get insight into the molecular mechanisms of this enzyme activity, a Tn5 transposon mutagenesis was performed. Transposon insertions resulting in a lack of arsenite oxidase activity disrupted aoxR and aoxS genes, showing that the aox operon transcription is regulated by the AoxRS two-component system. Remarkably, transposon insertions were also identified in rpoN coding for the alternative N sigma factor (σ54 of RNA polymerase and in dnaJ coding for the Hsp70 co-chaperone. Western blotting with anti-AoxB antibodies and quantitative RT-PCR experiments allowed us to demonstrate that the rpoN and dnaJ gene products are involved in the control of arsenite oxidase gene expression. Finally, the transcriptional start site of the aoxAB operon was determined using rapid amplification of cDNA ends (RACE and a putative -12/-24 σ54-dependent promoter motif was identified upstream of aoxAB coding sequences. Conclusion These results reveal the existence of novel molecular regulatory processes governing arsenite oxidase expression in H. arsenicoxydans. These data are summarized in a model that functionally integrates arsenite oxidation in the adaptive response to As(III in this microorganism.

  1. Discrimination of HLA null and low expression alleles by cytokine-induced secretion of recombinant soluble HLA.

    Science.gov (United States)

    Hinrichs, Jan; Figueiredo, Constança; Hirv, Kaimo; Mytilineos, Joannis; Blasczyk, Rainer; Horn, Peter A; Eiz-Vesper, Britta

    2009-04-01

    . Additionally, this discrimination between cytokine inducible and non-inducible defect alleles may be important in allotransplant settings in which a cytokine storm usually occurs following pre-transplant myeloablative conditioning or post-transplant immunosuppressive therapy.

  2. Antitumor activities of human autologous cytokine-induced killer (CIK) cells against hepatocellular carcinoma cells in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    Fu-Sheng Wang; Ming-Xu Liu; Bing Zhang; Ming Shi; Zhou-Yun Lei; Wen-Bing Sun; Qing-You Du; Ju-Mei Chen

    2002-01-01

    AIM: To characterize the anticancer function of cytokine-induced killer cells (CIK) and develop an adoptiveimmunotherapy for the patients with primary hepatocellularcarcinoma (HCC), we evaluated the proliferation rate,phenotype and the antitumor activity of human CIK cellsfrom healthy donors and HCC patients in vitro and in vivo.METHODS: Peripheral blood mononuclear cells (PBMC) fronhealthy donors and patients with primary HCC were incubatedin vitro and induced into ClK cells in the presence of variouscytokines such as interferon-gamma (IFN-γ), interleukin-1(IL-1), IL-2, and monoclonal antibody (mAb) against CD3.The phenotype and characterization of CIK cells wereidentified by flow cytometric analysis. The cytotoxicity of CIKcells was determined by 51 Cr release assay.RESULTS: The CIK cells were shown to be a heterogeneouspopulation with different cellular phenotypes. Thepercentage of CD3+/CD56+ positive cells, the dominanteffector cells, in total CIK cells from healthy donors andHCC patients, significantly increased from 0.1-0.13 % at day0 to 19.0-20.5 % at day 21 incubation, which suggested thatthe CD3+ CD56+ positive cells proliferated faster than othercell populations of CIK cells in the protocol used in thisstudy. After 28 day in vitro incubation, the ClK cells frompatients with HCC and healthy donors increased by morethan 300-fold and 500-fold in proliferation cell number,respectively. CIK cells originated from HCC patientspossessed a higher in vitro antitumor cytotoxic activity onautologous HCC cells than the autologous lymphokine-activated killer (LAK) cells and PBMC cells. In in vivoanimal experiment, CIK cells had stronger effects on theinhibition of tumor growth in Balb/c nude mice bearing BEL-7402-producing tumor than LAK cells (mean inhibitory rate,84.7 % vs 52.8 %, P < 0.05) or PBMC (mean inhibitoryrate, 84.7% vs37.1%, P<0.01).CONCLUSION: Autologous CIK cells are of highly efficientcytotoxic effector cells against primary hepatocellularcarcinoma

  3. The oxidative and adsorptive effectiveness of hydrous manganese dioxide for arsenite removal

    Institute of Scientific and Technical Information of China (English)

    Liu Ruiping; Yuan Baoling; Li Xing; Xia Shengji; Yang Yanling; Li Guibai

    2006-01-01

    This study focuses on the effectiveness of hydrous manganese dioxides (δMnO2) removing arsenite (As(Ⅲ)) from aqueous solution. Effects of such factors as permanganate oxidation, pH, humic acid and Ca2+ on As removal and possible mechanisms involved in have been investigated. Permanganate oxidation increases As removal to a certain extent; the higher pH results in the formation of more easily adsorbed As species, contributing to higher As removal; humic acid occupies adsorbing sites and decreases ζ potential of δMnO2, therefore inhibiting As removal; Ca2+ facilitates As adsorption on δMnO2, mainly through increasing ζ potential and decreasing repulsive forces between As and surface sites. δMnO2 exhibits oxidative and adsorptive potential for As(Ⅲ), and may be employed as adsorbents or filter coating for As removal in water treatment process.

  4. Developmental mechanisms of arsenite toxicity in zebrafish (Danio rerio) embryos

    Energy Technology Data Exchange (ETDEWEB)

    Li Dan [Department of Genetics, National Research Institute for Family Planning, Beijing (China); Graduate School of Peking Union Medical College, Beijing (China); Lu Cailing [Department of Genetics, National Research Institute for Family Planning, Beijing (China); Wang Ju; Hu Wei; Cao Zongfu; Sun Daguang [Department of Genetics, National Research Institute for Family Planning, Beijing (China); Graduate School of Peking Union Medical College, Beijing (China); Xia Hongfei [Department of Genetics, National Research Institute for Family Planning, Beijing (China); Ma Xu [Department of Genetics, National Research Institute for Family Planning, Beijing (China) and Graduate School of Peking Union Medical College, Beijing (China) and Department of Reproductive Genetics, WHO Collaborative Center for Research in Human Reproduction, Beijing (China)], E-mail: genetic@263.net.cn

    2009-02-19

    Arsenic usually accumulates in soil, water and airborne particles, from which it is taken up by various organisms. Exposure to arsenic through food and drinking water is a major public health problem affecting some countries. At present there are limited laboratory data on the effects of arsenic exposure on early embryonic development and the mechanisms behind its toxicity. In this study, we used zebrafish as a model system to investigate the effects of arsenite on early development. Zebrafish embryos were exposed to a range of sodium arsenite concentrations (0-10.0 mM) between 4 and 120 h post-fertilization (hpf). Survival and early development of the embryos were not obviously influenced by arsenite concentrations below 0.5 mM. However, embryos exposed to higher concentrations (0.5-10.0 mM) displayed reduced survival and abnormal development including delayed hatching, retarded growth and changed morphology. Alterations in neural development included weak tactile responses to light (2.0-5.0 mM, 30 hpf), malformation of the spinal cord and disordered motor axon projections (2.0 mM, 48 hpf). Abnormal cardiac function was observed as bradycardia (0.5-2.0 mM, 60 hpf) and altered ventricular shape (2.0 mM, 48 hpf). Furthermore, altered cell proliferation (2.0 mM, 24 hpf) and apoptosis status (2.0 mM, 24 and 48 hpf), as well as abnormal genomic DNA methylation patterning (2.0 mM, 24 and 48 hpf) were detected in the arsenite-treated embryos. All of these indicate a possible relationship between arsenic exposure and developmental failure in early embryogenesis. Our studies suggest that the negative effects of arsenic on vertebrate embryogenesis are substantial.

  5. Complex Regulation of Arsenite Oxidation in Agrobacterium tumefaciens

    OpenAIRE

    Kashyap, Des R.; Botero, Lina M.; Franck, William L.; Daniel J Hassett; McDermott, Timothy R.

    2006-01-01

    Seminal regulatory controls of microbial arsenite [As(III)] oxidation are described in this study. Transposon mutagenesis of Agrobacterium tumefaciens identified genes essential for As(III) oxidation, including those coding for a two-component signal transduction pair. The transposon interrupted a response regulator gene (referred to as aoxR), which encodes an ntrC-like protein and is immediately downstream of a gene (aoxS) encoding a protein with primary structural features found in sensor h...

  6. Involvement of HIF-2α-mediated inflammation in arsenite-induced transformation of human bronchial epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Yuan; Zhao, Yue; Xu, Wenchao; Luo, Fei; Wang, Bairu; Li, Yuan; Pang, Ying; Liu, Qizhan, E-mail: drqzliu@hotmail.com

    2013-10-15

    Arsenic is a well established human carcinogen that causes diseases of the lung. Some studies have suggested a link between inflammation and lung cancer; however, it is unknown if arsenite-induced inflammation causally contributes to arsenite-caused malignant transformation of cells. In this study, we investigated the molecular mechanisms underlying inflammation during neoplastic transformation induced in human bronchial epithelial (HBE) cells by chronic exposure to arsenite. The results showed that, on acute or chronic exposure to arsenite, HBE cells over-expressed the pro-inflammatory cytokines, interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1β (IL-1β). The data also indicated that HIF-2α was involved in arsenite-induced inflammation. Moreover, IL-6 and IL-8 were essential for the malignant progression of arsenite-transformed HBE cells. Thus, these experiments show that HIF-2α mediates arsenite-induced inflammation and that such inflammation is involved in arsenite-induced malignant transformation of HBE cells. The results provide a link between the inflammatory response and the acquisition of a malignant transformed phenotype by cells chronically exposed to arsenite and thus establish a previously unknown mechanism for arsenite-induced carcinogenesis. - Highlights: • Arsenite induces inflammation. • Arsenite-induced the increases of IL-6 and IL-8 via HIF-2α. • Inflammation is involved in arsenite-induced carcinogenesis.

  7. Effects of co-administration of dietary sodium arsenite and an NADPH oxidase inhibitor on the rat bladder epithelium

    International Nuclear Information System (INIS)

    Arsenite (AsIII), an inorganic arsenical, is a known human carcinogen, inducing tumors of the skin, urinary bladder and lung. It is metabolized to organic methylated arsenicals. Oxidative stress has been suggested as a mechanism for arsenic-induced carcinogenesis. Reactive oxygen species (ROS) can be important factors for carcinogenesis and tumor progression. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is known to produce intracellular ROS, therefore, we investigated the ability of apocynin (acetovanillone), an NADPH oxidase inhibitor, to inhibit the cytotoxicity and regenerative cell proliferation of arsenic in vitro and in vivo. Apocynin had similar effects in reducing the cytotoxicity of AsIII and dimethylarsinous acid (DMAIII) in rat urothelial cells in vitro. When tested at the same concentrations as apocynin, other antioxidants, such as L-ascorbate and N-acetylcysteine, did not inhibit AsIII-induced cytotoxicity but they were more effective at inhibiting DMAIII-induced cytotoxicity compared with apocynin. In vivo, female rats were treated for 3 weeks with 100 ppm AsIII. Immunohistochemical staining for 8-hydroxy-2'-deoxyguanosine (8-OHdG) showed that apocynin reduced oxidative stress partially induced by AsIII treatment on rat urothelium, and significantly reduced the cytotoxicity of superficial cells detected by scanning electron microscopy (SEM). However, based on the incidence of simple hyperplasia and the bromodeoxyuridine (BrdU) labeling index, apocynin did not inhibit AsIII-induced urothelial cell proliferation. These data suggest that the NADPH oxidase inhibitor, apocynin, may have the ability to partially inhibit arsenic-induced oxidative stress and cytotoxicity of the rat bladder epithelium in vitro and in vivo. However, apocynin did not inhibit the regenerative cell proliferation induced by arsenite in a short-term study.

  8. Arsenite as the probable active species in the human carcinogenicity of arsenic: mouse micronucleus assays on Na and K arsenite, orpiment, and Fowler's solution.

    OpenAIRE

    Tinwell, H; Stephens, S C; Ashby, J.

    1991-01-01

    Sodium arsenite, potassium arsenite, and Fowler's solution (arsenic trioxide dissolved in potassium bicarbonate) are equally active in the mouse bone marrow micronucleus assay (approximately 10 mg/kg by IP injection). The natural ore orpiment (principally As2S3) was inactive despite blood levels of arsenic of 300 to 900 ng/mL in treated mice at 24 hr. Sodium arsenite was active in three strains of mice. It is suggested that the human lung cancer observed among arsenic ore smelters and the ski...

  9. Arsenite induces apoptosis in human mesenchymal stem cells by altering Bcl-2 family proteins and by activating intrinsic pathway

    International Nuclear Information System (INIS)

    Purpose: Environmental exposure to arsenic is an important public health issue. The effects of arsenic on different tissues and organs have been intensively studied. However, the effects of arsenic on bone marrow mesenchymal stem cells (MSCs) have not been reported. This study is designed to investigate the cell death process caused by arsenite and its related underlying mechanisms on MSCs. The rationale is that absorbed arsenic in the blood circulation can reach to the bone marrow and may affect the cell survival of MSCs. Methods: MSCs of passage 1 were purchased from Tulane University, grown till 70% confluency level and plated according to the experimental requirements followed by treatment with arsenite at various concentrations and time points. Arsenite (iAsIII) induced cytotoxic effects were confirmed by cell viability and cell cycle analysis. For the presence of canonic apoptosis markers; DNA damage, exposure of intramembrane phosphotidylserine, protein and m-RNA expression levels were analyzed. Results: iAsIII induced growth inhibition, G2-M arrest and apoptotic cell death in MSCs, the apoptosis induced by iAsIII in the cultured MSCs was, via altering Bcl-2 family proteins and by involving intrinsic pathway. Conclusion: iAsIII can induce apoptosis in bone marrow-derived MSCs via Bcl-2 family proteins, regulating intrinsic apoptotic pathway. Due to the multipotency of MSC, acting as progenitor cells for a variety of connective tissues including bone, adipose, cartilage and muscle, these effects of arsenic may be important in assessing the health risk of the arsenic compounds and understanding the mechanisms of arsenic-induced harmful effects.

  10. Complexation of arsenite with phytochelatins reduces arsenite efflux and translocation from roots to shoots in Arabidopsis.

    Science.gov (United States)

    Liu, Wen-Ju; Wood, B Alan; Raab, Andrea; McGrath, Steve P; Zhao, Fang-Jie; Feldmann, Jörg

    2010-04-01

    Complexation of arsenite [As(III)] with phytochelatins (PCs) is an important mechanism employed by plants to detoxify As; how this complexation affects As mobility was little known. We used high-resolution inductively coupled plasma-mass spectrometry and accurate mass electrospray ionization-mass spectrometry coupled to HPLC to identify and quantify As(III)-thiol complexes and free thiol compounds in Arabidopsis (Arabidopsis thaliana) exposed to arsenate [As(V)]. As(V) was efficiently reduced to As(III) in roots. In wild-type roots, 69% of As was complexed as As(III)-PC4, As(III)-PC3, and As(III)-(PC2)2. Both the glutathione (GSH)-deficient mutant cad2-1 and the PC-deficient mutant cad1-3 were approximately 20 times more sensitive to As(V) than the wild type. In cad1-3 roots, only 8% of As was complexed with GSH as As(III)-(GS)3 and no As(III)-PCs were detected, while in cad2-1 roots, As(III)-PCs accounted for only 25% of the total As. The two mutants had a greater As mobility, with a significantly higher accumulation of As(III) in shoots and 4.5 to 12 times higher shoot-to-root As concentration ratio than the wild type. Roots also effluxed a substantial proportion of the As(V) taken up as As(III) to the external medium, and this efflux was larger in the two mutants. Furthermore, when wild-type plants were exposed to l-buthionine sulfoximine or deprived of sulfur, both As(III) efflux and root-to-shoot translocation were enhanced. The results indicate that complexation of As(III) with PCs in Arabidopsis roots decreases its mobility for both efflux to the external medium and for root-to-shoot translocation. Enhancing PC synthesis in roots may be an effective strategy to reduce As translocation to the edible organs of food crops.

  11. Protection against inflammatory β-cell damage by lysine deacetylase inhibition and microRNA expression?

    DEFF Research Database (Denmark)

    Vestergaard, Anna Lindeløv; Pallesen, Emil Marek Heymans; Novotny, Guy Wayne;

    Background and aims: Pro-inflammatory cytokines contribute to pancreatic β-cell apoptosis in type 1 and 2 diabetes mellitus. The detrimental effects resulting from cytokine-induced signaling in the β cell can be reduced by inhibition of class I classical lysine deacetylases (KDACi), especially HD...

  12. Competitive Adsorption of Arsenite and Silicic Acid on Goethite

    OpenAIRE

    Luxton, Todd Peter

    2002-01-01

    The adsorption behavior of silicic acid and arsenite alone and competitively on goethite over a broad pH range (3-11) at environmentally relevant concentrations was investigated utilizing pH adsorption data and zeta potential measurements. Both addition scenarios (Si before As(III) and As(III) before Si) were examined. The results of the adsorption experiments and zeta potential measurements were then used to model the single ion and competitive ion adsorption on goethite with the CD-MUSIC ...

  13. Subinhibitory arsenite concentrations lead to population dispersal in Thiomonas sp.

    Directory of Open Access Journals (Sweden)

    Marie Marchal

    Full Text Available Biofilms represent the most common microbial lifestyle, allowing the survival of microbial populations exposed to harsh environmental conditions. Here, we show that the biofilm development of a bacterial species belonging to the Thiomonas genus, frequently found in arsenic polluted sites and playing a key role in arsenic natural remediation, is markedly modified when exposed to subinhibitory doses of this toxic element. Indeed, arsenite [As(III] exposure led to a considerable impact on biofilm maturation by strongly increasing the extracellular matrix synthesis and by promoting significant cell death and lysis within microcolonies. These events were followed by the development of complex 3D-biofilm structures and subsequently by the dispersal of remobilized cells observed inside the previously formed hollow voids. Our results demonstrate that this biofilm community responds to arsenite stress in a multimodal way, enhancing both survival and dispersal. Addressing this complex bacterial response to As(III stress, which might be used by other microorganisms under various adverse conditions, may be essential to understand how Thiomonas strains persist in extreme environments.

  14. Effect of arsenite-oxidizing bacterium B. laterosporus on arsenite toxicity and arsenic translocation in rice seedlings.

    Science.gov (United States)

    Yang, Gui-Di; Xie, Wan-Ying; Zhu, Xi; Huang, Yi; Yang, Xiao-Jun; Qiu, Zong-Qing; Lv, Zhen-Mao; Wang, Wen-Na; Lin, Wen-Xiong

    2015-10-01

    Arsenite [As (III)] oxidation can be accelerated by bacterial catalysis, but the effects of the accelerated oxidation on arsenic toxicity and translocation in rice plants are poorly understood. Herein we investigated how an arsenite-oxidizing bacterium, namely Brevibacillus laterosporus, influences As (III) toxicity and translocation in rice plants. Rice seedlings of four cultivars, namely Guangyou Ming 118 (GM), Teyou Hang II (TH), Shanyou 63 (SY) and Minghui 63 (MH), inoculated with or without the bacterium were grown hydroponically with As (III) to investigate its effects on arsenic toxicity and translocation in the plants. Percentages of As (III) oxidation in the solutions with the bacterium (100%) were all significantly higher than those without (30-72%). The addition of the bacterium significantly decreased As (III) concentrations in SY root, GM root and shoot, while increased the As (III) concentrations in the shoot of SY, MH and TH and in the root of MH. Furthermore, the As (III) concentrations in the root and shoot of SY were both the lowest among the treatments with the bacterium. On the other hand, its addition significantly alleviated the As (III) toxicity on four rice cultivars. Among the treatments amended with B. laterosporus, the bacterium showed the best remediation on SY seedlings, with respect to the subdued As (III) toxicity and decreased As (III) concentration in its roots. These results indicated that As (III) oxidation accelerated by B. laterosporus could be an effective method to alleviate As (III) toxicity on rice seedlings.

  15. Diclofenac enhances proinflammatory cytokine-induced nitric oxide production through NF-κB signaling in cultured astrocytes

    International Nuclear Information System (INIS)

    Recently, the number of reports of encephalitis/encephalopathy associated with influenza virus has increased. In addition, the use of a non-steroidal anti-inflammatory drug, diclofenac sodium (DCF), is associated with a significant increase in the mortality rate of influenza-associated encephalopathy. Activated astrocytes are a source of nitric oxide (NO), which is largely produced by inducible NO synthase (iNOS) in response to proinflammatory cytokines. Therefore, we investigated whether DCF enhances nitric oxide production in astrocytes stimulated with proinflammatory cytokines. We stimulated cultured rat astrocytes with three cytokines, interleukin-1β, tumor necrosis factor-α and interferon-γ, and then treated the astrocytes with DCF or acetaminophen (N-acetyl-p-aminophenol: APAP). iNOS and NO production in astrocyte cultures were induced by proinflammatory cytokines. The addition of DCF augmented NO production, but the addition of APAP did not. NF-κB inhibitors SN50 and MG132 inhibited iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. Similarly, NF-κB p65 Stealth small interfering RNA suppressed iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. LDH activity and DAPI staining showed that DCF induces cell damage in cytokine-stimulated astrocytes. An iNOS inhibitor, L-NMMA, inhibited the cytokine- and DCF-induced cell damage. In conclusion, this study demonstrates that iNOS and NO are induced in astrocyte cultures by proinflammatory cytokines. Addition of DCF further augments NO production. This effect is mediated via NF-κB signaling and leads to cell damage. The enhancement of DCF on NO production may explain the significant increase in the mortality rate of influenza-associated encephalopathy in patients treated with DCF.

  16. Arsenite Sorption by Drinking-Water Treatment Residuals: Redox Effects

    Science.gov (United States)

    Makris, K. C.; Sarkar, D.; Datta, R.

    2005-05-01

    Arsenic (As) is a major human carcinogen and could pose a serious human health risk at concentrations as low as 50 ppb in drinking water. Elevated As concentrations in soils currently used for residential purposes (located on former agricultural lands amended with arsenical pesticides) have increased the possibility of human contact with soil-As. Studies have shown that As bioavailability in the environment is primarily a function of its chemical speciation, which depends upon the redox potential. Arsenic toxicity and carcinogenicity to living organisms is primarily due to exposure to the reduced species of As - arsenite, i.e., As(III), rather than the oxidized species - arsenate, i.e., As(V); the mobility of As(III) is much higher than As(V). One of the most promising methods to decrease the mobility of arsenite in the soil-water system is promoting its retention onto amorphous Fe/Al hydroxides. Drinking-Water Treatment Residuals (WTRs) are an inexpensive source of such Fe/Al hydroxides, which can be land-applied following the USEPA-regulated biosolids application rules. The WTRs are byproducts of drinking-water purification processes and generally contain sediment, organic carbon, and Al/Fe hydroxides. The hydroxides are typically amorphous and have tremendous affinity for oxyanions (e.g., arsenate). Preliminary work showed that WTRs are characterized by large internal surface area and porosity that partly explains their high affinity for As(V). The current study examines the potential of two WTRs (Fe-based and Al-based) to adsorb arsenite from solution. We hypothesize that As(III) adsorption onto the Fe-based WTR (whose stability is highly redox-sensitive) would be vastly different from the adsorption of As(III) onto the redox-insensitive Al-based WTR. Our main objective is to characterize As(III) sorption by both Fe- and Al-based WTRs by changing critical factors, such as the solid:solution ratio, contact time, and initial As(III) load. Results from this study

  17. Long-term performance of rapid oxidation of arsenite in simulated groundwater using a population of arsenite-oxidizing microorganisms in a bioreactor.

    Science.gov (United States)

    Li, Hao; Zeng, Xian-Chun; He, Zhong; Chen, Xiaoming; E, Guoji; Han, Yiyang; Wang, Yanxin

    2016-09-15

    A population of arsenite-oxidizing microorganisms enriched from the tailing of the Shimen realgar mine was used to generate biofilms on the surfaces of perlites. This bioreactor is able to completely oxidize 1100 μg/L As(III) dissolved in simulated groundwater into As(V) within 10 min; after 140 days of operation, approximately 20 min were required to completely oxidize the same concentration of As(III). Analysis for the 16S rRNA genes of the microbial community showed that Bacteroidetes and Proteobacteria are dominant in the reactor. Six different bacterial strains were randomly isolated from the reactor. Function and gene analysis indicated that all the isolates possess arsenite-oxidizing activity, and five of them are chemoautotrophic. Further analysis showed that a large diversity of AioAs and two types of RuBisCOs are present in the microbial community. This suggests that many chemoautotrophic arsenite-oxidizing microorganisms were responsible for quick oxidation of arsenite in the reactor. We also found that the reactor is easily regenerated and its number is readily expanded. To the best of our knowledge, the arsenite-oxidizing efficiency, which was expressed as the minimum time for complete oxidization of a certain concentration of As(III) under a single operation, of this bioreactor is the highest among the described bioreactors; it is also the most stable, economic and environment-friendly. PMID:27288673

  18. Evidence for toxicity differences between inorganic arsenite and thioarsenicals in human bladder cancer cells.

    Science.gov (United States)

    Naranmandura, Hua; Ogra, Yasumitsu; Iwata, Katsuya; Lee, Jane; Suzuki, Kazuo T; Weinfeld, Michael; Le, X Chris

    2009-07-15

    Arsenic toxicity is dependent on its chemical species. In humans, the bladder is one of the primary target organs for arsenic-induced carcinogenicity. However, little is known about the mechanisms underlying arsenic-induced carcinogenicity, and what arsenic species are responsible for this carcinogenicity. The present study aimed at comparing the toxic effect of DMMTA(V) with that of inorganic arsenite (iAs(III)) on cell viability, uptake efficiency and production of reactive oxygen species (ROS) toward human bladder cancer EJ-1 cells. The results were compared with those of a previous study using human epidermoid carcinoma A431 cells. Although iAs(III) was known to be toxic to most cells, here we show that iAs(III) (LC(50)=112 microM) was much less cytotoxic than DMMTA(V) (LC(50)=16.7 microM) in human bladder EJ-1 cells. Interestingly, pentavalent sulfur-containing DMMTA(V) generated a high level of intracellular ROS in EJ-1 cells. However, this was not observed in the cells exposed to trivalent inorganic iAs(III) at their respective LC(50) dose. Furthermore, the presence of N-acetyl-cysteine completely inhibited the cytotoxicity of DMMTA(V) but not iAs(III), suggesting that production of ROS was the main cause of cell death from exposure to DMMTA(V), but not iAs(III). Because the cellular uptake of iAs(III) is mediated by aquaporin proteins, and because the resistance of cells to arsenite can be influenced by lower arsenic uptake due to lower expression of aquaporin proteins (AQP 3, 7 and 9), the expression of several members of the aquaporin family was also examined. In human bladder EJ-1 cells, mRNA/proteins of AQP3, 7 and 9 were not detected by reverse transcription polymerase chain reaction (RT-PCR)/western blotting. In A431 cells, only mRNA and protein of AQP3 were detected. The large difference in toxicity between the two cell lines could be related to their differences in uptake of arsenic species.

  19. Evidence for toxicity differences between inorganic arsenite and thioarsenicals in human bladder cancer cells

    International Nuclear Information System (INIS)

    Arsenic toxicity is dependent on its chemical species. In humans, the bladder is one of the primary target organs for arsenic-induced carcinogenicity. However, little is known about the mechanisms underlying arsenic-induced carcinogenicity, and what arsenic species are responsible for this carcinogenicity. The present study aimed at comparing the toxic effect of DMMTAV with that of inorganic arsenite (iAsIII) on cell viability, uptake efficiency and production of reactive oxygen species (ROS) toward human bladder cancer EJ-1 cells. The results were compared with those of a previous study using human epidermoid carcinoma A431 cells. Although iAsIII was known to be toxic to most cells, here we show that iAsIII (LC50 = 112 μM) was much less cytotoxic than DMMTAV (LC50 = 16.7 μM) in human bladder EJ-1 cells. Interestingly, pentavalent sulfur-containing DMMTAV generated a high level of intracellular ROS in EJ-1 cells. However, this was not observed in the cells exposed to trivalent inorganic iAsIII at their respective LC50 dose. Furthermore, the presence of N-acetyl-cysteine completely inhibited the cytotoxicity of DMMTAV but not iAsIII, suggesting that production of ROS was the main cause of cell death from exposure to DMMTAV, but not iAsIII. Because the cellular uptake of iAsIII is mediated by aquaporin proteins, and because the resistance of cells to arsenite can be influenced by lower arsenic uptake due to lower expression of aquaporin proteins (AQP 3, 7 and 9), the expression of several members of the aquaporin family was also examined. In human bladder EJ-1 cells, mRNA/proteins of AQP3, 7 and 9 were not detected by reverse transcription polymerase chain reaction (RT-PCR)/western blotting. In A431 cells, only mRNA and protein of AQP3 were detected. The large difference in toxicity between the two cell lines could be related to their differences in uptake of arsenic species.

  20. INFLUENCE OF SODIUM ARSENITE ON GAP JUNCTION COMMUNICATION IN RAT LIVER EPITHELIAL CELLS

    Science.gov (United States)

    Influence of sodium arsenite on gap junction communication in rat-Iiver epitheiial cells. Arsenic is known to cause certain types of cancers, hepatitis, cirrhosis and neurological disorders as well as cardiovascular and reproductive effects and skin lesions. The mechanism...

  1. APOPTOSIS GENE EXPRESSION IN HUMAN EPDERMAL KERATINOCYTES TREATED WITH SODIUM ARSENITE USING REAL TIME PCR ARRAY

    Science.gov (United States)

    Arsenic exposure via contaminated drinking water is a great public health concern worldwide. Chronic arsenic exposure has been associated with human skin, lung and bladder cancer and other chronic effects. We have previous reported that sodium arsenite stimulated cell proliferati...

  2. Arsenite-induced autophagy is associated with proteotoxicity in human lymphoblastoid cells

    Energy Technology Data Exchange (ETDEWEB)

    Bolt, Alicia M.; Zhao, Fei; Pacheco, Samantha; Klimecki, Walter T., E-mail: klimecki@pharmacy.arizona.edu

    2012-10-15

    Epidemiological studies of arsenic-exposed populations have provided evidence that arsenic exposure in humans is associated with immunosuppression. Previously, we have reported that arsenite-induced toxicity is associated with the induction of autophagy in human lymphoblastoid cell lines (LCL). Autophagy is a cellular process that functions in the degradation of damaged cellular components, including protein aggregates formed by misfolded or damaged proteins. Accumulation of misfolded or damaged proteins in the endoplasmic reticulum (ER) lumen causes ER stress and activates the unfolded protein response (UPR). In an effort to investigate the mechanism of autophagy induction by arsenite in the LCL model, we examined the potential contribution of ER stress and activation of the UPR. LCL exposed to sodium arsenite for 8-days induced expression of UPR-activated genes, including CHOP and GRP78, at the RNA and the protein level. Evidence for activation of the three arms of the UPR was observed. The arsenite-induced activation of the UPR was associated with an accumulation of protein aggregates containing p62 and LC3, proteins with established roles in the sequestration and autophagic clearance of protein aggregates. Taken together, these data provide evidence that arsenite-induced autophagy is associated with the generation of ER stress, activation of the UPR, and formation of protein aggregates that may be targeted to the lysosome for degradation. -- Highlights: ► Arsenite induces endoplasmic reticulum stress and the unfolded protein response. ► Arsenite induces the formation of protein aggregates that contain p62 and LC3-II. ► Time-course data suggests that arsenite-induced autophagy precedes ER stress.

  3. Silymarin protects plasma membrane and acrosome integrity in sperm treated with sodium arsenite

    Directory of Open Access Journals (Sweden)

    Farzaneh Eskandari

    2016-01-01

    Full Text Available Background: Exposure to arsenic is associated with impairment of male reproductive function by inducing oxidative stress. Silymarin with an antioxidant property scavenges free radicals. Objective: The aim of this study was to investigate if silymarin can prevent the adverse effects of sodium arsenite on ram sperm plasma membrane and acrosome integrity. Materials and Methods: Ram epidydimal spermatozoa were divided into five groups: spermatozoa at 0 hr, spermatozoa at 180 min (control, spermatozoa treated with silymarin (20 μM + sodium arsenite (10 μM for 180 min, spermatozoa treated with sodium arsenite (10 μM for 180 min and spermatozoa treated with silymarin (20 μM for 180 min. Double staining of Hoechst and propidium iodide was performed to evaluate sperm plasma membrane integrity, whereas comassie brilliant blue staining was used to assess acrosome integrity. Results: Plasma membrane (p< 0.001 and acrosome integrity (p< 0.05 of the spermatozoa were significantly reduced in sodium arsenite group compared to the control. In silymarin + sodium arsenite group, silymarin was able to significantly (p< 0.001 ameliorate the adverse effects of sodium arsenite on these sperm parameters compared to sodium arsenite group. The incubation of sperm for 180 min (control group showed a significant (p< 0.001 decrease in acrosome integrity compared to the spermatozoa at 0 hour. The application of silymarin alone for 180 min could also significantly (p< 0.05 increase sperm acrosome integrity compared to the control. Conclusion: Silymarin as a potent antioxidant could compensate the adverse effects of sodium arsenite on the ram sperm plasma membrane and acrosome integrity.

  4. Immunotherapeutic effects of cytokine-induced killer cells combined with CCL21/IL15 armed oncolytic adenovirus in TERT-positive tumor cells.

    Science.gov (United States)

    Ye, Jun-Feng; Lin, Yuan-Qiang; Yu, Xiu-Hua; Liu, Ming-Yuan; Li, Yang

    2016-09-01

    The effective antitumor immune responses are dependent on coordinate interaction of various effector cells. Thus, the combination of adoptive immunotherapy and target gene therapy is capable of efficiently generating a productive antitumor immune response. We investigated whether combination of cytokine-induced killer (CIK) cells adoptive immunotherapy and CCL21/IL15 armed oncolytic adenovirus could induce the enhanced antitumor activity. The CCL21/IL15 co-expression oncolytic adenoviruses were constructed by using the AdEasy system, which uses homologous recombination with shuttle plasmids and full length Ad backbones. This conditionally replicating adenoviruses CRAd-CCL21-IL15 could induce apoptosis in TERTp-positive tumor cells for viral propagation, but do not replicate efficiently in normal cells, because the E1A promoter was replaced by telomerase reverse transcriptase promoter (TERTp). Our results showed that the combination of CIK cells and CRAd-CCL21-IL15 could induce higher antitumor activity than either CIK cells or CRAd-CCL21-IL15 alone. This combined treatment could induce the tumor specific cytotoxicity of CTLs (cytotoxic T lymphocytes) in vitro. Moreover, the treatment of established tumors with the combined therapy of CIK cells and CRAd-CCL21-IL15 resulted in tumor regression. This study suggests that the combined treatment by adoptive immunotherapy and gene therapy is a promising strategy for the therapy of tumor. PMID:27380620

  5. Cytokine-induced oxidative stress in cardiac inflammation and heart failure – how the ubiquitin proteasome system targets this vicious cycle

    Directory of Open Access Journals (Sweden)

    Antje eVoigt

    2013-03-01

    Full Text Available The ubiquitin proteasome system (UPS is critical for the regulation of many intracellular processes necessary for cell function and survival. The absolute requirement of the UPS for the maintenance of protein homeostasis and thereby for the regulation of protein quality control is reflected by the fact that deviation of proteasome function from the norm was reported in cardiovascular pathologies. Inflammation is a major factor contributing to cardiac pathology. Herein, cytokines induce protein translation and the production of free radicals, thereby challenging the cellular protein equilibrium. Here, we discuss current knowledge on the mechanisms of UPS-functional adaptation in response to oxidative stress in cardiac inflammation. The increasing pool of oxidant-damaged degradation-prone proteins in cardiac pathology accounts for the need for enhanced protein turnover by the UPS. This process is accomplished by an up-regulation of the ubiquitylation machinery and the induction of immunoproteasomes. Thereby, the inflamed heart muscle is cleared from accumulating misfolded proteins. Current advances on immunoproteasome-specific inhibitors in this field question the impact of the proteasome as a therapeutic target in heart failure.

  6. Retrospective Comparative Study of the Effects of Dendritic Cell Vaccine and Cytokine-Induced Killer Cell Immunotherapy with that of Chemotherapy Alone and in Combination for Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Jingxiu Niu

    2014-01-01

    Full Text Available Purpose. This retrospective study determined the delayed-type hypersensitivity (DTH skin test and safety of dendritic cell (DC vaccine and cytokine-induced killer (CIK cell immunotherapy and the survival compared to chemotherapy in 239 colorectal cancer (CRC patients. Methods. DTH and safety of the immunotherapy were recorded. The overall survival (OS and disease free survival curves were compared according to the immunotherapy and/or chemotherapy received with Kaplan-Meier estimates. Results. Of the 70 patients who received immunotherapy, 62.86% had a positive DTH skin test, 38.57% developed fever, 47.14% developed insomnia, 38.57% developed anorexia, 4.29% developed joint soreness, and 11.43% developed skin rash. For 204 resectable CRC patients, median survival time (MST (198.00 days was significantly longer in patients with immunotherapy plus chemotherapy than with chemotherapy alone (106.00 days (P=0.02. For 35 patients with unresectable or postsurgery relapsed CRC and who were confirmed to be dead, no statistical difference was observed in the MST between the patients treated with immunotherapy and with chemotherapy (P=0.41. MST in the patients treated with chemotherapy plus immunotherapy was 154 days longer than that of patients treated with chemotherapy alone (P=0.41. Conclusions. DC vaccination and CIK immunotherapy did not cause severe adverse effects, induce immune response against CRC, and prolong OS.

  7. Constitutive arsenite oxidase expression detected in arsenic-hypertolerant Pseudomonas xanthomarina S11.

    Science.gov (United States)

    Koechler, Sandrine; Arsène-Ploetze, Florence; Brochier-Armanet, Céline; Goulhen-Chollet, Florence; Heinrich-Salmeron, Audrey; Jost, Bernard; Lièvremont, Didier; Philipps, Muriel; Plewniak, Frédéric; Bertin, Philippe N; Lett, Marie-Claire

    2015-04-01

    Pseudomonas xanthomarina S11 is an arsenite-oxidizing bacterium isolated from an arsenic-contaminated former gold mine in Salsigne, France. This bacterium showed high resistance to arsenite and was able to oxidize arsenite to arsenate at concentrations up to 42.72 mM As[III]. The genome of this strain was sequenced and revealed the presence of three ars clusters. One of them is located on a plasmid and is organized as an "arsenic island" harbouring an aio operon and genes involved in phosphorous metabolism, in addition to the ars genes. Neither the aioXRS genes nor a specific sigma-54-dependent promoter located upstream of aioBA genes, both involved in regulation of arsenite oxidase expression in other arsenite-oxidizing bacteria, could be identified in the genome. This observation is in accordance with the fact that no difference was observed in expression of arsenite oxidase in P. xanthomarina S11, whether or not the strain was grown in the presence of As[III].

  8. Transporters of arsenite in rice and their role in arsenic accumulation in rice grain.

    Science.gov (United States)

    Ma, Jian Feng; Yamaji, Naoki; Mitani, Namiki; Xu, Xiao-Yan; Su, Yu-Hong; McGrath, Steve P; Zhao, Fang-Jie

    2008-07-22

    Arsenic poisoning affects millions of people worldwide. Human arsenic intake from rice consumption can be substantial because rice is particularly efficient in assimilating arsenic from paddy soils, although the mechanism has not been elucidated. Here we report that two different types of transporters mediate transport of arsenite, the predominant form of arsenic in paddy soil, from the external medium to the xylem. Transporters belonging to the NIP subfamily of aquaporins in rice are permeable to arsenite but not to arsenate. Mutation in OsNIP2;1 (Lsi1, a silicon influx transporter) significantly decreases arsenite uptake. Furthermore, in the rice mutants defective in the silicon efflux transporter Lsi2, arsenite transport to the xylem and accumulation in shoots and grain decreased greatly. Mutation in Lsi2 had a much greater impact on arsenic accumulation in shoots and grain in field-grown rice than Lsi1. Arsenite transport in rice roots therefore shares the same highly efficient pathway as silicon, which explains why rice is efficient in arsenic accumulation. Our results provide insight into the uptake mechanism of arsenite in rice and strategies for reducing arsenic accumulation in grain for enhanced food safety.

  9. Inhibitory Effects of Sodium Arsenite and Acacia Honey on Acetylcholinesterase in Rats

    Directory of Open Access Journals (Sweden)

    Aliyu Muhammad

    2015-01-01

    Full Text Available This study was conducted to investigate the effect of sodium arsenite and Acacia honey on acetylcholinesterase (AChE activity and electrolytes in the brain and serum of Wistar rats. Male Wistar albino rats in four groups of five rats each were treated with distilled water, sodium arsenite (5 mg/kg body weight, Acacia honey (20% v/v, and sodium arsenite and Acacia honey, daily for one week. The sodium arsenite and Acacia honey significantly P<0.05 decreased AChE activity in the brain with the combined treatment being more potent. Furthermore, sodium arsenite and Acacia honey significantly P<0.05 decreased AChE activity in the serum. Strong correlation was observed between the sodium and calcium ion levels with acetylcholinesterase activity in the brain and serum. The gas chromatography mass spectrometry analysis of Acacia honey revealed the presence of a number of bioactive compounds such as phenolics, sugar derivatives, and fatty acids. These findings suggest that sodium arsenite and/or Acacia honey modulates acetylcholinesterase activities which may be explored in the management of Alzheimer’s diseases but this might be counteracted by the hepatotoxicity induced by arsenics.

  10. Preparation of copper arsenite and its application in purification of copper electrolyte

    Institute of Scientific and Technical Information of China (English)

    XIAO Fa-xin; ZHENG Ya-jie; WANG Yong; JIAN Hong-sheng; LI Chun-hua; XU Wei; MA Yu-tian

    2008-01-01

    The preparation of copper arsenite with arsenic trioxide was presented and its application in the purification of copper electrolyte was proposed. The variables of n(OH-)/n(As), n(Cu)/n(As), NaOH concentration, reaction temperature and pH value have some effects on the yield of copper arsenite. The optimum conditions of preparing copper arsenite are that the molar ratio of alkali to arsenic is 2:1, NaOH concentration is 1 mol/L, the molar ratio of copper to arsenic is 2:1, pH value is 6.0 and reaction temperature is 20 ℃. The yield of copper arsenite is as high as 98.65% under optimum conditions and the molar ratio of Cu to As in the product is about 5:4. The results of the purification experiments show that the removal rate of antimony and bismuth is 53.85% and 53.33% respectively after 20 g/L copper arsenite is added. The purification of copper electrolyte with copper arsenite has the advantages of simple technique, good purification performance and low cost.

  11. Electrochemical and XAFS Studies of Effects of Carbonate on the Oxidation of Arsenite

    Energy Technology Data Exchange (ETDEWEB)

    Kim,J.; Korshin, G.; Frenkel, A.; Velichenko, A.

    2006-01-01

    Measurements of electrochemical (EC) arsenite oxidation demonstrated that the arsenite oxidation current increased in the presence of carbonate while the potential of the onset of EC arsenite oxidation exhibited a strong shift toward less positive values. Examination of pH and total carbonate concentration effects on the EC arsenite oxidation parameters showed that they were affected solely by the concentration of carbonate ion CO{sub 3}{sup 2-}, which appeared to form relatively weak mono- and dicarbonate complexes with arsenite. The EC activity of these complexes was determined to be almost an order of magnitude higher than that of free arsenite. However, X-ray absorption fine-structure (XAFS) measurements did not show any changes in the properties of the As(III) inner complexation shell associated with the presence of the bound carbonate ions. It was accordingly concluded that the strength of bonds between the bound carbonate and As(III) is close to that for As(III)-OH- interactions. The acceleration of the oxidation of carbonate-As(III) complexes was hypothesized to be associated with an additional pathway of the formation of As(IV) intermediates, in which the carbonate group present in the As(III) inner shell provides an electron to form a bound carbonate radical and also a good leaving group for facile cleavage from the transient As(IV) species.

  12. The Arx Anaerobic Arsenite-Oxidization Pathway Is Conserved In Halomonas And Ectothiorhodospira Strains Isolated From Big Soda Lake, Nevada

    OpenAIRE

    Conrad, Alison Tory

    2014-01-01

    Microorganisms play a significant role in environmental arsenic cycling. The most recent discovery to the ever growing collection of known arsenic metabolisms is photosynthesis-linked arsenite oxidation (photoarsenotrophy). However, it is poorly understood and has only been identified in thermal springs on Paoha Island of Mono Lake, CA. The arsenite oxidase ArxA is thought to be responsible for the oxidation of arsenite in photoarsenotrophy. However, the first and only isolated photoarsenotro...

  13. Arsenite-Oxidizing Hydrogenobaculum Strain Isolated from an Acid-Sulfate-Chloride Geothermal Spring in Yellowstone National Park

    OpenAIRE

    Donahoe-Christiansen, Jessica; D'Imperio, Seth; Jackson, Colin R.; Inskeep, William P.; McDermott, Timothy R.

    2004-01-01

    An arsenite-oxidizing Hydrogenobaculum strain was isolated from a geothermal spring in Yellowstone National Park, Wyo., that was previously shown to contain microbial populations engaged in arsenite oxidation. The isolate was sensitive to both arsenite and arsenate and behaved as an obligate chemolithoautotroph that used H2 as its sole energy source and had an optimum temperature of 55 to 60°C and an optimum pH of 3.0. The arsenite oxidation in this organism displayed saturation kinetics and ...

  14. The defensive effect of benfotiamine in sodium arsenite-induced experimental vascular endothelial dysfunction.

    Science.gov (United States)

    Verma, Sanjali; Reddy, Krishna; Balakumar, Pitchai

    2010-10-01

    The present study has been designed to investigate the effect of benfotiamine, a thiamine derivative, in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Sodium arsenite (1.5 mg(-1) kg(-1) day(-1) i.p., 2 weeks) was administered in rats to produce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating the serum and aortic concentrations of nitrite/nitrate. Further, the integrity of vascular endothelium in thoracic aorta was assessed by scanning electron microscopy. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide anion generation. The administration of sodium arsenite markedly produced VED by attenuating acetylcholine-induced endothelium-dependent relaxation, decreasing serum and aortic concentrations of nitrite/nitrate, and impairing the integrity of vascular endothelium. Further, sodium arsenite produced oxidative stress by increasing serum TBARS and aortic superoxide generation. The treatment with benfotiamine (25, 50, and 100 mg(-1) kg(-1) day(-1) p.o.) or atorvastatin (30 mg(-1) kg(-1) day(-1) p.o., a standard agent) prevented sodium arsenite-induced VED and oxidative stress. However, the beneficial effects of benfotiamine in preventing the sodium arsenite-induced VED were attenuated by co-administration with N-omega-nitro-L: -arginine methyl ester (L: -NAME) (25 mg(-1) kg(-1) day(-1), i.p.), an inhibitor of NOS. Thus, it may be concluded that benfotiamine reduces oxidative stress and activates endothelial nitric oxide synthase to enhance the generation and bioavailability of NO and subsequently improves the integrity of vascular endothelium to prevent sodium arsenite-induced experimental VED.

  15. Physico chemical studies on the composition of complex arsenites of metals Part IV: conductometric and potentiometric studies on the composition of cadmium arsenite

    Directory of Open Access Journals (Sweden)

    M. S. Bhadraver

    1962-07-01

    Full Text Available The formation and precipitation of cadmium arsenite has been studied by conductometric and potentiometric titrations between cadmium nitrate and sodium arsenite (meta at different concentrations with either of the substances used as the reagent in titration. In the case of direct titrations (cadmium nitrate added to sodium arsenite in the conductivity cell, one distinct break in the curves is observed corresponding to the formation of the Cd (AsO/sub 2//sub 2/ where the molecular ratio is 2:1. The direct and reverse potentiometric titrations curves give one maxima in dE/dV at point corresponding to the formation of the complex Cd (AsO/sub/2/sub/2 where the molecular ratio of reactants Cd:AsO/sub/2 is 1:2. The composition has been arrived at by comparing the calculated values with observed values by conductometric and potentiometric titrations. The composition of cadmium arsenite arrived at both by conductometry and potentiometry is best representative as Cd(AsO/sub/2/sub/2

  16. Chimeric antigen receptor-engineered cytokine-induced killer cells overcome treatment resistance of pre-B-cell acute lymphoblastic leukemia and enhance survival.

    Science.gov (United States)

    Oelsner, Sarah; Wagner, Juliane; Friede, Miriam E; Pfirrmann, Verena; Genßler, Sabrina; Rettinger, Eva; Buchholz, Christian J; Pfeifer, Heike; Schubert, Ralf; Ottmann, Oliver G; Ullrich, Evelyn; Bader, Peter; Wels, Winfried S

    2016-10-15

    Pre-emptive cancer immunotherapy by donor lymphocyte infusion (DLI) using cytokine-induced killer (CIK) cells may be beneficial to prevent relapse with a reduced risk of causing graft-versus-host-disease. CIK cells are a heterogeneous effector cell population including T cells (CD3(+) CD56(-) ), natural killer (NK) cells (CD3(-) CD56(+) ) and natural killer T (T-NK) cells (CD3(+) CD56(+) ) that exhibit non-major histocompatibility complex (MHC)-restricted cytotoxicity and are generated by ex vivo expansion of peripheral blood mononuclear cells in the presence of interferon (IFN)-γ, anti-CD3 antibody, interleukin-2 (IL-2) and interleukin-15 (IL-15). To facilitate selective target-cell recognition and enhance specific cytotoxicity against B-cell acute lymphoblastic leukemia (B-ALL), we transduced CIK cells with a lentiviral vector encoding a chimeric antigen receptor (CAR) that carries a composite CD28-CD3ζ domain for signaling and a CD19-specific scFv antibody fragment for cell binding (CAR 63.28.z). In vitro analysis revealed high and specific cell killing activity of CD19-targeted CIK/63.28.z cells against otherwise CIK-resistant cancer cell lines and primary B-ALL blasts, which was dependent on CD19 expression and CAR signaling. In a xenograft model in immunodeficient mice, treatment with CIK/63.28.z cells in contrast to therapy with unmodified CIK cells resulted in complete and durable molecular remissions of established primary pre-B-ALL. Our results demonstrate potent antileukemic activity of CAR-engineered CIK cells in vitro and in vivo, and suggest this strategy as a promising approach for adoptive immunotherapy of refractory pre-B-ALL. PMID:27253354

  17. Effects of dendritic cell-activated and cytokine-induced killer cell therapy on 22 children with acute myeloid leukemia after chemotherapy.

    Science.gov (United States)

    Bai, Yan; Zheng, Jin-e; Wang, Nan; Cai, He-hua; Zhai, Li-na; Wu, Yao-hui; Wang, Fang; Jin, Run-ming; Zhou, Dong-feng

    2015-10-01

    The efficiency of dendritic cell-activated and cytokine-induced killer cell (DC-CIK) therapy on children with acute myeloid leukemia (AML) after chemotherapy was investigated. Mononuclear cells were collected from children achieving complete remission after chemotherapy, cultured in vitro and transfused back into the same patient. Interleukin-2 (IL-2) was injected subcutaneously every other day 10 times at the dose of 1 × 10(6) units. Peripheral blood lymphocyte subsets and minimal residual disease (MRD) were detected by flow cytometry. Function of bone marrow was monitored by methods of morphology, immunology, cytogenetics and molecular biology. The side effects were also observed during the treatment. The average follow-up period for all the 22 patients was 71 months and relapse occurred in two AML patients (9.1%). The percentage of CD3(+)/CD8(+) cells in peripheral blood of 15 patients at the 3rd month after DC-CIK treatment (36.73% ± 12.51%) was dramatically higher than that before treatment (29.20% ± 8.34%, P 0.1% in 5 patients before the treatment, and became lower than 0.1% 3 months after the treatment. During the transfusion of DC-CIK, side effects including fever, chills and hives appeared in 7 out of 22 (31.82%) cases but disappeared quickly after symptomatic treatments. There were no changes in electrocardiography and liver-renal functions after the treatment. MRD in children with AML can be eliminated by DC-CIK therapy which is safe and has fewer side effects. PMID:26489623

  18. Co-Expansion of Cytokine-Induced Killer Cells and Vγ9Vδ2 T Cells for CAR T-Cell Therapy.

    Science.gov (United States)

    Du, Shou-Hui; Li, Zhendong; Chen, Can; Tan, Wee-Kiat; Chi, Zhixia; Kwang, Timothy Weixin; Xu, Xue-Hu; Wang, Shu

    2016-01-01

    Gamma delta (γδ) T cells and cytokine-induced killer (CIK) cells, which are a heterogeneous population of T lymphocytes and natural killer T (NKT) cells, have been separately expanded ex vivo and shown to be capable of targeting and mediating cytotoxicity against various tumor cells in a major histocompatibility complex-unrestricted manner. However, the co-expansion and co-administration of these immune cells have not been explored. In this study we describe an efficient method to expand simultaneously both CIK and Vγ9Vδ2 T cells, termed as CIKZ cells, from human peripheral blood mononuclear cells (PBMCs) using Zometa, interferon-gamma (IFN-γ), interleukin 2 (IL-2), anti-CD3 antibody and engineered K562 feeder cells expressing CD64, CD137L and CD86. A 21-day culture of PBMCs with this method yielded nearly 20,000-fold expansion of CIKZ cells with γδ T cells making up over 20% of the expanded population. The expanded CIKZ cells exhibited antitumor cytotoxicity and could be modified to express anti-CD19 chimeric antigen receptor (CAR), anti-CEA CAR, and anti-HER2 CAR to enhance their specificity and cytotoxicity against CD19-, CEA-, or HER2-positive tumor cells. The tumor inhibitory activity of anti-CD19 CAR-modified CIKZ cells was further demonstrated in vivo in a Raji tumor mouse model. The findings herein substantiate the feasibility of co-expanding CIK and γδ cells for adoptive cellular immunotherapy applications such as CAR T-cell therapy against cancer. PMID:27598655

  19. Closing the gap: discrimination of the expression profile of HLA questionable alleles by a cytokine-induced secretion approach using HLA-A*32:11Q.

    Science.gov (United States)

    Föll, D; Hinrichs, J; Tischer, S; Battermann, A; Schambach, A; Figueiredo, C; Immenschuh, S; Blasczyk, R; Eiz-Vesper, B

    2012-05-01

    Matching of human leukocyte antigen (HLA) alleles between donors and recipients plays a major role in hematopoietic stem cell transplantation (HSCT). Null or questionably expressed HLA allelic variants are a major issue in HLA matching, because the aberrant expression of such alleles can have a major impact on the outcome of HSCT and/or its complications such as graft-versus-host disease. The goal of this study was to investigate the potential of a recently developed cytokine-induced secretion assay to differentiate the expression levels of HLA-A*32:11Q (questionable) into a null (N) or low (L) expression variant. An amino acid mutation at position 164 of HLA-A*32:11Q disrupts the disulfide bridge in the α2 domain. HLA-A*32:11Q is not detectable by standard microlymphocytotoxicity assay. To this end, we cloned soluble HLA-A*32:11Q and a reference allele (HLA-A*32:01) into expression vectors and transfected/transduced HEK293 and K562 cells. Allele-expressing K562 cells were simultaneously transfected/transduced with a β2-microglobulin (B2M)-encoding vector to ensure the intact HLA structure with B2M. After treatment with proinflammatory cytokines, secreted soluble HLA molecules were determined by enzyme-linked immunosorbent assay in the supernatant and intracellular accumulation of the recombinant proteins by flow cytometry. HLA-A*32:11Q was nearly undetectable in untreated transfectants. Cytokine treatment increased the secretion of HLA-A*32:11Q to detectable levels and resulted in intracellular accumulation of the allele. There was no difference in mRNA transcription between the A*32 alleles. On the basis of these results, we recommend reclassification of HLA-A*32:11Q as a low expression (L) variant.

  20. Cytokine-induced killer cells showing multidrug resistance and remaining cytotoxic activity to tumor cells after transfected with mdr1 cDNA

    Institute of Scientific and Technical Information of China (English)

    李惠芳; 杨永红; 石永进; 王逸群; 朱平

    2004-01-01

    Background Routine treatment of cancer such as surgery, radiation or chemotherapy is sometimes unable to erdiacate metastatic malignant cells. So we tried a new method and increased the adoptive immunotherapy of Cytokine-induced killer (CIK) cells in tumor patients and the multidrug resistance (mdr1) cDNA was transfected into CIK cells. Methods CIK cells were obtained from peripheral blood and induced by IFN-γ, anti-CD3 monoclonal antibody, IL-2 and IL-1. CIK cells were transfected with plasmid PHaMDR containing human mdr1 cDNA by electroporation. RT-PCR was used to detect mdr1 mRNA in transfected CIK cells. P-glycoprotein (P-gp) expressed on surface of CIK cells was assayed by FITC-conjugated anti-P-gp monoclonal antibody and flow cytometry. Multidrug resistance to doxorubicin and colchicine and cytotoxic activity to human breast cancer cell line MCF7 were performed using MTT method.Results mdr1 mRNA was detected in transfected CIK cells. P-gp was expressed on the surface of the transfected CIK cells, and the P-gp positive cells reached 21%-37% of the total CIK cells after transfection. The IC50 to doxorubicin increased to 22.3-45.8 times, and that to colchicines to 6.7-11.35 times, as compared to those of untransfected CIK cells. However, the cytotoxic activity to MCF7 cell line remained unaltered.Conclusions CIK cells were successfully transfected with mdr1 cDNA by using electroporation. The transfected CIK cells had the characteristics of multidrug resistance without change in their cytotoxic activity to tumor cells.

  1. Preconditioning chemotherapy enhances the antitumor activity of cytokine -induced killer cells in Lewis lung carcinoma model%预处理化疗增强CIK细胞对Lewis肺癌的抑制作用

    Institute of Scientific and Technical Information of China (English)

    黄香; 黄桂春; 宋海珠; 陈一天; 陈龙邦

    2011-01-01

    目的 观察预处理化疗在小鼠Lewis肺癌模型中对细胞因子诱导的杀伤细胞(cytokine - induced killer cells,CIK cells)的抗肿瘤活性的增强作用,并探讨介导此增效作用的机制.方法 建立C57BL/6小鼠Lewis肺癌模型,以紫杉醇( Paclitaxel,PTX)联合顺铂(Cisplatin,DDP)作为预处理方案(TP方案),将荷瘤小鼠随机分为四组:对照组(给予生理盐水,normal saline,NS)、CIK组(给予CIK细胞)、TP组(给予TP方案)、TP - CIK组(TP方案预处理后联合CIK细胞).隔日测量肿瘤长短径监测肿瘤体积,观察各组治疗方案对Lewis肿瘤的抑制作用.分离小鼠肿瘤组织,分别行CD3、FoxP3( Forkhead box P3)分子免疫组化染色以评估肿瘤组织中T淋巴细胞、Treg细胞的浸润情况.利用绿色荧光蛋白(green fluorescence protein,GFP)转基因小鼠制备GFP+ CIK细胞,荧光显微镜追踪其体内迁移分布,观察预处理化疗对CIK细胞体内归巢功能的影响.结果 TP预处理化疗联合CIK细胞可明显抑制Lewis肺癌的生长(P<0.05),而单独CIK细胞免疫治疗或TP化疗均不能抑制Lewis肿瘤的生长(P>0.05).TP预处理化疗可增加CD3+T淋巴细胞至肿瘤组织的浸润,下调肿瘤组织中Treg细胞的比例,促进CIK细胞至肿瘤及脾脏组织的归巢.结论 TP预处理化疗可增强CIK细胞对Lewis肺癌的抑制作用,为TP预处理化疗联合CIK细胞免疫治疗的临床应用提供了实验基础与理论依据.%Objective To investigate the antitumor effect of cytokine - induced killer (CIK) cells induced by preconditioning chemotherapy and to elucidate the underlying mechanisms. Methods C57BL/6 mice were inoculated with Lewis cells to establish the murine lung carcinoma models and then randomly divided into four groups. Control group: given normal saline (NS) ; CIK group: treated with CIK cells; TP group: treated with TP regimen including paclitaxel (PTX) plus cisplatin (DDP); TP-CIK group: preconditioned with TP regimen

  2. Label-free signal-on aptasensor for sensitive electrochemical detection of arsenite.

    Science.gov (United States)

    Cui, Lin; Wu, Jie; Ju, Huangxian

    2016-05-15

    A signal-on aptasensor was fabricated for highly sensitive and selective electrochemical detection of arsenite with a label-free Ars-3 aptamer self-assembled on a screen-printed carbon electrode (SPCE) via Au-S bond. The Ars-3 aptamer could adsorb cationic polydiallyldimethylammonium (PDDA) via electrostatic interaction to repel other cationic species. In the presence of arsenite, the change of Ars-3 conformation due to the formation of Ars-3/arsenite complex led to less adsorption of PDDA, and the complex could adsorb more positively charged [Ru(NH3)6](3+) as an electrochemically active indicator on the aptasensor surface, which produced a sensitive "turn-on" response. The target-induced structure switching could be used for sensitive detection of arsenite with a linear range from 0.2 nM to 100 nM and a detection limit down to 0.15 nM. Benefiting from Ars-3 aptamer, the proposed system exhibited excellent specificity against other heavy metal ions. The SPCE-based aptasensor exhibited the advantages of low cost and simple fabrication, providing potential application of arsenite detection in environment.

  3. Label-free signal-on aptasensor for sensitive electrochemical detection of arsenite.

    Science.gov (United States)

    Cui, Lin; Wu, Jie; Ju, Huangxian

    2016-05-15

    A signal-on aptasensor was fabricated for highly sensitive and selective electrochemical detection of arsenite with a label-free Ars-3 aptamer self-assembled on a screen-printed carbon electrode (SPCE) via Au-S bond. The Ars-3 aptamer could adsorb cationic polydiallyldimethylammonium (PDDA) via electrostatic interaction to repel other cationic species. In the presence of arsenite, the change of Ars-3 conformation due to the formation of Ars-3/arsenite complex led to less adsorption of PDDA, and the complex could adsorb more positively charged [Ru(NH3)6](3+) as an electrochemically active indicator on the aptasensor surface, which produced a sensitive "turn-on" response. The target-induced structure switching could be used for sensitive detection of arsenite with a linear range from 0.2 nM to 100 nM and a detection limit down to 0.15 nM. Benefiting from Ars-3 aptamer, the proposed system exhibited excellent specificity against other heavy metal ions. The SPCE-based aptasensor exhibited the advantages of low cost and simple fabrication, providing potential application of arsenite detection in environment. PMID:26785310

  4. Construction of the recombinant broad-host-range plasmids providing their bacterial hosts arsenic resistance and arsenite oxidation ability.

    Science.gov (United States)

    Drewniak, Lukasz; Ciezkowska, Martyna; Radlinska, Monika; Sklodowska, Aleksandra

    2015-02-20

    The plasmid pSinA of Sinorhizobium sp. M14 was used as a source of functional phenotypic modules, encoding proteins involved in arsenite oxidation and arsenic resistance, to obtain recombinant broad-host-range plasmids providing their bacterial hosts arsenic resistance and arsenite oxidative ability. An arsenite oxidation module was cloned into pBBR1MCS-2 vector yielding plasmid vector pAIO1, while an arsenic resistance module was cloned into pCM62 vector yielding plasmid pARS1. Both plasmid constructs were introduced (separately and together) into the cells of phylogenetically distant (representing Alpha-, Beta-, and Gammaproteobacteria) and physiologically diversified (unable to oxidize arsenite and susceptible/resistant to arsenite and arsenate) bacteria. Functional analysis of the modified strains showed that: (i) the plasmid pARS1 can be used for the construction of strains with an increased resistance to arsenite [up to 20mM of As(III), (ii) the presence of the plasmid pAIO1 in bacteria previously unable to oxidize As(III) to As(V), contributes to the acquisition of arsenite oxidation abilities by these cells, (iii) the highest arsenite utilization rate are observed in the culture of strains harbouring both the plasmids pAIO1 and pARS1, (iv) the strains harbouring the plasmid pAIO1 were able to grow on arsenic-contaminated mine waters (∼ 3.0 mg As L(-1)) without any supplementation. PMID:25617684

  5. Cytotoxic capacity of IL-15-stimulated cytokine-induced killer cells against human acute myeloid leukemia and rhabdomyosarcoma in humanized preclinical mouse models

    Directory of Open Access Journals (Sweden)

    Eva eRettinger

    2012-04-01

    Full Text Available Allogeneic stem cell transplantation (allo-SCT has become an important treatment modality for patients with high risk acute myeloid leukemia (AML and is also under investigation for soft tissue sarcomas. The therapeutic success is still limited by minimal residual disease (MRD status ultimately leading to patients’ relapse. Adoptive donor lymphocyte infusions (DLI based on MRD status using IL-15-expanded cytokine-induced killer (CIK cells may prevent relapse without causing graft-versus-host-disease (GvHD. To generate preclinical data we developed mouse models to study anti-leukemic- and anti-tumor-potential of CIK cells in vivo. Immunodeficient mice (NOD/SCID/IL2Rγc-, NSG were injected intravenously with human leukemic cell lines THP-1, SH-2 and with human rhabdomyosarcoma (RMS cell lines RH41 and RH30 at minimal doses required for leukemia or tumor engraftment. Mice transplanted with THP-1 or RH41 cells were randomly assigned for analysis of CIK cell treatment. Organs of mice were analyzed by flow cytometry as well as quantitative polymerase chain reaction (qPCR for engraftment of malignant cells and CIK cells. Potential of CIK cells to induce GvHD was determined by histological analysis. Tissues of the highest degree of THP-1 cell expansion included bone marrow (BM followed by liver, lung, spleen, peripheral blood (PB, and brain. RH30 and RH41 engraftment mainly took place in liver and lung, but was also detectable in spleen and PB. In spite of delayed CIK cell expansion compared with malignant cells, CIK cells injected at an effector to target cell (E:T ratio of 1:1 were sufficient for significant reduction of RH41 cells, whereas against fast-expanding THP-1 cells an E:T ratio of 250:1 was needed to achieve comparable results. Our preclinical in vivo mouse models showed a reliably 100% engraftment of malignant cells which is essential for analysis of anti-cancer therapy. Furthermore our data demonstrated that IL-15-activated CIK cells

  6. Discovery of molecular pathways mediating 1,25-dihydroxyvitamin D3 protection against cytokine-induced inflammation and damage of human and male mouse islets of Langerhans.

    Science.gov (United States)

    Wolden-Kirk, H; Rondas, D; Bugliani, M; Korf, H; Van Lommel, L; Brusgaard, K; Christesen, H T; Schuit, F; Proost, P; Masini, M; Marchetti, P; Eizirik, D L; Overbergh, L; Mathieu, C

    2014-03-01

    Protection against insulitis and diabetes by active vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), in nonobese diabetic mice has until now mainly been attributed to its immunomodulatory effects, but also protective effects of this hormone on inflammation-induced β-cell death have been reported. The aim of this study was to clarify the molecular mechanisms by which 1,25(OH)2D3 contributes to β-cell protection against cytokine-induced β-cell dysfunction and death. Human and mouse islets were exposed to IL-1β and interferon-γ in the presence or absence of 1,25(OH)2D3. Effects on insulin secretion and β-cell survival were analyzed by glucose-stimulated insulin release and electron microscopy or Hoechst/propidium iodide staining, respectively. Gene expression profiles were assessed by Affymetrix microarrays. Nuclear factor-κB activity was tested, whereas effects on secreted chemokines/cytokines were confirmed by ELISA and migration studies. Cytokine exposure caused a significant increase in β-cell apoptosis, which was almost completely prevented by 1,25(OH)2D3. In addition, 1,25(OH)2D3 restored insulin secretion from cytokine-exposed islets. Microarray analysis of murine islets revealed that the expression of approximately 4000 genes was affected by cytokines after 6 and 24 hours (n = 4; >1.3-fold; P < .02), of which nearly 250 genes were modified by 1,25(OH)2D3. These genes belong to functional groups involved in immune response, chemotaxis, cell death, and pancreatic β-cell function/phenotype. In conclusion, these findings demonstrate a direct protective effect of 1,25(OH)2D3 against inflammation-induced β-cell dysfunction and death in human and murine islets, with, in particular, alterations in chemokine production by the islets. These effects may contribute to the beneficial effects of 1,25(OH)2D3 against the induction of autoimmune diabetes. PMID:24424042

  7. Evaluation on the Clinical Efficacy of Dendritic Cell-Activated Cytokine-Induced Killer Cells Combined with Conventional Therapy in the Treatment of Malignant Tumors

    Directory of Open Access Journals (Sweden)

    Hong WEI

    2016-06-01

    Full Text Available Objective: To evaluate the clinical efficacy of dendritic cell-activated cytokine-induced killer (DC-CIK cells combined with conventional therapy in the treatment of malignant tumors.Methods: A total of 100 patients with malignant tumors were randomly divided into two groups. Treatment group received conventional therapy combined with DC-CIK while control group received conventional therapy alone. The short-term efficacy, adverse reactions and changes of lymphocyte subpopulation were all compared between two groups after treatment.Results: The overall response rate (ORR was higher in treatment group (86.00% than in control group (54.00%, the difference was statistically significant (P<0.05. White blood cell count (WBC reduced after treatment when compared with treatment before (P=0.001, but liver and kidney function had no obvious change in treatment group (P>0.05. WBC reduced markedly, but the level of alanine aminotransferase (ALT increased obviously after treatment in control group (P<0.001. WBC was higher, but the level of ALT was lower in treatment group than in control group (P<0.001. However, there was no difference between two groups regarding serum creatinine (Scr and blood urea nitrogen (BUN (P>0.05. In treatment group, the levels of CD3+, CD3+CD4+, CD3+CD8+, and CD3+CD56+ increased (P<0.05, but the level of CD4+/CD8+ had no significant change (P>0.05. In control group, the levels of CD3+ and CD3+CD4+ reduced (P<0.05, while the levels of CD3+CD8+, CD3+CD56+ and CD4+/CD8+ had no significant change (P>0.05. The levels of CD3+, CD3+CD4+, CD3+CD8+ and CD3+CD56+ in treatment group were higher than those in control group (P<0.01, whereas CD4+/CD8+ was lower than that in control group (P<0.01.Conclusion: DC-CIK combined with conventional therapy, safe and effective, is capable of promoting the recovery of leukocytes and liver and kidney function, and improving the cellular immune function, which may provide a new therapeutic regimen for

  8. [Effectiveness of arsenite adsorption by ferric and alum water treatment residuals with different grain sizes].

    Science.gov (United States)

    Lin, Lu; Xu, Jia-Rui; Wu, Hao; Wang, Chang-Hui; Pei, Yuan-Sheng

    2013-07-01

    Effectiveness of arsenite adsorption by ferric and alum water treatment residuals (FARs) with different grain sizes was studied. The results indicated that the content of active Fe and Al, the specific surface area and pore volume in FARs with different grain sizes were in the range of 523.72-1 861.72 mmol x kg(-1), 28.15-265.59 m2 x g(-1) and 0.03-0.09 cm3 x g(-1), respectively. The contents of organic matter, fulvic acid, humic acid and humin were in the range of 46.97-91.58 mg x kg(-1), 0.02-32.27 mg x kg(-1), 22.27-34.09 mg x kg(-1) and 10.76-34.22 mg x kg(-1), respectively. Results of SEM and XRD analysis further demonstrated that FARs with different grain sizes were amorphousness. Batch experiments suggested that both the pseudo-first-order and pseudo-second-order equations could well describe the kinetics adsorption processes of arsenite by FARs. Moreover, the contents of arsenite absorbed by FARs increased with the increase of arsenite concentrations. The theoretical saturated adsorption capacities calculated from Langmuir isotherm model were in the range of 6.72-21.79 mg x g(-1). Interestingly, pH showed little effect on the arsenite adsorption capability of FARs. The capability of FARs had a close relationship with their physicochemical properties. Correlation analysis showed that the active Fe and Al contents and pore volume had major effects on the arsenite adsorption capability of FARs.

  9. Effect of rosiglitazone in sodium arsenite-induced experimental vascular endothelial dysfunction.

    Science.gov (United States)

    Kaur, Tajpreet; Goel, Rajesh Kumar; Balakumar, Pitchai

    2010-04-01

    The present study has been designed to investigate the effect of rosiglitazone, a peroxisome proliferator activated receptor gamma agonist in sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. The rats were administered sodium arsenite (1.5 mg/kg/day, i.p., 2 weeks) to induce VED. The development of VED was assessed by employing isolated aortic ring preparation and estimating serum nitrite/nitrate concentration. Further, the integrity of the aortic endothelium was assessed histologically using haematoxylin-eosin staining. Moreover, the oxidative stress was assessed by estimating serum thiobarbituric acid reactive substances, aortic reactive oxygen species and reduced form of glutathione. The administration of sodium arsenite produced VED by impairing acetylcholine-induced endothelium dependent relaxation, diminishing the integrity of vascular endothelium and decreasing the serum nitrite/nitrate concentration. In addition, sodium arsenite was noted to produce oxidative stress as it increased serum thiobarbituric acid reactive substances and aortic reactive oxygen species and consequently decreased glutathione. Treatment with rosiglitazone (3 mg/kg/day, p.o., 2 weeks and 5 mg/kg/day, p.o., 2 weeks) significantly prevented sodium arsenite-induced VED by enhancing acetylcholine-induced endothelium dependent relaxation, improving the integrity of vascular endothelium, increasing the nitrite/nitrate concentration and decreasing the oxidative stress. However, the vascular protective effect of rosiglitazone was markedly abolished by co-administration of nitric oxide synthase inhibitor, N-Omega-Nitro-L-Arginine Methyl Ester (L-NAME) (25 mg/kg/day, i.p., 2 weeks). Thus, it may be concluded that rosiglitazone reduces oxidative stress, activates eNOS and enhances the generation of nitric oxide to prevent sodium arsenite-induced VED in rats.

  10. Arsenite treatment induces oxidative stress, upregulates antioxidant system, and causes phytochelatin synthesis in rice seedlings.

    Science.gov (United States)

    Mishra, Shruti; Jha, A B; Dubey, R S

    2011-07-01

    The effects of arsenite treatment on generation of reactive oxygen species, induction of oxidative stress, response of antioxidative system, and synthesis of phytochelatins were investigated in two indica rice (Oryza sativa L.) cvs. Malviya-36 and Pant-12 grown in sand cultures for a period of 5-20 days. Arsenite (As(2)O(3); 25 and 50 μM) treatment resulted in increased formation of superoxide anion (O (2) (.-) ), elevated levels of H(2)O(2) and thiobarbituric acid reactive substances, showing enhanced lipid peroxidation. An enhanced level of ascorbate (AA) and glutathione (GSH) was observed irrespective of the variation in the level of dehydroascorbate (DHA) and oxidized glutathione (GSSG) which in turn influenced redox ratios AA/DHA and GSH/GSSG. With progressive arsenite treatment, synthesis of total acid soluble thiols and phytochelatins (PC) increased in the seedlings. Among antioxidative enzymes, the activities of superoxide dismutase (EC 1.15.1.1), catalase (EC 1.11.1.6), total ascorbate peroxidase (APX, EC 1.11.1.11), chloroplastic ascorbate peroxidase, guaiacol peroxidase (EC 1.11.1.7), monodehydroascorbate reductase (EC 1.6.5.4), and glutathione reductase (EC 1.6.4.2) increased in arsenite treated seedlings, while dehyroascorbate reductase (EC 1.8.5.1) activity declined initially during 5-10 days and increased thereafter. Results suggest that arsenite treatment causes oxidative stress in rice seedlings, increases the levels of many enzymatic and non-enzymatic antioxidants, and induces synthesis of thiols and PCs, which may serve as important components in mitigating arsenite-induced oxidative damage.

  11. Detoxification of arsenite through adsorption and oxidative transformation on pyrolusite

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Chengshuai; Wang, Xiangqing; Li, Xiujuan; Yang, Jinyan [Guangdong Institute of Eco-Environmental and Soil Sciences, Guangzhou (China); Cao, Weidong [Ministry of Agriculture Key Laboratory of Crop Nutrition and Fertilization, Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, Beijing (China); Qinghai University, Xining (China)

    2012-11-15

    Adsorption and oxidative transformation processes critically affect the mobility and toxicity of arsenic (As) in the environment. In this study, the detoxification of arsenite through adsorption and oxidation by pyrolusite was systematically investigated. Disappearance of aqueous As(III) in the solution can be efficiently achieved using pyrolusite. The As(III) oxidative transformation product arsenate or As(V) was obtained both in the solution and on the pyrolusite surface. The arsenic species adsorbed on pyrolusite exist in two forms: As(III) and As(V). Furthermore, over 64.8% of the adsorbed As cannot be desorbed. They were fixed more stably in the structure of the mineral to achieve a safer removal. Lower As(III) initial concentration increased As(III) detoxification rates. Elevating the reaction pH from 4.5 to 7.9 elicited a slight effect on the disappearance rate of As(III). Efficient As(III) detoxification can be achieved by pyrolusite within the studied pH range. The addition of low-molecular-weight carboxylic acids decreased the detoxification rate of As(III) through competition for active sites on pyrolusite. Co-existing divalent metal ions, such as Ca{sup 2+}, Ni{sup 2+}, and Mn{sup 2+}, also decreased the detoxification rate of As(III). However, the trivalent ion Cr{sup 3+} largely increased the detoxification rate through co-precipitation and adsorption processes. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  12. In vitro effect of sodium arsenite on Echinococcus granulosus protoscoleces.

    Science.gov (United States)

    Xing, Guoqiang; Wang, Bo; Lei, Ying; Liu, Chunli; Wang, Zhuo; Shi, Hongjuan; Yang, Rentan; Qin, Wenjuan; Jiang, Yufeng; Lv, Hailong

    2016-06-01

    Cystic echinococcosis (CE) caused by the metacestodes of Echinococcus granulosus is an important cosmopolitan zoonosis. Surgery is the main treatment option for CE. Meanwhile, chemotherapy is used as an significant adjunct to surgery. However, the benzimidazole carbamate group and the existing scolicidal agents may not be as effective as hoped. In this study, we aimed to explore the in vitro effect of sodium arsenite (NaAsO2) on Echinococcus granulosus protoscoleces, the causative agents of CE. Protoscoleces of E. granulosus were incubated in vitro with 4, 8, 12, 16, and 20μM NaAsO2. Viability and changes in morphology were investigated by 0.1% eosin staining. The ultrastructural alterations were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Additionally, caspase-3 activity was measured by colorimetric assay. Obvious protoscolicidal effect was seen with NaAsO2 at concentrations of 16μM and 20μM. Protoscolex mortality was 83.24% (16μM) and 100% (20μM) after 6 days post-incubation. SEM showed that the primary site of drug damage was the tegument of the protoscoleces. TEM analysis demonstrated that the internal tissues were severely affected and revealed an increase in the number of lipid droplets and vacuoles after treatment with 16μM NaAsO2. Meanwhile, the caspase-3 activity significantly increased in protoscoleces after 24h of NaAsO2 incubation compared to the untreated controls. Our study demonstrated the clear in vitro scolicidal effect of NaAsO2 against E. granulosus protoscoleces. However, the in vivo efficacy, specific mechanism, and any possible side effects of NaAsO2 remain to be investigated.

  13. Hyper Accumulation of Arsenic in Mutants of Ochrobactrum tritici Silenced for Arsenite Efflux Pumps.

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    Tânia Sousa

    Full Text Available Ochrobactrum tritici SCII24T is a highly As-resistant bacterium, with two previously described arsenic resistance operons, ars1 and ars2. Among a large number of genes, these operons contain the arsB and Acr3 genes that encode the arsenite efflux pumps responsible for arsenic resistance. Exploring the genome of O. tritici SCII24T, an additional putative operon (ars3 was identified and revealed the presence of the Acr3_2 gene that encodes for an arsenite efflux protein but which came to prove to not be required for full As resistance. The genes encoding for arsenite efflux pumps, identified in this strain, were inactivated to develop microbial accumulators of arsenic as new tools for bioremediation. Six different mutants were produced, studied and three were more useful as biotools. O. tritici wild type and the Acr3-mutants showed the highest resistance to As(III, being able to grow up to 50 mM of arsenite. On the other hand, arsB-mutants were not able to grow at concentrations higher than 1 mM As(III, and were the most As(III sensitive mutants. In the presence of 1 mM As(III, the strain with arsB and Acr3_1 mutated showed the highest intracellular arsenic concentration (up to 17 ng(As/mg protein, while in assays with 5 mM As(III, the single arsB-mutant was able to accumulate the highest concentration of arsenic (up to 10 ng(As/mg protein. Therefore, arsB is the main gene responsible for arsenite resistance in O. tritici. However, both genes arsB and Acr3_1 play a crucial role in the resistance mechanism, depending on the arsenite concentration in the medium. In conclusion, at moderate arsenite concentrations, the double arsB- and Acr3_1-mutant exhibited a great ability to accumulate arsenite and can be seen as a promising bioremediation tool for environmental arsenic detoxification.

  14. 亚砷酸钠对人胚肺成纤维细胞增殖活性及细胞周期的影响%Effects of sodium arsenite on human embryonic lung fibroblast proliferation and cell cycle

    Institute of Scientific and Technical Information of China (English)

    陈保林; 孙高峰; 谢惠芳

    2013-01-01

    目的 探讨亚砷酸钠对人胚肺成纤维细胞(HELF)增殖活性及细胞周期的影响.方法 将体外培养的HELF细胞分别暴露于浓度为0(对照)、20、40、60 μmol/L的亚砷酸钠培养基24、48和72 h.采用噻唑蓝(MTr)法检测细胞活力,采用流式细胞仪检测细胞周期分布.结果 与对照组相比,各浓度亚砷酸钠染毒24、48、72 h后细胞抑制率均升高,差异有统计学意义(P<0.05);HELF细胞抑制率与亚砷酸钠浓度及作用时长均呈正相关(P<0.05).HELF细胞G2+M期的比例仅在染毒24、48 h时均与亚砷酸钠染毒浓度呈正相关(P<0.05).HELF细胞S期比例在染毒48 h时与亚砷酸钠染毒浓度呈负相关(P<0.05).结论 亚砷酸钠染毒可降低HELF细胞的增殖活性,并能够选择性地将细胞阻滞在合成末期及分裂期(G2+M期).%Objective To investigate the effects of sodium arsenite on human embryo lung fibroblast (HELF) proliferation and cell cycle.Methods HELF cells were treated with sodium arsenite at the doses of 0 (control),20,40 and 60 μmol/L for for 24,48 and 72 hours respectively,MTT assay was used for cell proliferation detection and the cell cycle was determined by flow cytometry.Results Compared with the control group,after 24,48,72 hours of treatment with sodium arsenite at the three exposure doses,cell inhibition rates increased significantly(P<0.05);Cell inhibition rates were positively correlated with sodium arsenite doses (P<0.05).The ratios of HELF in G2+M phase was positively correlated with sodium arsenite doses after 24 and 48 hours of treatment.The proportions of cells in S phase was negatively correlated with sodium arsenite doses after 48 hours of treatment.Conclusion Sodium arsenite can affect human embryonic lung fibroblast proliferation activity,cell cycle data showes that sodium arsenite may restrict selectively cells at G2+M phase.

  15. Synergistic augmentation of ATP-induced interleukin-6 production by arsenite in HaCaT cells.

    Science.gov (United States)

    Sumi, Daigo; Asao, Masashi; Okada, Hideta; Yogi, Kuniko; Miyataka, Hideki; Himeno, Seiichiro

    2016-06-01

    Chronic arsenic exposure causes cutaneous diseases such as hyperkeratosis and skin cancer. However, little information has been available regarding the molecular mechanisms underlying these symptoms. Because extracellular ATP and interleukin-6 (IL-6) are involved in pathological aspects of cutaneous diseases, we examined whether sodium arsenite (As(III)) affects ATP-induced IL-6 production in human epidermal keratinocyte HaCaT cells. The results showed that the addition of As(III) into the medium of HaCaT cells dose dependently increased the production of IL-6 induced by extracellular ATP, although As(III) alone had no effect on IL-6 production. To elucidate the mechanism of the synergistic effect of As(III) on IL-6 production by extracellular ATP, we next examined the phosphorylation of p38, ERK and epidermal growth factor receptor (EGFR), since we found that these signaling molecules were stimulated by exposure to extracellular ATP. The results indicated that ATP-induced phosphorylation of p38, ERK and EGFR was synergistically enhanced by co-exposure to As(III). To clarify the mechanisms underlying the enhanced phosphorylation of p38, ERK and EGFR by As(III), we explored two possible mechanisms: the inhibition of extracellular ATP degradation and the inhibition of protein tyrosine phosphatases (PTPs) activity by As(III). The degradation of extracellular ATP was not changed by As(III), whereas the activity of PTPs was significantly inhibited by As(III). Our results suggest that As(III) augments ATP-induced IL-6 production in HaCaT cells through enhanced phosphorylation of the EGFR and p38/ERK pathways, which is associated with the inhibition of PTPs activity. PMID:26104857

  16. Characterization of arsenite tolerant Halomonas sp. Alang-4, originated from heavy metal polluted shore of Gulf of Cambay.

    Science.gov (United States)

    Jain, Raina; Jha, Sanjay; Mahatma, Mahesh K; Jha, Anamika; Kumar, G Naresh

    2016-01-01

    Arsenite [As(III)]-oxidizing bacteria were isolated from heavy metal contaminated shore of Gulf of Cambay at Alang, India. The most efficient bacterial strain Alang-4 could tolerate up to 15 mM arsenite [As(III)] and 200 mM of arsenate [As(V)]. Its 16S rRNA gene sequence was 99% identical to the 16S rRNA genes of genus Halomonas (Accession no. HQ659187). Arsenite oxidase enzyme localized on membrane helped in conversion of As(III) to As(V). Arsenite transporter genes (arsB, acr3(1) and acr3(2)) assisted in extrusion of arsenite from Halomonas sp. Alang-4. Generation of ROS in response to arsenite stress was alleviated by higher activities of catalase, ascorbate peroxidase, superoxide dismutase and glutathione S-transferase enzymes. Down-regulation in the specific activities of nearly all dehydrogenases of carbon assimilatory pathway viz., glucose-6-phosphate, pyruvate, α-ketoglutarate, isocitrate and malate dehydrogenases, was observed in presence of As(III), whereas, the specific activities of phosphoenol pyruvate carboxylase, pyruvate carboxylase and isocitrate lyase enzymes were found to increase two times in As(III) treated cells. The results suggest that in addition to efficient ars operon, alternative pathways of carbon utilization exist in the marine bacterium Halomonas sp. Alang-4 to overcome the toxic effects of arsenite on its dehydrogenase enzymes. PMID:26865328

  17. Arsenite medicinal use, metabolism, pharmacokinetics and monitoring in human hair.

    Science.gov (United States)

    Nicolis, I; Curis, E; Deschamps, P; Bénazeth, S

    2009-10-01

    Acute promyelocytic leukaemia (APL) is a distinctive subtype of acute myeloid leukaemias. Even through this human disease can be treated by the intravenous administration of all-trans retinoic acid (ATRA), 25% of patients typically relapse after the first treatment. In this context, the intravenous administration of APL patients with an aqueous solution of arsenic trioxide has also been demonstrated to be successful despite the established mammalian toxicity of this arsenic compound. Accordingly, the administration of a therapeutic dose of arsenic trioxide has resulted in an improved patient survival in both relapsing as well newly diagnosed APL patients. We present here a mini-review of the medicinal use of arsenite, its mammalian metabolism (with an emphasis on biomethylation pathways), its elimination and pharmacokinetics and the novel application of hair analysis as a biomonitoring material. This mini-review also introduces our own results on the analysis of hair of patients receiving arsenic trioxide therapy. In this work, instead of quantifying arsenic content in bulk hair, we performed longitudinal analysis in order to use hair as a marker of arsenic exposure correlated to a time scale. Taking into account the hair growth rate, the longitudinal analysis of hair is demonstrated to provide a chronological record of the treatment of patients with arsenic trioxide. The small quantity of material to be analysed required the use of Synchrotron radiation based X-ray fluorescence (SXRF) spectroscopy. The hair arsenic content was well correlated with the clinical background of patients and reflected the intake of arsenic trioxide. In particular, the onset of arsenic trioxide therapy and interruptions during therapy were reflected by total arsenic content, which suggested rapid elimination. Another type of experiment, micro-XRF cartography on thin hair slices, allowed us to obtain distribution maps of arsenic, which demonstrated that arsenic is located at the

  18. Global analysis of protein aggregation in yeast during physiological conditions and arsenite stress

    Directory of Open Access Journals (Sweden)

    Sebastian Ibstedt

    2014-09-01

    Full Text Available Protein aggregation is a widespread phenomenon in cells and associated with pathological conditions. Yet, little is known about the rules that govern protein aggregation in living cells. In this study, we biochemically isolated aggregation-prone proteins and used computational analyses to identify characteristics that are linked to physiological and arsenite-induced aggregation in living yeast cells. High protein abundance, extensive physical interactions, and certain structural properties are positively correlated with an increased aggregation propensity. The aggregated proteins have high translation rates and are substrates of ribosome-associated Hsp70 chaperones, indicating that they are susceptible for aggregation primarily during translation/folding. The aggregation-prone proteins are enriched for multiple chaperone interactions, thus high protein abundance is probably counterbalanced by molecular chaperones to allow soluble expression in vivo. Our data support the notion that arsenite interferes with chaperone activity and indicate that arsenite-aggregated proteins might engage in extensive aberrant protein–protein interactions. Expression of aggregation-prone proteins is down-regulated during arsenite stress, possibly to prevent their toxic accumulation. Several aggregation-prone yeast proteins have human homologues that are implicated in misfolding diseases, suggesting that similar mechanisms may apply in disease- and non-disease settings.

  19. AN INTEGRATED PHARMACOKINETIC AND PHARMACODYNAMIC STUDY OF ARSENITE ACTION 2. HEME OXYGENASE INDUCTION IN MICE

    Science.gov (United States)

    Heme oxygenase (HO) is the rate-limiting enzyme in heme degradation and its activity has a significant impact on intracellular heme pools. Rat studies indicate that HO induction is a sensitive, dose-dependent response to arsenite (AsIII) exposure in both liver and kidney. The o...

  20. SORPTION OF ARSENATE AND ARSENITE ON A RUTHENIUM COMPOUND: A MACROSCOPIC AND MICROSCOPIC STUDY

    Science.gov (United States)

    Sorption of arsenate and arsenite was examined on a ruthenium compound using macroscopic and microscopic techniques. Batch sorption experiments at pH 4,5,6, 7 and 8 were employed to construct constant solid solution ratio isotherms (CSI). After equilibration at the appropriate pH...

  1. The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues

    Energy Technology Data Exchange (ETDEWEB)

    Kurooka, Hisanori, E-mail: hkurooka@u-fukui.ac.jp [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Research and Education Program for Life Science, University of Fukui, Fukui (Japan); Sugai, Manabu [Department of Experimental Therapeutics, Translational Research Center, Kyoto University Hospital, Kyoto (Japan); Mori, Kentaro [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Yokota, Yoshifumi, E-mail: yokota@u-fukui.ac.jp [Division of Molecular Genetics, Department of Biochemistry and Bioinformative Sciences, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Research and Education Program for Life Science, University of Fukui, Fukui (Japan)

    2013-04-19

    Highlights: •Sodium arsenite induces cytoplasmic accumulation of Id3. •Arsenite binds to closely spaced N-terminal cysteine residues of Id3. •N-terminal cysteines are essential for arsenite-induced nuclear export of Id3. •Nuclear export of Id3 counteracts its transcriptional repression activity. -- Abstract: Ids are versatile transcriptional repressors that regulate cell proliferation and differentiation, and appropriate subcellular localization of the Id proteins is important for their functions. We previously identified distinct functional nuclear export signals (NESs) in Id1 and Id2, but no active NES has been reported in Id3. In this study, we found that treatment with the stress-inducing metalloid arsenite led to the accumulation of GFP-tagged Id3 in the cytoplasm. Cytoplasmic accumulation was impaired by a mutation in the Id3 NES-like sequence resembling the Id1 NES, located at the end of the HLH domain. It was also blocked by co-treatment with the CRM1-specific nuclear export inhibitor leptomycin B (LMB), but not with the inhibitors for mitogen-activated protein kinases (MAPKs). Importantly, we showed that the closely spaced N-terminal cysteine residues of Id3 interacted with the arsenic derivative phenylarsine oxide (PAO) and were essential for the arsenite-induced cytoplasmic accumulation, suggesting that arsenite induces the CRM1-dependent nuclear export of Id3 via binding to the N-terminal cysteines. Finally, we demonstrated that Id3 significantly repressed arsenite-stimulated transcription of the immediate-early gene Egr-1 and that this repression activity was inversely correlated with the arsenite-induced nuclear export. Our results imply that Id3 may be involved in the biological action of arsenite.

  2. The metalloid arsenite induces nuclear export of Id3 possibly via binding to the N-terminal cysteine residues

    International Nuclear Information System (INIS)

    Highlights: •Sodium arsenite induces cytoplasmic accumulation of Id3. •Arsenite binds to closely spaced N-terminal cysteine residues of Id3. •N-terminal cysteines are essential for arsenite-induced nuclear export of Id3. •Nuclear export of Id3 counteracts its transcriptional repression activity. -- Abstract: Ids are versatile transcriptional repressors that regulate cell proliferation and differentiation, and appropriate subcellular localization of the Id proteins is important for their functions. We previously identified distinct functional nuclear export signals (NESs) in Id1 and Id2, but no active NES has been reported in Id3. In this study, we found that treatment with the stress-inducing metalloid arsenite led to the accumulation of GFP-tagged Id3 in the cytoplasm. Cytoplasmic accumulation was impaired by a mutation in the Id3 NES-like sequence resembling the Id1 NES, located at the end of the HLH domain. It was also blocked by co-treatment with the CRM1-specific nuclear export inhibitor leptomycin B (LMB), but not with the inhibitors for mitogen-activated protein kinases (MAPKs). Importantly, we showed that the closely spaced N-terminal cysteine residues of Id3 interacted with the arsenic derivative phenylarsine oxide (PAO) and were essential for the arsenite-induced cytoplasmic accumulation, suggesting that arsenite induces the CRM1-dependent nuclear export of Id3 via binding to the N-terminal cysteines. Finally, we demonstrated that Id3 significantly repressed arsenite-stimulated transcription of the immediate-early gene Egr-1 and that this repression activity was inversely correlated with the arsenite-induced nuclear export. Our results imply that Id3 may be involved in the biological action of arsenite

  3. Effect of Sodium Arsenite on Rat Bone Marrow Mesenchymal Stem Cells: Cells Viability and Morphological Study

    Directory of Open Access Journals (Sweden)

    M.H. Abnosi

    2010-07-01

    Full Text Available Introduction & Objective: Sodium arsenite as an environmental pollutant being found in the air, water, and earth crust threats the human beings' health. The aim of this study was to investigate the effect of sodium arsenite on viability and morphology of mesenchymal stem cells in rat bone marrow.Materials & Methods: In this exprimental study the cells were extracted in DMEM containing 15% FBS and Pen/Strep until the 3rd passage then treated with 0, 0.1, 0.5, 2.5, 12.5 and 20 µM of sodium arsenite for 12, 24, 36 and 48 hrs. Viability of the cells was carried out with trypan blue and MTT staining, then 0.1 µM and 36 hrs treatment was selected for further investigations. Morphology of the cells was studied using fluorescent dye (Hochest, propidium iodide and acridine orange as well as protein profile of the cells were studied using SDS-PAGE. Data was analyzed using one and two way ANOVA.Results: Based on the two way ANOVA, cumulative effect of treatment time and used dosage caused highly significant reduction (p<0.001 in viability of rat bone marrow mesenchymal stem cells. One way ANOVA indicated that the viability of the cells reduced significantly (p<0.05 from 0.1 µM of sodium arsenite on wards in all the treatment time. Morphological changes including condensation and deformation of the nuclei, membrane disruption, and shrinkage of cytoplasm were also observed. Conclusion: Sodium arsenite toxicity caused morphological and protein profile changes as well as dose and time dependent reduction in viability of rat bone marrow mesenchymal stem cells.

  4. The Pho4 transcription factor mediates the response to arsenate and arsenite in Candida albicans.

    Science.gov (United States)

    Urrialde, Verónica; Prieto, Daniel; Pla, Jesús; Alonso-Monge, Rebeca

    2015-01-01

    Arsenate (As (V)) is the dominant form of the toxic metalloid arsenic (As). Microorganisms have consequently developed mechanisms to detoxify and tolerate this kind of compounds. In the present work, we have explored the arsenate sensing and signaling mechanisms in the pathogenic fungus Candida albicans. Although mutants impaired in the Hog1 or Mkc1-mediated pathways did not show significant sensitivity to this compound, both Hog1 and Mkc1 became phosphorylated upon addition of sodium arsenate to growing cells. Hog1 phosphorylation upon arsenate challenge was shown to be Ssk1-dependent. A screening designed for the identification of transcription factors involved in the arsenate response identified Pho4, a transcription factor of the myc-family, as pho4 mutants were susceptible to As (V). The expression of PHO4 was shortly induced in the presence of sodium arsenate in a Hog1-independent manner. Pho4 level affects Hog1 phosphorylation upon As (V) challenge, suggesting an indirect relationship between Pho4 activity and signaling in C. albicans. Pho4 also mediates the response to arsenite as revealed by the fact that pho4 defective mutants are sensitive to arsenite and Pho4 becomes phosphorylated upon sodium arsenite addition. Arsenite also triggers Hog1 phosphorylation by a process that is, in this case, independent of the Ssk1 kinase. These results indicate that the HOG pathway mediates the response to arsenate and arsenite in C. albicans and that the Pho4 transcription factor can differentiate among As (III), As (V) and Pi, triggering presumably specific responses. PMID:25717325

  5. meso-2,3-Dimercaptosuccinic acid and prevention of arsenite embryotoxicity and teratogenicity in the mouse.

    Science.gov (United States)

    Domingo, J L; Bosque, M A; Piera, V

    1991-08-01

    meso-2,3-Dimercaptosuccinic acid (DMSA), an antidote for the treatment of experimental and human poisoning by a number of heavy metals, has been reported to reduce the lethality of animals poisoned with arsenic more effectively than 2,3-dimercaptopropanol. In the present study, the effect of DMSA on arsenite-induced embryotoxic and teratogenic effects was evaluated in mice. In a first experiment, a series of four DMSA injections was administered sc to pregnant Swiss mice immediately after a single ip injection of 12 mg/kg of sodium arsenite (NaAsO2) given on Day 10 of gestation, and at 24, 48, and 72 hr thereafter. DMSA effectiveness was assessed at dosage levels of 0, 80, 160, and 320 mg/kg/day. Treatment with DMSA significantly reduced the embryolethality and the incidence of gross external and skeletal malformations and variations provoked by NaAsO2. Based on these findings, the effect of increasing the time interval between acute arsenite exposure and initiation of DMSA therapy was investigated in a second experiment. On Day 10 of gestation, DMSA (320 mg/kg) was administered sc to pregnant mice at 0, 0.25, 0.50, 1, 4, or 12 hr after a 12-mg/kg ip dose of NaAsO2. Embryotoxicity and teratogenicity derived from NaAsO2 exposure were significantly reduced when DMSA was given during the first hour after NaAsO2 injection. According to these results, a delay between acute arsenite intoxication and DMSA treatment should be avoided to have a practical beneficial effect on the arsenite exposed conceptus.

  6. Absorption of Arsenite on Several Iron (Hydro-)Oxides and Impact from Pre-processing Methods

    Institute of Scientific and Technical Information of China (English)

    YE Ying; JI Shanshan; WU Daidai; LI Jun; ZHANG Weirui

    2006-01-01

    The absorption reactions of arsenite on Fe (hydro-)oxides are studied. The three absorbent types are Fe(OH)3 gel and two Fe (hydro-)oxides, in which the Fe(OH)3 gel was dried in a microwave oven under vacuum at 80℃. It is found that pH changes from 9.71 to 10.36 in 6 minutes after the Fe (OH)3 gel was mixed with NaAsO2 solution, as the arsenite replaces the OH- in goethite and Fe(OH)3.At the 40th minute after the start of the reaction, pH decreases, which is most probably because that the monodentate surface complex of absorbed arsenite has changed into mononuclear-bidentate complex and released proton. The decline in pH values indicates not the end of the absorption but a change in the reaction type. Temperature and dissolved gas has little effect on these two types of reactions. The total absorption of arsenite increases after the absorbent is irradiated with ultrasound, which also lead to difficulty in separating the solids from solution. The absorption capacity for arsenite of Fe(OH)3 gel dried in a microwave oven under vacuum is 53.18% and 17.22% respectively better than that of Fe (OH)3 gel and gel dried at 80℃. The possible reasons are that the water molecules in the gel vibrates with high frequency under the effect of microwave irradiation, thereby producing higher porosity and improved surface activity.

  7. Metabolism of stem tissue during growth and its inhibition. II. Respiration and ether-soluble material

    Energy Technology Data Exchange (ETDEWEB)

    Christiansen, G.S.; Thimann, K.V.

    1950-01-01

    Measurements of respiration and ether soluble metabolites were made on etiolated pea steams grown in auxin solution to which iodoacetate, arsenite, or fluoride had been added. The role of respiration and metabolism in the increased sugar consumption of growth inhibited tissues is discussed in terms of the results from the experiment.

  8. Sodium meta-arsenite prevents the development of autoimmune diabetes in NOD mice

    International Nuclear Information System (INIS)

    Sodium meta-arsenite (SA) is an orally available arsenic compound. We investigated the effects of SA on the development of autoimmune type 1 diabetes. Female non-obese diabetic (NOD) mice were orally intubated with SA (5 mg/kg/day) from 8 weeks of age for 8 weeks. The cumulative incidence of diabetes was monitored until 30 weeks of age, islet histology was examined, and lymphocytes including T cells, B cells, CD4+ IFN-γ+ cells, CD8+ IFN-γ+ cells, CD4+ IL-4+ cells, and regulatory T cells were analyzed. We also investigated the diabetogenic ability of splenocytes using an adoptive transfer model and the effect of SA on the proliferation, activation, and expression of glucose transporter 1 (Glut1) in splenocytes treated with SA in vitro and splenocytes isolated from SA-treated mice. SA treatment decreased the incidence of diabetes and delayed disease onset. SA treatment reduced the infiltration of immunocytes in islets, and splenocytes from SA-treated mice showed a reduced ability to transfer diabetes. The number of total splenocytes and T cells and both the number and the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells in the spleen were significantly reduced in SA-treated NOD mice compared with controls. The number, but not the proportion, of regulatory T cells was decreased in SA-treated NOD mice. Treatment with SA either in vitro or in vivo inhibited proliferation of splenocytes. In addition, the expression of Glut1 and phosphorylated ERK1/2 was decreased by SA treatment. These results suggest that SA reduces proliferation and activation of T cells, thus preventing autoimmune diabetes in NOD mice. - Highlights: • SA prevents the development of diabetes and delays the age of onset in NOD mice. • SA decreases the number but not the proportion of T lymphocytes in NOD mice. • SA reduces IFN-γ-producing T lymphocytes in NOD mice. • SA reduces proliferation and activation of T lymphocytes in vitro and in vivo. • SA reduces the expression of glucose

  9. Sodium meta-arsenite prevents the development of autoimmune diabetes in NOD mice

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y.S.; Kim, D.; Lee, E.K. [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Kim, S. [Komipharm International Co. Ltd., 3188, Seongnam-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do 462-827 (Korea, Republic of); Choi, C.S. [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Endocrinology, Internal Medicine, Gachon University Gil Medical Center, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of); Gachon Medical Research Institute, Gil Hospital, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of); Jun, H.S., E-mail: hsjun@gachon.ac.kr [Lee Gil Ya Cancer and Diabetes Institute, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); College of Pharmacy and Gachon Institute of Pharmaceutical Science, Gachon University, 7-45 Songdo-dong, Yeonsu-ku, Incheon 406-840 (Korea, Republic of); Gachon Medical Research Institute, Gil Hospital, 1198 Guwol-Dong, Namdong-Gu, Incheon 405-760 (Korea, Republic of)

    2015-04-15

    Sodium meta-arsenite (SA) is an orally available arsenic compound. We investigated the effects of SA on the development of autoimmune type 1 diabetes. Female non-obese diabetic (NOD) mice were orally intubated with SA (5 mg/kg/day) from 8 weeks of age for 8 weeks. The cumulative incidence of diabetes was monitored until 30 weeks of age, islet histology was examined, and lymphocytes including T cells, B cells, CD4+ IFN-γ+ cells, CD8+ IFN-γ+ cells, CD4+ IL-4+ cells, and regulatory T cells were analyzed. We also investigated the diabetogenic ability of splenocytes using an adoptive transfer model and the effect of SA on the proliferation, activation, and expression of glucose transporter 1 (Glut1) in splenocytes treated with SA in vitro and splenocytes isolated from SA-treated mice. SA treatment decreased the incidence of diabetes and delayed disease onset. SA treatment reduced the infiltration of immunocytes in islets, and splenocytes from SA-treated mice showed a reduced ability to transfer diabetes. The number of total splenocytes and T cells and both the number and the proportion of CD4+ IFN-γ+ and CD8+ IFN-γ+ T cells in the spleen were significantly reduced in SA-treated NOD mice compared with controls. The number, but not the proportion, of regulatory T cells was decreased in SA-treated NOD mice. Treatment with SA either in vitro or in vivo inhibited proliferation of splenocytes. In addition, the expression of Glut1 and phosphorylated ERK1/2 was decreased by SA treatment. These results suggest that SA reduces proliferation and activation of T cells, thus preventing autoimmune diabetes in NOD mice. - Highlights: • SA prevents the development of diabetes and delays the age of onset in NOD mice. • SA decreases the number but not the proportion of T lymphocytes in NOD mice. • SA reduces IFN-γ-producing T lymphocytes in NOD mice. • SA reduces proliferation and activation of T lymphocytes in vitro and in vivo. • SA reduces the expression of glucose

  10. Cultivable diversity of thermophilic arsenite/ferrous-oxidizing microorganisms in hot springs of Taiwan

    Science.gov (United States)

    Lu, G.; Lin, Y.; Chang, Y.; Wang, P.; Lin, L.

    2009-12-01

    Elevated levels of arsenic in groundwater and surface water bodies have posed a stringent threat to the deterioration of the water quality for drinking and agriculture purposes around the world. In particular, arsenic liberated from volcanic and sedimentary rocks at high temperatures would be immobilized through adsorption on iron oxide and/or crystallization of iron-bearing minerals downstream at low temperatures. Understanding how microbially-catalytic reactions are involved in the changes of the redox state of arsenic and iron along a flow path would provide important constraints on the arsenic mobility in natural occurrences. The aims of this study were to isolate and characterize thermophilic arsenite- and iron-oxidizing microbes that would facilitate to establish the linkages between microbial distribution and in situ Fe/As cycling processes. Four source waters (LH05, LH08, SYK and MT) from acid-sulfate springs (pH 2-3, 60-97oC) located in the Tatun volcanic area of northern Taiwan were collected and inoculated into media targeting on autotrophic ferrous iron (FC3), arsenite (AC3 ,ACC3, AC7, ACC7), arsenite-resistant hydrogen (AH23), arsenite-resistant hydrogen-sulfur (AH2S3), and arsenite-resistant sulfur oxidations(AS3), and heterotrophic arsenite oxidation(AH3, AH7) at pH 3, and 7 at temperatures of 50, 70 and 80oC. Samples from the Kuantzuling mud springs (KTL) in southwestern Taiwan known with elevated arsenic levels (0.4 ppm) were also collected, inoculated into the heterotrophic medium and incubated at 50, 60, 70 and 80oC. Isolates obtained from KTL were subject to test on the AH7 and ACC7. Two positive enrichments for iron oxidation at 50oC and 70oC were confirmed by the steadily decrease of ferrous iron and increase of precipitates over 4 transfers for samples from the SYK spring. Diverse morphological types of microbes were enriched in all types of arsenite-bearing media at 50oC except for AH23. At 70oC, positive enrichments were found in media

  11. Draft genome sequence of the arsenite-oxidizing strain Aliihoeflea sp. 2WW, isolated from arsenic-contaminated groundwater

    NARCIS (Netherlands)

    L. Cavalca; A. Corsini; V. Andreoni; G. Muyzer

    2013-01-01

    Here, we report the draft genome sequence of the arsenite-oxidizing bacterium Aliihoeflea sp. strain 2WW, which consists of a 4.15-Mb chromosome and contains different genes that are involved in arsenic transformations.

  12. Effects of chronic exposure to sodium arsenite on hypothalamo-pituitary-testicular activities in adult rats: possible an estrogenic mode of action

    Directory of Open Access Journals (Sweden)

    Jana Subarna

    2006-02-01

    -HSD, 17 beta-HSD, and sorbitol dehydrogenase (SDH were significantly decreased, but those of acid phosphatase (ACP, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH were significantly increased. A decrease in dopamine or an increase in noradrenaline and 5-HT in hypothalamus and pituitary were also noted after arsenic exposure. Histological evaluation revealed extensive degeneration of different varieties of germ cells at stage VII of spermatogenic cycle in arsenic exposed rats. Administration of human chorionic gonadotrophin (hCG along with sodium arsenite partially prevented the degeneration of germ cells and enhanced paired testicular weights, epididymal sperm count, plasma and intratesticular testosterone concentrations, activities of delta 5, 3beta-HSD, 17 beta-HSD and sorbitol dehydrogenase along with diminution in the activities of ACP, ALP and LDH. Since many of the observed arsenic effects could be enhanced by oestradiol, it is suggested that arsenic might somehow acts through an estrogenic mode of action. Conclusion The results indicate that arsenic causes testicular toxicity by germ cell degeneration and inhibits androgen production in adult male rats probably by affecting pituitary gonadotrophins. Estradiol treatment has been associated with similar effects on pituitary testicular axis supporting the hypothesis that arsenite might somehow act through an estrogenic mode of action.

  13. Gemfibrozil, a Lipid-lowering Drug, Inhibits the Induction of Nitric-oxide Synthase in Human Astrocytes*

    OpenAIRE

    Pahan, Kalipada; Jana, Malabendu; Liu, Xiaojuan; Taylor, Bradley S.; Wood, Charles; Fischer, Susan M.

    2002-01-01

    Gemfibrozil, a lipid-lowering drug, inhibited cytokine-induced production of NO and the expression of inducible nitric-oxide synthase (iNOS) in human U373MG astroglial cells and primary astrocytes. Similar to gemfibrozil, clofibrate, another fibrate drug, also inhibited the expression of iNOS. Inhibition of human iNOS promoter-driven luciferase activity by gemfibrozil in cytokine-stimulated U373MG astroglial cells suggests that this compound inhibits the transcription of iNOS. Since gemfibroz...

  14. The novel role of fenofibrate in preventing nicotine- and sodium arsenite-induced vascular endothelial dysfunction in the rat.

    Science.gov (United States)

    Kaur, Jagdeep; Reddy, Krishna; Balakumar, Pitchai

    2010-09-01

    The present study investigated the effect of fenofibrate, an agonist of PPAR-alpha, in nicotine- and sodium arsenite-induced vascular endothelial dysfunction (VED) in rats. Nicotine (2 mg/kg/day, i.p., 4 weeks) and sodium arsenite (1.5 mg/kg/day, i.p., 2 weeks) were administered to produce VED in rats. The scanning electron microscopy study in thoracic aorta revealed that administration of nicotine or sodium arsenite impaired the integrity of vascular endothelium. Further, administration of nicotine or sodium arsenite significantly decreased serum and aortic concentrations of nitrite/nitrate and subsequently reduced acetylcholine-induced endothelium-dependent relaxation. Moreover, nicotine or sodium arsenite produced oxidative stress by increasing serum thiobarbituric acid reactive substances (TBARS) and aortic superoxide generation. However, treatment with fenofibrate (30 mg/kg/day, p.o.) or atorvastatin (30 mg/kg/day p.o., a standard agent) significantly prevented nicotine- and sodium arsenite-induced VED and oxidative stress by improving the integrity of vascular endothelium, increasing the concentrations of serum and aortic nitrite/nitrate, enhancing the acetylcholine-induced endothelium-dependent relaxation and decreasing serum TBARS and aortic superoxide anion generation. Conversely, co-administration of L-NAME (25 mg/kg/day, i.p.), an inhibitor of nitric oxide synthase, markedly attenuated these vascular protective effects of fenofibrate. The administration of nicotine or sodium arsenite altered the lipid profile by increasing serum cholesterol and triglycerides and consequently decreasing high-density lipoprotein levels, which were significantly prevented by treatment with fenofibrate or atorvastatin. It may be concluded that fenofibrate improves the integrity and function of vascular endothelium, and the vascular protecting potential of fenofibrate in preventing the development of nicotine- and sodium arsenite-induced VED may be attributed to its

  15. Induction of apoptotic death and retardation of neuronal differentiation of human neural stem cells by sodium arsenite treatment

    OpenAIRE

    Ivanov, Vladimir N.; Hei, Tom K.

    2012-01-01

    Chronic arsenic toxicity is a global health problem that affects more than 100 million people worldwide. Long-term health effects of inorganic sodium arsenite in drinking water may result in skin, lung and liver cancer and severe neurological abnormalities. We investigated in the present study whether sodium arsenite affects signaling pathways that control cell survival, proliferation and neuronal differentiation of human neural stem cells (NSC). We demonstrated that the critical signaling pa...

  16. Effects of cultivation conditions on the uptake of arsenite and arsenic chemical species accumulated by Pteris vittata in hydroponics.

    Science.gov (United States)

    Hatayama, Masayoshi; Sato, Takahiko; Shinoda, Kozo; Inoue, Chihiro

    2011-03-01

    The physiological responses of the arsenic-hyperaccumulator, Pteris vittata, such as arsenic uptake and chemical transformation in the fern, have been investigated. However, a few questions remain regarding arsenic treatment in hydroponics. Incubation conditions such as aeration, arsenic concentration, and incubation period might affect those responses of P. vittata in hydroponics. Arsenite uptake was low under anaerobic conditions, as previously reported. However, in an arsenite uptake experiment, phosphorous (P) starvation-dependent uptake of arsenate was observed under aerobic conditions. Time course-dependent analysis of arsenite oxidation showed that arsenite was gradually oxidized to arsenate during incubation. Arsenite oxidation was not observed in any of the control conditions, such as exposure to a nutrient solution or to culture medium only, or with the use of dried root; arsenite oxidation was only observed when live root was used. This result suggests that sufficient aeration allows the rhizosphere system to oxidize arsenite and enables the fern to efficiently take up arsenite as arsenate. X-ray absorption near edge structure (XANES) analyses showed that long-duration exposure to arsenic using a hydroponic system led to the accumulation of arsenate as the dominant species in the root tips, but not in the whole roots, partly because up-regulation of arsenate uptake by P starvation of the fern was caused and retained by long-time incubation. Analysis of concentration-dependent arsenate uptake by P. vittata showed that the uptake switched from a high-affinity transport system to a low-affinity system at high arsenate concentrations, which partially explains the increased arsenate abundance in the whole root.

  17. 亚砷酸钠对人永生化角质形成细胞株恶性转化的影响%Effect of sodium arsenite on malignant transformation of human immortalized keratinocyte cell lines

    Institute of Scientific and Technical Information of China (English)

    李艳玲; 胡玉贤; 张晓光; 王凌

    2016-01-01

    BACKGROUND:Studies have found that sodium arsenite can cause the malignant transformation and tumorigenicity of HaCaT cels, but whether low concentrations of sodium arsenite can cause the malignant transformation is rarely reported. OBJECTIVE:To study the effect of sodium arsenite on the malignant transformation of human immortalized keratinocyte cel lines. METHODS:HaCaT cels were treated with different concentrations of sodium arsenite. MTT assay was used to determine the effect of sodium arsenite on HaCaT cel morphology and proliferation, flow cytometry used to detect the effect of sodium arsenite on HaCaT cel cycle, and soft agar colony formation experiments assay used to determine the effect of sodium arsenite on HaCaT cel colony formation capacity. RESULTS AND CONCLUSION: HaCaT cels grew wel when the concentration of sodium arsenite was 5 mol/L, but the cel growth was inhibited under intervention with 10 and 50 mol/L sodium arsenite. HaCaT cels treated with 0.1 mol/L sodium arsenite were passaged to the 20th generation, and cel morphology had no notable changes; cels at passage 25 exhibited enlarged size and multiple nucleoli, which had a continued proliferation trend. Compared with the primarily cultured cels, 0.1 mol/L sodium arsenite-treated HaCaT cels at passages 15 and 25 had an increased proportion at S phase and G2/M phase, with strengthened proliferation ability and increased colony-forming efficiency, and moreover, the proliferation ability and colony-forming efficiency of passage 25 cels were higher than those of passage 15 cels. These experimental data show that high concentrations of sodium arsenite reduce HaCaT cel viability, and low concentrations of sodium sulfite have a certain influence on the morphology, cel cycle, proliferation ability and colony-forming efficiency of HaCaT cels, and moreover, the proliferation ability and colony-forming efficiency of human immortalized keratinocytes wil be strengthened with the increase of passage.%背景

  18. Syntheses, crystal structures and characterizations of two new bismuth(III) arsenites

    Energy Technology Data Exchange (ETDEWEB)

    Liu Junhui [State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002 (China); Graduate School of the Chinese Academy of Sciences, Beijing 100039 (China); Kong Fang [State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002 (China); Gai Yanli [State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002 (China); Graduate School of the Chinese Academy of Sciences, Beijing 100039 (China); Mao Jianggao, E-mail: mjg@fjirsm.ac.cn [State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002 (China)

    2013-01-15

    Two new bismuth arsenites with two different structural types, namely, Bi{sub 2}O(AsO{sub 3})Cl (1), Bi{sub 8}O{sub 6}(AsO{sub 3}){sub 2}(AsO{sub 4}){sub 2} (2), have been synthesized by the solid-state reactions. Compound 1 exhibits novel 2D bismuth arsenite layers with Bi{sub 4}O{sub 4} rings capped by oxide anions, which are further interconnected by Bi-Cl-Bi bridges into a 3D network. Compound 2 contains both arsenite and arsenate anions, its 3D structures are based on 1D bismuth arsenite and 1D bismuth arsenate chains both along b-axis, which are interconnected by oxide anions via Bi-O-Bi bridges, forming 1D tunnels of Bi{sub 4}As{sub 4} 8-membered rings (MRs) along b-axis, the lone pairs of the arsenite groups are orientated toward the centers of the above tunnels. Thermogravimetric analysis indicated that both compounds display high thermal stability. Optical property measurements revealed that they are wide band-gap semiconductors. Both compounds display broad green-light emission bands centered at 506 nm under excitation at 380 and 388 nm. - Graphical abstract: Solid state reactions of Bi{sub 2}O{sub 3} (BiCl{sub 3}) and As{sub 2}O{sub 3} yielded two new compounds with two different structural types, namely, Bi{sub 2}O(AsO{sub 3})Cl (1), Bi{sub 8}O{sub 6}(AsO{sub 3}){sub 2}(AsO{sub 4}){sub 2} (2). They represent the first examples of bismuth arsenates. Highlights: Black-Right-Pointing-Pointer Solid state reactions of Bi{sub 2}O{sub 3} (BiCl{sub 3}) and As{sub 2}O{sub 3} yielded two new phases. Black-Right-Pointing-Pointer They represent the first examples of bismuth arsenites. Black-Right-Pointing-Pointer The two compounds exhibit two different structural types.

  19. ArxA, a new clade of arsenite oxidase within the DMSO reductase family of molybdenum oxidoreductases

    Science.gov (United States)

    Zargar, Kamrun; Conrad, Alison; Bernick, David L.; Lowe, Todd M.; Stolc, Viktor; Hoeft, Shelley; Oremland, Ronald S.; Stolz, John; Saltikov, Chad W.

    2012-01-01

    Arsenotrophy, growth coupled to autotrophic arsenite oxidation or arsenate respiratory reduction, occurs only in the prokaryotic domain of life. The enzymes responsible for arsenotrophy belong to distinct clades within the DMSO reductase family of molybdenum-containing oxidoreductases: specifically arsenate respiratory reductase, ArrA, and arsenite oxidase, AioA (formerly referred to as AroA and AoxB). A new arsenite oxidase clade, ArxA, represented by the haloalkaliphilic bacterium Alkalilimnicola ehrlichii strain MLHE-1 was also identified in the photosynthetic purple sulfur bacterium Ectothiorhodospira sp. strain PHS-1. A draft genome sequence of PHS-1 was completed and an arx operon similar to MLHE-1 was identified. Gene expression studies showed that arxA was strongly induced with arsenite. Microbial ecology investigation led to the identification of additional arxA-like sequences in Mono Lake and Hot Creek sediments, both arsenic-rich environments in California. Phylogenetic analyses placed these sequences as distinct members of the ArxA clade of arsenite oxidases. ArxA-like sequences were also identified in metagenome sequences of several alkaline microbial mat environments of Yellowstone National Park hot springs. These results suggest that ArxA-type arsenite oxidases appear to be widely distributed in the environment presenting an opportunity for further investigations of the contribution of Arx-dependent arsenotrophy to the arsenic biogeochemical cycle.

  20. The protective role of vitamin E on the testicular tissue in rats exposed to sodium arsenite during the prenatal stage till sex maturity: A stereological analysis

    OpenAIRE

    Malek Soleimani Mehranjani; Rezvan Taefi

    2012-01-01

    Background: Vitamin E is an effective antioxidant, protecting cells against oxidative stress. Objective: In this investigation the protective effect of vitamin E on the testis during development and spermatogenesis in rats exposed to sodium arsenite was evaluated. Materials and Methods: Pregnant Wistar rats were divided into 4 groups (n=8) control, sodium arsenite (8 mg/kg/day), sodium arsenite+vitamin E (100 mg/kg/day) and vitamin E. Treatment was carried out from day seven of pregnancy till...

  1. Co-culture of neural crest stem cells (NCSC and insulin producing beta-TC6 cells results in cadherin junctions and protection against cytokine-induced beta-cell death.

    Directory of Open Access Journals (Sweden)

    Anongnad Ngamjariyawat

    Full Text Available PURPOSE: Transplantation of pancreatic islets to Type 1 diabetes patients is hampered by inflammatory reactions at the transplantation site leading to dysfunction and death of insulin producing beta-cells. Recently we have shown that co-transplantation of neural crest stem cells (NCSCs together with the islet cells improves transplantation outcome. The aim of the present investigation was to describe in vitro interactions between NCSCs and insulin producing beta-TC6 cells that may mediate protection against cytokine-induced beta-cell death. PROCEDURES: Beta-TC6 and NCSC cells were cultured either alone or together, and either with or without cell culture inserts. The cultures were then exposed to the pro-inflammatory cytokines IL-1β and IFN-γ for 48 hours followed by analysis of cell death rates (flow cytometry, nitrite production (Griess reagent, protein localization (immunofluorescence and protein phosphorylation (flow cytometry. RESULTS: We observed that beta-TC6 cells co-cultured with NCSCs were protected against cytokine-induced cell death, but not when separated by cell culture inserts. This occurred in parallel with (i augmented production of nitrite from beta-TC6 cells, indicating that increased cell survival allows a sustained production of nitric oxide; (ii NCSC-derived laminin production; (iii decreased phospho-FAK staining in beta-TC6 cell focal adhesions, and (iv decreased beta-TC6 cell phosphorylation of ERK(T202/Y204, FAK(Y397 and FAK(Y576. Furthermore, co-culture also resulted in cadherin and beta-catenin accumulations at the NCSC/beta-TC6 cell junctions. Finally, the gap junction inhibitor carbenoxolone did not affect cytokine-induced beta-cell death during co-culture with NCSCs. CONCLUSION: In summary, direct contacts, but not soluble factors, promote improved beta-TC6 viability when co-cultured with NCSCs. We hypothesize that cadherin junctions between NCSC and beta-TC6 cells promote powerful signals that maintain beta

  2. Global Analysis of Posttranscriptional Gene Expression in Response to Sodium Arsenite

    OpenAIRE

    Qiu, Lian-Qun; Abey, Sarah; Harris, Shawn; Shah, Ruchir; Gerrish, Kevin E.; Blackshear, Perry J.

    2014-01-01

    Background: Inorganic arsenic species are potent environmental toxins and causes of numerous health problems. Most studies have assumed that arsenic-induced changes in mRNA levels result from effects on gene transcription. Objectives: We evaluated the prevalence of changes in mRNA stability in response to sodium arsenite in human fibroblasts. Methods: We used microarray analyses to determine changes in steady-state mRNA levels and mRNA decay rates following 24-hr exposure to noncytotoxic conc...

  3. Arsenite-oxidizing and arsenate-reducing bacteria associated with arsenic-rich groundwater in Taiwan

    Science.gov (United States)

    Liao, Vivian Hsiu-Chuan; Chu, Yu-Ju; Su, Yu-Chen; Hsiao, Sung-Yun; Wei, Chia-Cheng; Liu, Chen-Wuing; Liao, Chung-Min; Shen, Wei-Chiang; Chang, Fi-John

    2011-04-01

    Drinking highly arsenic-contaminated groundwater is a likely cause of blackfoot disease in Taiwan, but microorganisms that potentially control arsenic mobility in the subsurface remain unstudied. The objective of this study was to investigate the relevant arsenite-oxidizing and arsenate-reducing microbial community that exists in highly arsenic-contaminated groundwater in Taiwan. We cultured and identified arsenic-transforming bacteria, analyzed arsenic resistance and transformation, and determined the presence of genetic markers for arsenic transformation. In total, 11 arsenic-transforming bacterial strains with different colony morphologies and varying arsenic transformation abilities were isolated, including 10 facultative anaerobic arsenate-reducing bacteria and one strictly aerobic arsenite-oxidizing bacterium. All of the isolates exhibited high levels of arsenic resistance with minimum inhibitory concentrations of arsenic ranging from 2 to 200 mM. Strain AR-11 was able to rapidly oxidize arsenite to arsenate at concentrations relevant to environmental groundwater samples without the addition of any electron donors or acceptors. We provide evidence that arsenic-reduction activity may be conferred by the ars operon(s) that were not amplified by the designed primers currently in use. The 16S rRNA sequence analysis grouped the isolates into the following genera: Pseudomonas, Bacillus, Psychrobacter, Vibrio, Citrobacter, Enterobacter, and Bosea. Among these genera, we present the first report of the genus Psychrobacter being involved in arsenic reduction. Our results further support the hypothesis that bacteria capable of either oxidizing arsenite or reducing arsenate coexist and are ubiquitous in arsenic-contaminated groundwater.

  4. Assessing sediment toxicity and arsenite concentration with bacterial and traditional methods

    Energy Technology Data Exchange (ETDEWEB)

    Petaenen, T.; Lyytikaeinen, M.; Lappalainen, J.; Romantschuk, M.; Kukkonen, J.V.K

    2003-04-01

    Different methods can be used to complement each other. - Three sediment samples LP (pool where logs are stored), LF (brook through landfill area), KN (Kaskesniemi) which is in Lake Pyhaeselkae downstream from the mill, were taken from an old sawmill area and one from the unpolluted Lake Hoeytiaeinen. The arsenite concentration was measured by GFAAS and two arsenite biosensing bacterial strains Pseudomonas fluorescens OS8 (pTPT31) and Escherichia coli MC1061 (pTOO31). The toxicity of sediment and pore water samples was determined by using luminescent bacteria (Flash test) and, further, whole sediment toxicity was measured using 10 days growth test and 50 days emergency test with midges (Chironomus riparius). With the flash test a lowered EC50 value was found only in sediment LF (EC50=0.17 v/v%). The Flash test indicated that all sediment samples taken from the sawmill area were highly toxic to bacteria, whereas growth and the emergence of chironomids showed no effects in other samples than LF. The midges tolerate well the contaminated environment. In contrast, bioavailability of arsenite of sediment samples KN and LF was quite high determined using the biosensor-strains in a direct contact assay. The bioavailable fraction of sediment LP was 6-10% out of the total arsenite concentration obtained with GFAAS (0.46-0.77 {mu}g g{sup -1} dw). The results show that the choice of analysis method grossly affects the outcome without any of the method giving an incorrect result. Different methods measure different parameters of a toxic sample and can thus be used to complement each other.

  5. Effects of arsenic on modification of promyelocytic leukemia (PML): PML responds to low levels of arsenite

    Energy Technology Data Exchange (ETDEWEB)

    Hirano, Seishiro, E-mail: seishiro@nies.go.jp [Research Center for Environmental Risk, National Institute for Environmental Studies (Japan); Graduate School of Pharmaceutical Sciences, Chiba University (Japan); Watanabe, Takayuki [Graduate School of Pharmaceutical Sciences, Chiba University (Japan); Kobayashi, Yayoi [Graduate School of Pharmaceutical Sciences, Chiba University (Japan); Center for Environmental Health Sciences, National Institute for Environmental Studies (Japan)

    2013-12-15

    Inorganic arsenite (iAs{sup 3+}) is a two-edged sword. iAs{sup 3+} is a well-known human carcinogen; nevertheless, it has been used as a therapeutic drug for acute promyelocytic leukemia (APL), which is caused by a fusion protein comprising retinoic acid receptor-α and promyelocytic leukemia (PML). PML, a nuclear transcription factor, has a RING finger domain with densely positioned cysteine residues. To examine PML-modulated cellular responses to iAs{sup 3+}, CHO-K1 and HEK293 cells were each used to establish cell lines that expressed ectopic human PML. Overexpression of PML increased susceptibility to iAs{sup 3+} in CHO-K1 cells, but not in HEK293 cells. Exposure of PML-transfected cells to iAs{sup 3+} caused PML to change from a soluble form to less soluble forms, and this modification of PML was observable even with just 0.1 μM iAs{sup 3+} (7.5 ppb). Western blot and immunofluorescent microscopic analyses revealed that the biochemical changes of PML were caused at least in part by conjugation with small ubiquitin-like modifier proteins (SUMOylation). A luciferase reporter gene was used to investigate whether modification of PML was caused by oxidative stress or activation of antioxidant response element (ARE) in CHO-K1 cells. Modification of PML protein occurred faster than activation of the ARE in response to iAs{sup 3+}, suggesting that PML was not modified as a consequence of oxidative stress-induced ARE activation. - Highlights: • PML was found in nuclear microspecles in response to arsenite. • Arsenite triggers SUMOylation of PML. • Arsenite modifies PML at as low as 0.1 μM. • Modification of PML is not caused by ARE activation.

  6. Arabidopsis NIP3;1 Plays an Important Role in Arsenic Uptake and Root-to-Shoot Translocation under Arsenite Stress Conditions.

    Science.gov (United States)

    Xu, Wenzhong; Dai, Wentao; Yan, Huili; Li, Sheng; Shen, Hongling; Chen, Yanshan; Xu, Hua; Sun, Yangyang; He, Zhenyan; Ma, Mi

    2015-05-01

    In Arabidopsis, the nodulin 26-like intrinsic protein (NIP) subfamily of aquaporin proteins consists of nine members, five of which (NIP1;1, NIP1;2, NIP5;1, NIP6;1, and NIP7;1) were previously identified to be permeable to arsenite. However, the roles of NIPs in the root-to-shoot translocation of arsenite in plants remain poorly understood. In this study, using reverse genetic strategies, Arabidopsis NIP3;1 was identified to play an important role in both the arsenic uptake and root-to-shoot distribution under arsenite stress conditions. The nip3;1 loss-of-function mutants displayed obvious improvements in arsenite tolerance for aboveground growth and accumulated less arsenic in shoots than those of the wild-type plants, whereas the nip3;1 nip1;1 double mutant showed strong arsenite tolerance and improved growth of both roots and shoots under arsenite stress conditions. A promoter-β-glucuronidase analysis revealed that NIP3;1 was expressed almost exclusively in roots (with the exception of the root tips), and heterologous expression in the yeast Saccharomyces cerevisiae demonstrated that NIP3;1 was able to mediate arsenite transport. Taken together, our results suggest that NIP3;1 is involved in arsenite uptake and root-to-shoot translocation in Arabidopsis, probably as a passive and bidirectional arsenite transporter.

  7. Aquaglyceroporins are involved in uptake of arsenite into murine gastrointestinal tissues.

    Science.gov (United States)

    Wang, Chun; Chen, Gang; Jiang, Junkang; Qiu, Lianglin; Hosoi, Kazuo; Yao, Chenjuan

    2009-01-01

    Aquaglyceroporins (AQGPs) are members of aquaporin (AQP) family and belong to a subgroup of this water channel family; they are transmembrane proteins that transport water as well as glycerol and other solutes of small molecules. Recent studies have also identified that AQGPs are important transporters of trivalent metalloid in some mammalian cells. However, the uptake routes of arsenite in mammals are still less defined. In this study, to understand the routes of arsenite intake in mammals, mice were treated with Hg(II), glycerol, and As(III) and uptake of As(III) into the gastrointestinal tissues was measured. The level of inorganic arsenic (iAs) in gastrointestinal tissues after As(III) stimulation was much higher than Hg(II) +As(III) or glycerol+As(III) group. RT-PCR results showed that AQGPs were extensively expressed in gastrointestinal tissues of mice. We also treated Caco-2 cells with Hg(II) and As(III); the level of iAs in a group treated with Hg(II)+As(III) decreased compared with As(III)-treated group. Our results suggested that AQGPs could be important transporters in arsenite uptake into gastrointestinal tissues of mice, but more data are need to prove if AQGPs is the only pathway involved in As transport in mammals or just one of them.

  8. Methylated Trivalent Arsenic-Glutathione Complexes are More Stable than their Arsenite Analog

    Directory of Open Access Journals (Sweden)

    Jürgen Gailer

    2008-05-01

    Full Text Available The trivalent arsenic glutathione complexes arsenic triglutathione, methylarsonous diglutathione, and dimethylarsinous glutathione are key intermediates in the mammalian metabolism of arsenite and possibly represent the arsenic species that are transported from the liver to the kidney for urinary excretion. Despite this, the comparative stability of the arsenic-sulfur bonds in these complexes has not been investigated under physiological conditions resembling hepatocyte cytosol. Using size-exclusion chromatography and a glutathione-containing phosphate buffered saline mobile phase (5 or 10 mM glutathione, pH 7.4 in conjunction with an arsenic-specific detector, we chromatographed arsenite, monomethylarsonous acid, and dimethylarsinous acid. The on-column formation of the corresponding arsenic-glutathione complexes between 4 and 37∘C revealed that methylated arsenic-glutathione complexes are more stable than arsenic triglutathione. The relevance of these results with regard to the metabolic fate of arsenite in mammals is discussed.

  9. Sodium arsenite induced biochemical perturbations in rats: ameliorating effect of curcumin.

    Science.gov (United States)

    Yousef, Mokhtar I; El-Demerdash, Fatma M; Radwan, Fatma M E

    2008-11-01

    The present study was undertaken to evaluate the therapeutic efficacy of curcumin in terms of normalization of altered biochemical parameters following sodium arsenite treatment in rats. Animals were divided into four groups. The first group was used as control. While, groups 2, 3 and 4 were orally treated with curcumin (Cur, 15 mg/kg BW), sodium arsenite (Sa, 5 mg/kg BW) and sodium arsenite plus curcumin, respectively. Results showed that the activities of transaminases and phosphatases were significantly decreased in liver due to Sa administration, whereas increased in plasma. The activity of brain and plasma acetylcholinesterase (AChE) was decreased in rats treated with Sa. Also, Sa significantly decreased plasma total protein (TP), albumin (Alb) and high density lipoprotein-cholesterol (HDL-c), while increased glucose, urea, creatinine, bilirubin, total lipid (TL), cholesterol, triglyceride (TG) and low density lipoprotein-cholesterol (LDL-c). Curcumin alone decreased the levels of glucose, urea, creatinine, TL, cholesterol, TG and LDL-c. Curcumin reduced Sa-induced transaminases, phosphatases, glucose, urea, creatinine, bilirubin, TL, cholesterol and TG. Moreover, curcumin induced Sa-reduced liver transaminases and phosphatases, plasma and brain AChE, and the levels of TP and Alb. Experimental results, therefore suggested that curcumin protects arsenic induced biochemical alterations in rats.

  10. Stress protein synthesis in human keratinocytes treated with sodium arsenite, phenyldichloroarsine, and nitrogen mustard

    International Nuclear Information System (INIS)

    Cells from bacteria to man respond to sublethal thermal and certain chemical stresses by synthesis of heat shock, or stress, proteins. The human epidermal keratinocyte is a target for a variety of cytotoxic substances. One response of cells exposed to such agents may be the synthesis of stress proteins. Human epidermal keratinocytes were treated thermally (43 degrees C) or chemically with sodium arsenite and the skin irritants phenyldichloroarsine and mechlorethamine. Proteins synthesized by keratinocytes were radiolabeled with [35S]methionine, separated on polyacrylamide gels under denaturing conditions, and visualized by fluorography. Quantitation by computer-assisted densitometry of fluorograms revealed different patterns of synthesis of two heat shock proteins (hsp's) with apparent molecular weights of 70 and 90 kDa after treatment with heat, sodium arsenite, phenyl-dichloroarsine, or mechlorethamine. Sodium arsenite induced the highest levels of synthesis of these two proteins, approximately 10-fold and 3-fold increases in hsp-70 and hsp-90, respectively. Phenyldichloroarsine at 0.5 microM produced a 2-fold increase in hsp-70 but no significant increase in hsp-90. Mechlorethamine, in contrast, had an apparent inhibitory effect on hsp-70 synthesis. These results suggest that some but not all skin irritants induce the synthesis of heat shock proteins in human keratinocytes

  11. Spatio-temporal detection of the Thiomonas population and the Thiomonas arsenite oxidase involved in natural arsenite attenuation processes in the Carnoulès Acid Mine Drainage

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    Agnès eHovasse

    2016-02-01

    Full Text Available The acid mine drainage (AMD impacted creek of the Carnoulès mine (Southern France is characterized by acid waters with a high heavy metal content. The microbial community inhabiting this AMD was extensively studied using isolation, metagenomic and metaproteomic methods, and the results showed that a natural arsenic (and iron attenuation process involving the arsenite oxidase activity of several Thiomonas strains occurs at this site. A sensitive quantitative Selected Reaction Monitoring (SRM-based proteomic approach was developed for detecting and quantifying the two subunits of the arsenite oxidase and RpoA of two different Thiomonas groups. Using this approach combined with 16S rRNA gene sequence analysis based on pyrosequencing and FISH, it was established here for the first time that these Thiomonas strains are ubiquitously present in minor proportions in this AMD and that they express the key enzymes involved in natural remediation processes at various locations and time points. In addition to these findings, this study also confirms that targeted proteomics applied at the community level can be used to detect weakly abundant proteins in situ.

  12. IL-15 improves the cytotoxicity of cytokine-induced killer cells against leukemia cells by upregulating CD3+CD56+ cells and downregulating regulatory T cells as well as IL-35.

    Science.gov (United States)

    Tao, Qianshan; Chen, Tianping; Tao, Lili; Wang, Huiping; Pan, Ying; Xiong, Shudao; Zhai, Zhimin

    2013-01-01

    Cytokine-induced killer (CIK) cells are usually generated from peripheral blood mononuclear cells with the stimulation of IL-2 in vitro. Unlike the conventional IL-2-stimulated CIK cells (IL-2-CIK cells), we investigated the characteristics and potential mechanism of IL-15-stimulated CIK cells (IL-15-CIK cells) in this study. Compared with IL-2-CIK cells, the percentage of CD3CD56 cells was significantly increased in IL-15-CIK cells, but the expression of regulatory T (Treg) cells and IL-35 was significantly decreased in IL-15-CIK cells. Meanwhile, the in vitro cytotoxicity against human myeloid leukemia cells K562 of IL-15-CIK cells was significantly augmented compared with IL-2-CIK cells. These data suggest that IL-15 may improve the cytotoxicity of CIK cells against leukemia cells by upregulating CD3CD56 cells and downregulating Treg cells and IL-35.

  13. Members of rice plasma membrane intrinsic proteins subfamily are involved in arsenite permeability and tolerance in plants.

    Science.gov (United States)

    Mosa, Kareem A; Kumar, Kundan; Chhikara, Sudesh; Mcdermott, Joseph; Liu, Zijuan; Musante, Craig; White, Jason C; Dhankher, Om Parkash

    2012-12-01

    Rice accumulates high level of arsenic (As) in its edible parts and thus plays an important role in the transfer of As into the food chain. However, the mechanisms of As uptake and its detoxification in rice are not well understood. Recently, members of the Nodulin 26-like intrinsic protein (NIP) subfamily of plant aquaporins were shown to transport arsenite in rice and Arabidopsis. Here we report that members of the rice plasma membrane intrinsic protein (PIP) subfamily are also involved in As tolerance and transport. Based on the homology search with the mammalian AQP9 and yeast Fps1 arsenite transporters, we identified and cloned five rice PIP gene subfamily members. qRT-PCR analysis of PIPs in rice root and shoot tissues revealed a significant down regulation of transcripts encoding OsPIP1;2, OsPIP1;3, OsPIP2;4, OsPIP2;6, and OsPIP2;7 in response to arsenite treatment. Heterologous expression of OsPIP2;4, OsPIP2;6, and OsPIP2;7 in Xenopus laevis oocytes significantly increased the uptake of arsenite. Overexpression of OsPIP2;4, OsPIP2;6, and OsPIP2;7 in Arabidopsis yielded enhanced arsenite tolerance and higher biomass accumulation. Further, these transgenic plants showed no significant accumulation of As in shoot and root tissues in long term uptake assays. Whereas, short duration exposure to arsenite caused both active influx and efflux of As in the roots. The data suggests a bidirectional arsenite permeability of rice PIPs in plants. These rice PIPs genes will be highly useful for engineering important food and biofuel crops for enhanced crop productivity on contaminated soils without increasing the accumulation of toxic As in the biomass or edible tissues.

  14. The toxic effects of Arsenite on the human umbilical vein endothelial cells%亚砷酸钠对人脐静脉血管内皮细胞的毒性效应

    Institute of Scientific and Technical Information of China (English)

    杨陆; 董雪; 赵琪珩; 刘飞

    2012-01-01

    Objective To explore the effect of sodium arsenite on the angiogenesis to provide theoretical explanation and practical measurement for arsenism. Methods The proliferation of human umbilical vein endothelial cells (HUVECs) was used as an in vitro model to evaluate the effects of arsenic on human vascular cells. Cell proliferation was assayed by CCK-8 kit. PI staining with flow cytometry was used to detect cell cycle changes. The mRNAs were analyzed by real time quantitative RT-PCR. Results Sodium arsenite inhibited proliferation of HUVEC in a dose-dependent manner when exposed to it in levels applied. The cell number of S phase was decreased, most of the cell were blocked in G0/G1 phase. Meanwhile, the mRNAs of c-Myc were decreased after exposure to sodium arsenite. Conclusions Sodium arsenite inhibits proliferation of HUVEC through the down regulation of c-Myc, suggesting they are the major signals for arsenic to exert its suppression on the proliferation of HUV-EC.%目的 探讨亚砷酸钠对体外培养的人脐静脉内皮细胞(Human umbilical vein endothelial cells,HUVECs)毒性效应的分子机制.方法 通过观察细胞形态和细胞增殖实验分别观察亚砷酸钠对细胞形态及增殖能力的影响;PI染色结合流式细胞仪检测细胞周期的变化;应用实时定量RT-PCR技术检测c-Jun、c-Myc的mRNA表达水平.结果 随着亚砷酸钠浓度增加,漂浮的细胞越来越多;细胞增殖抑制率越来越高;细胞周期结果显示,S期的细胞数明显减少,大多数细胞被阻滞在G0/G1期,呈典型的剂量-效应关系;亚砷酸钠下调HUVEC的c-Myc mRNAs水平.结论 亚砷酸钠通过下调c-Myc基因表达,抑制细胞增殖能力,提示其在地砷病引起的血管损伤中发挥重要作用.

  15. Linking microbial oxidation of arsenic with detection and phylogenetic analysis of arsenite oxidase genes in diverse geothermal environments.

    Science.gov (United States)

    Hamamura, N; Macur, R E; Korf, S; Ackerman, G; Taylor, W P; Kozubal, M; Reysenbach, A-L; Inskeep, W P

    2009-02-01

    The identification and characterization of genes involved in the microbial oxidation of arsenite will contribute to our understanding of factors controlling As cycling in natural systems. Towards this goal, we recently characterized the widespread occurrence of aerobic arsenite oxidase genes (aroA-like) from pure-culture bacterial isolates, soils, sediments and geothermal mats, but were unable to detect these genes in all geothermal systems where we have observed microbial arsenite oxidation. Consequently, the objectives of the current study were to measure arsenite-oxidation rates in geochemically diverse thermal habitats in Yellowstone National Park (YNP) ranging in pH from 2.6 to 8, and to identify corresponding 16S rRNA and aroA genotypes associated with these arsenite-oxidizing environments. Geochemical analyses, including measurement of arsenite-oxidation rates within geothermal outflow channels, were combined with 16S rRNA gene and aroA functional gene analysis using newly designed primers to capture previously undescribed aroA-like arsenite oxidase gene diversity. The majority of bacterial 16S rRNA gene sequences found in acidic (pH 2.6-3.6) Fe-oxyhydroxide microbial mats were closely related to Hydrogenobaculum spp. (members of the bacterial order Aquificales), while the predominant sequences from near-neutral (pH 6.2-8) springs were affiliated with other Aquificales including Sulfurihydrogenibium spp., Thermocrinis spp. and Hydrogenobacter spp., as well as members of the Deinococci, Thermodesulfobacteria and beta-Proteobacteria. Modified primers designed around previously characterized and newly identified aroA-like genes successfully amplified new lineages of aroA-like genes associated with members of the Aquificales across all geothermal systems examined. The expression of Aquificales aroA-like genes was also confirmed in situ, and the resultant cDNA sequences were consistent with aroA genotypes identified in the same environments. The aroA sequences

  16. In vitro modulation of MMP-2 and MMP-9 in human cervical and ovarian cancer cell lines by cytokines, inducers and inhibitors.

    Science.gov (United States)

    Roomi, M W; Monterrey, J C; Kalinovsky, T; Rath, M; Niedzwiecki, A

    2010-03-01

    Matrix metalloproteinases (MMPs) secreted by cervical and ovarian cancer, especially MMP-2 and MMP-9, play crucial roles in tumor invasion and metastasis. We examined the effect of cytokines, mitogens, inducers and inhibitors on MMP-2 and MMP-9 expression in cervical and ovarian cancer cell lines. Human cervical (HeLa and DoTc2-4510) and ovarian (SK-OV-3) cell lines were cultured in appropriate media. At near confluence, the cells were washed with PBS and incubated in serum-free medium with various concentrations of several cytokines, mitogens and inhibitors. After 24 h the media were removed and analyzed for MMP-2 and MMP-9 by gelatinase zymography and quantitated by densitometry. HeLa and SK-OV-3 cell lines expressed MMP-2 whereas DoTc2-4510 cells expressed MMP-9. Treatment of cervical cancer cell lines (HeLa and DoTc2-4510) with PMA had no effect on MMP-2 expression and a moderate stimulatory effect in ovarian cancer cell line SK-OV-3. MMP-9 was stimulated by phorbol 12-myristate 13-acetate in HeLa cells and enhanced in DoTc2-4510. Tumor necrosis factor-alpha and interleukin-1beta, had slight inhibitory effect on HeLa cell expression of MMP-2 while lipopolysaccharide stimulated MMP-2 in HeLa cells. Doxycycline, epigallocatechin gallate, a nutrient mixture, actinomycin-D, cyclohexamide, retinoic acid and dexamethasone inhibited MMP-2 in HeLa and SK-OV-3 cell lines and inhibited MMP-9 in DoTc2-4510. Our results show that cytokines, mitogens, inducers and inhibitors have an up or down regulatory effect on MMP-2 and MMP-9 expression in ovarian and cervical cancer cell lines, suggesting these agents may be effective strategies to treat these cancers.

  17. Arsenite Regulates Prolongation of Glycan Residues of Membrane Glycoprotein: A Pivotal Study via Wax Physisorption Kinetics and FTIR Imaging.

    Science.gov (United States)

    Lee, Chih-Hung; Hsu, Chia-Yen; Huang, Pei-Yu; Chen, Ching-Iue; Lee, Yao-Chang; Yu, Hsin-Su

    2016-03-22

    Arsenic exposure results in several human cancers, including those of the skin, lung, and bladder. As skin cancers are the most common form, epidermal keratinocytes (KC) are the main target of arsenic exposure. The mechanisms by which arsenic induces carcinogenesis remains unclear, but aberrant cell proliferation and dysregulated energy homeostasis play a significant role. Protein glycosylation is involved in many key physiological processes, including cell proliferation and differentiation. To evaluate whether arsenite exposure affected protein glycosylation, the alteration of chain length of glycan residues in arsenite treated skin cells was estimated. Herein we demonstrated that the protein glycosylation was adenosine triphosphate (ATP)-dependent and regulated by arsenite exposure by using Fourier transform infrared (FTIR) reflectance spectroscopy, synchrotron-radiation-based FTIR (SR-FTIR) microspectroscopy, and wax physisorption kinetics coupled with focal-plane-array-based FTIR (WPK-FPA-FTIR) imaging. We were able to estimate the relative length of surface protein-linked glycan residues on arsenite-treated skin cells, including primary KC and two skin cancer cell lines, HSC-1 and HaCaT cells. Differential physisorption of wax adsorbents adhered to long-chain (elongated type) and short-chain (regular type) glycan residues of glycoprotein of skin cell samples treated with various concentration of arsenite was measured. The physisorption ratio of beeswax remain/n-pentacosane remain for KC cells was increased during arsenite exposure. Interestingly, this increase was reversed after oligomycin (an ATP synthase inhibitor) pretreatment, suggesting the chain length of protein-linked glycan residues is likely ATP-dependent. This is the first study to demonstrate the elongation and termination of surface protein-linked glycan residues using WPK-FPA-FTIR imaging in eukaryotes. Herein the result may provide a scientific basis to target surface protein-linked glycan

  18. Low Dose and Long Term Toxicity of Sodium Arsenite Caused Caspase Dependent Apoptosis Based on Morphology and Biochemical Character

    Directory of Open Access Journals (Sweden)

    Mohammad Hussein Abnosi

    2012-01-01

    Full Text Available Objective: Although arsenite is toxic it is currently recommended for the treatment of malignancies. In this study the effects of sub-micromolar concentrations of sodium arsenite on the viability, morphology and mechanism of cell death of rat bone marrow mesenchymal stem cells (BMCs over 21 days was investigated.Materials and Methods: In this experimental study, BMCs were extracted in Dulbecco’s Modified Eagles Medium (DMEM containing 15% of fetal bovine serum (FBS and expanded till the 3rd passage. The cells were treated with 1, 10, 25, 50, 75 and 100 nM of sodium arsenite for 21 days and the viability of the cells estimated using 3-(4, 5-dimethylthiazol-2-yl-2, 5 diphenyl tetrazolium (MTT and trypan blue staining. Cells were then treated with the selected dose (25 nM of sodium arsenite to determine their colony forming ability (CFA and population doubling number (PDN. Morphology of the cells was studied using florescent dyes, and the integrity of the DNA was investigated using the comet assay and agarose gel electrophoresis. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL and the caspase 3 assay were then applied to understand the mechanism of cell death. Data was analyzed using one way ANOVA, Tukey test.Results: A significant reduction of viability, PDN and CFA was found following treatment of BMCs with 25 nM sodium arsenite (p<0.05. Cytoplasm shrinkage and a significant decrease in the diameter of the nuclei were also seen. Comet assay and agarose gel electrophoresis revealed DNA breakage, while positive TUNEL and activated caspase 3 confirmed the apoptosis.Conclusion: A low concentration of sodium arsenite (25 nM caused reduction of viability due to induction of apoptosis. Therefore, long term exposure to low dose of this chemical may have unwanted effects on BMCs.

  19. Possible vasculoprotective role of linagliptin against sodium arsenite-induced vascular endothelial dysfunction.

    Science.gov (United States)

    Jyoti, Uma; Kansal, Sunil Kumar; Kumar, Puneet; Goyal, Sandeep

    2016-02-01

    Vascular endothelial dysfunction (VED) interrupts the integrity and function of endothelial lining through enhanced markers of oxidative stress and decrease endothelial nitric oxide synthase (eNOS) expression. The main aim of the present study has been designed to investigate the possible vasculoprotective role of linagliptin against sodium arsenite-induced VED. Sodium arsenite (1.5 mg/kg, i.p., 2 weeks) abrogated the acetylcholine-induced, endothelium-dependent vasorelaxation by depicting the decrease in serum nitrite/nitrate concentration, reduced glutathione level, and simultaneously enhance the thiobarbituric acid reactive substances (TBARS) level, superoxide level, and tumor necrosis factor-alpha. These elevated markers interrupt the integrity of endothelial lining of thoracic aorta which was assessed histologically. The study elicits dose dependent effect of linagliptin (1.5 mg/kg, i.p. and 3 mg/kg, i.p.) or atorvastatin (30 mg/kg, p.o.) treatment, improved the endothelium-dependent independent relaxation, improve the integrity of endothelium lining which was assessed histologically by enhancing the serum nitrite/nitrate level, reduced glutathione level and simultaneously decreasing the TBARS level, superoxide anion level and tumor necrosis factor-alpha (TNF-α) level. L-NAME (25 mg/kg, i.p.), eNOS inhibitor, abrogated the ameliorative potential of linagliptin. However, the ameliorative potential of linagliptin has been enhanced by l-arginine (200 mg/kg, i.p.) which elicits that ameliorative potential of linagliptin was through eNOS signaling cascade and it may be concluded that linagliptin 3 mg/kg, i.p. has more significantly activated the eNOS and decreased the oxidative markers than linagliptin 1.5 mg/kg, i.p. and prevented sodium arsenite-induced VED.

  20. Arsenite induced oxidative damage in mouse liver is associated with increased cytokeratin 18 expression

    Energy Technology Data Exchange (ETDEWEB)

    Gonsebatt, M.E. [UNAM, Ciudad Universitaria, Dept. Medicina Genomica y Toxicologia Ambiental, Instituto de Investigaciones Biomedicas, Mexico (Mexico); Razo, L.M. del; Sanchez-Pena, L.C. [Seccion de Toxicologia, CINVESTAV, Mexico (Mexico); Cerbon, M.A. [Facultad de Quimica, UNAM, Departamento de Biologia, Mexico (Mexico); Zuniga, O.; Ramirez, P. [Facultad de Estudios Superiores Cuautitlan, UNAM, Laboratorio de Toxicologia Celular, Coordinacion General de Estudios de Posgrado e Investigacion, Cuautitlan Izcalli, Estado de Mexico (Mexico)

    2007-09-15

    Cytokeratins (CK) constitute a family of cytoskeletal intermediate filament proteins that are typically expressed in epithelial cells. An abnormal structure and function are effects that are clearly related to liver diseases as non-alcoholic steatohepatitis, cirrhosis and hepatocellular carcinoma. We have previously observed that sodium arsenite (SA) induced the synthesis of CK18 protein and promotes a dose-related disruption of cytoplasmic CK18 filaments in a human hepatic cell line. Both abnormal gene expression and disturbance of structural organization are toxic effects that are likely to cause liver disease by interfering with normal hepatocyte function. To investigate if a disruption in the CK18 expression pattern is associated with arsenite liver damage, we investigated CK18 mRNA and protein levels in liver slices treated with low levels of SA. Organotypic cultures were incubated with 0.01, 1 and 10 {mu}M of SA in the absence and presence of N-acetyl cysteine (NAC). Cell viability and inorganic arsenic metabolism were determined. Increased expression of CK18 was observed after exposure to SA. The addition of NAC impeded the oxidative effects of SA exposure, decreasing the production of thiobarbituric acid-reactive substances and significantly diminishing the up regulation of CK18 mRNA and protein. Liver arsenic levels correlated with increased levels of mRNA. Mice treated with intragastric single doses of 2.5 and 5 mg/kg of SA showed an increased expression of CK18. Results suggest that CK18 expression may be a sensible early biomarker of oxidative stress and damage induced by arsenite in vitro and in vivo. Then, during SA exposure, altered CK expression may compromise liver function. (orig.)

  1. The respiratory arsenite oxidase: structure and the role of residues surrounding the rieske cluster.

    Directory of Open Access Journals (Sweden)

    Thomas P Warelow

    Full Text Available The arsenite oxidase (Aio from the facultative autotrophic Alphaproteobacterium Rhizobium sp. NT-26 is a bioenergetic enzyme involved in the oxidation of arsenite to arsenate. The enzyme from the distantly related heterotroph, Alcaligenes faecalis, which is thought to oxidise arsenite for detoxification, consists of a large α subunit (AioA with bis-molybdopterin guanine dinucleotide at its active site and a 3Fe-4S cluster, and a small β subunit (AioB which contains a Rieske 2Fe-2S cluster. The successful heterologous expression of the NT-26 Aio in Escherichia coli has resulted in the solution of its crystal structure. The NT-26 Aio, a heterotetramer, shares high overall similarity to the heterodimeric arsenite oxidase from A. faecalis but there are striking differences in the structure surrounding the Rieske 2Fe-2S cluster which we demonstrate explains the difference in the observed redox potentials (+225 mV vs. +130/160 mV, respectively. A combination of site-directed mutagenesis and electron paramagnetic resonance was used to explore the differences observed in the structure and redox properties of the Rieske cluster. In the NT-26 AioB the substitution of a serine (S126 in NT-26 for a threonine as in the A. faecalis AioB explains a -20 mV decrease in redox potential. The disulphide bridge in the A. faecalis AioB which is conserved in other betaproteobacterial AioB subunits and the Rieske subunit of the cytochrome bc 1 complex is absent in the NT-26 AioB subunit. The introduction of a disulphide bridge had no effect on Aio activity or protein stability but resulted in a decrease in the redox potential of the cluster. These results are in conflict with previous data on the betaproteobacterial AioB subunit and the Rieske of the bc 1 complex where removal of the disulphide bridge had no effect on the redox potential of the former but a decrease in cluster stability was observed in the latter.

  2. Management of the virulent influenza virus infection by oral formulation of nonhydrolized carnosine and isopeptide of carnosine attenuating proinflammatory cytokine-induced nitric oxide production.

    Science.gov (United States)

    Babizhayev, Mark A; Deyev, Anatoly I

    2012-01-01

    important factors of natural immunity in controlling the initial stages of influenza A virus infection (inhibition of virus replication) and virus-induced regulation of cytokine gene expression. The protective effects of orally applied nonhydrolized formulated species of carnosine include at least direct interaction with nitric oxide, inhibition of cytotoxic NO-induced proinflammatory condition, and attenuation of the effects of cytokines and chemokines that can exert profound effects on inflammatory cells. These data are consistent with the hypothesis that natural products, such as chicken soup and chicken breast extracts rich in carnosine and its derivative anserine (beta-alanyl-1-methyl-L-histidine) could contribute to the pathogenesis and prevention of influenza virus infections and cold but have a limitation due to susceptibility to enzymatic hydrolysis of dipeptides with serum carnosinase and urine excretion after oral ingestion of a commercial chicken extract. The developed and patented by the authors formulations of nonhydrolized in digestive tract and blood natural carnosine peptide and isopeptide (gamma-glutamyl-carnosine) products have a promise in the Influenza A (H1N1) virus infection disease control and prevention. PMID:20841992

  3. Effect of sodium arsenite on spermatogenesis,plasma gonadotrophins and testosterone in rats

    Institute of Scientific and Technical Information of China (English)

    MahitoshSarkar; GargiRayChaudhuri; AlokeChattopadhyay; NarendraMohanBiswas

    2003-01-01

    Aim:To investigate the effect of arsenic on spermatogenesis.Methods:Mature(4 months old)Wistar rats were intraperitoneally administered sodium arsenite at doses of 4,5 or 6mg·kg-1·day-1 for 26 days.Different varieties of germ cells at stage Ⅶ seminiferous epithelium cycle,namely,type A spermatogonia(ASg),preleptotene spermatocytes(pLSc),midpachytene spermatocytes(mPSc) and step 7 spermatids(7Sd) were quantitatively evaluated, along with radioimmunoassay of plasma follicle-stimulating hormone(FSH),lutuneizing hormone(LH),testosterone and assessment of the epididymal sperm count.Results:In the 5 and 6 mg/kg groups,there were significant dosedependent decreases in the accessory sex organ weights,epididymal sperm count and plasma concentrations of LH,FSH and testosterone with massive degeneration of all the germ cells at stage Ⅶ,The changes were insignificant in the 4 mg/kg group.Conclusion:Arsenite has a suppressive influence on spermatogenesis and gonadotrophin and testosterone release in rats.

  4. The Effect of Vitamin E on the In Vitro Differentiation of Adult Rat Bone Marrow Mesenchymal Stem Cells to Osteoblast During Sodium Arsenite Exposure

    Directory of Open Access Journals (Sweden)

    M. Soleimani Mehranjani

    2016-01-01

    Full Text Available Introduction & Objective: Sodium arsenite disturbs the differentiation of adult rat bone marrow mesenchymal stem cells (rMSCs to Osteoblast through oxidative stress. We aimed to investigate the preventive effect of vitamin E, a strong antioxidant, in sodium arsenite toxicity on rMSCs differentiation to osteoblast. Materials & Methods: rMSCs were cultured in Dulbecco’s Modified Eagles Medium containing 15% Fetal Bovine Serum and divided into: control, sodium arsenite (20 nM, vitamin E (50 µM and sodium arsenite + vitamin E for 21 days in the osteogenic media containing 10% of fetal bovine serum. Cell viability, bone matrix mineralization, intercellular and extracellular calcium, alkaline phosphatase activity, DNA damage and cell morphological changes were evaluated. Data were analyzed using one-way ANOVA and Tukey's test and means were considered significantly different at P<0.05. Results: Cell viability, bone matrix mineralization, calcium deposition, alkaline phosphatase activity and nuclei diameter decreased significantly in the sodium arsenite group. The mentioned parameters increased significantly in cells treated with sodium arsenite + vitamin E to the control level (P<0.05. Cytoplasmic extensions were also observed in the vitamin E group. Conclusions: Vitamin E reduces sodium arsenite toxicity, increasing osteogenic differentiation in rMSCs. Sci J Hamadan Univ Med Sci . 2016; 22 (4 :276-285

  5. DNA damage in HBE cells induced by radon in combination with sodium arsenite%氡与亚砷酸钠致人永生化上皮细胞DNA损伤的联合毒作用

    Institute of Scientific and Technical Information of China (English)

    刘星; 聂继华; 陈志海; 金洹宇; 陈秋; 周新文; 焦旸; 童建; 安艳

    2013-01-01

    Objective To study DNA damage effect of radon in combination with sodium arsenite on HBE cells.Methods The HBE cells were exposed to various concentrations of radon (20 kBq/m3,0-75 min),sodium arsenite (0-50 mmol/L) and their combinations.Cell viability was tested by cell counting kit-8 (CCK-8).The combination index (CI) was calculated by different time exposed radon combined with different concentrations sodium arsenite.Single cell gel electrophoresis (SCGE) was applied for quantitative analysis of DNA damage.Results Radon with or without sodium arsenite inhibited the growth of HBE cells.Computed using median-effect principle,CI =0.41 indicated that radon and sodium arsenite had synergistic effect.Radon and sodium arsenite both could significantly increase tail DNA,tail moment and olive tail moment of HBE cells in SCGE compared with control(t =12.90-23.61,8.81-21.39,18.46-38.97,P<0.05; t=18.46-39.67,17.41-27.42,28.03-46.32,P<0.05).There was a dose-response relationship between radon level,sodium arsenite and DNA damage.The results of factorial analysis showed that there was a combination effect of DNA damage induced by radon and sodium arsenite (Ftail DNA% =76.07,P < 0.01 ; Ftail moment =290.51,P < 0.01 ; Foliver tail moment =273.46,P < 0.01).Conclusions There is a synergistic effect of DNA damage in HBE cells irradiated by radon in combination with sodium arsenite.%目的 探讨氡与亚砷酸钠联合染毒对人永生化上皮(HBE)细胞的DNA损伤作用.方法 以HBE细胞为研究对象,将HBE细胞暴露于20 000 Bq/m3氡浓度、不同时间(0~75 min)和不同浓度(0 ~ 50 000 μmol/L)亚砷酸钠以及联合作用,采用活细胞计数试剂盒(CCK-8)检测细胞存活率.通过中效原理,计算氡不同暴露时间和亚砷酸钠不同浓度联合作用联合指数(combination index,CI).以不同染氡时间(20 000 Bq/m3,10、20和40 min)和不同亚砷酸钠浓度(1.5、3.0和6.0 μmol/L)处理HBE细胞,应用单细胞凝胶电泳

  6. POSSIBLE ROLE OF LOCALIZED PROTEIN DENATURATION IN THE MECHANISM OF INDUCTION OF THERMOTOLERANCE BY HEAT, SODIUM-ARSENITE AND ETHANOL

    NARCIS (Netherlands)

    BURGMAN, PWJJ; KAMPINGA, HH; KONINGS, AWT

    1993-01-01

    Heat, sodium-arsenite, and ethanol-induced thermotolerance are compared, especially with regard to the induced resistance of proteins of the particulate fraction (PF) against heat-induced denaturation. While all three agents induce thermotolerance as expressed as an enhanced survival after hyperther

  7. ACQUISITION OF THERMOTOLERANCE INDUCED BY HEAT AND ARSENITE IN HELA S3-CELLS - MULTIPLE PATHWAYS TO INDUCE TOLERANCE

    NARCIS (Netherlands)

    KAMPINGA, HH; BRUNSTING, JF; KONINGS, AWT

    1992-01-01

    Recent data indicate that cells may acquire thermotolerance via more than one route. In this study, we observed differences in thermotolerance development in HeLa S3 cells induced by prior heating (15 minutes at 44-degrees-C) or pretreatment with sodium-arsenite (1 hour at 37-degrees-C, 100-mu-M). I

  8. Fe/Ti co-pillared clay for enhanced arsenite removal and photo oxidation under UV irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuan [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Guang Dong Electric Power Design Institute, China Energy Engineering Group Co. Ltd., Guangzhou 510663 (China); Cai, Xiaojiao [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Guo, Jingwei [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); The 718th Research Institute of CSIC, Handan 056027 (China); Zhou, Shimin [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Na, Ping, E-mail: naping@tju.edu.cn [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China)

    2015-01-01

    Graphical abstract: - Highlights: • An iron and titanium co-pillared montmorillonite (Fe-Ti/MMT) was synthesized for arsenite removal. • Variety of characterization results indicated that Fe and Ti species were pillared in MMT. • A possible mechanism of arsenite adsorption/oxidation with UV light was established. • The participation of Fe component can promote the process of photocatalytic oxidation in Fe-Ti/MMT + As(III) system. • Fe-Ti/MMT can function as both photocatalyst and adsorbent for arsenite removal. - Abstract: A series of iron and titanium co-pillared montmorillonites (Fe-Ti/MMT) were prepared using hydrolysis of inserted titanium and different iron content in montmorillonite (MMT). The Fe-Ti/MMT were characterized by X-ray fluorescence, N{sub 2} adsorption and desorption, X-ray diffraction, scanning electron microscopy (SEM) and transmission electron microscopy (TEM), confirming the effective insertion of Fe species and TiO{sub 2} in the MMT. The Fe-Ti/MMT was used to remove arsenite (As(III)) from aqueous solutions under different conditions. The result of As(III) adsorption under UV irradiation showed that the photo activity can be enhanced by incorporating Fe and Ti in MMT. Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis indicated that the hydroxyl groups bonded to metal oxide (M–OH) played an important role in the adsorption of As(III)

  9. Differential binding of monomethylarsonous acid compared to arsenite and arsenic trioxide with zinc finger peptides and proteins.

    Science.gov (United States)

    Zhou, Xixi; Sun, Xi; Mobarak, Charlotte; Gandolfi, A Jay; Burchiel, Scott W; Hudson, Laurie G; Liu, Ke Jian

    2014-04-21

    Arsenic is an environmental toxin that enhances the carcinogenic effect of DNA-damaging agents, such as ultraviolet radiation and benzo[a]pyrene. Interaction with zinc finger proteins has been shown to be an important molecular mechanism for arsenic toxicity and cocarcinogenesis. Arsenicals such as arsenite, arsenic trioxide (ATO), and monomethylarsonous acid (MMA(III)) have been reported to interact with cysteine residues of zinc finger domains, but little is known about potential differences in their selectivity of interaction. Herein we analyzed the interaction of arsenite, MMA(III), and ATO with C2H2, C3H1, and C4 configurations of zinc fingers using UV-vis, cobalt, fluorescence, and mass spectrometry. We observed that arsenite and ATO both selectively bound to C3H1 and C4 zinc fingers, while MMA(III) interacted with all three configurations of zinc finger peptides. Structurally and functionally, arsenite and ATO caused conformational changes and zinc loss on C3H1 and C4 zinc finger peptide and protein, respectively, whereas MMA(III) changed conformation and displaced zinc on all three types of zinc fingers. The differential selectivity was also demonstrated in zinc finger proteins isolated from cells treated with these arsenicals. Our results show that trivalent inorganic arsenic compounds, arsenite and ATO, have the same selectivity and behavior when interacting with zinc finger proteins, while methylation removes the selectivity. These findings provide insights on the molecular mechanisms underlying the differential effects of inorganic versus methylated arsenicals, as well as the role of in vivo arsenic methylation in arsenic toxicity and carcinogenesis.

  10. Safety investigation of cytokine induced killer cell therapy in patients with malignant tumor%细胞因子诱导的杀伤细胞治疗恶性肿瘤安全性分析

    Institute of Scientific and Technical Information of China (English)

    侯俊杰; 刘多; 倪志强; 周颖; 杨影; 方艳秋; 谭岩

    2015-01-01

    目的:观察细胞因子诱导的杀伤细胞( Cytokine-induced killer ,CIK)在治疗恶性肿瘤中出现的不良反应,分析不良反应发生的可能机制,制定出具有针对性的防治措施,指导临床工作. 方法:回顾性分析于2013年5月~2015年9月在我院接受CIK细胞治疗的1 240 例恶性肿瘤患者的临床资料,包括治疗相关的各种不良反应、实验室检查、采取的相应防治措施及疗效等. 结果:首次应用CIK细胞治疗后的不良反应包括:乏力( 10%)、发热( 7.25%)、寒战( 4%)、关节疼痛( 3%)、全身炎症反应综合征样反应( 3%)、消化道不适( 0.96%)、急性过敏样反应( 0.08%)、皮疹( 0.08%)、心绞痛( 0.08%)、肿瘤溶解综合征(0%)、感染(0%),随着治疗疗程增加,不良反应发生率增高,以发热为主要表现,于第4疗程后进入平台期,对于合并血压增高或下降、严重过敏样反应、类全身炎症反应综合征样反应、心绞痛者需对症处理,余无需特殊处理,在输注CIK细胞治疗前进行预处理可降低上述反应的发生率. 结论:CIK细胞治疗恶性肿瘤方法总体上安全可靠,相关不良反应可控且可恢复,罕见不良反应可能存在潜在风险.%Objective:To observe the adverse reactions of killer cytokine-induced (CIK) in the treatment of malignant tumor and to analyze the possible mechanism ,and to develop the targeted prevention and treatment measures .Methods: The clinical data, including various adverse reactions , laboratory tests and the corresponding preventive measures against adverse reactions .In 1 240 patients with malignant tumor after treated with CIK cells from May 2013 to September 2015 were retrospectively analyzed .Results:The main adverse reactions after the first infusion of CIK cells were weak (10%),fever(7.25%),shiver (4%),arthralgia (3%),systemic in flammatory response syndrome reaction ( 3%) , digestive tract discomfort ( 0.96%) , acute allergic reaction ( 0.08%) , rash (0

  11. Comparative Molecular Docking Studies with ABCC1 and Aquaporin 9 in the Arsenite Complex Efflux

    Science.gov (United States)

    Poojan, Shiv; Dhasmana, Anupam; Jamal, Qazi Mohammad Sajid; Haneef, Mohd; Lohani, Mohtashim

    2014-01-01

    Arsenic is the most toxic metalloid present in the natural environment in both organic and inorganic arsenic forms. Inorganic arsenic is often more hazardous than the organic form. Arsenite and arsenate compounds are the major inorganic forms which are toxic causing severe human health dysfunction including cancer. Excretion of arsenic from the system is found elusive. Therefore, it is of interest to screen channel proteins with the arsenic complex in the different combination of arsenic, GSH (glutathione) and arsenic, selenium using docking methods. The mode of arsenic removal. The complex structure revealed the mode of arsenic binding efficiency with the receptor aquaporine 9 and ABCC1 channel protein. This provides insights to understand the mechanism of arsenic efflux. These inferences find application in the design, identification and development of novel nutracetucal or any other formulation useful in the balance of arsenic efflux. PMID:25258480

  12. Comparative Molecular Docking Studies with ABCC1 and Aquaporin 9 in the Arsenite Complex Efflux.

    Science.gov (United States)

    Poojan, Shiv; Dhasmana, Anupam; Jamal, Qazi Mohammad Sajid; Haneef, Mohd; Lohani, Mohtashim

    2014-01-01

    Arsenic is the most toxic metalloid present in the natural environment in both organic and inorganic arsenic forms. Inorganic arsenic is often more hazardous than the organic form. Arsenite and arsenate compounds are the major inorganic forms which are toxic causing severe human health dysfunction including cancer. Excretion of arsenic from the system is found elusive. Therefore, it is of interest to screen channel proteins with the arsenic complex in the different combination of arsenic, GSH (glutathione) and arsenic, selenium using docking methods. The mode of arsenic removal. The complex structure revealed the mode of arsenic binding efficiency with the receptor aquaporine 9 and ABCC1 channel protein. This provides insights to understand the mechanism of arsenic efflux. These inferences find application in the design, identification and development of novel nutracetucal or any other formulation useful in the balance of arsenic efflux.

  13. Arsenite and arsenate removal from wastewater using cationic polymer-modified waste tyre rubber.

    Science.gov (United States)

    Imyim, Apichat; Sirithaweesit, Thitayati; Ruangpornvisuti, Vithaya

    2016-01-15

    Waste tyre rubber (WTR) granulate was modified with a cationic polymer, poly(3-acrylamidopropyl)trimethylammonium chloride (p(APTMACl)). The resulting WTR/p(APTMACl) was utilized for the adsorption of arsenite, As(III) and arsenate, As(V) from aqueous medium in both batch and column methods. The level of adsorption increased gradually with increasing monomer concentration and contact time. The adsorption behavior obeyed the Freundlich model, and the rate of adsorption could be predicted by employing the pseudo-second order model. In the column method, As(V) could be adsorbed onto the sorbent more effectively than As(III). Remarkable desorption of As(III) and As(V) (99 and 92%, respectively) from the adsorbent was achieved using 0.10 M HCl as eluent. An approach of evaluation of adsorption capacity uncertainty is proposed. PMID:26607568

  14. Investigation of the Interaction Between Sodium(meta) Arsenite and Catechin via ESI Tandem Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    CUI Sheng-yun; WEN Jin-feng; KIM Seung-jin; LEE Yong-ill

    2007-01-01

    Catechin, one of the main components of green tea, is considered to have the remedy effect of arsenic poison,although the chemical mechanism is not well known. In this study, sodium(meta) selenite, which is used as herbisolution to investigate the interaction between toxic inorganic arsenic compound and catechin via ESI tandem mass spectrometry. The interaction products of mono-methylated arsenic with catechin in the presence of methanol were identified in the negative mode. Collission induced dissociation(CID) mass spectrometric measurements indicate that monomethylated arsenic was "alkylated" strongly by conjugation at the sites of C2' and C5' in the phenyl ring B of the catechin. The interaction mechanism between sodium(meta) arsenite and catechin was proposed. The results provide useful information to understand the chemical pathway of the detoxification of the arsenic toxicity by catechin.

  15. Sodium arsenite reduces severity of dextran sulfate sodium-induced ulcerative colitis in rats

    Institute of Scientific and Technical Information of China (English)

    Joshua J. MALAGO; Hortensia NONDOLI

    2008-01-01

    The histopathological features and the associated clinical findings of ulcerative colitis (UC) are due to persistent inflammatory response in the colon mucosa. Interventions that suppress this response benefit UC patients. We tested whether sodium arsenite (SA) benefits rats with dextran sulfate sodium (DSS)-colitis. The DSS-colitis was induced by 5% DSS in drinking water. SA (10 mg/kg; intraperitoneally) was given 8 h before DSS treatment and then every 48 h for 3 cycles of 7,14 or 21 d. At the end of each cycle rats were sacrificed and colon sections processed for histological examination. DSS induced diarrhea, loose stools, hemoccult positive stools, gross bleeding, loss of body weight, loss of epithelium, crypt damage, depletion of goblet cells and infiltration of inflammatory cells. The severity of these changes increased ir the order of Cycles 1,2 and 3. Treatment of rats with SA significantly reduced this severity and improved the weight gain.

  16. EFFECTS OF ARSENITE IN TELOMERE AND TELOMERASE IN RELATION TO CELL PROLIFERATION AND APOPTOSIS IN HUMAN KERATINOCYTES AND LEUKEMIA CELLS IN VITRO

    Science.gov (United States)

    Telomeres are critical in maintaining chromosome and genomic stability. Arsenic, a human carcinogen as well as an anticancer agent, is known for its clastogenicity. To better understand molecular mechanisms of arsenic actions, we investigated arsenite effects on telomere and telo...

  17. Cytokine-Induced Modulation of Colorectal Cancer.

    Science.gov (United States)

    Mager, Lukas F; Wasmer, Marie-Hélène; Rau, Tilman T; Krebs, Philippe

    2016-01-01

    The emergence of novel immunomodulatory cancer therapies over the last decade, above all immune checkpoint blockade, has significantly advanced tumor treatment. For colorectal cancer (CRC), a novel scoring system based on the immune cell infiltration in tumors has greatly improved disease prognostic evaluation and guidance to more specific therapy. These findings underline the relevance of tumor immunology in the future handling and therapeutic approach of malignant disease. Inflammation can either promote or suppress CRC pathogenesis and inflammatory mediators, mainly cytokines, critically determine the pro- or anti-tumorigenic signals within the tumor environment. Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action. We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer. We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies.

  18. Molecular basis of arsenite (As+3-induced acute cytotoxicity in human cervical epithelial carcinoma cells

    Directory of Open Access Journals (Sweden)

    Muhammad Nauman Arshad

    2015-04-01

    Full Text Available Background: Rapid industrialization is discharging toxic heavy metals into the environment, disturbing human health in many ways and causing various neurologic, cardiovascular, and dermatologic abnormalities and certain types of cancer. The presence of arsenic in drinking water from different urban and rural areas of the major cities of Pakistan, for example, Lahore, Faisalabad, and Kasur, was found to be beyond the permissible limit of 10 parts per billion set by the World Health Organization. Therefore the present study was initiated to examine the effects of arsenite (As+3 on DNA biosynthesis and cell death. Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and flow cytometry. Results: We show that As+3 ions have a dose- and time-dependent cytotoxic effect through the activation of the caspase-dependent apoptotic pathway. In contrast to previous research, the present study was designed to explore the early cytotoxic effects produced in human cells during exposure to heavy dosage of As+3 (7.5 µg/ml. Even treatment for 1 h significantly increased the mRNA levels of p21 and p27 and caspases 3, 7, and 9. It was interesting that there was no change in the expression levels of p53, which plays an important role in G2/M phase cell cycle arrest. Conclusion: Our results indicate that sudden exposure of cells to arsenite (As+3 resulted in cytotoxicity and mitochondrial-mediated apoptosis resulting from up-regulation of caspases.

  19. Towards intrinsic MoS2 devices for high performance arsenite sensing

    Science.gov (United States)

    Li, Peng; Zhang, Dongzhi; Sun, Yan'e.; Chang, Hongyan; Liu, Jingjing; Yin, Nailiang

    2016-08-01

    Molybdenum disulphide (MoS2) is one of the most attractive two dimensional materials other than graphene, and the exceptional properties make it a promising candidate for bio/chemical sensing. Nevertheless, intrinsic properties and sensing performances of MoS2 are easily masked by the presence of the Schottky barrier (SB) at source/drain electrodes, and its impact on MoS2 sensors remains unclear. Here, we systematically investigated the influence of the SB on MoS2 sensors, revealing the sensing mechanism of intrinsic MoS2. By utilizing a small work function metal, Ti, to reduce the SB, excellent electrical properties of this 2D material were yielded with 2-3 times enhanced sensitivity. We experimentally demonstrated that the sensitivity of MoS2 is superior to that of graphene. Intrinsic MoS2 was able to realize rapid detection of arsenite down to 0.1 ppb without the influence of large SB, which is two-fold lower than the World Health Organization (WHO) tolerance level and better than the detection limit of recently reported arsenite sensors. Additionally, accurately discriminating target molecules is a great challenge for sensors based on 2D materials. This work demonstrates MoS2 sensors encapsulated with ionophore film which only allows certain types of molecules to selectively permeate through it. As a result, multiplex ion detection with superb selectivity was realized. Our results show prominent advantages of intrinsic MoS2 as a sensing material.

  20. Modulatory of effect of fresh Amaranthus caudatus and Amaranthus hybridus aqueous leaf extracts on detoxify enzymes and micronuclei formation after exposure to sodium arsenite

    OpenAIRE

    Adetutu Adewale; Awe Emmanuel Olorunju

    2013-01-01

    Vegetables are the cheapest and most available sources of important proteins, minerals, vitamins, and essential amino protein. These vegetables are commonly used in Africa for the treatment of illness. This study evaluated the protective effects of Amaranthus caudatus and A. hybridus against sodium arsenite-induced toxicity in rats. The effects of sodium arsenite and/or the plant extracts were assessed using bone marrow micronucleus assay and by measuring the activities of tumour maker enzyme...

  1. Facultative anoxygenic photosynthesis in cyanobacteria driven by arsenite and sulfide with evidence for the support of nitrogen fixation

    Science.gov (United States)

    Wolfe-Simon, F.; Hoeft, S. E.; Baesman, S. M.; Oremland, R. S.

    2010-12-01

    The rise in atmospheric oxygen (O2) over geologic time is attributed to the evolution and widespread proliferation of oxygenic photosynthesis in cyanobacteria. However, cyanobacteria maintain a metabolic flexibility that may not always result in O2 release. In the environment, cyanobacteria may use a variety of alternative electron donors rather than water that are known to be used by other anoxygenic phototrophs (eg. purple sulfur bacteria) including reduced forms of sulfur, iron, nitrogen, and arsenic. Recent evidence suggests cyanobacteria actively take advantage of at least a few of these alternatives. We used a classical Winogradsky approach to enrich for cyanobacteria from the high salinity, elevated pH and arsenic-enriched waters of Mono Lake (CA). Experiments, optimized for cyanobacteria, revealed light-dependent, anaerobic arsenite-oxidation in sub-cultured sediment-free enrichments dominated by a filamentous cyanobacteria. We isolated and identified the dominant member of this enrichment to be a member of the Oscillatoriales by 16S rDNA. Addition of 1 mM arsenite induced facultative anoxygenic photosynthesis under continuous and circadian light. This isolate also oxidized sulfide under the same light-based conditions. Aerobic conditions elicited no arsenite oxidation in the light or dark and the isolate grew as a typical cyanobacterium using oxygenic photosynthesis. Under near-infrared light (700 nm) there was a direct correlation of enhanced growth with an increase in the rate arsenite or sulfide oxidation suggesting the use of photosystem I. Additionally, to test the wide-spread nature of this metabolism in the Oscillatoriales, we followed similar arsenite- and sulfide-driven facultative anoxygenic photosynthesis as well as nitrogen fixation (C2H2 reduction) in the axenic isolate Oscillatoria sp. CCMP 1731. Future characterization includes axenic isolation of the Mono Lake Oscillatoria sp. as well as the arsenite oxidase responsible for electron

  2. Conjugative plasmid in Corynebacterium flaccumfaciens subsp. oortii that confers resistance to arsenite, arsenate, and antimony(III)

    Energy Technology Data Exchange (ETDEWEB)

    Hendrick, C.A.; Haskins, W.P.; Vidaver, A.K.

    1984-07-01

    Gene transfer systems for phytopathogenic corynebacteria have not been reported previously. In this paper a conjugative 46-megadalton plasmid (pDG101) found in Corynebacterium flaccumfaciens subsp. oorii CO101 is described that mediates resistance to arsenite, arsenate, and antimony(III). Transfer of the plasmid from CO101 to four other strains from the C. flaccumfaciens group occurred between cells immobilized on nitrocellulose filters or on agar surfaces. Transconjugant strains expressed the same levels of metal resistance as the donor strain and were able to act as donor strains in subsequent matings. The physical presence of the plasmid was detected by agarose gel electrophoresis. Arsenite-sensitive derivatives of the donor and transconjugant strains were obtained after heat treatment; these were cured of pDG101.

  3. Evaluation of the toxic effects of arsenite, chromate, cadmium, and copper using a battery of four bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Ko, Kyung-Seok; Lee, Pyeong-Koo [Korea Institute of Geoscience and Mineral Resources (KIGAM), Daejeon (Korea, Republic of). Geologic Environment Div.; Kong, In Chul [Yeungnam Univ., Kyungbuk (Korea, Republic of). Dept. of Environmental Engineering

    2012-09-15

    The sensitivities of four different kinds of bioassays to the toxicities of arsenite, chromate, cadmium, and copper were compared. The different bioassays exhibited different sensitivities, i.e., they responded to different levels of toxicity of each of the different metals. However, with the exception of the {alpha}-glucosidase enzyme activity, arsenite was the most toxic compound towards all the tested organisms, exhibiting the highest toxic effect on the seeds of Lactuca, with an EC{sub 50} value of 0.63 mg/L. The sensitivities of Lactuca and Raphanus were greater than the sensitivities of two other kinds of seeds tested. Therefore, these were the seeds appropriate for use in a seed germination assay. A high revertant mutagenic ratio (5:1) of Salmonella typhimurium was observed with an arsenite concentration of 0.1 {mu}g/plate, indicative of a high possibility of mutagenicity. These different results suggested that a battery of bioassays, rather than one bioassay alone, is needed as a more accurate and better tool for the bioassessment of environmental pollutants. (orig.)

  4. Arsenite-activated JNK signaling enhances CPEB4-Vinexin interaction to facilitate stress granule assembly and cell survival.

    Directory of Open Access Journals (Sweden)

    Yu-Wei Chang

    Full Text Available Stress granules (SGs are compartmentalized messenger ribonucleoprotein particles (mRNPs where translationally repressed mRNAs are stored when cells encounter environmental stress. Cytoplasmic polyadenylation element-binding protein (CPEB4 is a sequence-specific RNA-binding protein and translational regulator. In keeping with the results obtained from the study of other RNA-binding proteins, we found CPEB4 localized in SGs in various arsenite-treated cells. In this study, we identified that Vinexin, a CPEB4-interacting protein, is a novel component of SGs. Vinexin is a SH3-domain-containing adaptor protein and affects cell migration through its association with Vinculin to localize at focal adhesions (FAs. Unexpectedly, Vinexin is translocated from FAs to SGs under arsenite-induced stress. The recruitment of Vinexin to SGs depends on its interaction with CPEB4 and influences SG formation and cell survival. Arsenite-activated c-Jun N-terminal kinase (JNK signaling enhances the association between CPEB4 and Vinexin, which consequently facilitates SG localization of Vinexin. Taken together, this study uncovers a novel interaction between a translational regulator and an adaptor protein to influence SG assembly and cell survival.

  5. Arsenite-induced stress signaling: Modulation of the phosphoinositide 3′-kinase/Akt/FoxO signaling cascade

    Directory of Open Access Journals (Sweden)

    Ingrit Hamann

    2013-01-01

    Full Text Available FoxO transcription factors and their regulators in the phosphoinositide 3′-kinase (PI3K/Akt signaling pathway play an important role in the control of cellular processes involved in carcinogenesis, such as proliferation and apoptosis. We have previously demonstrated that physiologically relevant heavy metal ions, such as copper or zinc ions, can stimulate this pathway, triggering phosphorylation and nuclear export of FoxO transcription factors. The present study aims at investigating the effect of arsenite on FoxO transcription factors and the role of PI3K/Akt signaling therein. Exposure of HaCaT human keratinocytes to arsenite resulted in a distinct decrease of glutathione levels only at cytotoxic concentrations. In contrast, a strong phosphorylation of FoxO1a/FoxO3a and Akt was observed at subcytotoxic concentrations of arsenite in HaCaT human keratinocytes. A time- and concentration-dependent increase in phosphorylation of FoxO1a and FoxO3a at sites known to be phosphorylated by Akt as well as phosphorylation of Akt at Ser-473 was detected. These phosphorylations were blunted in the presence of wortmannin, pointing to the involvement of PI3K.

  6. Synthesis of Nano- alumina Powder from Impure Kaolin and its Application for Arsenite Removal from Aqueous Solutions

    Directory of Open Access Journals (Sweden)

    Ahmad Khodadadi Darban

    2013-07-01

    Full Text Available Adsorption is considered a cost-effective procedure, safer to handle with high removal efficiency. Activated alumina is the most commonly used adsorbent for the removal of arsenic from aqueous solutions. However, activated alumina has a low adsorption capacity and acts kinetically in a slow manner. An ideal adsorbent should have a high surface area, physical and/or chemical stability and be inexpensive. To meet this requirement, nanomeso porous γ-alumina with a high surface area (201.53 m2/g and small particle size (22–36 nm was prepared from inexpensive kaolin as the raw material, by precipitation method. The research results showed that adsorbent has the high adsorption capacity (for initial arsenite concentration up to 10 mg/L, in which 97.65% recovery was achieved. Optimal experimental conditions including pH, initial arsenite concentration and contact time were determined. Langmuir, Freundlich and Dubinin– Radushkevich isotherm models were applied to analyze the experimental data. The best interpretation for the experimental data was given by Langmuir adsorption isotherm equation and the maximum arsenite adsorbed by synthesized nano γ–alumina (qe was found to be 40 (mg/g.

  7. In vitro development of resistance to arsenite and chromium-VI in Lactobacilli strains as perspective attenuation of gastrointestinal disorder.

    Science.gov (United States)

    Upreti, Raj K; Sinha, Vartika; Mishra, Ritesh; Kannan, Ambrose

    2011-05-01

    Inadvertent intake of inorganic arsenic and chromium through drinking water and food causing their toxic insults is a major health problem. Intestinal bacteria including Lactobacilli play important regulatory roles on intestinal homeostasis, and their loss is known to cause gastrointestinal (GI) disorders. Probiotic Lactobacilli resistance to arsenite and chromium-VI could be an importantfactorfor the perspective attenuation of Gl-disorders caused by these toxic metals/metalloid. In the present study resistance of arsenite (up to 32 ppm), Cr-VI (up to 64 ppm), and arsenite plus Cr-VI (32 ppm each) were developed under in vitro condition following chronological chronic exposures in Lactobacilli strains. Comparative study of biochemical parameters such as membrane transport enzymes and structural constituents; dehydrogenase and esterase activity tests, which are respective indicators for respiratory and energy producing processes, and the general heterotrophic activity of cells, of resistant strains showed similarities with their respective normal parent strains. The resistant strains were also found to be sensitive to antibiotics. Findings indicate that these resistant probiotic Lactobacilli would be useful in the prophylactic interventions of arsenic and chromium GI-toxicity.

  8. Arsenite activates NFκB through induction of C-reactive protein

    Energy Technology Data Exchange (ETDEWEB)

    Druwe, Ingrid L.; Sollome, James J.; Sanchez-Soria, Pablo; Hardwick, Rhiannon N.; Camenisch, Todd D.; Vaillancourt, Richard R., E-mail: vaillancourt@pharmacy.arizona.edu

    2012-06-15

    C-reactive protein (CRP) is an acute phase protein in humans. Elevated levels of CRP are produced in response to inflammatory cytokines and are associated with atherosclerosis, hypertension, cardiovascular disease and insulin resistance. Exposure to inorganic arsenic, a common environmental toxicant, also produces cardiovascular disorders, namely atherosclerosis and is associated with insulin-resistance. Inorganic arsenic has been shown to contribute to cardiac toxicities through production of reactive oxygen species (ROS) that result in the activation of NFκB. In this study we show that exposure of the hepatic cell line, HepG2, to environmentally relevant levels of arsenite (0.13 to 2 μM) results in elevated CRP expression and secretion. ROS analysis of the samples showed that a minimal amount of ROS are produced by HepG2 cells in response to these concentrations of arsenic. In addition, treatment of FvB mice with 100 ppb sodium arsenite in the drinking water for 6 months starting at weaning age resulted in dramatically higher levels of CRP in both the liver and inner medullary region of the kidney. Further, mouse Inner Medullary Collecting Duct cells (mIMCD-4), a mouse kidney cell line, were stimulated with 10 ng/ml CRP which resulted in activation of NFκB. Pretreatment with 10 nM Y27632, a known Rho-kinase inhibitor, prior to CRP exposure attenuated NFκB activation. These data suggest that arsenic causes the expression and secretion of CRP and that CRP activates NFκB through activation of the Rho-kinase pathway, thereby providing a novel pathway by which arsenic can contribute to metabolic syndrome and cardiovascular disease. -- Highlights: ► Exposure to arsenic can induce the expression and secretion of CRP. ► Mice treated with NaAsO{sub 2} showed higher levels of CRP in both the liver and kidney. ► mIMCD-3 were stimulated with CRP which resulted in activation of NFκB. ► CRP activates NFκB through activation of the Rho-kinase pathway. ► Data

  9. Arsenite activates NFκB through induction of C-reactive protein

    International Nuclear Information System (INIS)

    C-reactive protein (CRP) is an acute phase protein in humans. Elevated levels of CRP are produced in response to inflammatory cytokines and are associated with atherosclerosis, hypertension, cardiovascular disease and insulin resistance. Exposure to inorganic arsenic, a common environmental toxicant, also produces cardiovascular disorders, namely atherosclerosis and is associated with insulin-resistance. Inorganic arsenic has been shown to contribute to cardiac toxicities through production of reactive oxygen species (ROS) that result in the activation of NFκB. In this study we show that exposure of the hepatic cell line, HepG2, to environmentally relevant levels of arsenite (0.13 to 2 μM) results in elevated CRP expression and secretion. ROS analysis of the samples showed that a minimal amount of ROS are produced by HepG2 cells in response to these concentrations of arsenic. In addition, treatment of FvB mice with 100 ppb sodium arsenite in the drinking water for 6 months starting at weaning age resulted in dramatically higher levels of CRP in both the liver and inner medullary region of the kidney. Further, mouse Inner Medullary Collecting Duct cells (mIMCD-4), a mouse kidney cell line, were stimulated with 10 ng/ml CRP which resulted in activation of NFκB. Pretreatment with 10 nM Y27632, a known Rho-kinase inhibitor, prior to CRP exposure attenuated NFκB activation. These data suggest that arsenic causes the expression and secretion of CRP and that CRP activates NFκB through activation of the Rho-kinase pathway, thereby providing a novel pathway by which arsenic can contribute to metabolic syndrome and cardiovascular disease. -- Highlights: ► Exposure to arsenic can induce the expression and secretion of CRP. ► Mice treated with NaAsO2 showed higher levels of CRP in both the liver and kidney. ► mIMCD-3 were stimulated with CRP which resulted in activation of NFκB. ► CRP activates NFκB through activation of the Rho-kinase pathway. ► Data provide

  10. Effects of sodium arsenite on skinkeratinocytes related gene expression%亚砷酸钠对皮肤细胞角化相关基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    李煜; 吴军; 郑玉建; 陈柔锦; 刘媛; 葛龙; 郎曼

    2016-01-01

    目的:探讨亚砷酸钠对人角质形成细胞角化相关因子 mRNA 表达的影响,为进一步阐述砷致皮肤角化机制的研究提供依据。方法用浓度为0.00(对照)、1.30、3.25、6.50μmol/L 的亚砷酸钠培养基培养 HaCaT 细胞24、48、72、96 h;采用 MTT 还原法检测细胞生长情况;采用实时荧光定量 PCR 法检测 HaCaT 细胞角蛋白1(Keratin1,K-1)、角蛋白10(Keratinl0,K-10)的 mRNA 的表达水平。结果(1)1.30μmol/L 的亚砷酸钠染毒能显著促进 HaCaT 细胞增殖,3.25μmol/L、6.50μmol/L 的亚砷酸钠染毒48 h 开始抑制 HaCaT 细胞的增殖,且与对照组相比差异均有统计学意义(P <0.05)。(2)1.30μmol/L 的亚砷酸钠染毒 HaCaT 细胞24 h 能促进 K1和 K10 mRNA 的表达上调,3.25μmol/L、6.50μmol/L 的亚砷酸钠染毒72 h 可使 HaCaT 细胞中 K1、K10 mRNA 的表达显著下调,且与对照组相比差异均有统计学意义(P <0.05)。结论亚砷酸钠浓度<1.30μmol/L 时,对人皮肤细胞的促增殖作用明显,促进皮肤角化进程;K1、K10的上调在皮肤细胞增殖和角化的过程中发挥一定作用。%Objective To investigate the effects of sodium arsenite on skin cell keratinocytes related gene expression and provide the basis for further elaboration for arsenic-caused skin keratinization mechanism. Methods The HaCaT cells were exposed to 0.00,1.30,3.25,6.25 μmol/L sodium arsenite for 24 h, 48 h,72 h,respectively.Then,cells growth status were measured with MTT colorimetric assay.Expres-sion levels of K1 and K10 mRNA are detected from HaCaT cells by real-time fluorescence quantitative (Real-Time Quantitative PCR).Results (1)1.30 μmol/L sodium arsenite can promote HaCaT cell prolif-eration.3.25 μmol/L,6.50 μmol/L sodium arsenite inhibited the growth of HaCaT cells after 48 h,and the difference was statistically significant (P <0.05)compared with

  11. Co-administration of sodium arsenite and ethanol: Protection by aqueous extract of Aframomum longiscapum seeds

    Directory of Open Access Journals (Sweden)

    Solomon E Owumi

    2012-01-01

    Full Text Available Background : Human exposure to arsenicals, its toxicity, subsequent adverse effects on health has been widely reported and implicated in the etiology of several cancers. Objectives : We investigated the effect of Aframomum longiscapum (AL extracts on sodium arsenite (SA and ethanol (EtOH-induced toxicities in rats. Materials and Methods : Male rats were fed SA, EtOH, and SA + EtOH, with or without AL for 5 weeks. Hepatic transaminases were assessed in serum, micronucleated polychromatic erythrocytes (mPCEs from bone marrow, liver histopathology, and semen quality from caudal epididymis were assessed, respectively, and data were represented as mean ± SD, analyzed by ANOVA. Results : SA, SA + EtOH, and AL alone induced mPCEs formation in rat bone marrow (P 0.05 across the treated groups. Hepatic histopathology indicated mild mononuclear cellular infiltration in the control group. Necrotic hepatocyte were observed in SA, SA + EtOH treated groups, with no visible lesions seen in the AL treated group. Mild hepatocyte congestion of the portal vessels was observed in AL + SA + EtOH-treated groups. Conclusion : The AL extract exhibited anticlastogenic and hepatoprotective potentials, reduced sperm count, motility, with no effect on viability and morphology. Our findings suggest that AL may mitigate the effect of arsenicals-induced clastogenicity implicated in chemical carcinogenesis.

  12. Development of a biosorbent for arsenite: structural modeling based on X-ray spectroscopy.

    Science.gov (United States)

    Teixeira, Monica Cristina; Ciminelli, Virginia S T

    2005-02-01

    This work describes a biological route for direct sorption of aqueous As(III) species, which are the most toxic and mobile arsenic species found in soils. Based upon the biochemical mechanisms that explain arsenic toxicity, we propose that a waste biomass with a high fibrous protein content obtained from chicken feathers can be used for selective As(III) adsorption. Prior to adsorption, the disulfide bridges present in the biomass are reduced by thioglycolate. Our investigations demonstrated that As(III) is specifically adsorbed on the biomass and, contrary to the behavior observed with inorganic sorbents, the lower is the pH the more effective is the removal. Arsenic uptake reaches values of up to 270 micromol As(III)/g of biomass. Analyses by synchrotron light techniques, such as XANES, demonstrated that arsenic is adsorbed in its trivalent state, an advantage over conventional techniques for As uptake, which usually require a previous oxidation stage. EXAFS analyses showed that each As atom is directly bound to three S atoms with an estimated distance of 2.26 A. The uptake mechanism is explained in terms of the structural similarities between the As(III)-biomass complex structure and that of arsenite ions and Ars-Operon system encoded proteins and phytochelatins. The biological route presented here offers the perspective of a direct removal of arsenic in its reduced form.

  13. Bacterial community succession during the enrichment of chemolithoautotrophic arsenite oxidizing bacteria at high arsenic concentrations

    Institute of Scientific and Technical Information of China (English)

    Nguyen Ai Le; Akiko Sato; Daisuke Inoue; Kazunari Sei; Satoshi Soda; Michihiko Ike

    2012-01-01

    To generate cost-effective technologies for the removal of arsenic from water,we developed an enrichment culture of chemolithoautotrophic arsenite oxidizing bacteria (CAOs) that could effectively oxidize widely ranging concentrations of As(Ⅲ) to As(Ⅴ).In addition,we attempted to elucidate the enrichment process and characterize the microbial composition of the enrichment culture.A CAOs enrichment culture capable of stably oxidizing As(Ⅲ) to As(Ⅴ) was successfully constructed through repeated batch cultivation for more than 700 days,during which time the initial As(Ⅲ) concentrations were increased in a stepwise manner from l to 10-12 mmol/L.As(Ⅲ) oxidation activity of the enrichment culture gradually improved,and 10-12 mmol/L As(Ⅲ) was almost completely oxidized within four days.Terminal restriction fragment length polymorphism analysis showed that the dominant bacteria in the enrichment culture varied drastically during the enrichment process depending on the As(Ⅲ) concentration.Isolation and characterization of bacteria in the enrichment culture revealed that the presence of multiple CAOs with various As(Ⅲ) oxidation abilities enabled the culture to adapt to a wide range of As(Ⅲ) concentrations.The CAOs enrichment culture constructed here may he useful for pretreatment of water from which arsenic is being removed.

  14. Polyphenols of Mangifera indica modulate arsenite-induced cytotoxicity in a human proximal tubule cell line

    Directory of Open Access Journals (Sweden)

    Gabino Garrido

    2012-04-01

    Full Text Available Inorganic arsenic is an ubiquitous environmental contaminant able to cause severe pathologies in humans, including kidney disorders. The possible protective effects of Mangifera indica L., Anacardiaceae, stem bark extract (MSBE and some mango phenols on the cytotoxicity of arsenite (AsIII in the proximal tubule cell line HK-2 was investigated. In cells cultured for 24 h in presence of AsIII, a dose-dependent loss of cell viability occurred that was significantly alleviated by MSBE, followed by gallic acid, catechin and mangiferin. Mangiferin complexed with Fe+++ proved more efficacious than mangiferin alone. MSBE and pure phenols increased significantly the cell surviving fraction in clonogenic assays. In cells pretreated with MSBE or phenols for 72 h the protection afforded by MSBE resulted decreased in comparison with the shorter experiments. Cells pretreated with a subcytotoxic amount of AsIII or cultured in continuous presence of low concentration of mangiferin proved to be more resistant to AsIII, while cells cultured in presence of albumin resulted more sensitive. Because all the above conditions share changes in expression/activity of P-glycoprotein (P-gp, a transporter potentially involved in arsenic resistance, the capability of M. indica phenols in modulating AsIII-induced cytotoxicity would be at least in part dependent on their interactions with P-gp.

  15. Arsenic Methylation in Arabidopsis thaliana Expressing an Algal Arsenite Methyltransferase Gene Increases Arsenic Phytotoxicity.

    Science.gov (United States)

    Tang, Zhong; Lv, Yanling; Chen, Fei; Zhang, Wenwen; Rosen, Barry P; Zhao, Fang-Jie

    2016-04-01

    Arsenic (As) contamination in soil can lead to elevated transfer of As to the food chain. One potential mitigation strategy is to genetically engineer plants to enable them to transform inorganic As to methylated and volatile As species. In this study, we genetically engineered two ecotypes of Arabidopsis thaliana with the arsenite (As(III)) S-adenosylmethyltransferase (arsM) gene from the eukaryotic alga Chlamydomonas reinhardtii. The transgenic A. thaliana plants gained a strong ability to methylate As, converting most of the inorganic As into dimethylarsenate [DMA(V)] in the shoots. Small amounts of volatile As were detected from the transgenic plants. However, the transgenic plants became more sensitive to As(III) in the medium, suggesting that DMA(V) is more phytotoxic than inorganic As. The study demonstrates a negative consequence of engineered As methylation in plants and points to a need for arsM genes with a strong ability to methylate As to volatile species. PMID:26998776

  16. Simultaneous arsenite oxidation and nitrate reduction at the electrodes of bioelectrochemical systems.

    Science.gov (United States)

    Nguyen, Van Khanh; Park, Younghyun; Yu, Jaecheul; Lee, Taeho

    2016-10-01

    Arsenic and nitrate contaminations in the soil and groundwater have urged the scientific community to explore suitable technologies for treatment of both contaminants. This study reports, for the first time, a novel application of bioelectrochemical systems for coupling As detoxification at the anode and denitrification at the cathode. A similar As(III) oxidation efficiency was achieved when anode potential was controlled by a potentiostat or a direct current (DC) power supply. However, a slightly lower nitrate reduction rate was obtained in reactors using DC power supply during simultaneous operation of nitrate reduction and As(III) oxidation. Microbial community analysis by denaturing gradient gel electrophoresis indicated the presence of some autotrophic As(III)-oxidizing bacteria, including Achromobacter spp., Ensifer spp., and Sinorhizobium spp., that can flexibly switch their original metabolism of using oxygen as sole electron acceptor to a new metabolism mode of using solid-state anode as sole electron acceptor driving for As(III) oxidation under anaerobic conditions. Although further research is required for validating their applicability, bioelectrochemical systems represent a brilliant technology for remediation of groundwater contaminated with nitrate and/or arsenite. PMID:27438874

  17. Metalloid tolerance based on phytochelatins is not functionally equivalent to the arsenite transporter Acr3p.

    Science.gov (United States)

    Wysocki, Robert; Clemens, Stephan; Augustyniak, Daria; Golik, Pawel; Maciaszczyk, Ewa; Tamás, Markus J; Dziadkowiec, Dorota

    2003-05-01

    Active transport of metalloids by Acr3p and Ycf1p in Saccharomyces cerevisiae and chelation by phytochelatins in Schizosaccharomyces pombe, nematodes, and plants represent distinct strategies of metalloid detoxification. In this report, we present results of functional comparison of both resistance mechanisms. The S. pombe and wheat phytochelatin synthase (PCS) genes, when expressed in S. cerevisiae, mediate only modest resistance to arsenite and thus cannot functionally compensate for Acr3p. On the other hand, we show for the first time that phytochelatins also contribute to antimony tolerance as PCS fully complement antimonite sensitivity of ycf1Delta mutant. Remarkably, heterologous expression of PCS sensitizes S. cerevisiae to arsenate, while ACR3 confers much higher arsenic resistance in pcsDelta than in wild-type S. pombe. The analysis of PCS and ACR3 homologues distribution in various organisms and our experimental data suggest that separation of ACR3 and PCS genes may lead to the optimal tolerance status of the cell.

  18. Adsorption of Arsenite by Six Submerged Plants from Nansi Lake, China

    Directory of Open Access Journals (Sweden)

    Zhibin Zhang

    2014-01-01

    Full Text Available Nansi Lake is the largest and the most important freshwater lake in north China for the South-North Water Transfer Project. Due to long-time and large-scale fish farming of history, the excess fish food and excretion usually release pentavalent arsenic, which is converted into trivalent arsenic (As (III in the lake sediment and released into lake water. Adsorption of arsenite using six submerged plants (Mimulicalyx rosulatus, Potamogeton maackianus, Hydrilla, Watermifoil, Pteris vittata, and Potamogeton crispus as adsorbing materials was investigated. The experimental data obtained have been analyzed using Langmuir, Freundlich, and Dubinin-Radushkevich isotherm models and the pseudo-first-order, pseudo-second-order, and intraparticle diffusion kinetics models. According to the results, the As (III equilibrium data agreed well with the Freundlich isotherm model. The adsorption capacity of the plants was in the following order: Potamogeton crispus > Pteris vittata > Potamogeton maackianus > Mimulicalyx rosulatus > Hydrilla > Watermifoil. The sorption system with the six submerged plants was better described by pseudo-second-order than by first-order kinetics. Moreover, the adsorption with Potamogeton crispus could follow intraparticle diffusion (IPD model. The initial adsorption and rate of IPD using Potamogeton crispus and Pteris vittata were higher than those using other plants studied.

  19. Brevilin A, a novel natural product, inhibits janus kinase activity and blocks STAT3 signaling in cancer cells.

    Directory of Open Access Journals (Sweden)

    Xing Chen

    Full Text Available Signal abnormalities in human cells usually cause unexpected consequences for individual health. We focus on these kinds of events involved in JAK-STAT signal pathways, especially the ones triggered by aberrant activated STAT3, an oncoprotein which participates in essential processes of cell survival, growth and proliferation in many types of tumors, as well as immune diseases. By establishing a STAT3 signal based high-throughput drug screening system in human lung cancer A549 cells, we have screened a library from natural products which contained purified compounds from medicinal herbs. One compound, named Brevilin A, exhibited both strong STAT3 signal inhibition and STAT3 signal dependent cell growth inhibition. Further investigations revealed that Brevilin A not only inhibits STAT3 signaling but also STAT1 signaling for cytokines induced phosphorylation of STAT3 and STAT1 as well as the expression of their target genes. In addition, we found Brevilin A could attenuate the JAKs activity by blocking the JAKs tyrosine kinase domain JH1. The levels of cytokine induced phosphorylation of STATs and other substrates were dramatically reduced by treatment of Brevilin A. The roles of Brevilin A targeting on JAKs activity indicate that Brevilin A may not only be used as a STAT3 inhibitor but also a compound blocking other JAK-STAT hyperactivation. Thus, these findings provided a strong impetus for the development of selective JAK-STAT inhibitors and therapeutic drugs in order to improve survival of patients with hyperactivated JAKs and STATs.

  20. Effects of Arsenite Resistance on the Growth and Functional Gene Expression of Leptospirillum ferriphilum and Acidithiobacillus thiooxidans in Pure Culture and Coculture.

    Science.gov (United States)

    Jiang, Huidan; Liang, Yili; Yin, Huaqun; Xiao, Yunhua; Guo, Xue; Xu, Ying; Hu, Qi; Liu, Hongwei; Liu, Xueduan

    2015-01-01

    The response of iron-oxidizing Leptospirillum ferriphilum YSK and sulfur-oxidizing Acidithiobacillus thiooxidans A01 to arsenite under pure culture and coculture was investigated based on biochemical characterization (concentration of iron ion and pH value) and related gene expression. L. ferriphilum YSK and At. thiooxidans A01 in pure culture could adapt up to 400 mM and 800 mM As(III) after domestication, respectively, although arsenite showed a negative effect on both strains. The coculture showed a stronger sulfur and ferrous ion oxidation activity when exposed to arsenite. In coculture, the pH value showed no significant difference when under 500 mM arsenite stress, and the cell number of At. thiooxidans was higher than that in pure culture benefiting from the interaction with L. ferriphilum. The expression profile showed that the arsenic efflux system in the coculture was more active than that in pure culture, indicating that there is a synergetic interaction between At. thiooxidans A01 and L. ferriphilum YSK. In addition, a model was proposed to illustrate the interaction between arsenite and the ars operon in L. ferriphilum YSK and At. thiooxidans A01. This study will facilitate the effective application of coculture in the bioleaching process by taking advantage of strain-strain communication and coordination.

  1. Effects of Arsenite Resistance on the Growth and Functional Gene Expression of Leptospirillum ferriphilum and Acidithiobacillus thiooxidans in Pure Culture and Coculture

    Directory of Open Access Journals (Sweden)

    Huidan Jiang

    2015-01-01

    Full Text Available The response of iron-oxidizing Leptospirillum ferriphilum YSK and sulfur-oxidizing Acidithiobacillus thiooxidans A01 to arsenite under pure culture and coculture was investigated based on biochemical characterization (concentration of iron ion and pH value and related gene expression. L. ferriphilum YSK and At. thiooxidans A01 in pure culture could adapt up to 400 mM and 800 mM As(III after domestication, respectively, although arsenite showed a negative effect on both strains. The coculture showed a stronger sulfur and ferrous ion oxidation activity when exposed to arsenite. In coculture, the pH value showed no significant difference when under 500 mM arsenite stress, and the cell number of At. thiooxidans was higher than that in pure culture benefiting from the interaction with L. ferriphilum. The expression profile showed that the arsenic efflux system in the coculture was more active than that in pure culture, indicating that there is a synergetic interaction between At. thiooxidans A01 and L. ferriphilum YSK. In addition, a model was proposed to illustrate the interaction between arsenite and the ars operon in L. ferriphilum YSK and At. thiooxidans A01. This study will facilitate the effective application of coculture in the bioleaching process by taking advantage of strain-strain communication and coordination.

  2. Effects of proliferation and apoptosis induced by sodium arsenite in Chang liver cells%亚砷酸钠对Chang肝细胞增殖与凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    牛姜水; 马艳; 符文慧; 郑玉建

    2012-01-01

    Objective To explore the effect of sodium arsenite on the proliferation and apoptosis of human hepatocyte cell line Chang in vitro. Methods After the Chang liver cells were treated with different concentrations of sodium arsenite (0-100 μmol/L) for 24, 48, 72 and 96 h in vitro, the proliferation of Chang liver cells was determined by MTT assay; The apoptosis rate of Chang liver cells in 48 h was identified by flow cytometry assay. Results Only the activity of Chang liver cells induced by 0.2 mol/L sodium arsenite was higher than normal groups after 24 h-treatment, but the difference was not significant. With the increase of exposure concentration and time, the Chang liver cells survival percentage showed a decreased tendency with a time and dose dependent manner. Compared with the normal group,the apoptosis rates of Chang liver cells significantly increased at 5-100 μmol/L (P<0.05); and when the drug concentration increased, the apoptosis rates of Chang liver cells showed an increasing tendency with a time-dose dependent manner. Conclusion Sodium arsenite has cytotoxicity to Chang liver cells, and it can inhibit the proliferation of cells, which may be involved in the process of apoptosis.%目的 探讨亚砷酸钠对正常人Chang肝细胞体外增殖及凋亡的影响.方法 采用0(对照)~100 μmol/L亚砷酸钠分别处理细胞24、48、72、96 h.采用MTT比色法检测细胞活力;采用流式细胞术检测染毒48 h时的细胞凋亡率.结果 仅0.2μmol/L亚砷酸钠染毒24 h的细胞活力略高于对照组,但差异无统计学意义;且随着亚砷酸钠染毒浓度的升高和染毒时间的延长,Chang肝细胞存活率均呈下降趋势,并具有剂量-效应和时间-效应关系.与对照组相比较,5~100 μmol/L亚砷酸钠染毒组Chang肝细胞凋亡率均显著升高,差异有统计学意义(P<0.05);且随着亚砷酸钠染毒浓度的升高,Chang肝细胞的凋亡率呈显著升高趋势,并具

  3. Effect of sodium arsenite on telomerase activity of human lung carcinoma Spc-A1 cells%亚砷酸钠对人肺癌Spc-A1细胞端粒酶活性的影响

    Institute of Scientific and Technical Information of China (English)

    施睿; 梁标

    2012-01-01

    目的:研究亚砷酸钠( NaAsO2)对人肺癌Spc-A1细胞株端粒酶活性及其催化亚单位hTERT表达的影响,探讨其抗癌机制.方法:四甲基偶氮唑蓝法(MTT)检测亚砷酸钠对Spc-A1细胞增殖的抑制作用;端粒酶活性采用端粒末端重复序列扩增-酶联免疫吸附法(TRAP-ELISA)测定;端粒酶催化亚单位hTERT mRNA表达采用反转录聚合酶链式反应法(RT-PCR)测定.结果:亚砷酸钠对人肺癌细胞株Spc-A1的增殖具有一定程度的抑制作用.在12h、24h和48h三个时间段均可见Spc-A1细胞端粒酶活性随着药物浓度的增加逐渐下降.并且,hTERT mRNA表达下调与端粒酶活性下降一致.结论:亚砷酸钠对Spc-A1细胞的增殖具有一定的抑制作用,下调癌细胞hTERT mRNA的表达来抑制端粒酶活性可能是其中一种机制.%Objective;To investigate the posssibLe anticarcinogenic mechanisms by studying the effect of sodium arsenite ( NaAsO2 ) on telomerase activity and human telomerase reverse transcriptase ( hTERE) gene expression of hu-man lung carcinoma Spc -Al cells. Methods: MTT ( Methyl Thiazolyl Tetrazolium) assay was used to determine the growth inhibition by sodium arsenite in Spc - Al cells. Telomerase activity was examined by telomeric repeat amplifi-cation protocol ELISA(TRAP - ELISA) . Expression of hTERE was assessed by reverse transcription polymerase chain reaction ( RT - PCR) . Results: NaAsO2 could inhibit the proliferation of Spc - Al cells in some degree. Elomerase ac-tivity of Spc - Al cells was declined gradually when the concentrations of NaAsO2 increased from 1 μg/ml to 2μg/ml to 4μg/ml during the period of 12h,24h and 48h respectively. And the down - regulation of expression of hTERTmR-NA was consistent with the change of telomerase activity. Conclusion: Sodium arsenite could obviously inhibit the pro-liferation of SPC - A - 1 cell. The inhibition of telomerase activity through decreasing expression of hTERT may be one of mechanisms.

  4. Modulatory of effect of fresh Amaranthus caudatus and Amaranthus hybridus aqueous leaf extracts on detoxify enzymes and micronuclei formation after exposure to sodium arsenite.

    Science.gov (United States)

    Adewale, Adetutu; Olorunju, Awe Emmanuel

    2013-10-01

    Vegetables are the cheapest and most available sources of important proteins, minerals, vitamins, and essential amino protein. These vegetables are commonly used in Africa for the treatment of illness. This study evaluated the protective effects of Amaranthus caudatus and A. hybridus against sodium arsenite-induced toxicity in rats. The effects of sodium arsenite and/or the plant extracts were assessed using bone marrow micronucleus assay and by measuring the activities of tumour maker enzymes such as gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP) in white albino Wister rats. The study showed that sodium arsenite significantly (P rats and were reverted back to near normal levels in rats pretreated with the plant extracts. A. caudatus and A. hybridus showed significant role in protecting the detoxifying enzymes; also, A. caudatus has a more protective effect on reducing the micronuclei formation when compared with A. hybridus. This study suggests that A. caudatus and A. hybridus possess anticarcinogenic effect. PMID:24174825

  5. Inhibition of tumor necrosis factor-α-induced expression of adhesion molecules in human endothelial cells by the saponins derived from roots of Platycodon grandiflorum

    International Nuclear Information System (INIS)

    Adhesion molecules play an important role in the development of atherogenesis and are produced by endothelial cells after being stimulated with various inflammatory cytokines. This study examined the effect of saponins that were isolated from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil saponins (CKS), on the cytokine-induced monocyte/human endothelial cell interaction, which is a crucial early event in atherogenesis. CKS significantly inhibited the TNFα-induced increase in monocyte adhesion to endothelial cells as well as decreased the protein and mRNA expression levels of vascular adhesion molecule-1 and intercellular cell adhesion molecule-1 on endothelial cells. Furthermore, CKS significantly inhibited the TNFα-induced production of intracellular reactive oxygen species (ROS) and activation of NF-κB by preventing IκB degradation and inhibiting IκB kinase activity. Overall, CKS has anti-atherosclerotic and anti-inflammatory activity, which is least in part the result of it reducing the cytokine-induced endothelial adhesion to monocytes by inhibiting intracellular ROS production, NF-κB activation, and cell adhesion molecule expression in endothelial cells

  6. Arsenite and its metabolites, MMAIII and DMAIII, modify CYP3A4, PXR and RXR alpha expression in the small intestine of CYP3A4 transgenic mice

    International Nuclear Information System (INIS)

    Arsenic is an environmental pollutant that has been associated with an increased risk for the development of cancer and several other diseases through alterations of cellular homeostasis and hepatic function. Cytochrome P450 (P450) modification may be one of the factors contributing to these disorders. Several reports have established that exposure to arsenite modifies P450 expression by decreasing or increasing mRNA and protein levels. Cytochrome P450 3A4 (CYP3A4), the predominant P450 expressed in the human liver and intestines, which is regulated mainly by the Pregnane X Receptor-Retinoid X Receptor alpha (PXR-RXR alpha) heterodimer, contributes to the metabolism of approximately half the drugs in clinical use today. The present study investigates the effect of sodium arsenite and its metabolites monomethylarsonous acid (MMAIII) and dimethylarsinous acid (DMAIII) on CYP3A4, PXR, and RXR alpha expression in the small intestine of CYP3A4 transgenic mice. Sodium arsenite treatment increases mRNA, protein and CYP3A4 activity in a dose-dependent manner. However, the increase in protein expression was not as marked as compared to the increase in mRNA levels. Arsenite treatment induces the accumulation of Ub-protein conjugates, indicating that the activation of this mechanism may explain the differences observed between the mRNA and protein expression of CYP3A4 induction. Treatment with 0.05 mg/kg of DMAIII induces CYP3A4 in a similar way, while treatment with 0.05 mg/kg of MMAIII increases mostly mRNA, and to a lesser degree, CYP3A4 activity. Sodium arsenite and both its metabolites increase PXR mRNA, while only DMAIII induces RXR alpha expression. Overall, these results suggest that sodium arsenite and its metabolites induce CYP3A4 expression by increasing PXR expression in the small intestine of CYP3A4 transgenic mice.

  7. Effects of exogenous glutathione on arsenic burden and NO metabolism in brain of mice exposed to arsenite through drinking water

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yan [China Medical University, Department of Environmental and Occupational Health, School of Public Health, Heping District, Shenyang, Liaoning (China); Liaoning University of Traditional Chinese Medicine, Department of Public Health Management, School of Professional Technology, Shenyang, Liaoning (China); Zhao, Fenghong; Jin, Yaping; Zhong, Yuan; Yu, Xiaoyun; Li, Gexin; Lv, Xiuqiang; Sun, Guifan [China Medical University, Department of Environmental and Occupational Health, School of Public Health, Heping District, Shenyang, Liaoning (China)

    2011-03-15

    Chronic exposure to inorganic arsenic (iAs) is associated with neurotoxicity. Studies to date have disclosed that methylation of ingested iAs is the main metabolic pathway, and it is a process relying on reduced glutathione (GSH). The aim of this study was to explore the effects of exogenous GSH on arsenic burden and metabolism of nitric oxide (NO) in the brain of mice exposed to arsenite via drinking water. Mice were exposed to sodium arsenite through drinking water contaminated with 50 mg/L arsenic for 4 weeks and treated intraperitoneally with saline solution, 200 mg/kg body weight (b.w), 400 mg/kg b.w, or 800 mg/kg b.w GSH, respectively, at the 4th week. Levels of iAs, monomethylarsenic acid, and dimethylarsenic acid (DMAs) in the liver, blood, and brain were determined by method of hydride generation coupled with atomic absorption spectrophotometry. Activities of nitric oxide synthase (NOS) and contents of NO in the brain were determined by colorimetric method. Compared with mice exposed to arsenite alone, administration of GSH increased dose-dependently the primary and secondary methylation ratio in the liver, which caused the decrease in percent iAs and increase in percent DMAs in the liver, as a consequence, resulted in significant decrease in iAs levels in the blood and total arsenic levels in both blood and brain. NOS activities and NO levels in the brain of mice in iAs group were significantly lower than those in control; however, administration of GSH could increase significantly activities of NOS and contents of NO. Findings from this study suggested that exogenous GSH could promote both primary and secondary arsenic methylation capacity in the liver, which might facilitate excretion of arsenicals, and consequently reduce arsenic burden in both blood and brain and furthermore ameliorate the effects of arsenicals on NO metabolism in the brain. (orig.)

  8. Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish

    International Nuclear Information System (INIS)

    Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic–pituitary–thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h. Result indicated that exposure to AsIII increased inorganic As in zebrafish to 0.46–0.72 mg kg−1, induced oxidative stress with H2O2 being increased by 1.4–2.5 times and caused oxidative damage with MDA being augmented by 1.6 times. AsIII exposure increased thyroxine levels by 1.3–1.4 times and modulated gene transcription in HPT axis. Our study showed AsIII caused oxidative damage, affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish. - Highlights: • 48 h-LC50 value of arsenite (AsIII) was 42 mg L−1 for zebrafish. • AsIII exposure elevated oxidative stress and caused oxidative damage in zebrafish. • AsIII exposure increased the content of thyroid hormone thyroxine. • AsIII exposure altered gene transcription in the HPT axis in zebrafish. - Short-term exposure of arsenite caused oxidative stress, disrupted thyroid endocrine system and altered gene transcription in the HPT axis in Zebrafish

  9. An aquaporin PvTIP4;1 from Pteris vittata may mediate arsenite uptake.

    Science.gov (United States)

    He, Zhenyan; Yan, Huili; Chen, Yanshan; Shen, Hongling; Xu, Wenxiu; Zhang, Haiyan; Shi, Lei; Zhu, Yong-Guan; Ma, Mi

    2016-01-01

    The fern Pteris vittata is an arsenic hyperaccumulator. The genes involved in arsenite (As(III)) transport are not yet clear. Here, we describe the isolation and characterization of a new P. vittata aquaporin gene, PvTIP4;1, which may mediate As(III) uptake. PvTIP4;1 was identified from yeast functional complement cDNA library of P. vittata. Arsenic toxicity and accumulating activities of PvTIP4;1 were analyzed in Saccharomyces cerevisiae and Arabidopsis. Subcellular localization of PvTIP4;1-GFP fusion protein in P. vittata protoplast and callus was conducted. The tissue expression of PvTIP4;1 was investigated by quantitative real-time PCR. Site-directed mutagenesis of the PvTIP4;1 aromatic/arginine (Ar/R) domain was studied. Heterologous expression in yeast demonstrates that PvTIP4;1 was able to facilitate As(III) diffusion. Transgenic Arabidopsis showed that PvTIP4;1 increases arsenic accumulation and induces arsenic sensitivity. Images and FM4-64 staining suggest that PvTIP4;1 localizes to the plasma membrane in P. vittata cells. A tissue location study shows that PvTIP4;1 transcripts are mainly expressed in roots. Site-directed mutation in yeast further proved that the cysteine at the LE1 position of PvTIP4;1 Ar/R domain is a functional site. PvTIP4;1 is a new represented tonoplast intrinsic protein (TIP) aquaporin from P. vittata and the function and location results imply that PvTIP4;1 may be involved in As(III) uptake.

  10. Comparison of four extraction procedures to assess arsenate and arsenite species in contaminated soils

    Energy Technology Data Exchange (ETDEWEB)

    Giral, Melanie [Department of Civil, Geological and Mining Engineering, Ecole Polytechnique de Montreal, P.O. Box 6079, Station Centre-Ville, Montreal, Quebec H3C 3A7 (Canada); Zagury, Gerald J., E-mail: gerald.zagury@polymtl.c [Department of Civil, Geological and Mining Engineering, Ecole Polytechnique de Montreal, P.O. Box 6079, Station Centre-Ville, Montreal, Quebec H3C 3A7 (Canada); Deschenes, Louise [The Interuniversity Research Centre for the Life Cycle of Products, Processes and Services (CIRAIG), Department of Chemical Engineering, Ecole Polytechnique de Montreal, P.O. Box 6079, Station Centre-Ville, Montreal, Quebec H3C 3A7 (Canada); Blouin, Jean-Pierre [Centre d' expertise en analyse environnementale du Quebec, Ministere de l' Environnement, du Developpement Durable et des Parcs, 850, boulevard Vanier, Laval, Quebec H7C 2M7 (Canada)

    2010-05-15

    Inorganic arsenic in soils poses an important environmental concern. Several studies reported an oxidation of arsenite to arsenate during its extraction from soils. The objectives of this study were to (1) identify, among published procedures, an extraction method which preserves the oxidation state of arsenic and (2) to assess the influence of soil physicochemical properties on the performance of these methods. Four extraction strategies were compared: 1) 10 M HCl, 2) 15% (v/v) H{sub 3}PO{sub 4}, 3) 10 mM phosphate + 0.5% (w/v) NaDDC, and, 4) 1 M H{sub 3}PO{sub 4} + 0.5 M ascorbic acid (C{sub 6}H{sub 8}O{sub 6}). Separation and analysis of As species was performed by HPLC-ICP/MS. Oxidation of As(III) into As(V) during extraction was more important in soils with high content of Mn oxides. Extraction of arsenic from soils with 1 M H{sub 3}PO{sub 4} + 0.5 M C{sub 6}H{sub 8}O{sub 6} under microwaves was the best strategy to extract the majority of As while minimizing conversion of As(III) into As(V). - Extraction of arsenic from soils with 1 M H{sub 3}PO{sub 4} + 0.5 M C{sub 6}H{sub 8}O{sub 6} under microwaves is a suitable method to extract the majority of As while minimizing conversion of As(III) into As(V).

  11. An aquaporin PvTIP4;1 from Pteris vittata may mediate arsenite uptake.

    Science.gov (United States)

    He, Zhenyan; Yan, Huili; Chen, Yanshan; Shen, Hongling; Xu, Wenxiu; Zhang, Haiyan; Shi, Lei; Zhu, Yong-Guan; Ma, Mi

    2016-01-01

    The fern Pteris vittata is an arsenic hyperaccumulator. The genes involved in arsenite (As(III)) transport are not yet clear. Here, we describe the isolation and characterization of a new P. vittata aquaporin gene, PvTIP4;1, which may mediate As(III) uptake. PvTIP4;1 was identified from yeast functional complement cDNA library of P. vittata. Arsenic toxicity and accumulating activities of PvTIP4;1 were analyzed in Saccharomyces cerevisiae and Arabidopsis. Subcellular localization of PvTIP4;1-GFP fusion protein in P. vittata protoplast and callus was conducted. The tissue expression of PvTIP4;1 was investigated by quantitative real-time PCR. Site-directed mutagenesis of the PvTIP4;1 aromatic/arginine (Ar/R) domain was studied. Heterologous expression in yeast demonstrates that PvTIP4;1 was able to facilitate As(III) diffusion. Transgenic Arabidopsis showed that PvTIP4;1 increases arsenic accumulation and induces arsenic sensitivity. Images and FM4-64 staining suggest that PvTIP4;1 localizes to the plasma membrane in P. vittata cells. A tissue location study shows that PvTIP4;1 transcripts are mainly expressed in roots. Site-directed mutation in yeast further proved that the cysteine at the LE1 position of PvTIP4;1 Ar/R domain is a functional site. PvTIP4;1 is a new represented tonoplast intrinsic protein (TIP) aquaporin from P. vittata and the function and location results imply that PvTIP4;1 may be involved in As(III) uptake. PMID:26372374

  12. Arsenite Removal from Simulated Groundwater by Biogenic Schwertmannite: A Column Trial

    Institute of Scientific and Technical Information of China (English)

    XIE Yue; ZHOU Li-Xiang

    2013-01-01

    To assess the feasibility of biogenic schwertmannite to act as a sorbent for removing arsenite from groundwater,a series of biogenic schwertmannite-packed column adsorption experiments were conducted on simulated As(Ⅲ)-containing groundwater.Empty bed contact time (EBCT),As(Ⅲ) concentration in effluent,and the removal efficiency of As(Ⅲ) through the column were investigated at pH 8.0 and temperature 25 ± 0.5 ℃.The results showed that the breakthrough curves were mainly dependent on EBCT values when the influent As(Ⅲ) concentration was 500 μg L-1 and the optimum EBCT was 4.0 min.When the effluent As(Ⅲ) concentration reached 10 and 50 μg L-1,the breakthrough volumes for the schwertmannite adsorption column were 4200 and 5600 bed volume (BV),with As(Ⅲ) adsorption capacity of 2.1 and 2.8 mg g-1,respectively.Biogenic schwertmannite could be regenerated by 1.0 mol L-1 NaOH solution,and more than 80% of As(Ⅲ) adsorbed on the surface of schwertmannite could be released after 3 successive regenerations.The breakthrough volume for the regenerated schwertmannite-packed column still maintained 4 000-4 200 BV when the As(Ⅲ) concentration in effluent was below 10 μg L-1.Compared with other sorbents for As(Ⅲ) removal,the biogenic schwertmannitepacked column had a higher breakthrough volume and a much higher adsorption capacity,implying that biogenic schwertmannite was a highly efficient and potential sorbent to purify As(Ⅲ)-contaminated groundwater.

  13. Sodium Arsenite Caused Mineralization Impairment in Rat Bone Marrow Mesenchymal Stem Cells Differentiating to Osteoblasts

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Abnosi

    2012-05-01

    Full Text Available Background: Sodium arsenite (SA recently has been recommended to be used in malignancy therapy. Our studies showed, SA in short and long period of treatment caused reduction of rats Bone Marrow Mesenchymal Stem Cells (MSCs viability and induced caspase dependent apoptosis. The aim of this study was to investigate the effect of SA on osteogenic differentiation of MSCs. Methods: MSCs were extracted and expanded to third passage, then cultured in DMEM supplemented with osteogenic media in presence of 1 and 25nM of SA for 21 days. The viability and the level of mineralization were determined using MTT assay and alizarin red respectively. In addition morphology and nuclear diameter of the cells were studied with the help of fluorescent dye. Furthermore, calcium content and alkalinphosphatase activity also were estimated using commercial kit. Data was statistically analyzed and the P<0.05 was taken as the level of significant. Results: The viability and mineralization of the cells treated with SA reduced significantly (P<0.05 after tenth day in compare with control. Also, chromatin condensation, reduction of nuclei diameter and cytoplasm shrinkage were observed in the cell treated with 1 and 25 nM concentrations. The calcium and alkalinphosphatase activity of the cells decreased significantly with 1 and 25 nM concentrations of SA when compared with control. Conclusion: Adverse effect of SA was observed on osteogenic differentiation of MSCs at 1 and 25 nM due to disruption of mineralization. We strongly suggest more investigation to be run on this chemical with respect to the therapy of the malignant patients.

  14. Quantitative detection of nitric oxide (NO) in apoptosis of esophagealcarcinoma cell induced by arsenite

    Institute of Scientific and Technical Information of China (English)

    Zhong Ying Shen; Wen Ying Shen; Ming Hua Chen; Chao Qun Hong; Jian Shen

    2000-01-01

    AIM To determine NO, NO synthase (NOS) and NOSmRNA of the esophageal carcinoma cells (SHEEC1)in apoptotic process induced by As2O3 and to explore the relationship between NO and apoptosis.METHODS The apoptosis of the cell line (SHEEC1) was induced by arsenite (As2O3, 5 μmol/L and10 μmol/L). In the process, at 2 h, 4 h, 8 h, 16 h and 24 h after administration of As2O3, NO production incultural medium was detected quantitatively by spectrophotometry; NOS Ⅱ was detected byimmunohistochemistry and NOS mRNA by in situ hybridization (ISH). The cells at endpoint of theexperiment were examined under transmitted electron microscope (TEM) for apoptosis.RESULTS The amount of NO released from SHEEC1 were increased from the basal condition (0.68×10-2μmol/L) up to the high level (2.38×10-2μmol/L) at h 16. The increment of NOS Ⅱ was found afteradministration of As2O3; the intracytoplasmic ISH signals of NOSmRNA in small size was found firstly at4 h, and then became highly predominant. Apoptotic changes of SHEEC1 occurred at 24 h under TEM.CONCLUSION After administration of As2O3, NO released from cultured SHEEC1 cells was detected withincreasing amount up to 16 h. The expression of NOS H and transcription of NOSmRNA are upregulated.The present findings suggest a concept that the NO may be a mediated and effective factor in apoptosisinduced by As2O3,

  15. Arsenite tolerance is related to proportional thiolic metabolite synthesis in rice (Oryza sativa L.).

    Science.gov (United States)

    Dave, Richa; Singh, Pradyumna Kumar; Tripathi, Preeti; Shri, Manju; Dixit, Garima; Dwivedi, Sanjay; Chakrabarty, Debasis; Trivedi, Prabodh Kumar; Sharma, Yogesh Kumar; Dhankher, Om Prakash; Corpas, Francisco Javier; Barroso, Juan B; Tripathi, Rudra Deo

    2013-02-01

    Thiol metabolism is the primary detoxification strategy by which rice plants tolerate arsenic (As) stress. In light of this, it is important to understand the importance of harmonised thiol metabolism with As accumulation and tolerance in rice plant. For this aim, tolerant (T) and sensitive (S) genotypes were screened from 303 rice (Oryza sativa) genotypes on exposure to 10 and 25 μM arsenite (As(III)) in hydroponic culture. On further As accumulation estimation, contrasting (13-fold difference) T (IC-340072) and S (IC-115730) genotypes were selected. This difference was further evaluated using biochemical and molecular approaches to understand involvement of thiolic metabolism vis-a-vis As accumulation in these two genotypes. Various phytochelatin (PC) species (PC(2), PC(3) and PC(4)) were detected in both the genotypes with a dominance of PC(3). However, PC concentrations were greater in the S genotype, and it was noticed that the total PC (PC(2) + PC(3 )+ PC(4))-to-As(III) molar ratio (PC-SH:As(III)) was greater in T (2.35 and 1.36 in shoots and roots, respectively) than in the S genotype (0.90 and 0.15 in shoots and roots, respectively). Expression analysis of several metal(loid) stress-related genes showed significant upregulation of glutaredoxin, sulphate transporter, and ascorbate peroxidase in the S genotype. Furthermore, enzyme activity of phytochelatin synthase and cysteine synthase was greater on As accumulation in the S compared with the T genotype. It was concluded that the T genotype synthesizes adequate thiols to detoxify metalloid load, whereas the S genotype synthesizes greater but inadequate levels of thiols to tolerate an exceedingly greater load of metalloids, as evidenced by thiol-to-metalloid molar ratios, and therefore shows a phytotoxicity response.

  16. Regulation of Arsenite Oxidation by the Phosphate Two-Component System PhoBR in Halomonas sp. HAL1

    OpenAIRE

    Fang eChen; Yajing eCao; Sha eWei; Yanzhi eLi; Xiangyang eLi; Qian eWang; Gejiao eWang

    2015-01-01

    Previously, the expression of arsenite [As(III)] oxidase genes aioBA was reported to be regulated by a three-component regulatory system, AioXSR, in a number of As(III)-oxidizing bacterial strains. However, the regulation mechanism is still unknown when aioXSR genes are absent in some As(III)-oxidizing bacterial genomes, such as in Halomonas sp. HAL1. In this study, transposon mutagenesis and gene knock-out mutation were performed, and two mutants, HAL1-phoR931 and HAL1-△phoB, were obtained i...

  17. Regulation of arsenite oxidation by the phosphate two-component system PhoBR in Halomonas sp. HAL1

    OpenAIRE

    Chen, Fang; Cao, Yajing; Wei, Sha; Li, Yanzhi; Li, Xiangyang; Wang, Qian; Wang, Gejiao

    2015-01-01

    Previously, the expression of arsenite [As(III)] oxidase genes aioBA was reported to be regulated by a three-component regulatory system, AioXSR, in a number of As(III)-oxidizing bacterial strains. However, the regulation mechanism is still unknown when aioXSR genes are absent in some As(III)-oxidizing bacterial genomes, such as in Halomonas sp. HAL1. In this study, transposon mutagenesis and gene knock-out mutation were performed, and two mutants, HAL1-phoR 931 and HAL1-▵phoB, were obtained ...

  18. Combined effects of fluoride and arsenite on the expression of Runx-related transcription 2 mRNA in bone of rats

    Institute of Scientific and Technical Information of China (English)

    郑冲

    2014-01-01

    Objective To explore the combined effects of fluoride and arsenite on the expression of Runx-related transcription 2(Runx2)mRNA in bone of Sprague Dawley(SD)rats.Methods Fifty four SD rats were selected[body mass(109.71±10.52)g,half male and half female].3×3 Factorial experimental design was used to evaluate the combined effects of fluoride and arsenite on the expression of Runx2 mRNA by random number table.

  19. Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite.

    OpenAIRE

    Keyse, S M; Tyrrell, R M

    1989-01-01

    We have shown that UVA (320-380 nm) radiation, hydrogen peroxide, and sodium arsenite induce a stress protein of approximately 32 kDa in human skin fibroblasts. The synthesis and cloning of cDNA from arsenite-induced mRNA populations have now allowed us to unequivocally identify the 32-kDa protein as heme oxygenase. By mRNA analysis we have shown that the heme oxygenase gene is also induced in cultured human skin fibroblasts by UVA radiation, hydrogen peroxide, cadmium chloride, iodoacetamide...

  20. Sodium arsenite accelerates TRAIL-mediated apoptosis in melanoma cells through upregulation of TRAIL-R1/R2 surface levels and downregulation of cFLIP expression

    OpenAIRE

    Ivanov, Vladimir N.; Hei, Tom K.

    2006-01-01

    AP-1/cJun, NF-κB and STAT3 transcription factors control expression of numerous genes, which regulate critical cell functions including proliferation, survival and apoptosis. Sodium arsenite is known to suppress both the IKK-NF-κB and JAK2-STAT3 signaling pathways and to activate the MAPK/JNK-cJun pathways, thereby committing some cancers to undergo apoptosis. Indeed, sodium arsenite is an effective drug for the treatment of acute promyelocytic leukemia with little nonspecific toxicity. Malig...

  1. Suppression of PAI-1 expression through inhibition of the EGFR-mediated signaling cascade in rat kidney fibroblast by ascofuranone.

    Science.gov (United States)

    Cho, Hyun-Ji; Kang, Jeong-Han; Kim, Teoan; Park, Kwang-Kyun; Kim, Cheorl-Ho; Lee, In-Seon; Min, Kwan-Sik; Magae, Junji; Nakajima, Hiroo; Bae, Young-Seuk; Chang, Young-Chae

    2009-05-15

    Fibrosis in glomerulosclerosis causes progressive loss of renal function. Transforming growth factor (TGF)-beta, one of the major profibrotic cytokines, induces the synthesis of plasminogen activator inhibitor (PAI)-1, a factor that plays a crucial role in the development of fibrosis. Here, we found that an isoprenoid antibiotic, ascofuranone, suppresses expression of profibrotic factors including matrix proteins and PAI-1 induced by TGF-beta in renal fibroblasts. Ascofuranone selectively inhibits phosphorylation of epidermal growth factor receptor (EGFR), and downstream kinases such as Raf-1, MEK-1/2, and ERK-1/2. PAI-1 transcription also is suppressed by treatment with kinase inhibitors for MEK-1/2 or EGFR, and with small interfering RNA for EGFR. Ascofuranone inhibits cellular metalloproteinase activity, and an inhibitor of metalloproteinases suppresses EGFR phosphorylation and PAI-1 transcription. These results suggest that ascofuranone suppresses expression of profibrotic factors through the inhibition of an EGFR-dependent signal transduction pathway activated by metalloproteinases.

  2. HIF-1α inhibition blocks the cross talk between multiple myeloma plasma cells and tumor microenvironment

    International Nuclear Information System (INIS)

    Multiple myeloma (MM) is a malignant disorder of post-germinal center B cells, characterized by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow (BM). The reciprocal and complex interactions that take place between the different compartments of BM and the MM cells result in tumor growth, angiogenesis, bone disease, and drug resistance. Given the importance of the BM microenvironment in MM pathogenesis, we investigated the possible involvement of Hypoxia-Inducible transcription Factor-1 alpha (HIF-1α) in the PCs-bone marrow stromal cells interplay. To test this hypothesis, we used EZN-2968, a 3rd generation antisense oligonucleotide against HIF-1α, to inhibit HIF-1α functions. Herein, we provide evidence that the interaction between MM cells and BM stromal cells is drastically reduced upon HIF-1α down-modulation. Notably, we showed that upon exposure to HIF-1α inhibitor, neither the incubation with IL-6 nor the co-culture with BM stromal cells were able to revert the anti-proliferative effect induced by EZN-2968. Moreover, we observed a down-modulation of cytokine-induced signaling cascades and a reduction of MM cells adhesion capability to the extracellular matrix proteins in EZN-2968-treated samples. Taken together, these results strongly support the concept that HIF-1α plays a critical role in the interactions between bone BM cells and PCs in Multiple Myeloma. - Highlights: • HIF-1α inhibition induces a mild apoptotic cell death. • Down-modulation of cytokine-induced signaling cascades upon HIF-1α inhibition. • Reduced interaction between MM cells and BMSCs upon HIF-1α down-modulation. • Reduced PCs adhesion to the extracellular matrix protein induced by EZN-2968. • HIF-1α inhibition may be an attractive therapeutic strategy for Multiple Myeloma

  3. HIF-1α inhibition blocks the cross talk between multiple myeloma plasma cells and tumor microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Borsi, Enrica, E-mail: enrica.borsi2@unibo.it [Department of Experimental Diagnostic and Specialty Medicine (DIMES), “L. and A. Seràgnoli”, Bologna University School of Medicine, S. Orsola' s University Hospital (Italy); Perrone, Giulia [Fondazione IRCCS Istituto Nazionale dei Tumori, Hematology Department, Via Venezian 1, 20133 Milano (Italy); Terragna, Carolina; Martello, Marina; Zamagni, Elena; Tacchetti, Paola; Pantani, Lucia; Brioli, Annamaria; Dico, Angela Flores; Zannetti, Beatrice Anna; Rocchi, Serena; Cavo, Michele [Department of Experimental Diagnostic and Specialty Medicine (DIMES), “L. and A. Seràgnoli”, Bologna University School of Medicine, S. Orsola' s University Hospital (Italy)

    2014-11-01

    Multiple myeloma (MM) is a malignant disorder of post-germinal center B cells, characterized by the clonal proliferation of malignant plasma cells (PCs) within the bone marrow (BM). The reciprocal and complex interactions that take place between the different compartments of BM and the MM cells result in tumor growth, angiogenesis, bone disease, and drug resistance. Given the importance of the BM microenvironment in MM pathogenesis, we investigated the possible involvement of Hypoxia-Inducible transcription Factor-1 alpha (HIF-1α) in the PCs-bone marrow stromal cells interplay. To test this hypothesis, we used EZN-2968, a 3rd generation antisense oligonucleotide against HIF-1α, to inhibit HIF-1α functions. Herein, we provide evidence that the interaction between MM cells and BM stromal cells is drastically reduced upon HIF-1α down-modulation. Notably, we showed that upon exposure to HIF-1α inhibitor, neither the incubation with IL-6 nor the co-culture with BM stromal cells were able to revert the anti-proliferative effect induced by EZN-2968. Moreover, we observed a down-modulation of cytokine-induced signaling cascades and a reduction of MM cells adhesion capability to the extracellular matrix proteins in EZN-2968-treated samples. Taken together, these results strongly support the concept that HIF-1α plays a critical role in the interactions between bone BM cells and PCs in Multiple Myeloma. - Highlights: • HIF-1α inhibition induces a mild apoptotic cell death. • Down-modulation of cytokine-induced signaling cascades upon HIF-1α inhibition. • Reduced interaction between MM cells and BMSCs upon HIF-1α down-modulation. • Reduced PCs adhesion to the extracellular matrix protein induced by EZN-2968. • HIF-1α inhibition may be an attractive therapeutic strategy for Multiple Myeloma.

  4. Stress-induced Start Codon Fidelity Regulates Arsenite-inducible Regulatory Particle-associated Protein (AIRAP) Translation*

    Science.gov (United States)

    Zach, Lolita; Braunstein, Ilana; Stanhill, Ariel

    2014-01-01

    Initial steps in protein synthesis are highly regulated processes as they define the reading frame of the translation machinery. Eukaryotic translation initiation is a process facilitated by numerous factors (eIFs), aimed to form a “scanning” mechanism toward the initiation codon. Translation initiation of the main open reading frame (ORF) in an mRNA transcript has been reported to be regulated by upstream open reading frames (uORFs) in a manner of re-initiation. This mode of regulation is governed by the phosphorylation status of eIF2α and controlled by cellular stresses. Another mode of translational initiation regulation is leaky scanning, and this regulatory process has not been extensively studied. We have identified arsenite-inducible regulatory particle-associated protein (AIRAP) transcript to be translationally induced during arsenite stress conditions. AIRAP transcript contains a single uORF in a poor-kozak context. AIRAP translation induction is governed by means of leaky scanning and not re-initiation. This induction of AIRAP is solely dependent on eIF1 and the uORF kozak context. We show that eIF1 is phosphorylated under specific conditions that induce protein misfolding and have biochemically characterized this site of phosphorylation. Our data indicate that leaky scanning like re-initiation is responsive to stress conditions and that leaky scanning can induce ORF translation by bypassing poor kozak context of a single uORF transcript. PMID:24898249

  5. Modulatory of effect of fresh Amaranthus caudatus and Amaranthus hybridus aqueous leaf extracts on detoxify enzymes and micronuclei formation after exposure to sodium arsenite

    Directory of Open Access Journals (Sweden)

    Adetutu Adewale

    2013-01-01

    Full Text Available Vegetables are the cheapest and most available sources of important proteins, minerals, vitamins, and essential amino protein. These vegetables are commonly used in Africa for the treatment of illness. This study evaluated the protective effects of Amaranthus caudatus and A. hybridus against sodium arsenite-induced toxicity in rats. The effects of sodium arsenite and/or the plant extracts were assessed using bone marrow micronucleus assay and by measuring the activities of tumour maker enzymes such as gamma glutamyl transferase (GGT and alkaline phosphatase (ALP in white albino Wister rats. The study showed that sodium arsenite significantly (P < 0.05 induced the formation of micronucleated polychromatic erythrocytes and the activities of ALP and GGT when compared with control. The levels of white blood cell, hemoglobin, and lymphocyte count were altered in sodium arsenite fed rats and were reverted back to near normal levels in rats pretreated with the plant extracts. A. caudatus and A. hybridus showed significant role in protecting the detoxifying enzymes; also, A. caudatus has a more protective effect on reducing the micronuclei formation when compared with A. hybridus. This study suggests that A. caudatus and A. hybridus possess anticarcinogenic effect.

  6. Ribosomal protein S7 regulates arsenite-induced GADD45α expression by attenuating MDM2-mediated GADD45α ubiquitination and degradation.

    Science.gov (United States)

    Gao, Ming; Li, Xiaoguang; Dong, Wen; Jin, Rui; Ma, Hanghang; Yang, Pingxun; Hu, Meiru; Li, Yi; Hao, Yi; Yuan, Shengtao; Huang, Junjian; Song, Lun

    2013-05-01

    The stress-responding protein, GADD45α, plays important roles in cell cycle checkpoint, DNA repair and apoptosis. In our recent study, we demonstrate that GADD45α undergoes a dynamic ubiquitination and degradation in vivo, which process can be blocked by the cytotoxic reagent, arsenite, resulting in GADD45α accumulation to activate JNKs cell death pathway, thereby revealing a novel mechanism for the cellular GADD45α functional regulation. But the factors involved in GADD45α stability modulations are unidentified. Here, we demonstrated that MDM2 was an E3 ubiquitin ligase for GADD45α. One of MDM2-binding partner, ribosomal protein S7, interacted with and stabilized GADD45α through preventing the ubiquitination and degradation of GADD45α mediated by MDM2. This novel function of S7 is unrelated to p53 but seems to depend on S7/MDM2 interaction, for the S7 mutant lacking MDM2-binding ability lost its function to stabilize GADD45α. Further investigations indicated that arsenite treatment enhanced S7-MDM2 interaction, resulting in attenuation of MDM2-dependent GADD45α ubiquitination and degradation, thereby leading to GADD45α-dependent cell death pathway activation. Silencing S7 expression suppressed GADD45α-dependent cytotoxicity induced by arsenite. Our findings thus identify a novel function of S7 in control of GADD45α stabilization under both basal and stress conditions and its significance in mediating arsenite-induced cellular stress.

  7. Biotransformation of arsenite and bacterial aox activity in drinking water produced from surface water of floating houses: Arsenic contamination in Cambodia.

    Science.gov (United States)

    Chang, Jin-Soo

    2015-11-01

    The potential arsenite bioteansformation activity of arsenic was investigated by examining bacterial arsenic arsenite-oxidizing gene such as aoxS, aoxR, aoxA, aoxB, aoxC, and aoxD in high arsenic-contaminated drinking water produced from the surface water of floating houses. There is a biogeochemical cycle of activity involving arsenite oxidase aox system and the ars (arsenic resistance system) gene operon and aoxR leader gene activity in Alcaligenes faecalis SRR-11 and aoxS leader gene activity in Achromobacter xylosoxidans TSL-66. Batch experiments showed that SRR-11 and TSL-66 completely oxidized 1 mM of As (III) to As (V) within 35-40 h. The leaders of aoxS and aoxR are important for gene activity, and their effects in arsenic bioremediation and mobility in natural water has a significant ecological role because it allows arsenite oxidase in bacteria to control the biogeochemical cycle of arsenic-contaminated drinking water produced from surface water of floating houses.

  8. The advances in molecular mechanisms of arsenite-induced autophagy%砷诱导细胞自噬的分子机制研究进展

    Institute of Scientific and Technical Information of China (English)

    李小娜; 时小燕

    2015-01-01

    Arsenite , as a type of metal element , has a dual role to humans . Long‐term and chronic exposure to arsenite is associated with a series of diseases . In addition , Arsenite has obviously curative effects on treating not only acute myelocytic leukemia , but also many other solid tumors . Recently , many researches have showed that autophagy occurs in tumor formation and therapies by arsenite . Therefore , it is necessary to review the advance in the molecular mechanism of arsenite‐induced autophagy .%砷是一种类金属元素,对人体具有双重作用。人群长期慢性砷暴露可导致一系列疾病。此外,砷化合物不仅对急性早幼粒细胞白血病具有明显疗效,其抗癌效应也在许多实体肿瘤治疗中体现。近期研究表明,砷暴露和砷治疗肿瘤过程中均有自噬发生。因此,回顾砷诱导细胞自噬分子机制的研究进展,为砷暴露致癌及其疾病治疗的研究提供线索。

  9. Evidence for a Role of p38 Kinase in Hypoxia-inducible Factor 1-independent Induction of Vascular Endothelial Growth Factor Expression by Sodium Arsenite

    NARCIS (Netherlands)

    Duyndam, M.C.A.; Hulscher, S.T.M.; Wall, E. van der; Pinedo, H.M.; Boven, E.

    2002-01-01

    Recently we have demonstrated that sodium arsenite induces the expression of hypoxia-inducible factor 1α (HIF-1α) protein and vascular endothelial growth factor (VEGF) in OVCAR-3 human ovarian cancer cells. We now show that arsenic trioxide, an experimental anticancer drug, exerts the same effects.

  10. Characterization of the arsenite oxidizer Aliihoeflea sp. strain 2WW and its potential application in the removal of arsenic from groundwater in combination with Pf-ferritin

    NARCIS (Netherlands)

    A. Corsini; M. Colombo; G. Muyzer; L. Cavalca

    2015-01-01

    A heterotrophic arsenite-oxidizing bacterium, strain 2WW, was isolated from a biofilter treating arsenic-rich groundwater. Comparative analysis of 16S rRNA gene sequences showed that it was closely related (98.7 %) to the alphaproteobacterium Aliihoeflea aesturari strain N8T. However, it was physiol

  11. Evidence for a role of p38 kinase in hypoxia-inducible factor 1-independent induction of vascular endothelial growth factor expression by sodium arsenite.

    NARCIS (Netherlands)

    Duyndam, M.C.A.; Hulscher, ST; Wall, van der E.; Pinedo, H.M.; Boven, E.

    2003-01-01

    Recently we have demonstrated that sodium arsenite induces the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) protein and vascular endothelial growth factor (VEGF) in OVCAR-3 human ovarian cancer cells. We now show that arsenic trioxide, an experimental anticancer drug, exerts the same e

  12. SORPTION OF ARSENATE AND ARSENITE ON RUO2 X H2O: ANALYSIS OF SORBED PHASE OXIDATION STATE BY XANES IN ADVANCED PHOTON SOURCE ACTIVITY REPORT 2002

    Science.gov (United States)

    The sorption reactions of arsenate (As(V)) and arsenite (As(III)) on RuO2 x H2O were examined by X-ray Absorption Near Edge Spectroscopy (XANES) to elucidate the solid state speciation of sorbed As. At all pH values studied (pH 4-8), RuO2 x H

  13. Draft Genome Sequence of Halomonas sp. Strain HAL1, a Moderately Halophilic Arsenite-Oxidizing Bacterium Isolated from Gold-Mine Soil

    OpenAIRE

    Lin, Yanbing; Fan, Haoxin; Hao, Xiuli; Johnstone, Laurel; Hu, Yao; Wei, Gehong; Alwathnani, Hend A.; Wang, Gejiao; Rensing, Christopher

    2012-01-01

    We report the draft genome sequence of arsenite-oxidizing Halomonas sp. strain HAL1, isolated from the soil of a gold mine. Genes encoding proteins involved in arsenic resistance and transformation, phosphate utilization and uptake, and betaine biosynthesis were identified. Their identification might help in understanding how arsenic and phosphate metabolism are intertwined.

  14. Inhibition of microbial arsenate reduction by phosphate.

    Science.gov (United States)

    Slaughter, Deanne C; Macur, Richard E; Inskeep, William P

    2012-03-20

    The ratio of arsenite (As(III)) to arsenate (As(V)) in soils and natural waters is often controlled by the activity of As-transforming microorganisms. Phosphate is a chemical analog to As(V) and, consequently, may competitively inhibit microbial uptake and enzymatic binding of As(V), thus preventing its reduction to the more toxic, mobile, and bioavailable form - As(III). Five As-transforming bacteria isolated either from As-treated soil columns or from As-impacted soils were used to evaluate the effects of phosphate on As(V) reduction and As(III) oxidation. Cultures were initially spiked with various P:As ratios, incubated for approximately 48 h, and analyzed periodically for As(V) and As(III) concentration. Arsenate reduction was inhibited at high P:As ratios and completely suppressed at elevated levels of phosphate (500 and 1,000 μM; P inhibition constant (K(i))∼20-100 μM). While high P:As ratios effectively shut down microbial As(V) reduction, the expression of the arsenate reductase gene (arsC) was not inhibited under these conditions in the As(V)-reducing isolate, Agrobacterium tumefaciens str. 5B. Further, high phosphate ameliorated As(V)-induced cell growth inhibition caused by high (1mM) As pressure. These results indicate that phosphate may inhibit As(V) reduction by impeding As(V) uptake by the cell via phosphate transport systems or by competitively binding to the active site of ArsC. PMID:21741807

  15. 小檗碱对脂多糖诱导的THP-1细胞相关炎性反应因子的影响%Effects of berberine on inflammatory cytokines induced by lipopolysaccharide in THP-1 cells

    Institute of Scientific and Technical Information of China (English)

    刘司漩; 刘云峰; 尹建红; 章毅; 许林鑫; 杨静

    2014-01-01

    Objective To observe the effects of berberine (BBR) on expression of inflammatory cytokines in THP-1 cells induced by lipopolysaccharide (LPS),and investigate the anti-inflammatory effects of BBR.Methods For analysing the toxicity of BBR on THP-1 cells,THP-1 cells were divided into control group,and different concentrations of BBR groups (BBR 5,10,20,50 μmol/L).After incubation for 6,24 and 48 hours,lactate dehydrogenase (LDH) released from THP-1 cells was used to assay the cytotoxicity of BBR.For analysis of the effects of BBR on inflammatory cytokines induced by LPS in THP-1 cells,THP-1 cells were divided into control group,LPS group (1 μg/mL LPS),and different concentrations of BBR with LPS groups (BBR 5,10 and 20 μmol/L + 1 μg/mL LPS).After 6,24 or 48 hours of incubation,the concentrations of inter4eukin (IL)-1 β,IL-6,IL-8 and tumor necrosis factor(TNF)-α in the culture medium were measured by enzyme-linked immunosorbent assay (ELISA).Results The survival rates of THP-1 cells were all over 90%after treated with BBR lower than 20 μmol/L for 6,24 and 48 hours.BBR decreased the release of IL-1β,IL-6,IL-8 and TNF-α from THP-1 cells in a dose-dependent manner.After 6 hours,20 μmol/L of BBR decreased the secretion of IL-1 β,IL-8 and TNF-α significantly compared with LPS group (P < 0.05).After 24 hours,the secretion of IL-8 and TNF-α was decreased significantly in 20 μmol/L of BBR + LPS group compared with those in LPS group (P < 0.05).After 48 hours,the secretion of TNF-α was decreased signifi-cantly (F=92.625,P < 0.05) in 5 μmol/L BBR + LPS group,the secrection of IL-1β、IL-6 and TNF-α were decreased (all P < 0.05) in 10 μmol/L BBR + LPS group,and the secretion of IL-1β,IL-6 and TNF-α were decreased in 20 μmol/L BBR + LPS group compared with those in LPS group (all P < 0.05).Conclusion BBR can decrease the secretion of inflammatory cytokines in THP-1 cells induced by LPS in a dose-dependent manner.%目的 通过观察小檗碱对

  16. Effect of dendritic cells stimulated by different ways on cytotoxic activity of cord blood derived cytokine induced killer cells and natural killer cells%不同方式刺激脐血树突状细胞对细胞因子诱导杀伤细胞和自然杀伤细胞杀伤活性的影响

    Institute of Scientific and Technical Information of China (English)

    黎阳; 黄绍良; 吴燕峰; 魏菁; 包蓉; 周敦华

    2005-01-01

    目前对造血干细胞移植(hematopoietic stem cell transplantation,HSCT)后残留肿瘤细胞的清除需通过过继免疫治疗等手段来解决.通过特定细胞因子联合扩增脐血中细胞因子诱导杀伤(cytokine-induced killer,CIK) 细胞、自然杀伤(natural killer,NK)细胞,可增强脐血移植(UCBT)后的移植物抗白血病(graft-versus-leukemia,GVL)效应.树突状细胞(dendritic cells ,DC)在免疫应答的诱导中具有独特地位,

  17. A Raman spectroscopic study of arsenite and thioarsenite species in aqueous solution at 25°C

    Directory of Open Access Journals (Sweden)

    Janecky David R

    2002-02-01

    Full Text Available The Raman spectra of thioarsenite and arsenite species in aqueous solution were obtained at room temperature. Solutions at constant ΣAs + ΣS of 0.1 and 0.5 mol kg-1 were prepared with various ΣS/ΣAs ratios (0.1–9.0 and pH values (~7–13.2. Our data suggest that the speciation of As under the conditions investigated is more complicated than previously thought. The Raman measurements offer evidence for at least six separate S-bearing As species whose principal bands are centered near 365, 385, 390, 400, 415 and 420 cm-1. The data suggest that at least two different species may give rise to bands at 385 cm-1, bringing the probable minimum number of species to seven. Several additional species are possible but could not be resolved definitively. In general, the relative proportions of these species are dependent on total As concentration, ΣS/ΣAs ratio and pH. At very low ΣS/ΣAs ratios we also observe Raman bands attributable to the dissociation products of H3AsO3(aq. Although we were unable to assign precise stoichiometries for the various thioarsenite species, we were able to map out general pH and ΣS/ΣAs conditions under which the various thioarsenite and arsenite species are predominant. This study provides a basis for more detailed Raman spectroscopic and other types of investigations of the nature of thioarsenite species.

  18. Heme oxygenase is the major 32-kDa stress protein induced in human skin fibroblasts by UVA radiation, hydrogen peroxide, and sodium arsenite

    International Nuclear Information System (INIS)

    We have shown that UVA (320-380 nm) radiation, hydrogen peroxide, and sodium arsenite induce a stress protein of approximately 32 kDa in human skin fibroblasts. The synthesis and cloning of cDNA from arsenite-induced mRNA populations have now allowed us to unequivocally identify the 32-kDa protein as heme oxygenase. By mRNA analysis we have shown that the heme oxygenase gene is also induced in cultured human skin fibroblasts by UVA radiation, hydrogen peroxide, cadmium chloride, iodoacetamide, and menadione. The known antioxidant properties of heme catabolites taken together with the observation of a high level of induction of the enzyme in cells from an organ not involved in hemoglobin breakdown strongly supports the proposal that the induction of heme oxygenase may be a general response to oxidant stress and constitutes an important cellular defense mechanism against oxidative damage

  19. Study of sodium arsenite induced biochemical changes on certain biomolecules of the freshwater catfish Clarias batrachus

    Directory of Open Access Journals (Sweden)

    Randhir Kumar

    2012-01-01

    Full Text Available Toxic impact of sublethal concentration (1 mg/L; 5% of 96h LC50 value of sodium arsenite (NaAsO2 on certain biomolecules (proteins, nucleic acids, lipids, and glycogen of five tissue components (muscles, liver, brain, skin, and gills of the freshwater catfish Clarias batrachus was analysed. The important toxic manifestations include marked decrease in the concentration of proteins (21.72-45.42% in muscles; 3.42-53.94% in liver; 15.39-45.42% in brain; 15.40-4.00% in skin and 11.35-64.13% in gills, DNA (0.55-22.95% in muscles; 8.33-14.06% in liver; 5.30-18.40% in brain; 13.57-52.80% in skin; and 12.38-31.01% in gills, RNA (42.68-76.16% in muscles; 10.68-39.75% in liver; 5.66-29.05% in brain; 7.72-27.93% in skin and 21.47-44.38% in gills and glycogen (24.00-51.72% in muscles; 49.11-72.45% in liver; 11.49-26.03% in brain; 26.13-38.05% in skin and 17.80-37.97% in gills. Excepting liver where the lipid content increases (15.82-24.13%, the fat content also showed depletion in their concentration (10.40-29.83% in muscles; 8.30-34.45% in brain; 8.94-31.47% in skin and 12.75-28.86% in gills, in the rest of the organ systems.Foi analisado o impacto tóxico da concentração subletal (1 mg/L; 5% do valor de LC50 de 96h do arsenito de sódio (NaAsO2 sobre certas biomoléculas (proteinas, ácidos nucleicos, lipídios e glicogênio de cinco tecidos (músculos, fígado, cérebro, pele e brânquias do bagre Clarias batrachus. As manifestações tóxicas importantes incluiram o decréscimo acentuado na concentração de proteinas (21,72-45,42% nos músculos; 3,42-53,94% no fígado; 15,39-45,42% no cérebro; 15,40-4,00% na pele e 11,35-64,13% nas brânquias, DNA (0,55-22,95% nos músculos; 8,33-14,06% no fígado; 5,30-18,40% no cérebro; 13,57-52,80% na pele e 12,38-31,01% nas brânquias, RNA (42,68-76,16% nos músculos; 10,68-39,75% no fígado; 5,66-29,05% no cérebro; 7,72-27,93% na pele e 21,47-44,38% nas brânquias e glicogênio (24,00-51,72% nos músculos; 49

  20. Effects of chronic exposure to sodium arsenite on hypothalamo-pituitary-testicular activities in adult rats: possible an estrogenic mode of action

    OpenAIRE

    Jana Subarna; Jana Kuladip; Samanta Prabhat

    2006-01-01

    Abstract Background Inorganic arsenic is a major water pollutant and a known human carcinogen that has a suppressive influence on spermatogenesis and androgenesis in male reproductive system. However, the actual molecular events resulting in male reproductive dysfunctions from exposure to arsenic remain unclear. In this context, we evaluated the mode of action of chronic oral exposure of sodium arsenite on hypothalamo-pituitary- testicular activities in mature male albino rats. Methods The ef...

  1. A Novel Role of the NRF2 Transcription Factor in the Regulation of Arsenite-Mediated Keratin 16 Gene Expression in Human Keratinocytes

    OpenAIRE

    Endo, Hitoshi; Sugioka, Yoshihiko; Nakagi, Yoshihiko; Saijo, Yasuaki; Yoshida, Takahiko

    2008-01-01

    Background Inorganic sodium arsenite (iAs) is a ubiquitous environmental contaminant and is associated with an increased risk of skin hyperkeratosis and cancer. Objectives We investigated the molecular mechanisms underlying the regulation of the keratin 16 (K16) gene by iAs in the human keratinocyte cell line HaCaT. Methods We performed reverse transcriptase polymerase chain reaction, luciferase assays, Western blots, and electrophoretic mobility shift assays to determine the transcriptional ...

  2. Application of Adenosine Triphosphate Affinity Probe and Scheduled Multiple-Reaction Monitoring Analysis for Profiling Global Kinome in Human Cells in Response to Arsenite Treatment

    OpenAIRE

    Guo, Lei; Xiao, Yongsheng; Wang, Yinsheng

    2014-01-01

    Phosphorylation of cellular components catalyzed by kinases plays important roles in cell signaling and proliferation. Quantitative assessment of perturbation in global kinome may provide crucial knowledge for elucidating the mechanisms underlying the cytotoxic effects of environmental toxicants. Here, we utilized an adenosine triphosphate (ATP) affinity probe coupled with stable isotope labeling by amino acids in cell culture (SILAC) to assess quantitatively the arsenite-induced alteration o...

  3. Elevated levels of NO in both unchallenged and LPS-challenged C. parvum-primed mice are attributable to the activity of a cytokine-inducible isoform of iNOS.

    Science.gov (United States)

    Smith, S R; Manfra, D; Davies, L; Terminelli, C; Denhardt, G; Donkin, J

    1997-01-01

    Elevated levels of nitric oxide (NO2-/NO3-) were detected in the serum of mice 3-7 days after priming with Corynebacterium parvum (Propionibacterium acnes). The serum NO2-/NO3- response was completely inhibited when C. parvum-primed (C. parrum) mice were treated with N(G)-monomethyl-L-arginine (L-NMMA) or aminoguanidine (AG) on days 6 and 7 post priming. The response was also inhibited when the mice were treated with interleukin-10 (IL-10) and the cytokine was most effective when given in multiple doses beginning on the day of priming. In contrast to L-NMMA and AG, IL-10 had no effect on the serum NO2-/NO3- response when administered to the mice on days 6 and 7 post priming. The inducible isoform of NOS (iNOS) appeared to be responsible for the elevated NO2-/NO3- response in C. parvum mice because iNOS transcripts were readily detected in their livers. Moreover, these transcripts as well as the circulating levels of NO2-/NO3- were dramatically reduced when the mice were treated with anti-tumor necrosis factor alpha (anti-TNF-alpha) or anti-interferon-gamma (anti-IFN-gamma) monoclonal antibodies (mAbs) during the priming interval. There was a modest increase (less than twofold) in the serum NO2-/NO3- response following a lipopolysaccharide (LPS) challenge to C. parvum mice (C. parvum/LPS mice). LPS had a more dramatic stimulatory effect if the levels of NO2-/NO3- preexisting in C. parvum/LPS mice were reduced by treatment with L-NMMA, AG, or IL-10 before the challenge. Thus the levels of NO2-/NO3- that preexisted in C. parvum/LPS mice appeared to influence their ability to mount a NO2-/NO3- response subsequent to the LPS challenge. The NO2-/NO3- response did not contribute to lethality in C. parvum/LPS mice because anti-TNF-alpha and anti-IFN-gamma mAbs were protective but had no effect on serum NO2-/NO3- levels when administered to mice 24 h before the LPS challenge. PMID:9000533

  4. Preliminary morphological and morphometric study of rat cerebellum following sodium arsenite exposure during rapid brain growth (RBG) period

    International Nuclear Information System (INIS)

    The effects of arsenic exposure during rapid brain growth (RBG) period were studied in rat brains with emphasis on the Purkinje cells of the cerebellum. The RBG period in rats extends from postnatal day 4 (PND 4) to postnatal day 10 (PND 10) and is reported to be highly vulnerable to environmental insults. Mother reared Wistar rat pups were administered intraperitoneal injections (i.p.) of sodium arsenite (aqueous solution) in doses of 1.0, 1.5 and 2.0 mg/kg body weight (bw) to groups II, III and IV (n = 6 animals/group) from PND 4 to 10 (sub acute). Control animals (group I) received distilled water by the same route. On PND 11, the animals were perfusion fixed with 4% paraformaldehyde in 0.1 M phosphate buffer (PB) with pH 7.4. The cerebellum obtained from these animals was post-fixed and processed for paraffin embedding. Besides studying the morphological characteristics of Purkinje cells in cresyl violet (CV) stained paraffin sections (10 μm), morphometric analysis of Purkinje cells was carried out using Image Analysis System (Image Proplus software version 4.5) attached to Nikon Microphot-FX microscope. The results showed that on PND 11, the Purkinje cells were arranged in multiple layers extending from Purkinje cell layer (PL) to outer part of granule cell layer (GL) in experimental animals (contrary to monolayer arrangement within PL in control animals). Also, delayed maturation (well defined apical cytoplasmic cones and intense basal basophilia) was evident in Purkinje cells of experimental animals on PND 11. The mean Purkinje cell nuclear area was significantly increased in the arsenic treated animals compared to the control animals. The observations of the present study (faulty migration, delayed maturation and alteration in nuclear area measurements of Purkinje cells subsequent to arsenic exposure) thus provided the morphological evidence of structural alterations subsequent to arsenite induced developmental neurotoxicity which could be presumed to be

  5. Nitric Oxide Inhibits Coxiella burnetii Replication and Parasitophorous Vacuole Maturation

    Science.gov (United States)

    Howe, Dale; Barrows, Lorraine F.; Lindstrom, Nicole M.; Heinzen, Robert A.

    2002-01-01

    Nitric oxide is a recognized cytotoxic effector against facultative and obligate intracellular bacteria. This study examined the effect of nitric oxide produced by inducible nitric oxide synthase (iNOS) up-regulated in response to cytokine stimulation, or by a synthetic nitric oxide donor, on replication of obligately intracellular Coxiella burnetii in murine L-929 cells. Immunoblotting and nitrite assays revealed that C. burnetii infection of L-929 cells augments expression of iNOS up-regulated in response to gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α). Infection in the absence of cytokine stimulation did not result in demonstrable up-regulation of iNOS expression or in increased nitrite production. Nitrite production by cytokine-treated cells was significantly inhibited by the iNOS inhibitor S-methylisothiourea (SMT). Treatment of infected cells with IFN-γ and TNF-α or the synthetic nitric oxide donor 2,2′-(hydroxynitrosohydrazino)bis-ethanamine (DETA/NONOate) had a bacteriostatic effect on C. burnetii replication. Inhibition of replication was reversed upon addition of SMT to the culture medium of cytokine-treated cells. Microscopic analysis of infected cells revealed that nitric oxide (either cytokine induced or donor derived) inhibited formation of the mature (large) parasitophorous vacuole that is characteristic of C. burnetii infection of host cells. Instead, exposure of infected cells to nitric oxide resulted in the formation of multiple small, acidic vacuoles usually containing one C. burnetii cell. Removal of nitrosative stress resulted in the coalescence of small vacuoles to form a large vacuole harboring multiple C. burnetii cells. These experiments demonstrate that nitric oxide reversibly inhibits replication of C. burnetii and formation of the parasitophorous vacuole. PMID:12183564

  6. Arsenite Interacts with Dibenzo[def,p]chrysene (DBC) at Low Levels to Suppress Bone Marrow Lymphoid Progenitors in Mice.

    Science.gov (United States)

    Ezeh, Peace C; Lauer, Fredine T; Liu, Ke Jian; Hudson, Laurie G; Burchiel, Scott W

    2015-07-01

    Arsenite (As(+3)) and dibenzo[def,p]chrysene (DBC), a polycyclic aromatic hyrdrocarbon (PAH), are found in nature as environmental contaminants. Both are known to individually suppress the immune system of humans and mice. In order to determine their potential interactive and combined immunosuppressive effects, we examined murine bone marrow (BM) immune progenitor cells' responses following combined oral exposures at very low levels of exposure to As(+3) and DBC. Oral 5-day exposure to DBC at 1 mg/kg (cumulative dose) was found to suppress mouse BM lymphoid progenitor cells, but not the myeloid progenitors. Previously established no-effect doses of As(+3) in drinking water (19 and 75 ppb for 30 days) produced more lymphoid suppression in the bone marrow when mice were concomitantly fed a low dose of DBC during the last 5 days. The lower dose (19 ppb) As(+3) had a stronger suppressive effect with DBC than the higher dose (75 ppb). Thus, the interactive toxicity of As(+3) and DBC in vivo could be As(+3) dose dependent. In vitro, the suppressive interaction of As(+3) and DBC was also evident at low concentrations (0.5 nM), but not at higher concentrations (5 nM) of As(+3). These studies show potentially important interactions between As(+3) and DBC on mouse BM at extremely low levels of exposure in vivo and in vitro. PMID:25739538

  7. Protective effects of the dietary supplementation of turmeric (Curcuma longa L.) on sodium arsenite-induced biochemical perturbation in mice.

    Science.gov (United States)

    Karim, Md Rezaul; Haque, Abedul; Islam, Khairul; Ali, Nurshad; Salam, Kazi Abdus; Saud, Zahangir Alam; Hossain, Ekhtear; Fajol, Abul; Akhand, Anwarul Azim; Himeno, Seiichiro; Hossain, Khaled

    2010-12-01

    The present study was undertaken to evaluate the protective effect of turmeric powder on arsenic toxicity through mice model. Swiss albino male mice were divided into four groups. The first group was used as control, while groups 2, 3, and 4 were treated with turmeric powder (T, 50 mg/kg body weight/day), sodium arsenite (Sa, 10 mg/kg body weight/day) and turmeric plus Sa (T+Sa), respectively. Results showed that oral administration of Sa reduced the weight gain of the mice compared to the control group and food supplementation of turmeric prevented the reduction of weight gain. Turmeric abrogated the Sa-induced elevation of serum urea, glucose, triglyceride (TG) level and alanine aminotransferase (ALT) activity except the activity of alkaline phosphatase (ALP). Turmeric also prevented the Sa-induced perturbation of serum butyryl cholinesterase activity (BChE). Therefore, ameliorating effect of turmeric on Sa-treated mice suggested the future application of turmeric to reduce or to prevent arsenic toxicity in human.

  8. Short-term exposure of arsenite disrupted thyroid endocrine system and altered gene transcription in the HPT axis in zebrafish.

    Science.gov (United States)

    Sun, Hong-Jie; Li, Hong-Bo; Xiang, Ping; Zhang, Xiaowei; Ma, Lena Q

    2015-10-01

    Arsenic (As) pollution in aquatic environment may adversely impact fish health by disrupting their thyroid hormone homeostasis. In this study, we explored the effect of short-term exposure of arsenite (AsIII) on thyroid endocrine system in zebrafish. We measured As concentrations, As speciation, and thyroid hormone thyroxine levels in whole zebrafish, oxidative stress (H2O2) and damage (MDA) in the liver, and gene transcription in hypothalamic-pituitary-thyroid (HPT) axis in the brain and liver tissues of zebrafish after exposing to different AsIII concentrations for 48 h. Result indicated that exposure to AsIII increased inorganic As in zebrafish to 0.46-0.72 mg kg(-1), induced oxidative stress with H2O2 being increased by 1.4-2.5 times and caused oxidative damage with MDA being augmented by 1.6 times. AsIII exposure increased thyroxine levels by 1.3-1.4 times and modulated gene transcription in HPT axis. Our study showed AsIII caused oxidative damage, affected thyroid endocrine system and altered gene transcription in HPT axis in zebrafish.

  9. Expansion of new type cytokine induced killer cells in vitro with peripheral blood mononuclearcells in ad-vanced breast cancer in PBMC%应用晚期乳腺癌患者外周血单个核细胞体外增殖诱导新型CIK细胞的实验研究

    Institute of Scientific and Technical Information of China (English)

    鲁祥石; 宋传健; 崔静; 秦莉; 梅芬; 张艳桥; 赵娟; 吕慧敏; 张本宁

    2014-01-01

    目的:应用晚期乳腺癌患者外周血来源的单个核细胞体外培养诱导产生新型( Cytokine in-duced killer cells ,CIK)细胞的可能性,为乳腺癌患者应用自体免疫细胞治疗提供理论基础。方法取8例晚期乳腺癌患者外周血提取单个核细胞,经体外培养诱导增殖,并应用细胞计数法和流式细胞仪检测增殖细胞表面特异性标志CD3、CD16和CD56,应用51Cr release assay 及MTT方法测定其对MCF7及BT20乳腺癌细胞株的杀伤能力。应用ELISA试验方法对诱导得到的新型CIK细胞的培养上清液进行解析。结果经过体外18天培养,平均得到8.2×108个以上纯度为95.2%~98.1%的CD16+、CD56+和CD16+CD56+阳性高纯度NK细胞的新型CIK细胞,且对乳腺癌细胞株MCF7及BT20具有明显的抑制作用。结论成功应用晚期乳腺癌外周血单个核细胞选择性扩增诱导高纯度NK细胞的新型CIK细胞,且证明其对MCF7及BT20乳腺癌细胞具有明显抑制作用,为应用自体高纯度NK细胞的新型CIK细胞为基础的过继性免疫细胞治疗乳腺癌提供理论研究基础。%Objective To investigate new type cytokine induced killer cells expansion using advanced breast cancer′s peripheral blood .Methods peripheral blood mononuclear cells were isolated from 8 advanced breast cancer volunteers and co -cultured with Cytokine induced killer cells .These cells were placed in plastic flasks containing CIK-MediumTM supplemented with 10% auto-plasma in the presence of IL -2 ( 1 000 IU/mL) .The cultures were fed with CIK-MediumTM supplemented with IL -2 following the proliferation capacity . Cell proliferation was measured by cell counting during the cultivation .Fourteen days after cultivation ,cell mark-ers CD3/CD16/CD56 were examined by flow cytometry .51Cr and MTT assays were employed in cytotoxicity as-says.Cytokines were assayed by ELISA method .Results CD16+,CD16+CD56+,CD56+CIK cells were 5

  10. Co-delivery of doxorubicin and arsenite with reduction and pH dual-sensitive vesicle for synergistic cancer therapy

    Science.gov (United States)

    Zhang, Lu; Xiao, Hong; Li, Jingguo; Cheng, Du; Shuai, Xintao

    2016-06-01

    Drug resistance is the underlying cause for therapeutic failure in clinical cancer chemotherapy. A prodrug copolymer mPEG-PAsp(DIP-co-BZA-co-DOX) (PDBD) was synthesized and assembled into a nanoscale vesicle comprising a PEG corona, a reduction and pH dual-sensitive hydrophobic membrane and an aqueous lumen encapsulating doxorubicin hydrochloride (DOX.HCl) and arsenite (As). The dual stimulation-sensitive design of the vesicle gave rise to rapid release of the physically entrapped DOX.HCl and arsenite inside acidic lysosomes, and chemically conjugated DOX inside the cytosol with high glutathione (GSH) concentration. In the optimized concentration range, arsenite previously recognized as a promising anticancer agent from traditional Chinese medicine can down-regulate the expressions of anti-apoptotic and multidrug resistance proteins to sensitize cancer cells to chemotherapy. Consequently, the DOX-As-co-loaded vesicle demonstrated potent anticancer activity. Compared to the only DOX-loaded vesicle, the DOX-As-co-loaded one induced more than twice the apoptotic ratio of MCF-7/ADR breast cancer cells at a low As concentration (0.5 μM), due to the synergistic effects of DOX and As. The drug loading strategy integrating chemical conjugation and physical encapsulation in stimulation-sensitive carriers enabled efficient drug loading in the formulation.Drug resistance is the underlying cause for therapeutic failure in clinical cancer chemotherapy. A prodrug copolymer mPEG-PAsp(DIP-co-BZA-co-DOX) (PDBD) was synthesized and assembled into a nanoscale vesicle comprising a PEG corona, a reduction and pH dual-sensitive hydrophobic membrane and an aqueous lumen encapsulating doxorubicin hydrochloride (DOX.HCl) and arsenite (As). The dual stimulation-sensitive design of the vesicle gave rise to rapid release of the physically entrapped DOX.HCl and arsenite inside acidic lysosomes, and chemically conjugated DOX inside the cytosol with high glutathione (GSH) concentration. In the

  11. Regulation of Arsenite Oxidation by the Phosphate Two-Component System PhoBR in Halomonas sp. HAL1

    Directory of Open Access Journals (Sweden)

    Fang eChen

    2015-09-01

    Full Text Available Previously, the expression of arsenite [As(III] oxidase genes aioBA was reported to be regulated by a three-component regulatory system, AioXSR, in a number of As(III-oxidizing bacterial strains. However, the regulation mechanism is still unknown when aioXSR genes are absent in some As(III-oxidizing bacterial genomes, such as in Halomonas sp. HAL1. In this study, transposon mutagenesis and gene knock-out mutation were performed, and two mutants, HAL1-phoR931 and HAL1-△phoB, were obtained in strain HAL1. The phoR and phoB constitute a two-component system which is responsible for phosphate (Pi acquisition and assimilation. Both of the mutants showed negative As(III-oxidation phenotypes in low Pi condition (0.1 mM but not under normal Pi condition (1 mM. The phoBR complementation strain HAL1-△phoB-C reversed the mutants’ null phenotypes back to wild type status. Meanwhile, lacZ reporter fusions using pCM-lacZ showed that the expression of phoBR and aioBA were both induced by As(III but were not induced in HAL1-phoR931 and HAL1-△phoB. Using 15 consensus Pho box sequences, a putative Pho box was found in the aioBA regulation region. PhoB was able to bind to the putative Pho box in vivo (bacterial one-hybrid detection and in vitro (electrophoretic mobility gel shift assay, and an 18-bp binding sequence containing nine conserved bases were determined. This study provided the evidence that PhoBR regulates the expression of aioBA in Halomonas sp. HAL1 under low Pi condition. The new regulation model further implies the close metabolic connection between As and Pi.

  12. The functions of crucial cysteine residues in the arsenite methylation catalyzed by recombinant human arsenic (III methyltransferase.

    Directory of Open Access Journals (Sweden)

    Shuping Wang

    Full Text Available Arsenic (III methyltransferase (AS3MT is a cysteine (Cys-rich enzyme that catalyzes the biomethylation of arsenic. To investigate how these crucial Cys residues promote catalysis, we used matrix-assisted laser desorption ionization-time of flight-mass spectrometry (MALDI-TOF-MS to analyze Cys residues in recombinant human arsenic (III methyltransferase (hAS3MT. We detected two disulfide bonds, Cys250-Cys32 and Cys368-Cys369, in hAS3MT. The Cys250-Cys32 disulfide bond was reduced by glutathione (GSH or other disulfide bond reductants before the enzymatic methylation of arsenite (iAs3+. In addition to exposing residues around the active sites, cleavage of the Cys250-Cys32 pair modulated the conformation of hAS3MT. This adjustment may stabilize the binding of S-Adenosyl-L-methionine (AdoMet and favor iAs3+ binding to hAS3MT. Additionally, we observed the intermediate of Cys250-S-adenosylhomocysteine (AdoHcy, suggesting that Cys250 is involved in the transmethylation. In recovery experiments, we confirmed that trivalent arsenicals were substrates for hAS3MT, methylation of arsenic occurred on the enzyme, and an intramolecular disulfide bond might be formed after iAs3+ was methylated to dimethylarsinous acid (DMA3+. In this work, we clarified both the functional roles of GSH and the crucial Cys residues in iAs3+ methylation catalyzed by hAS3MT.

  13. Phytochelatins and antioxidant systems respond differentially during arsenite and arsenate stress in Hydrilla verticillata (L.f.) Royle.

    Science.gov (United States)

    Srivastava, S; Mishra, S; Tripathi, R D; Dwivedi, S; Trivedi, P K; Tandon, P K

    2007-04-15

    Serious contamination of aquatic systems by arsenic (As) in different parts of the world calls for the development of an in situ cost-effective phytoremediation technology. In the present investigation, plants of Hydrilla verticillata (L.f.) Royle were exposed to various concentrations of arsenate (As(V)) (0-250 microM) and arsenite (AsIII) (0-25 microM) and analyzed for accumulation responses vis-à-vis biochemical changes. Total As accumulation was found to be higher in plants exposed to AsIII (315 microg g(-1) dw at 25 microM) compared to As(V) (205 microg g(-1) dw at 250 microM) after 7 d of treatment. Plants tolerated low concentrations of As(III) and As(V) by detoxifying the metalloid through augmented synthesis of thiols such as phytochelatins and through increased activity of antioxidant enzymes. While As(V) predominantly stimulated antioxidant enzyme activity, As(III) primarily caused enhanced levels of thiols. The maximum amount of As chelated by PCs was found to be about 39% in plants exposed to As(III) (at 10 microM) and 35% in As(V) exposed plants (at 50 microM) after 4 d. Only the respective highest concentrations of As(III) (25 microM) and As(V) (250 microM) proved toxic for normal plant growth after prolonged treatment. Thus, H. verticillata forms a promising candidate for the phytoremediation of As contaminated water.

  14. Arsenite tolerance in rice (Oryza sativa L.) involves coordinated role of metabolic pathways of thiols and amino acids.

    Science.gov (United States)

    Tripathi, Preeti; Tripathi, Rudra Deo; Singh, Rana Pratap; Dwivedi, Sanjay; Chakrabarty, Debasis; Trivedi, Prabodh K; Adhikari, Bijan

    2013-02-01

    Thiolic ligands and several amino acids (AAs) are known to build up in plants against heavy metal stress. In the present study, alteration of various AAs in rice and its synchronized role with thiolic ligand was explored for arsenic (As) tolerance and detoxification. To understand the mechanism of As tolerance and stress response, rice seedlings of one tolerant (Triguna) and one sensitive (IET-4786) cultivar were exposed to arsenite (0-25 μM) for 7 days for various biochemical analyses using spectrophotometer, HPLC and ICPMS. Tolerant and sensitive cultivars respond differentially in terms of thiol metabolism, essential amino acids (EEAs) and nonessential amino acids (NEEAs) vis-á-vis As accumulation. Thiol biosynthesis-related enzymes were positively correlated to As accumulation in Triguna. Conversely, these enzymes, cysteine content and GSH/GSSG ratio declined significantly in IET-4786 upon As exposure. The level of identified phytochelatin (PC) species (PC(2), PC(3) and PC(4)) and phytochelatin synthase activity were also more pronounced in Triguna than IET-4786. Nearly all EAAs were negatively affected by As-induced oxidative stress (except phenylalanine in Triguna), but more significantly in IET-4786 than Triguna. However, most of the stress-responsive NEAAs like glutamic acid, histidine, alanine, glycine, tyrosine, cysteine and proline were enhanced more prominently in Triguna than IET-4786 upon As exposure. The study suggests that IET-4786 appears sensitive to As due to reduction of AAs and thiol metabolic pathway. However, a coordinated response of thiolic ligands and stress-responsive AAs seems to play role for As tolerance in Triguna to achieve the effective complexation of As by PCs.

  15. MS title: Catalytic oxidation and removal of arsenite in the presence of Fe ions and zero-valent Al metals.

    Science.gov (United States)

    Hsu, Liang-Ching; Chen, Kai-Yue; Chan, Ya-Ting; Deng, Youjun; Hwang, Che-En; Liu, Yu-Ting; Wang, Shan-Li; Kuan, Wen-Hui; Tzou, Yu-Min

    2016-11-01

    Arsenic immobilization in acid mine drainage (AMD) is required prior to its discharge to safeguard aquatic organisms. Zero-valent aluminum (ZVAl) such as aluminum beverage cans (AlBC) was used to induce the oxidation of As(III) to As(V) and enhance the subsequent As removal from an artificially prepared AMD. While indiscernible As(III) oxidation was found in aerated ZVAl systems, the addition of 0.10-0.55mM Fe(II) or Fe(III) into the AMD significantly promoted the As(V) production. Reactions between Fe(II) and H2O2, which was produced through an oxidative reaction of ZVAl with dissolved oxygen, generated OH radicals. Such OH radicals subsequently induced the As(III) oxidation. Over the course of the Fenton like reaction, ZVAl not only directly generated the H2O2, but indirectly enhanced the OH radical production by replenishing Fe(II). Arsenite oxidation in the aerated ZVAl/Fe and AlBC/Fe systems followed zero- and first-order kinetics. Differences in the kinetic reactions of ZVAl and AlBC with respect to As(III) oxidation were attributed to higher productive efficiency of the oxidant in the AlBC systems. After the completion of As(III) oxidation, As(V) could be removed simultaneously with Al(III) and Fe(III) by increasing solution's pH to 6 to produce Al/Fe hydroxides as As(V) scavengers or to form Al/Fe/As co-precipitates. PMID:27285595

  16. Regulation of arsenite oxidation by the phosphate two-component system PhoBR in Halomonas sp. HAL1.

    Science.gov (United States)

    Chen, Fang; Cao, Yajing; Wei, Sha; Li, Yanzhi; Li, Xiangyang; Wang, Qian; Wang, Gejiao

    2015-01-01

    Previously, the expression of arsenite [As(III)] oxidase genes aioBA was reported to be regulated by a three-component regulatory system, AioXSR, in a number of As(III)-oxidizing bacterial strains. However, the regulation mechanism is still unknown when aioXSR genes are absent in some As(III)-oxidizing bacterial genomes, such as in Halomonas sp. HAL1. In this study, transposon mutagenesis and gene knock-out mutation were performed, and two mutants, HAL1-phoR 931 and HAL1-▵phoB, were obtained in strain HAL1. The phoR and phoB constitute a two-component system which is responsible for phosphate (Pi) acquisition and assimilation. Both of the mutants showed negative As(III)-oxidation phenotypes in low Pi condition (0.1 mM) but not under normal Pi condition (1 mM). The phoBR complementation strain HAL1-▵phoB-C reversed the mutants' null phenotypes back to wild type status. Meanwhile, lacZ reporter fusions using pCM-lacZ showed that the expression of phoBR and aioBA were both induced by As(III) but were not induced in HAL1-phoR 931 and HAL1-▵phoB. Using 15 consensus Pho box sequences, a putative Pho box was found in the aioBA regulation region. PhoB was able to bind to the putative Pho box in vivo (bacterial one-hybrid detection) and in vitro (electrophoretic mobility gel shift assay), and an 18-bp binding sequence containing nine conserved bases were determined. This study provided the evidence that PhoBR regulates the expression of aioBA in Halomonas sp. HAL1 under low Pi condition. The new regulation model further implies the close metabolic connection between As and Pi. PMID:26441863

  17. Diversity and abundance of the arsenite oxidase gene aioA in geothermal areas of Tengchong, Yunnan, China.

    Science.gov (United States)

    Jiang, Zhou; Li, Ping; Jiang, Dawei; Wu, Geng; Dong, Hailiang; Wang, Yanhong; Li, Bing; Wang, Yanxin; Guo, Qinghai

    2014-01-01

    A total of 12 samples were collected from the Tengchong geothermal areas of Yunnan, China, with the goal to assess the arsenite (AsIII) oxidation potential of the extant microbial communities as inferred by the abundance and diversity of the AsIII oxidase large subunit gene aioA relative to geochemical context. Arsenic concentrations were higher (on average 251.68 μg/L) in neutral or alkaline springs than in acidic springs (on average 30.88 μg/L). aioA abundance ranged from 1.63 × 10(1) to 7.08 × 10(3) per ng of DNA and positively correlated with sulfide and the ratios of arsenate (AsV):total dissolved arsenic (AsTot). Based on qPCR estimates of bacterial and archaeal 16S rRNA gene abundance, aioA-harboring organisms comprised as much as ~15% of the total community. Phylogenetically, the major aioA sequences (270 total) in the acidic hot springs (pH 3.3-4.4) were affiliated with Aquificales and Rhizobiales, while those in neutral or alkaline springs (pH 6.6-9.1) were inferred to be primarily bacteria related to Thermales and Burkholderiales. Interestingly, aioA abundance at one site greatly exceeded bacterial 16S rRNA gene abundance, suggesting these aioA genes were archaeal even though phylogenetically these aioA sequences were most similar to the Aquificales. In summary, this study described novel aioA sequences in geothermal features geographically far removed from those in the heavily studied Yellowstone geothermal complex.

  18. 恶性肿瘤患者应用细胞因子诱导的杀伤细胞治疗后不良反应分析%Adverse reactions in patients with malignant tumor after treatment with cytokine-induced killer cells

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

      目的观察细胞因子诱导的杀伤细胞(cytokine-induced killer,CIK)治疗恶性肿瘤中出现的不良反应、不良反应出现的可能原因及针对性治疗措施。方法回顾分析2008年3月-2012年10月730例恶性肿瘤患者回输CIK细胞悬液后各种不良反应的临床表现、实验室检查结果、采取的治疗措施及分析可能的原因。结果 CIK细胞回输后的不良反应有:发热(6.85%)、皮疹(1.64%)、消化道不适(0.96%)、关节疼痛(0.41%)、类过敏样反应及溶瘤综合征(均为0.14%)、类全身炎症反应综合征样反应(0.68%),除合并血压下降、严重过敏样反应及溶瘤综合征需对症处理外,余无需特殊处理。不良反应原因可能与CIK细胞的归巢特征及个体差异有关。结论此疗法是安全有效的过继免疫治疗方法,相关不良反应经积极对症处理后可恢复。%Objective To study the causes and countermeasures of adverse reactions in patients with malignant tumor after treatment with cytokine-induced killer (CIK) cells. Methods Clinical manifestations, laboratory findings, treatment measures and causes of adverse reactions in 730 patients with malignant tumor after treated with CIK cells from March 2008 to October 2012 were retrospectively analyzed. Results The main adverse reactions after infusion of CIK cells were fever(6.85%), rash(1.64%), digestive discomfort(0.96%), arthralgia (0.41%), anaphylactoid reaction (0.14%), tumor lysis syndrome (0.14%), and systemic inflammatory response syndrome reaction (0.68%). All the side effects were not specifically treated except for hypotension, severe anaphylactoid reaction and tumor lysis syndrome. The adverse reactions were related with the homing characteristics of CIK cells and individual difference. Conclusion CIK cells therapy is a safe and effective adoptive immunotherapy for malignant tumor and its adverse reactions can be treated expectantly.

  19. Inhibition of PMA-induced endothelial cell activation and adhesion by over-expression of domain negative IκBα protein

    Institute of Scientific and Technical Information of China (English)

    Jian-Feng Wei; Ke Sun; Shi-Guo Xu; Hai-Yang Xie; Shu-Sen Zheng

    2005-01-01

    AIM: NF-κB, regulate the expression of cytokine-inducible genes involving immune and inflammatory responses, will be potential therapy approach for allograft from rejection. In this study, we use pCMV-IκBαM vector to inhibit NF-κB activation and investigate the effect of pCMV-IκBαM in inhibition of T cells adhesion to endothelial cells. METHODS: The NF-κB activity was detected with pNF-κB reporter gene and electrophoretic mobility shift assay. Expression of cell surface molecules was detected by RT-PCR and flow cytometer. The cell-cell adhesion assay was performed to determine the effect of pCMV-IκBαM in inhibition of T cells adhesion to endothelial cells. RESULTS: We could find that NF-κB activity is inhibited by over-expression of non-degraded IκBα protein. Expression of adhesion molecules like ICAM-1, VCAM-1, and P-selectin as well as cell-cell adhesion were inhibited significantly by transfection of the pCMV-IκBαM vector. CONCLUSION: Our results indicate that the pCMVIκBαM, which inhibit the activity of NF-κB through over-expression of non-degraded IκBα protein, can be used for gene therapy in diseases involving NF-κB activation abnormally like organ transplantation via inhibiting cell adhesion.

  20. Arsenite selectively inhibits mouse bone marrow lymphoid progenitor cell development in vivo and in vitro and suppresses humoral immunity in vivo.

    Directory of Open Access Journals (Sweden)

    Peace C Ezeh

    Full Text Available It is known that exposure to As(+3 via drinking water causes a disruption of the immune system and significantly compromises the immune response to infection. The purpose of these studies was to assess the effects of As(+3 on bone marrow progenitor cell colony formation and the humoral immune response to a T-dependent antigen response (TDAR in vivo. In a 30 day drinking water study, mice were exposed to 19, 75, or 300 ppb As(+3. There was a decrease in bone marrow cell recovery, but not spleen cell recovery at 300 ppb As(+3. In the bone marrow, As(+3 altered neither the expression of CD34+ and CD38+ cells, markers of early hematopoietic stem cells, nor CD45-/CD105+, markers of mesenchymal stem cells. Spleen cell surface marker CD45 expression on B cells (CD19+, T cells (CD3+, T helper cells (CD4+ and cytotoxic T cells (CD8+, natural killer (NK+, and macrophages (Mac 1+ were not altered by the 30 day in vivo As(+3 exposure. Functional assays of CFU-B colony formation showed significant selective suppression (p<0.05 by 300 ppb As(+3 exposure, whereas CFU-GM formation was not altered. The TDAR of the spleen cells was significantly suppressed at 75 and 300 ppb As(+3. In vitro studies of the bone marrow revealed a selective suppression of CFU-B by 50 nM As(+3 in the absence of apparent cytotoxicity. Monomethylarsonous acid (MMA(+3 demonstrated a dose-dependent and selective suppression of CFU-B beginning at 5 nM (p<0.05. MMA(+3 suppressed CFU-GM formation at 500 nM, a concentration that proved to be nonspecifically cytotoxic. As(+5 did not suppress CFU-B and/or CFU-GM in vitro at concentrations up to 500 nM. Collectively, these results demonstrate that As(+3 and likely its metabolite (MMA(+3 target lymphoid progenitor cells in mouse bone marrow and mature B and T cell activity in the spleen.

  1. Arsenite-oxidizing bacteria exhibiting plant growth promoting traits isolated from the rhizosphere of Oryza sativa L.: Implications for mitigation of arsenic contamination in paddies.

    Science.gov (United States)

    Das, Suvendu; Jean, Jiin-Shuh; Chou, Mon-Lin; Rathod, Jagat; Liu, Chia-Chuan

    2016-01-25

    Arsenite-oxidizing bacteria exhibiting plant growth promoting (PGP) traits can have the advantages of reducing As-uptake by rice and promoting plant growth in As-stressed soil. A gram-positive bacterium Bacillus flexus ASO-6 resistant to high levels of As (32 and 280 mM for arsenite and arsenate, respectively) and exhibiting elevated rates of As(III) oxidation (Vmax=1.34 μM min(-1) 10(-7) cell) was isolated from rhizosphere of rice. The presence of aoxB gene and exhibition of As(III)-oxidase enzyme activity of this strain was observed. The ability of the strain to produce siderophore, IAA, ACC-deaminase and to solubilize phosphate was verified. The rice seed treated with the strain exhibited significantly improved seed germination and seedling vigor compared with the un-inoculated seeds. The bacterial inoculation significantly increased root biomass, straw yield, grain yield, chlorophyll and carotenoid in the rice plant. Moreover, As uptake from root to shoot and As accumulation in straw and grain decreased significantly as a result of the bacterial inoculation. Noteworthy, the inoculation effect is more prominent in non-flooded soil than it is in flooded soil. Owing to its wide action spectrum, this As(III)-oxidizing PGPB could serve as a potential bio-inoculant for mitigation of As in paddies and sustainable rice production in As-contaminated areas. PMID:26448489

  2. p27{sup Kip1} inhibits tissue factor expression

    Energy Technology Data Exchange (ETDEWEB)

    Breitenstein, Alexander, E-mail: alexander.breitenstein@usz.ch [Cardiology, University Heart Center, University Hospital Zurich (Switzerland); Cardiovascular Research, Physiology Institute, University of Zurich (Switzerland); Center for Integrative Human Physiology (ZHIP), University of Zurich (Switzerland); Akhmedov, Alexander; Camici, Giovanni G.; Lüscher, Thomas F.; Tanner, Felix C. [Cardiology, University Heart Center, University Hospital Zurich (Switzerland); Cardiovascular Research, Physiology Institute, University of Zurich (Switzerland); Center for Integrative Human Physiology (ZHIP), University of Zurich (Switzerland)

    2013-10-04

    Highlights: •p27{sup Kip1}regulates the expression of tissue factor at the transcriptional level. •This inhibitory effect of p27{sup Kip1} is independently of its cell regulatory action. •The current study provides new insights into a pleiotrophic function of p27{sup Kip1}. -- Abstract: Background: The cyclin-dependent kinase inhibitor (CDKI) p27{sup Kip1} regulates cell proliferation and thus inhibits atherosclerosis and vascular remodeling. Expression of tissue factor (TF), the key initator of the coagulation cascade, is associated with atherosclerosis. Yet, it has not been studied whether p27{sup Kip1} influences the expression of TF. Methods and results: p27{sup Kip1} overexpression in human aortic endothelial cells was achieved by adenoviral transfection. Cells were rendered quiescent for 24 h in 0.5% fetal-calf serum. After stimulation with TNF-α (5 ng/ml), TF protein expression and activity was significantly reduced (n = 4; P < 0.001) in cells transfected with p27{sup Kip1}. In line with this, p27{sup Kip1} overexpression reduced cytokine-induced TF mRNA expression (n = 4; P < 0.01) and TF promotor activity (n = 4; P < 0.05). In contrast, activation of the MAP kinases p38, ERK and JNK was not affected by p27{sup Kip1} overexpression. Conclusion: This in vitro study suggests that p27{sup Kip1} inhibits TF expression at the transcriptional level. These data indicate an interaction between p27{sup Kip1} and TF in important pathological alterations such as atherosclerosis and vascular remodeling.

  3. Poly(ADP-ribose) polymerase 1 inhibition protects human aortic endothelial cells against LPS-induced inflammation response

    Institute of Scientific and Technical Information of China (English)

    Xiaonu Peng; Wenjun Li; Wei Zhang

    2012-01-01

    Atherosclerosis is a chronic inflammatory disease.Tolllike receptor 4 (TLR4) is an important signaling receptor and plays a critical role in the inflammatory response.Poly(ADP-ribose) polymerase 1 (PARP1) is a nuclear enzyme that can regulate the expression of various inflammatory genes.In this study,we investigated the role and the underlying mechanisms of PARP1 on lipopolysaccharide (LPS)-induced inflammation in human aortic endothelial cells.Compared with the control,LPS stimulation increased the protein expression of TLR4 and PARP1.TLR4 inhibition reduced LPS-induced upregulation of inducible nitric oxide synthase (iNOS) and ICAM-1 as well as PARP1. Nuclear factor κB (NF-κB) inhibition decreased ICAM-1 and iNOS expression.Inhibition of PARP1 decreased protein expression of inflammatory cytokines induced by LPS stimulation,probably through preventing NF-KB nuclear translocation. Our study demonstrated that LPS increased ICAM-1 and iNOS expression via TLR4/PARP1/NF-KB pathway.PARP1 might be an indispensable factor in TLR4-mediated inflammation after LPS stimulation.PARP1 inhibition might shed light on the treatment of LPS-induced inflammatory cytokines expression during atherosclerosis.

  4. Overexpression of rice glutaredoxins (OsGrxs) significantly reduces arsenite accumulation by maintaining glutathione pool and modulating aquaporins in yeast.

    Science.gov (United States)

    Verma, Pankaj Kumar; Verma, Shikha; Meher, Alok Kumar; Pande, Veena; Mallick, Shekhar; Bansiwal, Amit Kumar; Tripathi, Rudra Deo; Dhankher, Om Parkash; Chakrabarty, Debasis

    2016-09-01

    Arsenic (As) is an acute poison and class I carcinogen, can cause a serious health risk. Staple crops like rice are the primary source of As contamination in human food. Rice grown on As contaminated areas accumulates higher As in their edible parts. Based on our previous transcriptome data, two rice glutaredoxins (OsGrx_C7 and OsGrx_C2.1) were identified that showed up-regulated expression during As stress. Here, we report OsGrx_C7 and OsGrx_C2.1 from rice involved in the regulation of intracellular arsenite (AsIII). To elucidate the mechanism of OsGrx mediated As tolerance, both OsGrxs were cloned and expressed in Escherichia coli (Δars) and Saccharomyces cerevisiae mutant strains (Δycf1, Δacr3). The expression of OsGrxs increased As tolerance in E. coli (Δars) mutant strain (up to 4 mM AsV and up to 0.6 mM AsIII). During AsIII exposure, S. cerevisiae (Δacr3) harboring OsGrx_C7 and OsGrx_C2.1 have lower intracellular AsIII accumulation (up to 30.43% and 24.90%, respectively), compared to vector control. Arsenic accumulation in As-sensitive S. cerevisiae mutant (Δycf1) also reduced significantly on exposure to inorganic As. The expression of OsGrxs in yeast maintained intracellular GSH pool and increased extracellular GSH concentration. Purified OsGrxs displays in vitro GSH-disulfide oxidoreductase, glutathione reductase and arsenate reductase activities. Also, both OsGrxs are involved in AsIII extrusion by altering the Fps1 transcripts in yeast and protect the cell by maintaining cellular GSH pool. Thus, our results strongly suggest that OsGrxs play a crucial role in the maintenance of the intracellular GSH pool and redox status of the cell during both AsV and AsIII stress and might be involved in regulating intracellular AsIII levels by modulation of aquaporin expression and functions.

  5. D-MEKK1, the Drosophila orthologue of mammalian MEKK4/MTK1, and Hemipterous/D-MKK7 mediate the activation of D-JNK by cadmium and arsenite in Schneider cells

    Directory of Open Access Journals (Sweden)

    Iordanov Mihail S

    2006-02-01

    Full Text Available Abstract Background The family of c-Jun NH2-terminal kinases (JNK plays important roles in embryonic development and in cellular responses to stress. Toxic metals and their compounds are potent activators of JNK in mammalian cells. The mechanism of mammalian JNK activation by cadmium and sodium arsenite involves toxicant-induced oxidative stress. The study of mammalian signaling pathways to JNK is complicated by the significant degree of redundancy among upstream JNK regulators, especially at the level of JNK kinase kinases (JNKKK. Results Using Drosophila melanogaster S2 cells, we demonstrate here that cadmium and arsenite activate Drosophila JNK (D-JNK via oxidative stress as well, thus providing a simpler model system to study JNK signaling. To elucidate the signaling pathways that lead to activation of D-JNK in response to cadmium or arsenite, we employed RNA interference (RNAi to knock down thirteen upstream regulators of D-JNK, either singly or in combinations of up to seven at a time. Conclusion D-MEKK1, the fly orthologue of mammalian MEKK4/MTK1, and Hemipterous/D-MKK7 mediates the activation of D-JNK by cadmium and arsenite.

  6. Prophylactic neuroprotective efficiency of co-administration of Ginkgo biloba and Trifolium pretense against sodium arsenite-induced neurotoxicity and dementia in different regions of brain and spinal cord of rats.

    Science.gov (United States)

    Abdou, Heba M; Yousef, Mokhtar I; El Mekkawy, Desouki A; Al-Shami, Ahmed S

    2016-08-01

    The present study was carried out to evaluate the potential protective role of co-administration of Ginkgo biloba, Trifolium pretenseagainst sodium arsenite-induced neurotoxicity in different parts of brain (Cerebral cortex, Hippocampus, striatum and Hind brain) and in the spinal cord of rats. Sodium arsenite caused impairment in the acquisition and learning in all the behavioral tasks and caused significant increase in tumor necrosis factor-α,thiobarbituric acid-reactive substances andlipid profile, while caused significant decrease in glutathione, total thiol content, total antioxidant capacity, acetylcholinesterase, monoamine oxidase and ATPases activities. These results were confirmed by histopathological, fluorescence and scanning electron microscopy examination of different regions of brain. From these results sodium arsenite-induced neurodegenerative disorder in different regions of brain and spinal cord and this could be mediated through modifying the intracellular brain ions homeostasis, cholinergic dysfunction and oxidative damage. The presence of Ginkgo biloba and/orTrifolium pretense with sodium arsenite minimized its neurological damages. It was pronounced that using Ginkgo biloba and Trifolium pretense in combination was more effective as protective agents compared to use eachone of them alone. PMID:27234133

  7. IL-1 beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells

    DEFF Research Database (Denmark)

    Jacobsen, M.L.B.; Ronn, S.G.; Bruun, C.;

    2009-01-01

    of genes encoding the Fas receptor and several chemokines. We have previously shown that suppressor of cytokine signalling (SOCS)-3 inhibits IL-1 beta- and IFN-gamma-induced nitric oxide production in a beta cell line. The aim of this study was to investigate whether SOCS-3 can influence cytokine......Chemokines recruit activated immune cells to sites of inflammation and are important mediators of insulitis. Activation of the pro-apoptotic receptor Fas leads to apoptosis-mediated death of the Fas-expressing cell. The pro-inflammatory cytokines IL-1 beta and IFN-gamma regulate the transcription......-induced Fas and chemokine expression in beta cells. Using a beta cell line with inducible Socs3 expression or primary neonatal rat islet cells transduced with a Socs3-encoding adenovirus, we employed real-time RT-PCR analysis to investigate whether SOCS-3 affects cytokine-induced chemokine and Fas m...

  8. IL-1beta-induced chemokine and Fas expression are inhibited by suppressor of cytokine signalling-3 in insulin-producing cells

    DEFF Research Database (Denmark)

    Jacobsen, M L B; Rønn, S G; Bruun, C;

    2008-01-01

    the transcription of genes encoding the Fas receptor and several chemokines. We have previously shown that suppressor of cytokine signalling (SOCS)-3 inhibits IL-1beta- and IFN-gamma-induced nitric oxide production in a beta cell line. The aim of this study was to investigate whether SOCS-3 can influence cytokine......AIMS/HYPOTHESIS: Chemokines recruit activated immune cells to sites of inflammation and are important mediators of insulitis. Activation of the pro-apoptotic receptor Fas leads to apoptosis-mediated death of the Fas-expressing cell. The pro-inflammatory cytokines IL-1beta and IFN-gamma regulate......-induced Fas and chemokine expression in beta cells. METHODS: Using a beta cell line with inducible Socs3 expression or primary neonatal rat islet cells transduced with a Socs3-encoding adenovirus, we employed real-time RT-PCR analysis to investigate whether SOCS-3 affects cytokine-induced chemokine and Fas m...

  9. 树突状细胞共培养因子诱导的杀伤细胞联合化疗治疗中晚期非小细胞肺癌的临床疗效%Clinical Efficacy of Dendritic Cells Co-cultured with Cytokine Induced Killer Cells Com-bined with Chemotherapy for Middle and Advanced Non-small Cell Lung Cancer

    Institute of Scientific and Technical Information of China (English)

    罗敏; 张娟; 薛军

    2015-01-01

    Objective To investigate the effect of co-culture of dendritic cells and cytokine-induced killer cells on cyto-kine-induced killer cells,and the 2 co-cultured cells combined with oxaliplatin for advanced non-small cell lung cancer.Methods Patients with non-small cell lung cancer and malignant pleural effusions take density gradient centrifugation dendritic cells in vitro to obtain mature dendritic cells;from healthy patients monocytes in vitro obtained killer cells;2 cells were identified by flow cy-tometry after co-culture phenotypes,in vitro cytotoxicity was analyzed by MTT assay in advanced non-small cell lung cancer.Re-sults Malignant pleural effusion dendritic precursor cells were obtained after in vitro maturation of dendritic cells,dendritic cells cultured 9 days and showed markers CD83,CD80,CD86 and MHC-II related HLA-DR molecules than former culture were signifi-cantly higher ( P<0.05);after 2 weeks in dendritic cells co-cultured with killer cells and killer cells cultured alone,CD3 +, CD4 +,CD8 +number increased significantly,there had statistically significant difference (P<0.05) between groups.Dendrit-ic cells-killer cells in patients with advanced non-small cell lung cancer had inhibited the use of lethal than simply killer cells, there had statistical difference (P<0.05).Dendritic cells co-cultured with killer cells in combination with oxaliplatin for ad-vanced non-small cell lung cancer has the effect of killing in vitro,there had statistically difference (P<0.05).Conclusion Malignant pleural effusion derived dendritic cell precursors can induce mature dendritic cells cultured,mature dendritic cells com-bined with killer cells can promote the proliferation and lethal of killer cells,combined with oxaliplatin can enhancement killing effect of advanced non-small cell lung cancer.%目的 探讨树突状细胞与细胞因子诱导的杀伤细胞共培养对细胞因子诱导的杀伤细胞的作用及两者共培养后联合化疗药物奥沙利铂对

  10. Autologous tumor antibody-pulsed dendritic cells combined with cytokine-induced killer cells in the clinical treatment of lung adenocarcinoma%自体肿瘤抗原致敏的树突状细胞联合细胞因子诱导杀伤细胞应用于肺腺癌治疗的临床研究

    Institute of Scientific and Technical Information of China (English)

    钟国成; 张小玉; 孙薏; 李硕; 匡红; 敬新蓉; 闵敏; 陈健

    2010-01-01

    目的:探讨负载自身肿瘤裂解物的树突状细胞(dendritic cells, DCs)联合细胞因子诱导杀伤 (cytokine induced killer, CIK) 细胞治疗肺腺癌的临床疗效及安全性.方法:选择30例肺腺癌患者,分离获得外周血单个核细胞(peripheral blood mononuclear cells, PBMCs),其中贴壁细胞经重组人粒细胞巨噬细胞集落刺激因子(recombinant human granulocyte-macrophage colony stimulating factor, rhGM-CSF)和重组人白细胞介素- 4(recombinant human interleukin-4, rhIL-4)诱导产生DCs,并负载自体肺腺癌细胞裂解物,培养获得Ag-DCs;悬浮细胞经干扰素-α(interferon,IFN-α)、白细胞介素-2(interleukin-2,IL-2)、抗CD3单克隆抗体和白细胞介素-1α(interleukin-1α,IL-1α)体外诱导产生CIK细胞; 将Ag-DCs与CIK细胞共培养,观察CIK细胞体外对肺腺癌细胞株A549和自体肿瘤细胞的杀伤活性;30 例患者接受Ag-DCs+CIK细胞过继免疫治疗,观察疗效.结果: Ag-DCs与CIK细胞共培养后,提高了CIK细胞对A549细胞和自体肿瘤细胞的杀伤活性;Ag-DCs联合CIK细胞治疗肺腺癌,可增强患者细胞免疫功能,改善生活质量,提高临床疗效;除一过性发热和畏寒外,未见其他不良反应.结论:Ag-DCs联合CIK细胞可作为中晚期肺腺癌的一种有效治疗手段.

  11. N-acetylcysteine and meso-2,3-dimercaptosuccinic acid alleviate oxidative stress and hepatic dysfunction induced by sodium arsenite in male rats

    Science.gov (United States)

    Abu El-Saad, Ahmed M; Al-Kahtani, Mohammed A; Abdel-Moneim, Ashraf M

    2016-01-01

    Environmental exposure to arsenic represents a serious challenge to humans and other animals. The aim of the present study was to test the protective effect of antioxidant N-acetylcysteine (NAC) either individually or in combination with a chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA), against sodium arsenite oral toxicity in male rats. Five groups were used: control; arsenic group (orally administrated in a concentration of 2 mg/kg body weight [b.w.]); the other three groups were orally administrated sodium arsenite in a concentration of 2 mg/kg b.w. followed by either NAC (10 mg/kg b.w., intraperitoneally [i.p.]), DMSA (50 mg/kg b.w., i.p.) or NAC plus DMSA. Arsenic toxicity caused significant rise in serum aspartate aminotransferase, alanine aminotransferase and total bilirubin, and a significant decrease in total protein (TP) and albumin levels after 3 weeks of experimental period. In addition, arsenic-treated rats showed significantly higher arsenic content in liver and significant rise in hepatic malondialdehyde level. By contrast, sharp decreases in glutathione content and catalase and glutathione reductase activities were discernible. NAC and/or DMSA counteracted most of these physiologic and biochemical defects. NAC monotherapy was more effective than DMSA in increasing TP, while DMSA was more effective in decreasing alanine aminotransferase. The combined treatment was superior over monotherapies in recovery of TP and glutathione. Biochemical data were well supported by histopathological and ultrastructural findings. In conclusion, the combination therapy of NAC and DMSA may be an ideal choice against oxidative insult induced by arsenic poisoning.

  12. Anabaena sp. mediated bio-oxidation of arsenite to arsenate in synthetic arsenic (III) solution: Process optimization by response surface methodology.

    Science.gov (United States)

    Jana, Animesh; Bhattacharya, Priyankari; Swarnakar, Snehasikta; Majumdar, Swachchha; Ghosh, Sourja

    2015-11-01

    Blue green algae Anabaena sp. was cultivated in synthetic arsenite solution to investigate its bio-oxidation potential for arsenic species. Response surface methodology (RSM) was employed based on a 3-level full factorial design considering four factors, viz. initial arsenic (III) concentration, algal dose, temperature and time. Bio-oxidation (%) of arsenic (III) was considered as response for the design. The study revealed that about 100% conversion of As (III) to As (V) was obtained for initial As (III) concentration of 2.5-7.5 mg/L at 30 °C for 72 h of exposure using 3 g/L of algal dose signifying a unique bio-oxidation potential of Anabaena sp. The dissolved CO2 (DCO2) and oxygen (DO) concentration in solution was monitored during the process and based on the data, a probable mechanism was proposed wherein algal cell acts like a catalytic membrane surface and expedites the bio-oxidation process. Bioaccumulation of arsenic, as well as, surface adsorption on algal cell was found considerably low. Lipid content of algal biomass grown in arsenite solution was found slightly lower than that of algae grown in synthetic media. Toxicity effects on algal cells due to arsenic exposure were evaluated in terms of comet assay and chlorophyll a content which indicated DNA damage to some extent along with very little decrease in chlorophyll a content. In summary, the present study explored the potential application of Anabaena sp. as an ecofriendly and sustainable option for detoxification of arsenic contaminated natural water with value-added product generation.

  13. Study on Solar Photocatalytic Oxidation of Arsenite by Loaded Mn/TiO2%负载型 Mn/TiO2太阳光催化氧化三价砷的研究

    Institute of Scientific and Technical Information of China (English)

    魏志钢; 梁凯; 左俊辉; 邹燕娣; 潘湛昌; 胡光辉

    2015-01-01

    通过溶胶凝胶法制备了泡沫镍负载Mn/TiO2催化剂,并将其应用于太阳光氧化三价砷的研究,考察了Mn/TiO2的摩尔比、TiO2负载次数、溶液pH值及菲涅尔透镜的使用对氧化三价砷速度的影响。实验结果表明,Mn/TiO2的最佳摩尔比为1%,4 h后三价砷完全氧化为五价砷;TiO2最佳的负载次数为2次;当溶液pH值为9时,催化剂催化氧化三价砷的速度最快,3h三价砷完全氧化为五价砷;菲涅尔透镜的使用,显著地缩短催化剂氧化三价砷的时间;吸附剂-催化剂联用后,溶液体积20 L、三价砷质量浓度为100μg/L时,3.5 h后能将溶液中的砷全部去除。%Mn/TiO2 catalyst is successfully prepared on foam nickel substrates by sol -gel technique and applied in the study on solar photocatalytic oxidation of arsenite .The effects of molar ratio of Mn/TiO2 ,coating cycles of TiO2 ,solution pH ,and use of the Fresnel lens on the oxidation rate of As(Ⅲ) are investigated .It is shown that the optimum molar ratio of Mn/TiO2 is 1% and then the arsenite is completely oxidized to arsenate after 4 hours;the optimum coating cycles of TiO2 is two ;when the solution pH is 9 ,the oxidation rate of arsenite is fastest and the arsenite is completely oxidized to arsenate after 3 hours;the oxidation time of arsenite is significantly shortened when the Fresnel lens is used;by combined use of pho-tocatalyst and adsorbent ,the arsenic is completely removed after 3 .5 hours when the volume of solution is 20 liters and the arsenite concentration is 100μg/L .

  14. 三价砷氧化细菌Acidovorax sp.GW2中As(Ⅲ)氧化酶基因和调控序列的克隆鉴定%Isolation and identification of arsenite oxidase gene and regulatory sequences in an arsenite-oxidizing bacterium Acidovorax sp. GW2

    Institute of Scientific and Technical Information of China (English)

    赵凯; 黄银燕; 王倩; 王革娇

    2011-01-01

    Using reverse transcriptase PCR method and a bacterial fosmid library screening, an arsenite oxidase gene cluster were isolated from an arsenite-oxidizing bacterium Acidovorax sp. GW2. There are seven genes including aoxRSXABCD putatively encoding the transcriptional regulator AoxR of a two-component signal transduction system (68% identity), a periplasmic sensor histidine kinase AoxS (55 % identity), a periplasmic binding protein AoxX (55 % identity), arsenite oxidase AoxAB(74 % and 71% identity, respectively), nitroreductase AoxC (46 % identity) and cytochrome c AoxD (63 % identity) respectively. According to the reverse transcriptase PCR experiments,aoxR and aoxS encoding for a two-component system proteins are co-transcribed and located in opposite to structural genes aoxABCD.aoxX and aoxRS are not in the same operon. Functional analyses through gene knock-out of aoxS, aoxX and aoxD showed that aoxS and aoxX are the essential genes in arsenite oxidation of GW2, and the loss of aoxD did not show significant effects on arsenite oxidation.%通过反向PCR和细菌Fosmid文库筛选,克隆得到1株二三价砷[As(Ⅲ)]氧化细菌Acidovorax sp.GW2的As(Ⅲ)氧化酶Aox基因簇,包括aoxRSXABCD 7个基因,分别预测编码双组分信号传导系统转录调控子AoxR(同源性68%),周质感应组氨酸激酶AoxS(同源性55%),周质结合蛋白AoxX(同源性55%),砷氧化酶AoxAB(同源性分别为74%和71%),硝基还原酶AoxC(同源性46%),细胞色素C AoxD(同源性63%).反转录PCR结果显示,编码双组分系统的aoxRS基因共转录,而与之转录方向相反的结构基因aoxABCD处于同一操纵子中,aoxX基因和aoxRS基因不在同一操纵子中.通过对aoxS、aoxX、aoxD的基因敲除功能研究发现aoxS和aoxX基因为GW2三价砷氧化的必需基因,aoxD的功能丧失减慢了三价砷的氧化速率,但非关键基因.

  15. Involvement of NO in sodium arsenite-induced yeast cell death%NO参与亚砷酸钠诱导酵母细胞死亡的调控

    Institute of Scientific and Technical Information of China (English)

    吴丽华; 仪慧兰; 张虎芳

    2012-01-01

    以模式生物酵母细胞为材料,研究亚砷酸钠胁迫对细胞死亡率和胞内NO水平的影响,以探讨NO在砷诱导细胞死亡中的作用.结果显示,浓度为1~7mmol·L^-1的亚砷酸钠可降低酵母细胞活性,诱导细胞死亡,随着处理浓度的升高和作用时间的延长,细胞死亡率增高;死细胞出现核固缩和核降解等凋亡特征;凋亡抑制剂Z-Asp-CH2-DCB(2"mol·L^-1)与3mmol·L^-1亚砷酸钠共同作用后,酵母细胞死亡率下降.在亚砷酸钠胁迫的过程中,酵母细胞内NO水平升高;一定浓度的NO清除剂c-PTIO(0.2mmol·L^-1)或NO生成抑制剂NaN3(1mmol·L^-1)均可降低亚砷酸钠引起的酵母细胞死亡率.结果表明,砷胁迫诱导的胞内NO升高是酵母细胞死亡的一个诱因,亚砷酸钠诱发的酵母细胞死亡中可能存在细胞凋亡过程.%Arsenic is a toxic metalloid widely distributed in the environment. Chronic exposure to arsenic is associated with increased risk of various diseases, such as neurotoxicity, birth defects and metabolic disorders. People exposed to high levels of arsenic are prone to skin, bladder, and lung cancer and occlusive vascular disease. However, the exact mechanisms of arsenic toxicity are not yet well understood. In this study, cytotoxie effects of sodium arsenite on yeast Saccharomyees cerevisiae were investigated with or without some antagonists. For arsenic treatments, yeast cells harvested from the early log phase were incubated in the fresh yeast extract peptone dextrose (YPD) media containing varying amounts of sodium arsenite. For other combination treatments, selected antagonists including broad caspase inhibitor Z-Asp-2,6-dichlorobenzoyloxymethylketone (Z-Asp-CH2-DCB), nitric oxide (NO) scavenger 2-( 4-carboxyphenyl)-4,4,5,5-teramethylimidazoline-l-oxyl-3-oxide ( c-PTIO ) and nitrate reductase inhibitor NaN3 were respectively added into YPD media in the presence of 3 mmol. L^-1 sodium arsenite. The results showed that

  16. 同种异体半相合细胞因子诱导的杀伤细胞治疗晚期肝癌的疗效及安全性评估%Curative effect and safety of haploidentical allogeneic cytokine-induced killer in treatment of advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    杨帆; 郑小芳; 刘畅; 陈文捷; 程锦涛; 阳莉; 卢建溪; 张琪

    2015-01-01

    Objective To investigate the curative effect and safety of haploidentical allogeneic cytokine-induced killer (CIK)in treatment of advanced hepatocellular carcinoma.Methods The peripheral blood mononuclear cell (PBMC) of the healthy immediate family members of 21 patients with advanced hepatocellular carcinoma (HCC) were collected,induced into haploidentical allogeneic CIK in vitro and transfused to the patients for 4 cycles.The curative effect and safety were assessed.Results The 21 patients were followed up for half a year.The survival rate was 81 % (1 7 /21 ).Among the 21 patients,1 1 cases were with stable disease and 1 0 cases were with progressive disease (including 4 dead cases).Six patients developed fever of different degrees during the treatment and one patient developed rash.The platelet counts of the patients at the fourth cycle after the treatment decreased compared with that before the treatment ,with significance difference (P 0.05 ).Conclusions Haploidentical allogeneic CIK in treatment of advanced HCC may effectively improve the quality of life and the adverse reactions are tolerable,which is a relatively safe therapy.%目的:探讨同种异体半相合细胞因子诱导的杀伤(CIK)细胞治疗晚期肝癌的疗效及安全性。方法采集21例晚期肝细胞癌(肝癌)患者健康一级直系亲属的外周血单个核细胞,在体外诱导成异体半相合 CIK 细胞后回输给患者,回输4个周期。评估治疗效果和安全性。结果随访半年,21例患者的存活率为81%(17/21),疾病稳定患者11例,疾病进展患者10例(含4例死亡病例)。6例患者治疗期间出现不同程度的发热,1例出现皮疹。与治疗前相比,患者治疗后第4周期的血小板数量降低,差异有统计学意义(P <0.05),而患者治疗后第1、4周期的白细胞、中性粒细胞、淋巴细胞、血红蛋白,肝、肾功能差异均无统计学意义(均为 P >0.05)。

  17. Clinical Efficacy of Capecitabine Combined with Autologous Cytokine-induced Killer Cells Maintenance Therapy in Treatment of Metastatic Triple Negative Breast Cancer%自体CIK细胞联合卡培他滨维持治疗复发转移性三阴性乳腺癌效果观察

    Institute of Scientific and Technical Information of China (English)

    宋树玺; 刘永叶; 丁震宇; 于卉影; 韩雅玲; 谢晓冬

    2015-01-01

    Objective To analyze the clinical efficacy and safety of capecitabine combined with autologous cytokine-induced killer cells ( CIK) maintenance therapy in treatment of metastatic triple negative breast cancer ( MTNBC) . Methods The MTNBC patients undergoing capecitabine-based chemotherapy as first line treatment, whose therapeutic effect was SD or above were selected and divided into treatment group and control group randomly. The treatment group received capecitabine maintenance therapy with autologous CIK after the first line treatment. The control group underwent only capecitabine mainte-nance therapy. Baseline assessment was taken 15 d after the end of the last cycle of chemotherapy. The patients were followed up once every two cycles. The median follow-up time was 11. 2 months. T lymphocyte subpopulation in peripheral blood was measured, the side effects, PFS and OS of both groups were observed. Results CD3+CD8+CTL and CD4+CD25+Treg of treatment group were compared at the time of baseline assessment and 1 month after three cycles of chemotherapy. There was no statistically significant difference (P>0. 05). CD3+T, CD3+CD4+Th, CD3+CD56+CIK showed significant im-provement, compared with that before treatment (P0. 05). Conclusion Maintenance therapy of Capecitabine combined with autologous CIK cells in treatment of MTNBC after first-line treatment improves the immune function to enhance the ability of antitumor by natural immunity, which can prolong PFS, and is safe as well. In short, it can improve the therapeutic effect of maintenance therapy in patients with MTNBC.%目的 探讨自体细胞因子诱导杀伤细胞( CIK)免疫治疗联合卡培他滨治疗复发转移性三阴性乳腺癌( metastatic triple negative breast cancer, MTNBC)的临床效果和安全性. 方法 选取一线应用卡培他滨化疗后效果评价病情稳定( SD)或以上的MTNBC患者,随机分为治疗组和对照组. 两组均应用卡培他滨维持化疗,治疗组在此

  18. DC/CIKs细胞通过无 miRNA 的 exosome 蛋白刺激后能增强对胰腺癌细胞的免疫作用%Increasing the immune activity of exosomes:the effect of miRNA-depleted exosome proteins on activating dendritic cell/cytokine-induced killer cells against pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Ri-sheng QUE; Cheng LIN; Guo-ping DING; Zheng-rong WU; Li-ping CAO

    2016-01-01

    Background: Tumor-derived exosomes were considered to be potential candidates for tumor vaccines because they are abundant in immune-regulating proteins, whereas tumor exosomal miRNAs may induce immune tolerance, thereby having an opposite immune function. Objective: This study was designed to separate exosomal protein and depleted exosomal microRNAs (miRNAs), increasing the immune activity of exosomes for activating dendritic cell/cytokine-induced kil er cel s (DC/CIKs) against pancreatic cancer (PC). Methods:PC-derived exosomes (PEs) were extracted from cultured PANC-1 cel supernatants and then ruptured; this was fol owed by ultrafiltered exosome lysates (UELs). DCs were stimulated with lipopolysaccharide (LPS), PE, and UEL, fol owed by co-culture with CIKs. The anti-tumor effects of DC/CIKs against PC were evaluated by proliferation and kil ing rates, tumor ne-crosis factor-α(TNF-α) and perforin secretion. Exosomal miRNAs were depleted after lysis and ultrafiltration, while 128 proteins were retained, including several immune-activating proteins. Results: UEL-stimulated DC/CIKs showed a higher killing rate than LPS- and PE-stimulated DC/CIKs. Conclusions: miRNA-depleted exosome proteins may be promising agonists for specifical y activating DC/CIKs against PC.%目的:本文通过分离提取无小 RNA(miRNA)的外来体(exosome)刺激树突细胞/细胞因子活化杀伤细胞(DC/CIKs),激活其对于胰腺癌细胞的免疫杀伤作用。  创新点:无 miRNA的 exosome超速离心裂解产物可以通过激活 DC/CIKs 细胞增强其对肿瘤细胞的杀伤作用。  方法:通过收集PANC-1细胞的上清并超速离心提取其中的exosome。提取的DC细胞分别通过脂多糖、肿瘤来源exosome及无miRNA的exosome刺激后,与CIK细胞共培养。通过计算增值与杀伤效率,肿瘤坏死因子-α(TNF-α)及穿孔素的分泌,比较各组间CIK细胞对胰腺癌细胞的杀伤作用。  结论:经

  19. A meta-analysis of cytokine-induced killer cells therapy in combination with chemotherapy for intermediate and advanced gastric cancer%细胞因子诱导的杀伤细胞联合化疗对比单纯化疗治疗中晚期胃癌的Meta分析

    Institute of Scientific and Technical Information of China (English)

    屈涛; 杨林; 张弘纲; 崔成旭

    2015-01-01

    Objective To evaluate the results of CIK cells transfusion therapy combined with chemotherapy over chemo-therapy alone for intermediate and advanced gastric cancer. Method According to the integration and elimination stand-ard,the cases evaluated the results of CIK cells transfusion therapy combined with chemotherapy over chemotherapy alone for intermediate and advanced gastric cancer were strictly selected,retrieving database dated to June 2014 collected via searching database including Pubmed,CNKI,CBM and Wanfang database. RevMan5. 3 and Stata11. 2softwares were used for statistical analysis. Result A total of 5 good studies were included in the meta-analysis. The results of meta-analysis showed that CIK cells transfusion therapy combined with chemotherapy was associated with more PRs(OR=2. 14,95% CI=1. 17~3. 89) and less PSs(OR=0. 53,95% CI=0. 29~0. 95) than chemotherapy alone. Meanwhile,2-year overall rate (OR=1. 93,95% CI=1. 13~3. 30) and 5-year overall rate(OR=2. 18,95%CI=1. 09~4. 13) for combination therapy were higher than chemotherapy alone. Conclusion The result of meta-analysis suggests that CIK cells transfusion therapy combined with chemotherapy for intermediate and advanced gastric cancer has some distinct advantages over chemotherapy alone. Further studies are needed to validate the conclusion.%目的:评价细胞因子诱导的杀伤细胞( cytokine-induced killer cells,CIK)治疗联合化疗对比单纯化疗治疗中晚期胃癌的有效性。方法检索PubMed、中国知网中文数据库、中国生物医学文献数据库和万方中文数据库,检索时限为数据库建库至2014年6月,筛选关于CIK联合化疗对比单纯化疗治疗中晚期胃癌相关的病例对照研究或队列研究,使用RevMan5.3和Stata11.2进行统计分析。结果共纳入5篇文献, Meta分析显示,部分缓解部分[OR=2.14,95%置信区间(confidence interval,CI)=1.17~3.89]及完全进展部分(OR=0.53,95%CI=0.29~0.95)两种方案差异有显著性。2

  20. Treatment of refractory non-Hodgkin's lymphoma of the spleen with combined autologous cytokine induced killer cells and IL-2: A case report%自体CIK细胞联合IL-2治疗难治性脾非霍奇金淋巴瘤1例

    Institute of Scientific and Technical Information of China (English)

    杨洋; 陈云燕; 张文英; 刘洋; 王瑶; 代汉仁; 韩为东; 张峰; 姚善谦; 杨波; 脱帅; 卢学春; 朱宏丽; 脱朝伟; 蔡力力; 迟小华; 于睿莉

    2012-01-01

    目的 观察自体细胞因子诱导的杀伤细胞输注联合IL-2治疗老年淋巴瘤的有效性和安全性.方法 1例老年脾脏恶性淋巴瘤患者在经过手术切除脾脏原发肿瘤、8个疗程的R-CHOP方案免疫化疗后出现淋巴瘤肝脏转移,此时采集患者外周血单核细胞,在体外经干扰素-γ (IFN-γ)、白介素-2(IL-2)和抗CD3单克隆抗体诱导成CIK细胞,每次回输细胞数为2-3×109个,回输后应用IL-2 100mU/d,皮下注射,连续10d,28d为1个周期.观察治疗前后患者肝功能、肿瘤相关生物学指标及影像学变化.结果 患者共完成8个周期的CIK细胞输注,每次回输后未出现不良反应,肝功能指标、LDH水平均降至正常,PET/CT检查示治疗后肝脏淋巴瘤转移灶消失,达到完全缓解.结论 自体CIK细胞输注联合IL-2疗法对于清除治疗后淋巴瘤的微小残留灶和(或)转移灶安全有效.%Objective To observe the efficiency and safety of combined autologous cytokine induced killer(CIK) cells and IL-2 in treatment of splenic lymphoma in old patients. Methods Hepatic metastasis of splenic primary malignant lymphoma occurred in an old patient after splenectomy and 8 cycles of R-CHOP chemotherapy. Peripheral blood mononuclear cells (PBMC) were collected. CIK cells were induced with in vitro interferon gamma (IFN-γ), IL-2 and anti-CD3 monoclonal antibody (mAb). Liver function, tumor-related biological indexes and image changes were observed after 2-3×109 CIK cells were re-transfused into the patient each time and IL-2 100mU/d was subcutaneously injected for 10 days, 28 days a cycle. Results No adverse reaction occurred in the patient after 8 cycles of CIK cells transfusion. The liver function and serum LDH level became normal(P<0.05). PET-CT showed that hepatic metastasis of lymphoma disappeared and completely relieved. Conclusion Combined autologous CIK cells and IL-2 is safe and effective for small residual or metastatic foci of lymphoma in old

  1. Curative Effect of Decitabine Combined with Cytokine-Induced Killer Cells in Two Elderly Patients with Acute Myeloid Leukemia%地西他滨联合自体CIK细胞治疗2例高龄急性髓系白血病的疗效观察

    Institute of Scientific and Technical Information of China (English)

    常城; 杨波; 张琳; 朱宏丽; 卢学春; 郭搏; 蔡力力; 韩为东; 王瑶

    2013-01-01

    本研究旨在观察低甲基化药物地西他滨联合自体细胞因子诱导的杀伤细胞(CIK)治疗老年急性髓系白血病(AML)的安全性及有效性.本科于2006-2012年收治2例80岁以上老年AML患者(M4型和M6型),均继发于骨髓增生异常综合征.对这2例患者先后采取单用自体CIK细胞输注、地西他滨或(和)自体CIK细胞方案治疗,系统观察了2例CIK治疗前后淋巴细胞亚群、临床相关指标(血液学反应、输血频率、白血病相关基因表达、缓解情况、生活质量)及生存期的变化.结果表明,与单用自体CIK细胞输注和单用地西他滨治疗相比,地西他滨联合自体CIK细胞治疗方案可减轻骨髓抑制程度,降低输血频率及输血量,延长部分缓解持续时间,同时表达的白血病相关基因减少,生存期显著延长,患者生活质量得到明显改善.结论:地西他滨联合自体CIK细胞治疗老年AML患者安全有效.%This study was aimed to evaluate the effectiveness and safety of low methylation drug decitabine combined with autologous cytokine induced killer cells (CIK) to treat the elderly patients with acute myeloid leukemia (AML). Two AML patients aged over 80 years old were diagnosed and treated in our department from 2006 to 2012; both companied with MDS history, and one case was M4-type, another case was M6-type according to FAB classification. The changes in lymphocyte subsets, hematologic response, transfusion frequency, leukemic gene expression, obtaining CRorPR, quality of life and survival time of the patients with different treatment regimen (decitabine alone; CIK alone; decitabine combined with CIK) were systematically observed. The results showed that therapy of decitabine combined with CIK cells could reduce bone marrow suppression extent, decrease the frequency and volume of blood transfusion, and prolong the duration of partial remission, compared with the single use of CIK cell infusion and single use of decitabine

  2. Effects of sodium arsenite on mRNA transcription of keratinizing related and nuclear factor E2-related factor 2 genes in HaCaT cells%亚砷酸钠对人皮肤永生化角质形成细胞角化相关基因和核转录因子红系相关因子2mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    胡新欣; 高彦辉; 张微; 孙惠昕; 孙殿军

    2012-01-01

    previous results of cell proliferation,0.00(control),6.25,12.50,and 25.00 μmol/L of sodium arsenite were selected to treat HaCaT cells for 48 h,respectively.The mRNA expression of keratin 1,keratin 10,involucrin,loricrin and Nrf2 were detected by real-time fluorescent quantitative PCR.Results Compared with the control group (100.05%),HaCaT cell proliferation rates(83.06%,51.04%,39.52%,24.51%,16.99% and 9.04%) were significantly lower in 6.25,12.50,25.00,50.00,75.00 and 100.00 μ mol/L of sodium arsenite groups and the 50% inhibiting concentration was 12.38 μmol/L.Compared with the control group( 1.06 ± 0.28,1.00 ± 0.12,1.00 ± 0.08),the mRNA expression of keratin 1,involucrin and loricrin (0.08 ± 0.04,0.13 ± 0.12,0.05 ± 0.03;0.47 ± 0.11,0.21 ± 0.09,0.10 ± 0.15; 0.50 ± 0.27,0.31 ± 0.10,0.57 ± 0.23) were significantly decreased(all P < 0.05) in HaCaT cells treated with 6.25,12.50,25.00 μmol/L sodium arsenite,respectively.But keratin 10 mRNA expression showed a rise trend and the 6.25 μmoL/L sodium arsenite group (1.83 ± 0.45) was significantly higher than that of the control( 1.07 ± 0.14,P < 0.05 ).The Nrf2 mRNA expressions of HaCaT cells in 12.50,25.00 μmol/L sodium arsenite groups(0.13 ± 0.07,0.69 ± 0.33) were significantly lower than that of the control ( 1.00 ± 0.09,all P < 0.05 ).Conclusions The cellular proliferation and keratinization are decreased when HaCaT cells are exposed to sodium arsenite,which may be regulated by lowering Nrf2 mRNA transcription.

  3. Comparative investigations of sodium arsenite, arsenic trioxide and cadmium sulphate in combination with gamma-radiation on apoptosis, micronuclei induction and DNA damage in a human lymphoblastoid cell line

    International Nuclear Information System (INIS)

    In the field of radiation protection the combined exposure to radiation and other toxic agents is recognised as an important research area. To elucidate the basic mechanisms of simultaneous exposure, the interaction of the carcinogens and environmental toxicants cadmium and two arsenic compounds, arsenite and arsenic trioxide, in combination with gamma-radiation in human lymphoblastoid cells (TK6) were investigated. Gamma-radiation induced significant genotoxic effects such as micronuclei formation, DNA damage and apoptosis, whereas arsenic and cadmium had no significant effect on these indicators of cellular damage at non-toxic concentrations. However, in combination with gamma-radiation arsenic trioxide induced a more than additive apoptotic rate compared to the sum of the single effects. Here, the level of apoptotic cells was increased, in a dose-dependent way, up to two-fold compared to the irradiated control cells. Arsenite did not induce a significant additive effect at any of the concentrations or radiation doses tested. On the other hand, arsenic trioxide was less effective than arsenite in the induction of DNA protein cross-links. These data indicate that the two arsenic compounds interact through different pathways in the cell. Cadmium sulphate, like arsenite, had no significant effect on apoptosis in combination with gamma-radiation at low concentrations and, at high concentrations, even reduced the radiation-induced apoptosis. An additive effect on micronuclei induction was observed with 1 μM cadmium sulphate with an increase of up to 80% compared to the irradiated control cells. Toxic concentrations of cadmium and arsenic trioxide seemed to reduce micronuclei induction. The results presented here indicate that relatively low concentrations of arsenic and cadmium, close to those occurring in nature, may interfere with radiation effects. Differences in action of the two arsenic compounds were identified

  4. Colonic insufflation with carbon monoxide gas inhibits the development of intestinal inflammation in rats

    Directory of Open Access Journals (Sweden)

    Takagi Tomohisa

    2012-09-01

    Full Text Available Abstract Background The pathogenesis of inflammatory bowel disease (IBD is complex, and an effective therapeutic strategy has yet to be established. Recently, carbon monoxide (CO has been reported to be capable of reducing inflammation by multiple mechanisms. In this study, we evaluated the role of colonic CO insufflation in acute colitis induced by trinitrobenzene sulfonic acid (TNBS in rats. Methods Acute colitis was induced with TNBS in male Wistar rats. Following TNBS administration, the animals were treated daily with 200 ppm of intrarectal CO gas. The distal colon was removed to evaluate various parameters of inflammation, including thiobarbituric acid (TBA-reactive substances, tissue-associated myeloperoxidase (MPO activity, and the expression of cytokine-induced neutrophil chemoattractant (CINC-1 in colonic mucosa 7 days after TNBS administration. Results The administration of TNBS induced ulceration with surrounding edematous swelling in the colon. In rats treated with CO gas, the colonic ulcer area was smaller than that of air-treated rats 7 days after TNBS administration. The wet colon weight was significantly increased in the TNBS-induced colitis group, which was markedly abrogated by colonic insufflation with CO gas. The increase of MPO activity, TBA-reactive substances, and CINC-1 expression in colonic mucosa were also significantly inhibited by colonic insufflation with CO gas. Conclusions Colonic insufflation with CO gas significantly ameliorated TNBS-induced colitis in rats. Clinical application of CO gas to improve colonic inflammatory conditions such as IBD might be useful.

  5. Sodium arsenite represses the expression of myogenin in C2C12 mouse myoblast cells through histone modifications and altered expression of Ezh2, Glp, and Igf-1

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Gia-Ming [Environmental Toxicology Graduate Program, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States); Present address: The University of Chicago, Section of Hematology/Oncology, 900 E. 57th Street, Room 7134, Chicago, IL 60637 (United States); Bain, Lisa J., E-mail: lbain@clemson.edu [Environmental Toxicology Graduate Program, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States); Department of Biological Sciences, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States)

    2012-05-01

    Arsenic is a toxicant commonly found in water systems and chronic exposure can result in adverse developmental effects including increased neonatal death, stillbirths, and miscarriages, low birth weight, and altered locomotor activity. Previous studies indicate that 20 nM sodium arsenite exposure to C2C12 mouse myocyte cells delayed myoblast differentiation due to reduced myogenin expression, the transcription factor that differentiates myoblasts into myotubes. In this study, several mechanisms by which arsenic could alter myogenin expression were examined. Exposing differentiating C2C12 cells to 20 nM arsenic increased H3K9 dimethylation (H3K9me2) and H3K9 trimethylation (H3K9me3) by 3-fold near the transcription start site of myogenin, which is indicative of increased repressive marks, and reduced H3K9 acetylation (H3K9Ac) by 0.5-fold, indicative of reduced permissive marks. Protein expression of Glp or Ehmt1, a H3-K9 methyltransferase, was also increased by 1.6-fold in arsenic-exposed cells. In addition to the altered histone remodeling status on the myogenin promoter, protein and mRNA levels of Igf-1, a myogenic growth factor, were significantly repressed by arsenic exposure. Moreover, a 2-fold induction of Ezh2 expression, and an increased recruitment of Ezh2 (3.3-fold) and Dnmt3a (∼ 2-fold) to the myogenin promoter at the transcription start site (− 40 to + 42), were detected in the arsenic-treated cells. Together, we conclude that the repressed myogenin expression in arsenic-exposed C2C12 cells was likely due to a combination of reduced expression of Igf-1, enhanced nuclear expression and promoter recruitment of Ezh2, and altered histone remodeling status on myogenin promoter (− 40 to + 42). -- Highlights: ► Igf-1 expression is decreased in C2C12 cells after 20 nM arsenite exposure. ► Arsenic exposure alters histone remodeling on the myogenin promoter. ► Glp expression, a H3–K9 methyltransferase, was increased in arsenic-exposed cells. ► Ezh2

  6. Alkalilimnicola ehrlichii sp. nov., a novel, arsenite-oxidizing haloalkaliphilic gammaproteobacterium capable of chemoautotrophic or heterotrophic growth with nitrate or oxygen as the electron acceptor

    Science.gov (United States)

    Hoeft, S.E.; Blum, J.S.; Stolz, J.F.; Tabita, F.R.; Witte, B.; King, G.M.; Santini, J.M.; Oremland, R.S.

    2007-01-01

    A facultative chemoautotrophic bacterium, strain MLHE-1T, was isolated from Mono Lake, an alkaline hypersaline soda lake in California, USA. Cells of strain MLHE-1T were Gram-negative, short motile rods that grew with inorganic electron donors (arsenite, hydrogen, sulfide or thiosulfate) coupled with the reduction of nitrate to nitrite. No aerobic growth was attained with arsenite or sulfide, but hydrogen sustained both aerobic and anaerobic growth. No growth occurred when nitrite or nitrous oxide was substituted for nitrate. Heterotrophic growth was observed under aerobic and anaerobic (nitrate) conditions. Cells of strain MLHE-1T could oxidize but not grow on CO, while CH4 neither supported growth nor was it oxidized. When grown chemoautotrophically, strain MLHE-1T assimilated inorganic carbon via the Calvin-Benson-Bassham reductive pentose phosphate pathway, with the activity of ribulose 1,5-bisphosphate carboxylase (RuBisCO) functioning optimally at 0.1 M NaCl and at pH 7.3. Strain MLHE-1T grew over broad ranges of pH (7.3-10.0; optimum, 9.3), salinity (115-190 g l-1; optimum 30 g l-1) and temperature (113-40 ??C; optimum, 30 ??C). Phylogenetic analysis of 16S rRNA gene sequences placed strain MLHE-1T in the class Gammaproteobacteria (family Ectothiorhodospiraceae) and most closely related to Alkalispirillum mobile (98.5%) and Alkalilimnicola halodurans (98.6%), although none of these three haloalkaliphilic micro-organisms were capable of photoautotrophic growth and only strain MLHE-1T was able to oxidize As(III). On the basis of physiological characteristics and DNA-DNA hybridization data, it is suggested that strain MLHE-1T represents a novel species within the genus Alkalilimnicola for which the name Alkalilimnicola ehrlichii is proposed. The type strain is MLHE-1T (=DSM 17681T =ATCC BAA-1101T). Aspects of the annotated full genome of Alkalilimnicola ehrlichii are discussed in the light of its physiology. ?? 2007 IUMS.

  7. N-acetylcysteine and meso-2,3 dimercaptosuccinic acid alleviate oxidative stress and hepatic dysfunction induced by sodium arsenite in male rats

    Directory of Open Access Journals (Sweden)

    Abu El-Saad AM

    2016-10-01

    Full Text Available Ahmed M Abu El-Saad,1,4 Mohammed A Al-Kahtani,2 Ashraf M Abdel-Moneim3,4 1Department of Biology, Faculty of Medicine, Dammam University, Dammam, Saudi Arabia; 2Department of Biology, Faculty of Science, King Khalid University, Abha, Saudi Arabia; 3Department of Biological Sciences, Faculty of Science, King Faisal University, Al-Ahsa, Saudi Arabia; 4Department of Zoology, Faculty of Science, Alexandria University, Alexandria, Egypt Abstract: Environmental exposure to arsenic represents a serious challenge to humans and other animals. The aim of the present study was to test the protective effect of antioxidant N-acetylcysteine (NAC either individually or in combination with a chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA, against sodium arsenite oral toxicity in male rats. Five groups were used: control; arsenic group (orally administrated in a concentration of 2 mg/kg body weight [b.w.]; the other three groups were orally administrated sodium arsenite in a concentration of 2 mg/kg b.w. followed by either NAC (10 mg/kg b.w., intraperitoneally [i.p.], DMSA (50 mg/kg b.w., i.p. or NAC plus DMSA. Arsenic toxicity caused significant rise in serum aspartate aminotransferase, alanine aminotransferase and total bilirubin, and a significant decrease in total protein (TP and albumin levels after 3 weeks of experimental period. In addition, arsenic-treated rats showed significantly higher arsenic content in liver and significant rise in hepatic malondialdehyde level. By contrast, sharp decreases in glutathione content and catalase and glutathione reductase activities were discernible. NAC and/or DMSA counteracted most of these physiologic and biochemical defects. NAC monotherapy was more effective than DMSA in increasing TP, while DMSA was more effective in decreasing alanine aminotransferase. The combined treatment was superior over monotherapies in recovery of TP and glutathione. Biochemical data were well supported by histopathological and

  8. Isolation and Identification of a Microbacterium Strain with Arsenite-Oxidizing and Arsenate-Reducing Abilities%一株兼具砷氧化还原功能微杆菌的筛选和鉴定

    Institute of Scientific and Technical Information of China (English)

    陈来琳; 曾琳; 柯林

    2011-01-01

    [目的]为获取兼具砷氧化还原功能的多功能菌株.[方法]通过多次分离、纯化,先从广西河池砷污染地区的水源洞水样中筛选出砷耐受菌,再从砷耐受菌中筛选出在好氧条件下既能还原As(V)又能氧化As(Ⅲ)的多功能菌株CLL-B7.[结果]经测定16S rDNA的序列,鉴定菌株属于Microbacterium sp,,GenBank中的注册号是JF975617.该菌株能耐受高达115 mmol/L As(V)和40 mmol/L As(Ⅲ),不能利用除营养肉汤外的多种有机碳源,在pH 6条件下生长情况最好.该菌株在3d内几乎能完全还原10 mmol/L As(V),并从第7天开始表现出砷氧化功能.[结论]该菌株能在好氧环境下进行砷还原,可能利用有机碳源作为电子供体.%[Objective] The research aimed to obtain bacteria with both arsenite-oxidizing and arsenate-reducing abilities. [ Method] A number of arsenite-resistant bacteria were isolated from arsenic-contaminated aquifers in Hechi, Guangxi Province. Among them, a rarely reported strain named CLL-B7 with both arsenite-oxidizing and arsenate-reducing abilities was screened and identified. [ Result J The phylogenetic analysis indicated that the strain belonged to the genus Microbacterium. The 16S rRNA gene sequence was deposited in the GenBank database under accession number JF975617. Strain CLL-B7 only grew in LB but couldn't use other organic carbon sources. And the optimal pH for its growth was 6. The strain was tolerant to 40 mmol/L arsenite and 115 mmol/L arsenate, which was able to reduce 10 mmol/l, arsenate in the first three days but the oxidation of arsenite was observed on day 7. [Conclusion] The strain could reduce arsenate in aerobic conditions indicating that it used organic carbon as the electron donor.

  9. LSC-DC-CIK对慢性粒细胞白血病干细胞杀伤作用的体外试验研究%Killing effects of cytokines-induced killer cells on chronic myelocytic leukemia(CML) stem cells in vitro

    Institute of Scientific and Technical Information of China (English)

    庞华; 孙雯雯; 梁芳芳; 司玉玲; 窦金霞

    2013-01-01

    Objective To investigate the killing effects of cytokines-induced killer cells (CIK) co-cultured with dendritic cells derived from chronic myelocytic leukemia (CML) stem cells on CML stem cells (K562). Methods Bone marrow mononuclear cells (BMMC) were isolated from CML donors. CD34+CD38-CD44+ cells (LSC) were isolated and purified by flow cytometry (FCM), which were cultured and induced to LSC-DC. The BMMCs from the same donors were induced to CIK. LSC-DC and CIK were co-cultured, and co-cultured cells were observed under a light microscope. FCM technique was used to analyze the cellular immuno -phenotype. The expressions of BCR/ABL fusion gene in LSC and LSC -DC were detected by fluorescence in situ hybridization (FISH). The killing and apoptotic effects of LSC-DC-CIK on CML stem cells (K562) were measure by FCM. Results LSC-DCs were successfully induced from leukemia stem cells. The expression rates of CD40, CD80, CD83, CD86 and HLA-DR in LSC-DC increased significantly, as compared with cells before induction, the expression rates of CD3, CD8 and CD56 in co-cultured CIK were significantly higher than those in CIK (P<0.01). The killing rate of CIK co-cultured with LSC-DC on K562 cells was 66.94%, which was obviously higher than that (31.89%) of CIK (P<0.01). Moreover, the apoptotic rate of K562 cells induced by LSC-DC-CIK was 52.28%, which was significantly higher than that (37.51%) induced by CIK (P<0.01), but there was no significant apoptotic effect on leukemia stem cells. Conclusion The functions of LSC -DC derived from CML are normal, LSC-DC co-cultured with CIK could effectively kill stem cells of CML, but could not significantly induce the apoptosis of stem cells.%目的 研究慢性粒细胞白血病(CML)患者来源的干细胞体外扩增诱导生成树突细胞(DC),与同来源的细胞因子诱导的杀伤细胞(CIK)共培养,对慢性粒细胞白血病细胞株K562干细胞的杀伤作用.方法 提取CML患者的骨髓单个核细胞(BMMC),利用流

  10. DC-CIK联合化疗治疗晚期非小细胞肺癌的临床疗效%Dendritic cell-cytokine induced killer cells combined with chemotherapy in treatment of advanced non-small cell lung cancer patients: The clinical effectiveness

    Institute of Scientific and Technical Information of China (English)

    张俊萍; 王江涛; 贾林梓; 毛光华; 史天良; 杨晓玲; 肖艳; 张丽彬; 冯慧晶; 韩亚萍; 智婷

    2011-01-01

    Objective: To evaluate the safety and therapeutic effect of dentritic cell (DC) -cytokine induced killer cells (CIKs) combined with chemotherapy in treatment of advanced non-small cell lung cancer (NSCLC) patients. Methods; Fifty patients with advanced NSCLC ( stage Ⅲ to Ⅳ ) , who were admitted to Tumor Hospital of Shanxi Province from August 2008 to January 2010, were treated by DC-CIK combined with chemotherapy (docetaxel + cisplatin) and were taken as the combined treatment group; another fifty advanced NSCLC patients who were treated with chemotherapy alone ( docetaxel + cisplatin) during the same period were taken as controls. The immune function, therapeutic effect, 1-year survival , life quality, and side effects were compared between the two groups. Furthermore, the safety and therapeutic effects of DC-CIK therapy were observed. Results; DC-CIK cells from NSCLC patients were successfully induced, the ratios of CD3+ CD8+ and CD3 + CD56+ cells in DC-CIK cells were significantly increased after culture (P <0.05). There were no obvious changes of T cell subsets in the peripheral blood after combined therapy, and the therapy increased IFN-γ level (P < 0.05). In the chemotherapy group, the ratios of CD3+CD4 + , CD3+ CD8+, CD3- CD56 + cells and IL-2, TNF-α levels were significantly decreased after cell culture (P < 0.05); and the ratios of CD3+ CD8+ , CD3+ CD56 + cells in DCCIK was increased ( P < 0.05 ) . The disease control rate ( DCR) of combined therapy group was higher than that in chemotherapy group (78.0% vs 56.0% , P <0.05) ; the 1-year survival rates of combined therapy group and chemotherapy group were 50% and 44% , respectively, showing no significant difference (P>0.05). The combined therapy group had less side effects(including bone marrow suppression, nausea and vomiting, and peripheral nerve toxicity) compared with the control chemotherapy group ( P < 0.05). The physical condition and appetite of NSCLC patients in the combined

  11. 转染肿瘤细胞总RNA的树突状细胞联合CIK细胞抗小鼠肝癌作用的实验研究%Study on Anti-mouse Hepatocellular Carcinoma Effect of Cytokine-induced Kill Cells Activated by Dendritic Cells Transfected With Mouse Hepatocellular Carcinoma Total RNA in vitro

    Institute of Scientific and Technical Information of China (English)

    罗善超; 刘剑勇; 赵荫农; 张志明; 崔英; 张春燕; 张力图

    2012-01-01

    Objective To investigate anti-mouse hepatocellular carcinoma( HCC ) effect of cytokine-induced killer cells( CIK ) activated by dendritic cells( DC ) transfected with mouse HCC total RNA in vitro. Methods The DC precursors and DC harvested from the bone marrow were incubated with recombinant murine granulocyte marcophage-colony stimulating factor( rmGM-CSF ) and recombinant murine interleukin-4( nrJL-4 ) in vitro. Splenocytes were isolated from mouse spleen. Nonadherent splenocytes were induced to CIK by recombinant murine IFN-gamma( rmlFN-γ ),anti-mouse CD3( anti-CD3 ), recombinant murine interleukin-2( rmIL-2 ),recombinant murine IL-lb( rmIL-lb )in vitro. Tumor-derived total RNA extracted from actively growing H22 cells was mixed with DC to transfect DC in vitro. The phenotypes of DCs( DCs transfected with total RNA or DCs non-transfected with total RNA ) were analyzed by flow cytometry. Dendritic cells and CIK cells were co-cultured as effector cells. Mouse H22 cells and S180 cells were used as target cells in the LDH release methods to determine their cytotoxic activity.Results The expressions of MHC-Ⅰ,MHC-Ⅱ,CD83,CD86 were up-regulated and the expressions of CD14 was down-regulated after DC was transfected with tumor total RNA. DC transfected total RNA of H22 cells achieved higher cytotoxicity on H22 cells than on S180 cells( P < 0.05 ). CIK cells activated by DC transfected total RNA of H22 cells achieved the highest cytotoxicity on H22 cells in all groups( P <0.05 ). Conclusion CIK cells activated by DC transfected total RNA of H22 cells present efficient and specific anti-mouse immune response of HCC on H22 cells in vitro.%目的 探讨转染小鼠肝癌H22细胞总RNA的树突状细胞(DC)疫苗体外抗小鼠肝癌的免疫作用.方法 提取小鼠四肢长骨骨髓,在rmGM-CSF和rmIL-4体外刺激下增殖分化为DC.制备小鼠脾淋巴细胞,在体外经rmIFN-γ、anti-CD3、rmIL-2和rmIL-1b诱导成为细胞因子诱导的杀伤

  12. The small heat shock protein, HSP30, is associated with aggresome-like inclusion bodies in proteasomal inhibitor-, arsenite-, and cadmium-treated Xenopus kidney cells.

    Science.gov (United States)

    Khan, Saad; Khamis, Imran; Heikkila, John J

    2015-11-01

    In the present study, treatment of Xenopus laevis A6 kidney epithelial cells with the proteasomal inhibitor, MG132, or the environmental toxicants, sodium arsenite or cadmium chloride, induced the accumulation of the small heat shock protein, HSP30, in total and in both soluble and insoluble protein fractions. Immunocytochemical analysis revealed the presence of relatively large HSP30 structures primarily in the perinuclear region of the cytoplasm. All three of the stressors promoted the formation of aggresome-like inclusion bodies as determined by immunocytochemistry and laser scanning confocal microscopy using a ProteoStat aggresome dye and additional aggresomal markers, namely, anti-γ-tubulin and anti-vimentin antibodies. Further analysis revealed that HSP30 co-localized with these aggresome-like inclusion bodies. In most cells, HSP30 was found to envelope or occur within these structures. Finally, we show that treatment of cells with withaferin A, a steroidal lactone with anti-inflammatory, anti-tumor, and proteasomal inhibitor properties, also induced HSP30 accumulation that co-localized with aggresome-like inclusion bodies. It is possible that proteasomal inhibitor or metal/metalloid-induced formation of aggresome-like inclusion bodies may sequester toxic protein aggregates until they can be degraded. While the role of HSP30 in these aggresome-like structures is not known, it is possible that they may be involved in various aspects of aggresome-like inclusion body formation or transport.

  13. Comparative hepatotoxicity and clastogenicity of sodium arsenite and three petroleum products in experimental Swiss Albino Mice: the modulatory effects of Aloe vera gel.

    Science.gov (United States)

    Gbadegesin, Michael A; Odunola, Oyeronke A; Akinwumi, Kazeem A; Osifeso, Olabode O

    2009-10-01

    Petroleum products (PPs) consist of complex chemical mixtures, mainly hydrocarbons. Their composition varies considerably with source and use. Inappropriate manual handling and use of PPs, in countries like Nigeria, results in excessive skin contact with the possibility of hazard to health. There has been inadequate evidence to classify diesel, kerosene and hydraulic oil as human carcinogens and there is limited evidence for their toxicity and carcinogenicity in experimental animals. We compared the hepatotoxicity and clastogenicity of diesel, petrol or hydraulic oil with that of sodium arsenite (Na(2)AsO(2)) in mice. Our findings showed that these PPs are capable of inducing gamma-glutamyl transferase (gammaGT) activity in the serum and liver to levels comparable with that induced by Na(2)AsO(2). Mice treated with individual PPs have elevated mean liver and serum gammaGT at levels that are significantly different from the values observed for the negative control group. Also, the individual PPs alone have micronuclei formation induction activity similar to Na(2)AsO(2). We found that treatment with Aloe vera gel before the PPs significantly reduced mean liver and serum gammaGT, and the mean number of micronuclei scored when compared with groups administered each of the PPs alone, supporting the presence of hepatoprotective components in Aloe vera. PMID:19583991

  14. Separation/Preconcentration and Speciation Analysis of Trace Amounts of Arsenate and Arsenite in Water Samples Using Modified Magnetite Nanoparticles and Molybdenum Blue Method

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Karimi

    2014-01-01

    Full Text Available A new, simple, and fast method for the separation/preconcentration and speciation analysis of arsenate and arsenite ions using cetyltrimethyl ammonium bromide immobilized on alumina-coated magnetite nanoparticles (CTAB@ACMNPs followed by molybdenum blue method is proposed. The method is based on the adsorption of arsenate on CTAB@ACMNPs. Total arsenic in different samples was determined as As(V after oxidation of As(III to As(V using potassium permanganate. The arsenic concentration has been determined by UV-Visible spectrometric technique based on molybdenum blue method and amount of As(III was calculated by subtracting the concentration of As(V from total arsenic concentration. MNPs and ACMNPs were characterized by VSM, XRD, SEM, and FT-IR spectroscopy. Under the optimal experimental conditions, the preconcentration factor, detection limit, linear range, and relative standard deviation (RSD of arsenate were 175 (for 350 mL of sample solution, 0.028 μg mL−1, 0.090–4.0 μg mL−1, and 2.8% (for 2.0 μg mL−1, n=7, respectively. This method avoided the time-consuming column-passing process of loading large volume samples in traditional SPE through the rapid isolation of CTAB@ACMNPs with an adscititious magnet. The proposed method was successfully applied to the determination and speciation of arsenic in different water samples and suitable recoveries were obtained.

  15. 牛膝多糖刺激的DC联合CIK细胞对SW480的杀伤作用研究%Effect of Achyranthes bidentata polysaccharides stimulated dendritic cells co-cultured with cytokine induced killer cells against SW480 cells

    Institute of Scientific and Technical Information of China (English)

    周智东; 夏大静

    2013-01-01

    Achyranthes bidentata polysaccharides (ABPS) was extracted from the root ofA.bidentata.Dendritic cells(DC),which were stimulated with ABPS and/or tumor antigen SW480,were co-cultured with cytokine induced killer cells (CIK) to test the cytotoxic effect on colon cancer cell line SW480.Peripheral bloodmononuclear cells (PBMNCs) which were separated from human peripheral blood were cultured to DC and CIK separately.①DC were divided into four groups:pure DC served as control group; ABPS (50 mg · L-1) stimulated DC served as experimental group; SW480 tumor antigen stimulated DC served as the second experimental group; ABPS(50 mg · L-1) and SW480 tumor antigen co-stimulated DC served as the third experimental group.Flow cytometry was used to detect the difference of the positive rate of molecules in the cell surface of DC,include CD80,CD86,CD11c,CD40,HLA-DR (6 samples for each group).②The four DC groups were mixed with CIK at the ratio 1∶5 and acted as effect cells (DC +CIK groups),and the colon cancer cell line SW480 acted as target cells.The effect cells and the target cells were mixed together at the ratio 30∶1,20∶1 and 10∶1 separately,and the CCK-8 kit was used to test the cytotoxic effect on colon cancer cell line SW480.③ At the mixing ratio 30∶1 of effect cells and target cells,ELISA was used to test the level of cytokines secretion,including IL-2,IL-12p70,IL-17 and TNF-α,in the liquid supernatant of every test group (3 duplication per sample).The results showed as following:① The positive rates of CD80,CD11c,HLA-DR,in the cell surface of DC which was co-stimulated by ABPS (50 mg · L-1) and SW480 tumor antigen,were obviously higher than the other DC groups (P < 0.05),and the positive rates of CD86,CD40 were obviously higher than the pure DC group (P<0.05),and there was no remarkable difference with the other two DC groups.②At the mixing ratio 30∶1,20∶1 and 10∶1 of the effect cells and the target cells,the cytotoxic effect of ABPS

  16. Oxidative damage induced by sodium arsenite in human bronchial epithelial cells in cultured%亚砷酸钠对人支气管上皮细胞的氧化损伤作用

    Institute of Scientific and Technical Information of China (English)

    刘星; 聂继华; 陈志海; 金洹宇; 陈秋; 周新文; 焦旸; 童建; 安艳

    2012-01-01

    Objective To study the effect of oxidative damage induced by sodium arsenite in human bronchial epithelial cells (HBE cells). Methods The cultured HBE cells were treated with sodium arsenite at the doses of 0-50 000 μmol/L respectively for 24 h. The cell viability was tested by Cell Counting Kit-8(CCK-8). HBE cells were exposed to sodium arsenite at the doses of 0-6 μmol/L respectively for 24 h, and the reactive oxygen species(ROS) level,the malondialdehyde(MDA) and the superoxi dismutase(SOD) content in HBE cells were detected respectively. Single cell gel electrophoresis(SCGE) was applied to the quantitative analysis of DNA damage in HBE cells. Results Compared with the control group, the level of ROS and the content of MDA were significantly increased (P<0.05), while the content of SOD was significantly decreased in exposure groups (P<0.05). Sodium arsenite could significantly increase DNA Olive tail moment in HBE cells in exposure groups compared with the control group (P<0.05). Conclusion Sodium arsenite may increase the oxidative damage in HBE cells incultured. It is suggested that oxidative stress might be an important mechanism for the toxicity of sodium arsenite to HBE cells.%目的 探讨不同浓度亚砷酸钠对永生化人支气管上皮细胞氧化损伤的影响.方法 体外培养永生化人支气管上皮(HBE)细胞,加入终浓度为0~50000 μmol/L的亚砷酸钠溶液暴露24h,测定细胞活性;加入终浓度为0~6μmol/L的亚砷酸钠溶液暴露24h,测定活性氧(ROS)、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活力及细胞DNA链断裂情况.结果 与对照组比较,各浓度亚砷酸钠染毒组HBE细胞内ROS、MDA含量和Olive尾矩均显著升高,细胞存活率和SOD活力均显著下降,差异有统计学意义(P<0.05);且随着亚砷酸钠染毒浓度的升高,HBE细胞内MDA、ROS含量和Olive尾矩均呈明显的上升趋势(P<0.05),细胞存活率和SOD活力均呈明显的下降趋势(P<0.05).

  17. Effectiveness of Arsenite Adsorption by Ferric and Alum Water Treatment Residuals with Different Grain Sizes%不同粒径铁铝泥对砷(Ⅲ)的吸附效果

    Institute of Scientific and Technical Information of China (English)

    林璐; 胥嘉瑞; 吴昊; 王昌辉; 裴元生

    2013-01-01

    以给水处理厂废弃铁铝泥(ferric and alum water treatment residuals,FARs)为载体,考察了不同粒径FARs对砷(Ⅲ)的吸附效果.不同粒径FARs的有效铁铝含量、比表面积和孔体积分别为523.72 ~1 861.72 mmol·kg-1、28.15 ~ 265.59 m2·g-1和0.03~0.09 cm3·g-1,总有机质、富里酸、胡敏酸和胡敏素分别为46.97 ~ 91.58、0.02~ 32.27、22.27~34.09和10.76 ~34.22 mg·kg-1.SEM和XRD检测表明,不同粒径FARs均以无定形结构存在.批量实验结果表明,准一级和准二级动力学方程均能较好地反映FARs吸附砷(Ⅲ)的动力学过程.不同粒径FARs对砷(Ⅲ)的吸附量随着浓度的增加而增高,用Langmuir等温线方程拟合获得理论饱和吸附量在6.72~21.79 mg·g-1之间.pH值对FARs吸附砷(Ⅲ)的作用影响不大.砷(Ⅲ)吸附量大小与不同粒径FARs的理化性质的变化趋势基本一致,由相关性分析可得,有效铁铝含量和孔体积大小是影响FARs对砷(Ⅲ)吸附的主要因素.%Effectiveness of arsenite adsorption by ferric and alum water treatment residuals (FARs) with different grain sizes was studied.The results indicated that the content of active Fe and Al,the specific surface area and pore volume in FARs with different grain sizes were in the range of 523.72-1 861.72 mmol·kg-1,28.15-265.59 m2·g-1 and 0.03-0.09 cm3 ·g-1,respectively.The contents of organic matter,fulvic acid,humic acid and humin were in the range of 46.97-91.58 mg·kg-1,0.02-32.27 mg·kg-1,22.27-34.09 mag· kg-1 and 10.76-34.22 mg·kg-1,respectively.Results of SEM and XRD analysis further demonstrated that FARs with different grain sizes were amorphousness.Batch experiments suggested that both the pseudo-first-order and pseudo-second-order equations could well describe the kinetics adsorption processes of arsenite by FARs.Moreover,the contents of arsenite absorbed by FARs increased with the increase of arsenite concentrations.The theoretical saturated adsorption

  18. Characterizing mRNA interactions with RNA granules during translation initiation inhibition.

    Directory of Open Access Journals (Sweden)

    Chiara Zurla

    Full Text Available When cells experience environmental stresses, global translational arrest is often accompanied by the formation of stress granules (SG and an increase in the number of p-bodies (PBs, which are thought to play a crucial role in the regulation of eukaryotic gene expression through the control of mRNA translation and degradation. SGs and PBs have been extensively studied from the perspective of their protein content and dynamics but, to date, there have not been systematic studies on how they interact with native mRNA granules. Here, we demonstrate the use of live-cell hybridization assays with multiply-labeled tetravalent RNA imaging probes (MTRIPs combined with immunofluorescence, as a tool to characterize the polyA+ and β-actin mRNA distributions within the cytoplasm of epithelial cell lines, and the changes in their colocalization with native RNA granules including SGs, PBs and the RNA exosome during the inhibition of translational initiation. Translation initiation inhibition was achieved via the induction of oxidative stress using sodium arsenite, as well as through the use of Pateamine A, puromycin and cycloheximide. This methodology represents a valuable tool for future studies of mRNA trafficking and regulation within living cells.

  19. Inhibition in multiclass classification

    OpenAIRE

    Huerta, Ramón; Vembu, Shankar; Amigó, José M.; Nowotny, Thomas; Elkan, Charles

    2012-01-01

    The role of inhibition is investigated in a multiclass support vector machine formalism inspired by the brain structure of insects. The so-called mushroom bodies have a set of output neurons, or classification functions, that compete with each other to encode a particular input. Strongly active output neurons depress or inhibit the remaining outputs without knowing which is correct or incorrect. Accordingly, we propose to use a classification function that embodies unselective inhibition and ...

  20. Therapeutic effect of sodium arsenite on rheumatoid arthritis in rabbit%亚砷酸治疗兔类风湿关节炎的实验研究

    Institute of Scientific and Technical Information of China (English)

    曹俊; 胡宾; 沈敬华

    2013-01-01

    目的 探讨亚砷酸对卵蛋白诱导性关节炎滑膜细胞Caspase-3、细胞色素C的影响.方法 将48只家兔随机分为正常对照组、模型对照组、亚砷酸低剂量组(1.0 mg·kg-1·d-1)、亚砷酸中剂量组(2.0 mg·kg-1·d-1)、亚砷酸高剂量组(4.0 mg·kg-1·d-1),激素组醋酸尼松龙(10 mg·d-1),每组8只.建立卵蛋白诱导关节炎兔模型,给药2周后,采用分光光度法检测滑膜细胞中的Caspase-3活性及免疫组化染色测定细胞色素C.结果 检测结果显示模型组膝关节直径、表面温度均显著升高,与正常组比较由显著性差异(P<0.01);亚砷酸低剂量组、中剂量组、高剂量组均可显著性提高滑膜细胞Caspase-3、CytC水平(P<0.01或P<0.05).结论 推测亚砷酸作用于线粒体,使线粒体内的细胞色素C释放,激活Caspases,诱导滑膜细胞凋亡发生.%Objective To observe the effects of Sodium Arsenite( SDA )on the levels of Caspase-3 and CytC with the model of rabbit rheumatoid arthritis induced by ovalbumin. Methods Forty-eight rabbits were randomly divided into six groups: normal control group, model group,low-dose of SDA group( 1.0 mg · kg-1 · d-1 ), middle-dose of SDA group( 2. 0 mg · kg-1 · d-1 ),high-dose of SDA group( 4.0 mg · kg"1 · d"1 ) and prednisolone group( 10 mg · d-1 ). The model rabbit with rheumatoid arthritis induced by ovalbumin was established. After two weeks of therapy,the activity of Caspase-3 was assessed by Caspase-3 assay kit. CytC was examined by immu-nohistologica levaluation. Results After inducement, the articular diameters of both knees and the temperature of the articular skin showed an obvious increase, compared with normal group( P<0.01 ),Arsenious acid increased the key factors of the apoptotic pathway. There are differences compared with model group( P <0. 01 ). Conclusions Sodium arsenite has effect in mitochondria,resulting in Cyt-C release and activation of Caspases, and thus induce synoviocytes

  1. 分散式饮水中三价砷的去除%Study on the removal of arsenite from dispersed drinking water

    Institute of Scientific and Technical Information of China (English)

    袁涛; 罗启芳

    2001-01-01

    The feasible methods for oxidation and removal of arsenite[As(Ⅲ)]from dispersed drinking water were based on the removal of arsenate[As(V)] by ferric sulfate. The results showed that the spotaneous oxidation of As(III) to As(V) was very slow and could not be enhanced by aerating for 24h. The removal rate of As(III) could reach that of As(V) when pre-aerating water samples with ozone for 60s, putting 7.5ml/L hydrogen peroxide solution, adding 2.5mg/L javelle water (sodium hypochlorite) or 15mg/L bleaching powder(numerated by chlorine).The oxidation by using javelle water was rather stable when samples were varied in pH value, hardness, initial concentration of As(III) and As(III)/As(V) ratio. The effective oxidation could be reached with 1.25mg/L javelle water when the initial concentration of As(III) was ≤0.8mg/L. Moreover, the field study also confirmed the oxidation effect of javelle water. It is suggested that javelle water is an effective, economic and technologic feasible oxidationagent for removing arsenite from dispersed drinking water.%在利用硫酸铁去除五价砷[As(V)]的基础上研究了三价砷[As(III)]的氧化及去除,以寻求适合于分散式饮水中As(III)的氧化方法。结果显示:水中As(III)的自然氧化过程相当缓慢,曝气24h亦难以加速其氧化;通入臭氧60s,或按7.5ml/L投加双氧水,按投氯量加2.5mg/L次氯酸钠或15mg/L的漂白粉等,均可有效氧化1.0mg/LAs(III),使砷去除率近似于As(V)的去除率;选取次氯酸钠作为氧化剂,进一步研究发现其氧化效果不受水质pH值、硬度、As(III)初浓度、As(III)/As(V)的配比等的影响,而且1.25mg/L投加量可有效氧化≤0.8mg/L的As(III),现场实验亦证实了其氧化效果。本研究结果表明,次氯酸钠是一种效果可靠、经济技术可行的分散式饮水三价砷的氧化剂。

  2. Contribution of aquaporin 9 and multidrug resistance-associated protein 2 to differential sensitivity to arsenite between primary cultured chorion and amnion cells prepared from human fetal membranes.

    Science.gov (United States)

    Yoshino, Yuta; Yuan, Bo; Kaise, Toshikazu; Takeichi, Makoto; Tanaka, Sachiko; Hirano, Toshihiko; Kroetz, Deanna L; Toyoda, Hiroo

    2011-12-01

    Arsenic trioxide (arsenite, As(III)) has shown a remarkable clinical efficacy, whereas its side effects are still a serious concern. Therefore, it is critical to understand the effects of As(III) on human-derived normal cells for revealing the mechanisms underlying these side effects. We examined the effects of As(III) on primary cultured chorion (C) and amnion (A) cells prepared from human fetal membranes. A significant dose-dependent As(III)-mediated cytotoxicity was observed in the C-cells accompanied with an increase of lactate dehydrogenase (LDH) release. Higher concentrations of As(III) were required for the A-cells to show cytotoxicity and LDH release, suggesting that the C-cells were more sensitive to As(III) than the A-cells. The expression levels of aquaporin 9 (AQP9) were approximately 2 times higher in the C-cells than those in the A-cells. Both intracellular arsenic accumulation and its cytotoxicity in the C-cells were significantly abrogated by sorbitol, a competitive AQP9 inhibitor, in a dose-dependent manner. The protein expression levels of multidrug resistance-associated protein (MRP) 2 were downregulated by As(III) in the C-cells, but not in the A-cells. No significant differences in the expression levels of MRP1 were observed between C- and A-cells. The protein expression of P-glycoprotein (P-gp) was hardly detected in both cells, although a detectable amount of its mRNA was observed. Cyclosporine A, a broad-spectrum inhibitor for ABC transporters, and MK571, a MRP inhibitor, but not PGP-4008, a P-gp specific inhibitor, potently sensitized both cells to As(III)-mediated cytotoxicity. These results suggest that AQP9 and MRP2 are involved in controlling arsenic accumulation in these normal cells, which then contribute to differential sensitivity to As(III) cytotoxicity between these cells.

  3. Survey of environmental arsenit in Gang Fang-Ying village%土右旗缸房营村环境砷的调查

    Institute of Scientific and Technical Information of China (English)

    赵瑞君; 马涛; 武文宏; 郝怀志; 冯晓冬

    2001-01-01

    目的调查缸房营村砷中毒的原因。方法采集该村饮用井水、粮食、土壤、灌溉水测定其水砷含量。结果 260眼饮用水井有160眼井的水砷含量超过国家饮用水标准,超标率61.54%,且患病率与饮水时间、水砷浓度呈正相关,粮食、土壤、灌溉水中的砷含量均未超标。结论确认了该村的砷中毒为饮水型地方性砷中毒。%Objective To study the correlation of endemic arsenic diseases in Gang Fang-Ying village.Methods Arsenic content of water,grain,and soil in this village were determind.Results Of the 260 shares of drinking well deter mined,arsenic content exceed the level are 160 shares,it takes 61.54 percent.The rate of suffering illness relate with drinking time and arsenit content.Arsenic contained in grain,soil,and water is within the mormal limit.Conclusions On the basis of the investigation,it can be affirmed that endemic arsenic disease in this village results from arsenic content in drinking water which exceeded the level.

  4. The distribution of arsenate and arsenite in shoots and roots of Holcus lanatus is influenced by arsenic tolerance and arsenate and phosphate supply.

    Science.gov (United States)

    Quaghebeur, Mieke; Rengel, Zdenko

    2003-07-01

    The recent discovery that phytochelatins are important for arsenic (As) detoxification in terrestrial plants results in the necessity to understand As speciation and metabolism in plant material. A hydroponic study was therefore conducted to examine the effects of different levels of phosphate and arsenate [As(V)] on As speciation and distribution in tolerant and non-tolerant clones of Holcus lanatus. Speciation of As in tissue (using high-performance liquid chromatography-inductively coupled plasma mass spectrometry) revealed that the predominant species present were the inorganic As species (As(V) and arsenite [As(III)]), although small levels (<1%) of organic As species (dimethylarsinic acid and monomethylarsonic acid) were detected in shoot material. In roots, the proportion of total As present as As(III) generally increased with increasing levels of As(V) in the nutrient solution, whereas in shoots, the proportion of total As present as As(III) generally decreased with increasing levels of As(V). H. lanatus plants growing in the high-phosphorus (P) (100 micro M) solution contained a higher proportion of As(V) (with regard to total As) in both roots and shoots than plants supplied with low P (10 micro M); in addition, tolerant clones generally contained a higher proportion of As(V) with regard to total As than non-tolerant clones. The study further revealed that As(V) can be reduced to As(III) in both roots and shoots. Although the reduction capacity was limited, the reduction was closely regulated by As influx for all treatments. The results therefore provide a new understanding about As metabolism in H. lanatus.

  5. Gastrointestinal protective efficacy of Kolaviron (a bi-flavonoid from Garcinia kola following a single administration of sodium arsenite in rats: Biochemical and histopathological studies

    Directory of Open Access Journals (Sweden)

    Akinleye S Akinrinde

    2015-01-01

    Full Text Available Background: Arsenic intoxication is known to produce symptoms including diarrhea and vomiting, which are indications of gastrointestinal dysfunction. Objective: We investigated whether Kolaviron (KV administration protected against sodium arsenite (NaAsO 2 -induced damage to gastric and intestinal epithelium in rats. Materials and Methods: Control rats (Group I were given a daily oral dose of corn oil. Rats in other groups were given a single dose of NaAsO 2 (100 mg/kg; intraperitoneal alone (Group II or after pretreatment for 7 days with KV at 100 mg/kg (Group III and 200 mg/kg (Group IV. Rats were sacrificed afterward and portions of the stomach, small intestine and colon were processed for histopathological examination. Hydrogen peroxide, reduced glutathione, malondialdehyde (MDA concentrations as well as activities of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPX, glutathione S-transferase (GST and myeloperoxidase (MPO were measured in the remaining portions of the different gastrointestinal tract (GIT segments. Results: NaAsO 2 caused significant increases (P < 0.05 in MDA levels and MPO activity, with significant reductions (P < 0.05 in GST, GPX, CAT and SOD activities in the stomach and intestines. KV significantly reversed the changes (P < 0.05 in a largely dose-dependent manner. The different segments had marked inflammatory cellular infiltration, with hyperplasia of the crypts, which occurred to much lesser degrees with KV administration. Conclusion: The present findings showed that KV might be a potent product for mitigating NaAsO 2 toxicity in the GIT.

  6. Down Regulation of CIAPIN1 Reverses Multidrug Resistance in Human Breast Cancer Cells by Inhibiting MDR1

    Directory of Open Access Journals (Sweden)

    Xuemei Wang

    2012-06-01

    Full Text Available Cytokine-induced apoptosis inhibitor 1 (CIAPIN1, initially named anamorsin, a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signaling pathway. Current study has revealed that CIAPIN1 may have wide and important functions, especially due to its close correlations with malignant tumors. However whether or not it is involved in the multi-drug resistance (MDR process of breast cancer has not been elucidated. To explore the effect of CIAPIN1 on MDR, we examined the expression of P-gp and CIAPIN1 by immunohistochemistry and found there was positive correlation between them. Then we successfully interfered with RNA translation by the infection of siRNA of CIAPIN1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi the drug resistance was reduced significantly and the expression of MDR1mRNA and P-gp in MCF7/ADM cell lines showed a significant decrease. Also the expression of P53 protein increased in a statistically significant way (p ≤ 0.01 after RNAi exposure. In addition, flow cytometry analysis reveals that cell cycle and anti-apoptotic enhancing capability of cells changed after RNAi treatment. These results suggested CIAPIN1 may participate in breast cancer MDR by regulating MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic capability of cells.

  7. Lead Adsorption and Arsenite Oxidation by Cobalt Doped Birnessite%掺钴水钠锰矿对铅的吸附及对砷的氧化

    Institute of Scientific and Technical Information of China (English)

    殷辉; 冯雄汉; 邱国红; 谭文峰; 刘凡

    2011-01-01

    In order to study the effects of transition metal ions on the physic-chemical properties of manganese dioxides as environmental friendly materials,three-dimensional nano-microsphere cobalt-doped birnessite was synthesized by reduction of potassium permanganate by mixtures of concentrated hydrochloride and cobalt(Ⅱ) chloride.Powder X-ray diffraction,chemical analysis,N2 physical adsorption,field emission scanning electron microscopy(FE-SEM) and X-ray photoelectron spectra(XPS) were used to characterize the crystal structure,chemical composition and micro-morphologies of products.In the range of molar ratios from 0.05 to 0.20,birnessite was fabricated exclusively.It was observed that cobalt incorporated into the layers of birnessite and had little effect on the crystal structure and micromorpholgy,but crystallinity decreased after cobalt doping.Both chemical analysis and XPS results showed that manganese average oxidation state decreased after cobalt doping,and the percentage of Mn3 + increased.Co(Ⅲ)OOH existed mainly in the structure.With the increase of cobalt,hydroxide oxygen percentage in molar increased from 12.79% for undoped birnessite to 13.05%,17.69% and 17.79% for doped samples respectively.Adsorption capacity for lead and oxidation of arsenite of birnessite were enhanced by cobalt doping.The maximum capacity of Pb2 + adsorption increased in the order HB(2 538 mmol/kg) CoB5(2 798 mmol/kg) CoB10(2 932 mmol/kg) CoB20(3 146 mmol/kg).Oxidation percentage of arsenite in simulated waste water by undoped birnessite was 76.5%,those of doped ones increased by 2.0%,12.8% and 18.9% respectively.Partial of Co3 + substitution for Mn^4+ results in the increase of negative charge of the layer and the content of hydroxyl group,which could account for the improved adsorption capacity of Pb^2 +.After substitution of manganese by cobalt,oxidation capacity of arsenite by birnessite increases likely due to the higher standard redox

  8. Autologous cytokine-induced killer cells therapy on the quality of life of patients with breast cancer after adjuvant chemotherapy: A prospective study%自体细胞因子诱导的杀伤细胞治疗对辅助化疗后乳腺癌患者生活质量影响的前瞻性研究

    Institute of Scientific and Technical Information of China (English)

    梁雪峰; 马东初; 丁震宇; 刘兆喆; 郭放; 刘良; 于卉影; 韩雅玲; 谢晓冬

    2013-01-01

    Objective To explore the effect of autologous cytokine-induced killer cells on the quality of life in patient with breast cancer who have already finished the adjuvant chemotherapy.Methods One hundred and twenty-eight postoperative patients with breast cancer who underwent anthracycline-based adjuvant chemotherapy were enrolled in this prospective study,and they were randomized into 2 groups,i.e.,treatment group,which received the therapy of CIK cells transfusion,and control group,which was given regular follow-up.Meanwhile,patients with positive hormone receptor in the two groups were given endocrine therapy,and the patients with positive axillary lymph nodes were given radiotherapy to the chest wall and regional lymph nodes.The difference of quality of life between the two groups was analyzed according to the EORTC QLQ-BR53 quality of life questionnaire,and the adverse reactions were monitored.Results As regarding the functional evaluation,the physical function scores of patients of the treatment group were (83.43 ± 14.87) and (88.55 ± 11.62) at 3 and 6 months after the CIK cell therapy,respectively,significantly higher than the baseline value [(74.83 ± 13.82),P < 0.05)].Global health status/QOL scores were (83.30 ± 19.09) and (89.68 ± 10.81),significantly higher than the baseline value [(77.72 ±21.05),P <0.05].As regarding symptoms,the scores of fatigue,nausea,vomiting and loss of appetite of patients in the treatment group were higher than the baseline value,with significant differences (P <0.05).The nausea and vomiting scores in the control group at 3 and 6 months of followedup were (26.67 ± 22.56) and (21.47 ± 21.06),significantly lower than the baseline values [(33.31 ±27.07),P < 0.05].The scores of worrying about the future in the patients of treatment group were (47.56 ± 30.84) and (42.33 ±26.95) after 3 and 6 months,significantly better than the baseline value [(57.41 ±30.63),P <0.05].The systematic therapy side effects scores were

  9. 组蛋白修饰改变在亚砷酸钠毒性效应中的作用研究%Effect of histone modification in the toxic effects of sodium arsenite

    Institute of Scientific and Technical Information of China (English)

    牛林梅; 章征保; 曾晓雯; 朱小年; 陈雯; 李道传

    2014-01-01

    OBJECTIVE:We attempted to investigate the function and regulation mechanism of histone H3 modifications in the toxicity induced by sodium arsenite. METHODS:We constructed histone H3 lysine modified defective cell lines by expressing the site-specific H3 mutation plasmids in HBE cells. MTT assay was used to test the cytotoxicity of these cells when exposed to sodium arsenite. Cytokinesis-block micronucleus (CBMN) assay was conducted to examine the function of H3K4 methylation on the effect of the DNA damage. Meanwhile,the HBE cells were treated with sodium arsenite and the mRNA levels of H3K4 methyltransferases and demethyltransferases and the protein levels of the H3K4 methylation were measured by qRT-PCR and Western blot assay to explore the regulation of H3K4 methylation when exposed to sodium arsenite. RESULTS:We found that the cell vitality was reduced about 60% and the rate of cytokinesis-block micronucleus increased more than 2 times when H3K4 methylation defective HBE cells were exposure to low concentrations (1 µmol/L) of sodium arsenite (P<0.01). The reduction of H3K4 methylation could increase the sensitivity of HBE cells treated with sodium arsenite. We also found that H3K4me2/3 were hypermethylated when exposed to 1 µmol/L sodium arsenite and H3K4 demethylase (lysine-specific demethylase 1,LSD1) was decreased in this process (P<0.05). CONCLUSION:The increased H3K4 methylation might be regulated by reduced LSD1,which may be involved in the cytotoxicity and genotoxity induced by sodium arsenite.%目的:探讨组蛋白H3修饰在亚砷酸钠暴露引起的毒性效应中的作用及其调控机制。方法:在HBE细胞中构建组蛋白H3赖氨酸修饰位点突变的细胞株,用亚砷酸钠作用于细胞,四甲基噻唑蓝(MTT)法检测其细胞毒性;用微核实验检测组蛋白H3K4突变后对亚砷酸钠诱导DNA损伤的影响;用蛋白印迹检测亚砷酸钠对H3K4甲基化蛋白表达的影响并用qRT-PCR筛查了其上游修饰

  10. 砷暴露对大鼠原代星形胶质细胞分泌胶质细胞源性递质的影响%Effects of arsenite on gliotransmitter release from primary cultured astrocytes

    Institute of Scientific and Technical Information of China (English)

    王艳; 戴莉莉; 赵凤红; 金亚平

    2015-01-01

    Objective To investigate the impairment mechanism of learning and memory function induced by arsenite exposure through studying the effects of sodium arsenite on gliotransmitter release from astrocytes.Methods Primary cultured astrocytes were isolated from neonatal (0-3 days) Wistar rats and determined by glial fibrillary acidic protein (GFAP) immunofluorescence staining.The primary cultured astrocytes were randomly divided into four groups,in which astrocytes were exposed to 0.0,2.5,5.0,or 10.0 μmol/L sodium arsenite,respectively,for 24 h.Intracellular free Ca2+ concentration ([Ca2+]i) in astrocytes was measured by fluorescence dual wavelength spectrophotometer;,concentrations of glutamate,D-serine,glycine and γ-aminobutyric acid were measured by high performance liquid chromatography (HPLC).Results More than 95% cells were positive for GFAP immunofluorescence staining.The difference of [Ca2+]i among groups treated with sodium arsenite was statistically significant (F =20.030,P < 0.05).[Ca2+]i increased significantly in group treated with 10.0 μmol/L sodium arsenite [(263.27 ± 14.80)nmol/L] compared with those in groups treated with 0.0,2.5,5.0 μmol/L sodium arsenite [(204.24 ± 27.21),(214.49 ± 21.85),(232.74 ± 23.14)nmol/L,all P < 0.05].The differences of the levels of D-serine,glycine and γ-aminobutyric acidamong groups treated with sodium arsenite were significant (F =26.599,33.539,5.599,all P < 0.05).The levels of D-serine [(21.580 ± 1.313),(21.936 ± 1.539),(23.401 ± 1.648)μmol/L],glycine [(26.353 ± 2.449),(29.711 ± 1.530),(29.234 ± 2.057)μmol/L] and γ-aminobutyric acid [(27.277 ± 3.421),(30.213 ± 2.098),(29.364 ± 2.588)μmol/L] released by astrocytes increased significantly in groups treated with 2.5,5.0,10.0 μmol/L sodium arsenite compared with those in groups treated with 0.0 μmol/L sodium arsenite [(16.017 ± 1.046),(16.763 ± 3.007),(22.736 ± 4.139)μmol/L,all P < 0.05].Conclusion Arsenite could affect gliotransmitter

  11. 亚砷酸钠和砷酸钠染毒大鼠尿液砷形态分析%Analysis on the arsenic speciation in urine of rats treated with sodium arsenite and sodium arsenate

    Institute of Scientific and Technical Information of China (English)

    吴军; 吴顺华; 张杰; 郑玉建

    2010-01-01

    目的 分析亚砷酸钠和砷酸钠染毒大鼠尿液中砷形态代谢产物水平,寻找不同价态砷代谢的差异,为进一步探讨砷代谢产物与砷毒性作用机制间的关系提供基础数据.方法 Wistar大鼠70只,体质量80~120 g,按体质量随机分为7组,即对照组、亚砷酸钠高、中、低剂量组和砷酸钠高、中、低剂量组,每组10只.各组大鼠染毒1个月后,收集12 h尿液,采用高效液相色谱-氢化物发生原子荧光光谱法(HPLC-HGAFS)测定尿液中砷形态代谢产物水平,并通过二甲基砷酸(DMA)加标回收率测定来评价结果准确度.结果 亚砷酸钠中剂量组尿液中各种代谢物[3价无机砷(iAs~(3+))、5价无机砷(iAs~(5+))、DMA]水平[(121.66±1.26)、(10.26±2.68)、(204.91±0.56)μg/L]高于高剂量组[(113.20±0.75)、(5.16±1.32)、(147.70±0.77)μg/L,P均<0.05]和低剂量组[(79.35±2.12)、(5.13±2.25)、(56.35±1.23)μg/L,P均<0.05];砷酸钠中剂量组尿液中iAs~(3+)和DMA水平[(315.81±1.69)、(245.12±1.18)μg/L]高于高剂量组[(85.03±0.56)、(110.34±1.04)μg/L,P均<0.05]和低剂量组[(22.97±2.67)、(15.75±2.15)μg/L,P均<0.05].亚砷酸钠高、低剂量组尿液中iAs~(3+)和DMA水平高于砷酸钠组(P均<0.05);而亚砷酸钠中剂量组尿液中iAs~(3+)和DMA水平低于砷酸钠组(P均<0.05).亚砷酸钠高、中、低剂量组DMA的平均加标回收率为94.80%~102.70%,砷酸钠高、中、低剂量组DMA的平均加标回收率为95.33%~108.40%.结论 染砷价态及外暴露剂量不同,大鼠体内砷代谢物的形态和水平就不同;不同价态无机砷在大鼠体内的代谢径路不完全相同.%Objective To analyze the levels and speciation of arsenic metabolites in urine of rats treated with sodium arsenite and sodium arsenate in order to investigate the different aspects of metabolism between sodium arsenite and sodium arsenate,thus to understand further the basic data about relationship between it's metabolism and

  12. Contribution of aquaporin 9 and multidrug resistance-associated protein 2 to differential sensitivity to arsenite between primary cultured chorion and amnion cells prepared from human fetal membranes

    Energy Technology Data Exchange (ETDEWEB)

    Yoshino, Yuta [Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Yuan, Bo, E-mail: yuanbo@toyaku.ac.jp [Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, 1550 4th St, RH584E Box 2911 San Francisco, CA 94158-2911 (United States); Kaise, Toshikazu [Laboratory of Environmental Chemodynamics, School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Takeichi, Makoto [Yoneyama Maternity Hospital, 2-12 Shin-machi, Hachioji, Tokyo 192-0065 (Japan); Tanaka, Sachiko; Hirano, Toshihiko [Department of Clinical Pharmacology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan); Kroetz, Deanna L. [Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, 1550 4th St, RH584E Box 2911 San Francisco, CA 94158-2911 (United States); Toyoda, Hiroo [Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392 (Japan)

    2011-12-15

    Arsenic trioxide (arsenite, As{sup III}) has shown a remarkable clinical efficacy, whereas its side effects are still a serious concern. Therefore, it is critical to understand the effects of As{sup III} on human-derived normal cells for revealing the mechanisms underlying these side effects. We examined the effects of As{sup III} on primary cultured chorion (C) and amnion (A) cells prepared from human fetal membranes. A significant dose-dependent As{sup III}-mediated cytotoxicity was observed in the C-cells accompanied with an increase of lactate dehydrogenase (LDH) release. Higher concentrations of As{sup III} were required for the A-cells to show cytotoxicity and LDH release, suggesting that the C-cells were more sensitive to As{sup III} than the A-cells. The expression levels of aquaporin 9 (AQP9) were approximately 2 times higher in the C-cells than those in the A-cells. Both intracellular arsenic accumulation and its cytotoxicity in the C-cells were significantly abrogated by sorbitol, a competitive AQP9 inhibitor, in a dose-dependent manner. The protein expression levels of multidrug resistance-associated protein (MRP) 2 were downregulated by As{sup III} in the C-cells, but not in the A-cells. No significant differences in the expression levels of MRP1 were observed between C- and A-cells. The protein expression of P-glycoprotein (P-gp) was hardly detected in both cells, although a detectable amount of its mRNA was observed. Cyclosporine A, a broad-spectrum inhibitor for ABC transporters, and MK571, a MRP inhibitor, but not PGP-4008, a P-gp specific inhibitor, potently sensitized both cells to As{sup III}-mediated cytotoxicity. These results suggest that AQP9 and MRP2 are involved in controlling arsenic accumulation in these normal cells, which then contribute to differential sensitivity to As{sup III} cytotoxicity between these cells. -- Highlights: Black-Right-Pointing-Pointer Examination of effect of As{sup III} on primary cultured chorion (C) and amnion

  13. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    International Nuclear Information System (INIS)

    Highlights: → In 3T3-L1 adipocytes iAs3+ decreases insulin-stimulated glucose uptake. → iAs3+ attenuates insulin-induced phosphorylation of AKT S473. → iAs3+ activates the cellular adaptive oxidative stress response. → iAs3+ impairs insulin-stimulated ROS signaling. → iAs3+ decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 μM) inorganic arsenite (iAs3+) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs3+ exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs3+ exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4 expression may also be involved in arsenic-induced insulin resistance in adipocytes

  14. Prolonged inorganic arsenite exposure suppresses insulin-stimulated AKT S473 phosphorylation and glucose uptake in 3T3-L1 adipocytes: Involvement of the adaptive antioxidant response

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Peng [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); School of Public Health, China Medical University, Shenyang 110001 (China); Hou, Yongyong; Zhang, Qiang; Woods, Courtney G.; Yarborough, Kathy; Liu, Huiyu [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Sun, Guifan [School of Public Health, China Medical University, Shenyang 110001 (China); Andersen, Melvin E. [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [The Hamner Institutes for Health Sciences, Research Triangle Park, NC 27709 (United States)

    2011-04-08

    Highlights: {yields} In 3T3-L1 adipocytes iAs{sup 3+} decreases insulin-stimulated glucose uptake. {yields} iAs{sup 3+} attenuates insulin-induced phosphorylation of AKT S473. {yields} iAs{sup 3+} activates the cellular adaptive oxidative stress response. {yields} iAs{sup 3+} impairs insulin-stimulated ROS signaling. {yields} iAs{sup 3+} decreases expression of adipogenic genes and GLUT4. -- Abstract: There is growing evidence that chronic exposure of humans to inorganic arsenic, a potent environmental oxidative stressor, is associated with the incidence of type 2 diabetes (T2D). One critical feature of T2D is insulin resistance in peripheral tissues, especially in mature adipocytes, the hallmark of which is decreased insulin-stimulated glucose uptake (ISGU). Despite the deleterious effects of reactive oxygen species (ROS), they have been recognized as a second messenger serving an intracellular signaling role for insulin action. Nuclear factor erythroid 2-related factor 2 (NRF2) is a central transcription factor regulating cellular adaptive response to oxidative stress. This study proposes that in response to arsenic exposure, the NRF2-mediated adaptive induction of endogenous antioxidant enzymes blunts insulin-stimulated ROS signaling and thus impairs ISGU. Exposure of differentiated 3T3-L1 cells to low-level (up to 2 {mu}M) inorganic arsenite (iAs{sup 3+}) led to decreased ISGU in a dose- and time-dependent manner. Concomitant to the impairment of ISGU, iAs{sup 3+} exposure significantly attenuated insulin-stimulated intracellular ROS accumulation and AKT S473 phosphorylation, which could be attributed to the activation of NRF2 and induction of a battery of endogenous antioxidant enzymes. In addition, prolonged iAs{sup 3+} exposure of 3T3-L1 adipocytes resulted in significant induction of inflammatory response genes and decreased expression of adipogenic genes and glucose transporter type 4 (GLUT4), suggesting chronic inflammation and reduction in GLUT4

  15. Methods of Telomerase Inhibition

    OpenAIRE

    Andrews, Lucy G.; Tollefsbol, Trygve O.

    2008-01-01

    Telomerase is central to cellular immortality and is a key component of most cancer cells although this enzyme is rarely expressed to significant levels in normal cells. Therefore, the inhibition of telomerase has garnered considerable attention as a possible anticancer approach. Many of the methods applied to telomerase inhibition focus on either of the two major components of the ribonucleoprotein holoenzyme, that is, the telomerase reverse transcriptase (TERT) catalytic subunit or the telo...

  16. 不同剂量亚砷酸钠染毒大鼠唾液砷水平及其与血砷、尿砷间关系研究%Relations between saliva arsenic levels and serum arsenic and urinary arsenic of rats after exposed to different levels of sodium arsenite

    Institute of Scientific and Technical Information of China (English)

    王大朋; 张利明; 李建; 刘建; 金洹宇; 刘星; 纪春燕; 傅春玲; 安艳

    2012-01-01

    Objective To investigate the relations between saliva arsenic levels and serum arsenic and urinary arsenic of rats after exposed to different levels of sodium arsenite.Methods Thirty-two SD rats were randomly divided into four groups(8 rats in each group),namely the control group,the low,the medium,and the high doses of sodium arsenite exposure groups.Rats of the control group were given 0.9% NaCI by gavage,and other three groups were given sodium arsenite of 0.2,2.0,20.0 mg/kg body weight by gavage.All animals were administrated every other day for two weeks,then saliva,blood,urine and tissue organs were collected,organ coefficients were calculated,total arsenic concentrations in blood and urine were detected by Atomic Fluorescence Spectrometry(AFS-230) and total arsenic concentration in saliva was detected by Inductively Coupled Plasma Mass Spectrometer(ICP-MS).Results The weight gain values of rats exposed to sodium arsenite were lower than that of the control group,the difference was statistically significant between the highest dose group[(76.13 ± 17.19)g]and the control group[(103.00 ± 12.31)g,P < 0.05].The liver and kidney organ coefficients in the highest dose group [(3.92 ± 0.54)%,(0.96 ± 0.15)%]were significantly higher than that in the control group[(3.27 ± 0.35)%,(0.76 ± 0.05)%,P < 0.05 or < 0.01].The total arsenic concentrations in saliva[(0.044 ± 0.019),(0.211 ± 0.071),(1.128 ± 0.380)mg/L],blood[(11.832 ± 1.887),(45.032 ± 7.216),(121.839 ± 17.323)mg/L]and urine[(0.138 ± 0.085),(0.874 ± 0.328),(8.843 ± 1.754)mg/L]in the three treatment groups were significantly higher compared with that of the control group [(0.018 ± 0.014),(2.267 ± 0.370),(0.025 ± 0.011)mg/L,all P < 0.05],furthermore,there was a significant difference among the three treatment groups (all P < 0.05).The arsenic contents in saliva were significantly correlated with blood arsenic and urinary arsenic,the correlation coefficient was 0.934 and 0

  17. Study on the mutagenesis effects of low-dose sodium arsenite by Ames test%Ames试验对低剂量亚砷酸钠致突变性的研究

    Institute of Scientific and Technical Information of China (English)

    高艳芳; 裴秋玲

    2008-01-01

    Objective To test whether sodium arsenite can induce in vitro reverse mutation of Salmonella typhimurium histamine-auxotroph mutant. Methods Ames test was carded out with Salmonella typhimurium strains TA97,TA98,TA100 and TA102 by standard method with or without the liver microsomal enzyme activation system (+S9,-S9). Results At concentrations of sodium arsenite from 500.00 to 5000.00 μg/plate, no colonies were seen on the plates of TA97,TA98,TA100 or TA102, with or without the presence of S9. At concentrations of sodium arsenite of 0.01,0.10,10.00 μg/plate and with the presence of S9, twice as many colonies grew on the plates of TA102 as the negative control(P<0.05). Without S9 activation,twice as many colonies grew on the plates of TA100 as the negative control(P<0.05)at concentrations of sodium arsenite of 1.00,10.00 μg/plate(P<0.05). The reverse mutation colonies induced by sodium arsenite in TA98 strain were twice as many as negative control group at concentrations of 0.01,0.10 μg/plate(P<0.05). There was no obvious increase of the strain clones in the other(P0.05). Conclusions With and without S9 activation, the doses of 500.00,5000.00 μg/plate sodium arsenite resulted in a toxic effect and a reduction of the revertants among the strain. At concentrations of 0.01~10.00 μg/plate, sodium arsenite exhibited mutngenesis effects.%目的 体外观察亚砷酸钠诱发鼠伤寒沙门杆菌组氨酸营养缺陷型突变菌株的回复突变(Ames)作用,探讨低剂量亚砷酸钠的致突变性.方法 采用Ames试验中标准平板掺人法,检测不同剂量亚砷酸钠(5000.00、500.00、10.00、1.00、0.10、0.01μg/皿)及阳性、阴性对照在加与不加肝微粒体酶活化系统(+S9、-S9)条件下诱发TA97、TA98、TA100和TA102菌株的致突变作用.结果 +S9或-S9时,500.00、5000.00μg/皿亚砷酸钠作用下,TA97、TA98、TA100、TA102菌株均没有生长;+S9时,0.01、0.10、10.00μg/皿亚砷酸钠诱发TA102产生的回变菌落数

  18. Metabolism of stem tissue during growth and its inhibition. III. Nitrogen metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Christiansen, G.S.; Thimann, K.V.

    1950-01-01

    The nitrogen metabolism of isolated pea stem sections as affected by arsenite, fluoride, and iodoacetate growth inhibitors in auxin solutions was studied. The changes in growth and metabolism caused by these inhibitors are discussed.

  19. Chronic combined effects of fluoride and arsenite on the Runx2 and downstream related factors of bone metabolism in rats%慢性氟砷联合暴露对大鼠骨骼Runx2及其下游相关因子的影响

    Institute of Scientific and Technical Information of China (English)

    洪峰; 郑冲; 徐德淦; 钱亚利

    2013-01-01

    Osterix、RANKL蛋白含量间呈正相关(氟染毒量与蛋白含量间相关系数分别为0.647、0.354、0.582和0.613),骨氟含量与蛋白含量间相关系数分别为0.559、0.387、0.487、0.525,P值均<0.01,砷染毒剂量与Runx2呈负相关(相关系数为-0.527,P<0.05),与MMP-9、RANKL、Osterix无相关关系(P>0.05).氟砷联合染毒与Runx2、MMP-9、RANKL、Osterix蛋白含量具有交互效应(F值分别为3.88、15.66、2.92、6.42,P值均<0.05).结论 氟砷联合暴露对大鼠骨骼代谢Runx2及其下游相关因子的交互作用表现为拮抗作用.%Objective To observe the chronic combined effects of sodium fluoride and sodium arsenite on the Runx2 and downstream related factors of bone metabolism in SD rats.Methods SD rats were divided randomly into nine groups of 6 each by factorial experimental design (half female and half male),and supplied with the different doses of fluoride,arsenite and fluoride plus arsenite containing in deionized water(untreated control containing 0 mg/kg fluoride and 0 mg/kg arsenite,and low-fluoride and high supplemented with 5 and 20 mg/kg fluoride,and low-arsenite and high supplemented with 2.5 and 10 mg/kg arsenite,and low-fluoride plus low-arsenite,and low-fluoride plus high-arsenite,and high-fluoride plus low-arsenite,and high-fluoride plus high-arsenite,respectively).After 6 months exposure,the concentration of Runx2,matrix metallopeptidase 9(MMP-9),Osterix,Receptor activator for nuclear factor-κβ ligand (RANKL) were detected by enzyme-linked immunosorbent assay method,respectively.Results There were no dental fluorosis found in the control group,low-arsenic group and high-arsenic group.There were significant differences in the constituent ratio of dental fluorosis among the rats from low-fluoride and high-fluoride (that is 5 rats out of 6 and 6 rats out of 6) compared with the control group (0 rat out of 6) (x2 =8.57,12.00,P < 0.05).The bone fluorine level increased with the increase of fluoride

  20. Quorum sensing inhibition

    DEFF Research Database (Denmark)

    Persson, T.; Givskov, Michael Christian; Nielsen, J.

    2005-01-01

    /receptor transcriptional regulator in some clinically relevant Gram-negative bacteria. The present review contains all reported compound types that are currently known to inhibit the QS transcriptional regulator in Gram-negative bacteria. These compounds are sub-divided into two main groups, one comprising structural...

  1. Enzyme inhibition by iminosugars

    DEFF Research Database (Denmark)

    López, Óscar; Qing, Feng-Ling; Pedersen, Christian Marcus;

    2013-01-01

    Imino- and azasugar glycosidase inhibitors display pH dependant inhibition reflecting that both the inhibitor and the enzyme active site have groups that change protonation state with pH. With the enzyme having two acidic groups and the inhibitor one basic group, enzyme-inhibitor complexes...

  2. 不同价态无机砷染毒大鼠肝脏砷形态分析%Distribution of arsenic metabloite in liver of rats treated with arsenite and arsenate

    Institute of Scientific and Technical Information of China (English)

    吴军; 杨晓燕; 姜平; 张杰; 郑玉建

    2011-01-01

    Objective To analyze the difference in distribution of arsenic metabolite in liver of the rats treated with arsenite and arsenate, and to explore metabolism and toxicity of arsenic. Methods Seventy-two Wistar rats were devided into 7 groups. After three months' treatment, the liver samples of the rats were collected and kept in deep freeze refrigerator. With high efficiency liquid chromatography and hydride genesis atomic fluorescence spectroscopy( HPLC-HGAFS ), the speciation and concentrations of arsenate and arsenite and their metabolic products in the liver were determined. Meanwhile, the recovery rate of monomethylarsonic acid(MMA) was determined to estimate the accuracy of the results. The arsenic accumulation was evaluated based on the content of total arsenic in liver and the differences in pathway and capability of methylation were estimated according to levels of primary methylated index(PMI) and secondary methylated index(SMI) of arsenic in the liver. Results There were significant differences in the levels of total arsenic between high,moderate,and low arsenite groups( 1 142. 9 ±50. 4,484. 6 ± 37.4,323. 3 ±20. 2 ng/g wet weight) and between high,moderate,and low arsenate groups (3 695. 2 ± 345.9,1 833.8 ± 229. 6,1 170. 5 ± 77.4 ng/g wet weight) ( P < 0. 05 for all). Except high dose group,the level of iAs3 + ( 118.4 ± 23.9,252. 3 ± 14. 3 ng/g wet weight) and dimethylarsinic acid(DMA) ( 353.2 ± 45.6,55. 2 ±10. 6 ng/g wet weight) in the liver of moderate and low arsenite group were lower than the level of iAs3+ (558.7 ±39. 0,759. 5 ± 67.6 ng/g wet weight)and DMA ( 1269. 7 ± 219. 9,402. 1 ± 60. 5 ng/g wet weight)in moderate and low arsenate groups(P <0. 05). The level of MMA( 13.0 ±2. 88,15.8 ±3. 14 ng/g wet weight)in the liver of moderate and low arsenite group were higher than the level of MMA(5. 35 ± 1.18,8. 87 ± 1.66 ng/g wet weight) of the moderate and low arsenate groups( P <0. 05 ). The level of PMI and SMI of different

  3. Experimental studies on mechanism of the proliferation inhibition in human lymphocytes induced by sodium arsenite%亚砷酸钠对人淋巴细胞增殖抑制机制的实验研究

    Institute of Scientific and Technical Information of China (English)

    郑玉建; 闫玲; 吴顺华; 张杰

    2006-01-01

    目的探讨亚砷酸钠(NaAsO2)对人淋巴细胞体外增殖抑制的影响.方法用不同浓度的NaAsO2处理细胞后,通过噻唑蓝还原法,吖啶橙荧光染色法和流式细胞术观察NaAsO2对淋巴细胞增殖的影响.结果 NaAsO2低、中、高剂量对淋巴细胞增殖有抑制作用,荧光染色法测得凋亡率分别为10.07%、18.79%、28.35%.结论 NaAsO2抑制淋巴细胞增殖,可能与其诱导凋亡有关.

  4. Plastics for corrosion inhibition

    CERN Document Server

    Goldade, Victor A; Makarevich, Anna V; Kestelman, Vladimir N

    2005-01-01

    The development of polymer composites containing inhibitors of metal corrosion is an important endeavour in modern materials science and technology. Corrosion inhibitors can be located in a polymer matrix in the solid, liquid or gaseous phase. This book details the thermodynamic principles for selecting these components, their compatibility and their effectiveness. The various mechanisms of metal protection – barrier, inhibiting and electromechanical – are considered, as are the conflicting requirements placed on the structure of the combined material. Two main classes of inhibited materials (structural and films/coatings) are described in detail. Examples are given of structural plastics used in friction units subjected to mechano-chemical wear and of polymer films/coatings for protecting metal objects against corrosion.

  5. Prednisone inhibits the IL-1β-induced expression of COX-2 in HEI-OC1 murine auditory cells through the inhibition of ERK-1/2, JNK-1 and AP-1 activity.

    Science.gov (United States)

    Hong, Hua; Jang, Byeong-Churl

    2014-12-01

    Hearing loss can be induced by multiple causes, including cochlear inflammation. Prednisone (PDN) is a well-known steroid clinically used in the treatment of hearing loss. In the present study, we investigated the inhibitory effects and the mechanisms of action of PDN on the expression of cyclooxygenase (COX)-2, an inflammatory enzyme involved in the production of prostaglandins (PGs), in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells (a murine auditory cell line) treated with the inflammatory cytokine, interleukin (IL)-1β. The exposure of HEI-OC1 cells to IL-1β increased COX-2 protein and mRNA expression, COX-2 promoter-driven luciferase activity and COX-2 enzymatic activity [as indicated by the increased production of prostaglandin E2 (PGE2), a major COX-2 metabolite]. However, PDN markedly inhibited the IL-1β-induced COX-2 protein and mRNA expression, COX-2 promoter activity and PGE2 production in the HEI-OC1 cells without affecting COX-2 protein and mRNA stability. PDN further inhibited the IL-1β-induced activation of extracellular signal-regulated kinase (ERK)-1/2 and c-Jun N-terminal kinase (JNK)-1, but had no effect on the cytokine-induced activation of p38 MAPK and proteolysis of IκB-α, a nuclear factor-κB (NF-κB) inhibitory protein. PDN also partially suppressed the IL-1β‑induced activation of activator protein (AP)-1 (but not that of NF-κB) promoter-driven luciferase activity. Of note, the inhibitory effects of PDN on the IL-1β-induced expression of COX-2 and the activation of ERK-1/2 and JNK-1 in the HEI-OC1 cells were significantly diminished by RU486, a glucocorticoid receptor (GR) antagonist, suggesting that PDN exerts its inhibitory effects through GR. To the best of our knowledge, our study demonstrates for the first time that PDN inhibits the IL-1β-induced COX-2 expression and activity in HEI-OC1 cells by COX-2 transcriptional repression, which is partly associated with the inhibition of ERK-1/2, JNK-1 and AP-1 activation.

  6. Combined effects of fluoride and arsenite on the expression of Runx-related transcription 2 mRNA in bone of rats%氟砷联合对大鼠骨组织Runx相关基因2 mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    郑冲; 洪峰; 徐德淦; 钱亚利

    2014-01-01

    目的 探讨氟砷联合对大鼠骨组织Runxa相关基因2(Runx2)mRNA表达的影响.方法 SD大鼠54只,体质量为(109.71±10.52)g,雌雄各半.采用随机数字表法,按3×3析因设计方法分成9组,分别为对照组[0 mg/kg氟化钠(NaF)+0.0 mg/kg亚砷酸钠(NaAsO2)]、低氟组(5 mg/kg NaF)、高氟组(20 mg/kgNaF)、低砷组(2.5 mg/kg NaAsO2)、高砷组(10.0 mg/kg NaAsO2)、低氟低砷组(5 mg/kg NaF+2.5 mg/kgNaAsO2)、高氟低砷组(20 mg/kg NaF+ 2.5 mg/kg NaAsO2)、低氟高砷组(5 mg/kg NaF+10.0 mg/kg NaAsO2)、高氟高砷组(20 mg/kg NaF+10.0 mg/kg NaAsO2),每组6只,雌雄各半,灌胃染毒6个月.实验结束时提取大鼠股骨组织总RNA,实时荧光定量RT-PCR法检测Runx2 mRNA的表达.结果 对照组、低氟组、高氟组、低砷组、高砷组、低氟低砷组、低氟高砷组、高氟低砷组、高氟高砷组Runx2 mRNA表达量分别为1.024±0.015、1.377±0.014、1.587±0.012、1.182±0.015、1.343±0.010、1.444±0.019、1.504±0.013、1.608±0.013、1.714±0.009.实验各组Runx2 mRNA表达量均高于对照组(P均<0.05),Runx2 mRNA表达量随染氟、砷剂量增高而增加,存在剂量-效应关系(P均< 0.01).析因分析结果表明,氟、砷单独作用时可影响Runx2 mRNA的表达水平(F值分别为46.967、8.317,P均<0.05),且二者具有交互作用(F=105.271,P<0.01).结论 氟或砷单独作用能够促进大鼠骨组织Runx2 mRNA表达,且二者具有交互作用.%Objective To explore the combined effects of fluoride and arsenite on the expression of Runx-related transcription 2 (Runx2) mRNA in bone of Sprague Dawley (SD) rats.Methods Fifty four SD rats were selected[body mass(109.71 ± 10.52)g,half male and half female].3 × 3 Factorial experimental design was used to evaluate the combined effects of fluoride and arsenite on the expression of Runx2 mRNA by random number talbe.Rats were exposed to NaF,NaAsO2 and NaF plus NaAsO2 for 6 months by oral perfusion at gradient doses

  7. Beneficial bacteria inhibit cachexia.

    Science.gov (United States)

    Varian, Bernard J; Goureshetti, Sravya; Poutahidis, Theofilos; Lakritz, Jessica R; Levkovich, Tatiana; Kwok, Caitlin; Teliousis, Konstantinos; Ibrahim, Yassin M; Mirabal, Sheyla; Erdman, Susan E

    2016-03-15

    Muscle wasting, known as cachexia, is a debilitating condition associated with chronic inflammation such as during cancer. Beneficial microbes have been shown to optimize systemic inflammatory tone during good health; however, interactions between microbes and host immunity in the context of cachexia are incompletely understood. Here we use mouse models to test roles for bacteria in muscle wasting syndromes. We find that feeding of a human commensal microbe, Lactobacillus reuteri, to mice is sufficient to lower systemic indices of inflammation and inhibit cachexia. Further, the microbial muscle-building phenomenon extends to normal aging as wild type animals exhibited increased growth hormone levels and up-regulation of transcription factor Forkhead Box N1 [FoxN1] associated with thymus gland retention and longevity. Interestingly, mice with a defective FoxN1 gene (athymic nude) fail to inhibit sarcopenia after L. reuteri therapy, indicating a FoxN1-mediated mechanism. In conclusion, symbiotic bacteria may serve to stimulate FoxN1 and thymic functions that regulate inflammation, offering possible alternatives for cachexia prevention and novel insights into roles for microbiota in mammalian ontogeny and phylogeny. PMID:26933816

  8. 三氧化二砷通过抑制IKK/NF-κB信号通路活化发挥促乳腺癌细胞凋亡效应%Arsenic trioxide induces apoptosis in MCF7 human breast cancer cells by inhibiting IKK/NF-κB pathway activation

    Institute of Scientific and Technical Information of China (English)

    郝一; 李译; 高明; 董雯; 胡美茹; 宋伦

    2012-01-01

    目的 探讨IKK/NF-κB信号通路在三氧化二砷(As2O3)诱导乳腺癌细胞凋亡反应中的作用.方法 以乳腺癌细胞MCF7为靶细胞,以As2O3为刺激源,锥虫蓝(台盼蓝)拒染方法检测死亡细胞比率;双荧光素酶报告基因法检测MCF7细胞中NF-κB的活化状态;Western印迹方法检测IKK/NF-κB途径各信号分子的表达水平和活化状态;RT-PCR方法检测IKK/NF-κB途径下游靶基因的表达水平.结果 As2O3可显著诱导MCF7细胞凋亡;同时NF-κB的转录活化水平及其下游凋亡反应相关靶基因的表达水平也明显下降.在此过程中,I-κB的表达水平和NF-κB关键组成亚基(p65、p50)的核浆分布状态没有改变,但IKK激酶的两个催化亚基IKKα和IKKβ的表达水平明显下调.一过性高表达IKKα和IKKβ不仅能够恢复NF-κB的活化状态,而且能够拮抗As2O3诱导的乳腺癌细胞凋亡反应.结论 As2O3可通过在蛋白激酶水平抑制IKK/NF-κB信号通路活化从而发挥促乳腺癌细胞凋亡效应.%Objective To explore the role of IKK/NF-kB signaling pathway in mediating the apoptotic effect in human breast cancer cells exposed to arsenic trioxide (arsenite, As2O3). Methods MCF7 cells were treated with arsenite. Cell death was detected by phenol blue staining. Luciferase assay was used to detect the transactivation status of NF -kB in the MCF7 cells. The expression levels of IKKa, IKKP,I-kB and the cytoplasmic/nuclear distribution of p65 and p50 were detected by Western blotting. The expression levels of NF-kB downstream target genes were determined by RT-PCR. Results Arsenite induced apoptosis in MCF7 cells, along with significant inhibition of NF -kB transactivation and NF-kB target genes expression. Interestingly, the expression level of I-kB and cytoplasmic/nuclear distribution of p65 and p50 were not altered, but both IKKa and IKKp levels were dramatically down-regulated under the same conditions. Moreover, overexpressed IKKa or IKKp recovered

  9. Damage of Rat Vascular Endothelial Cells Induced by Fluoride and Arsenite in Vitro%氟、砷对体外培养大鼠血管内皮细胞的损伤作用

    Institute of Scientific and Technical Information of China (English)

    靳曙光; 于敬红; 李环

    2015-01-01

    Objective To observe the damage effects of fluoride and arsenite on rat vascular endothelial cells. Method Rat aorta endothelial cells were cultured in vitro,and were contaminated with NaF at 0,600 and 900μmol/L and NaAsO2 at 0,0. 1,1. 0 μmol/L compatibility for 48 h. Cell morphology was observed with light microscopy,cell activity was detected by MTT, apoptosis was tested by flow cytometry, and DNA damage in endothelial cells was analyzed through single cell gel electrophoresis. Results The cells of non-exposed control group and the low concentration group grew well,which showed pebble-shaped and spindle-shaped. But the cells, some of what were round with necrosis,appeared poor growth state in the alone or associated high concentrations groups. The cell activity and DNA damage in fluoride and arsenite alone or associated high concentrations groups was lower and more seriously than in non-exposed control group and low concentration group (P<0. 05),and the cells apoptosis showed the opposite result. Conclusion Fluoride and arsenite alone or in combination can reduce the activity of vascular endothelial cells,induce apoptosis and DNA damage,and with an obvious dose-response relationship.%目的 观察氟、砷对大鼠血管内皮细胞的损伤作用.方法 体外分离培养大鼠胸主动脉血管内皮细胞,浓度按氟化钠(NaF)0,600,900μmol/L与亚砷酸钠(NaAsO2)0,0. 1,1. 0μmol/L配伍,染毒培养时间为48 h.光镜观察细胞生长形态,四甲基偶氮唑盐比色法( MTT法)检测细胞活性,流式细胞仪检测细胞凋亡情况,单细胞凝胶电泳法分析内皮细胞DNA损伤情况.结果 非染毒对照组及氟、砷低浓度组细胞生长良好,呈梭形和卵石形,氟、砷单独及联合高浓度组细胞生长状态较差,部分细胞呈圆形,有坏死;氟、砷单独及联合高浓度组细胞活性低于非染毒对照组及氟、砷低浓度组(P<0. 05);氟、砷单独及联合高浓度组细胞凋亡率高于非染毒对照

  10. 生物成因次生铁矿物对酸性矿山废水中三价砷的吸附%THERMODYNAMICS AND KINETICS OF ADSORPTION OF ARSENITE IN ACID MINING DRAINAGE BY BIOGENIC SECONDARY IRON MINERALS

    Institute of Scientific and Technical Information of China (English)

    谢越; 周立祥

    2012-01-01

    Schwertmannite, jarosite and goethite are common secondary iron minerals found in acid mining drainage. They were formed biological under normal temperature and pressure with the aid of Acidithiobacillus ferrooxidans in this study. Batch adsorption experiments were conducted under three different temperatures ( 15℃ , 25℃ and 35℃) to explore arse-nite adsorption behaviors of the three biogenic secondary iron minerals in simulated acid mining drainage ( pH3. 0) . It was found that arsenite adsorption of the three biogenic minerals were of the second order of reaction and could well be described by the Lagergren pseudo-second order rate equation, with correlation coefficient being 0. 94. Their adsorption enthalpy was 11.76 , 18.40 and 9. 34 kJ mol-1, separately for the three different minerals and their △G's were all <0. The adsorption of arsenite was a kind of endothemnic spontaneous process.%在常温常压条件下,利用嗜酸性氧化亚铁硫杆菌的促进作用,生物合成了酸性矿山废水中常见的三种次生铁矿物:施氏矿物(schwertmannite)、黄钾铁矾(jarosite)和针铁矿(goethite).在15℃、25℃、35℃三个不同温度下,通过序批式吸附试验研究,在pH3.0的模拟酸性矿山废水条件下,3种生物成因次生铁矿物对As(Ⅲ)的吸附性能.结果表明:3种生物成因的次生矿物对As(Ⅲ)的吸附属于拟二级反应,可以用Lagergren 拟二级速率方程进行拟合,相关系数均在0.97以上.吸附速率常数K分别为施氏矿物0.094 g mg-1 min-1,针铁矿0.042 g mg-1 min-1,黄钾铁矾0.02 g mg-1 min-1.3种生物成因铁矿物对As(Ⅲ)的吸附等温线符合Langmuir方程和Freundlich方程,相关系数均在0.94以上.吸附反应的焓变Δ/分别为11.76、18.40和9.34 kJ mol-1,ΔG均小于0,吸附过程属于吸热的自发反应.

  11. Glossogyne tenuifolia Extract Inhibits TNF-α-Induced Expression of Adhesion Molecules in Human Umbilical Vein Endothelial Cells via Blocking the NF-kB Signaling Pathway.

    Science.gov (United States)

    Hsuan, Chin-Feng; Hsu, Hsia-Fen; Tseng, Wei-Kung; Lee, Thung-Lip; Wei, Yu-Feng; Hsu, Kwan-Lih; Wu, Chau-Chung; Houng, Jer-Yiing

    2015-01-01

    Chronic inflammation plays a pivotal role in the development of atherosclerosis, where the pro-inflammatory cytokine-induced expression of endothelial adhesion molecules and the recruitment of monocytes are the crucial events leading to its pathogenesis. Glossogyne tenuifolia ethanol extract (GTE) is shown to have potent anti-inflammatory and antioxidant activities. We evaluated the effects of GTE and its major components, luteolin (lut), luteolin-7-glucoside (lut-7-g), and oleanolic acid (OA) on TNF-α-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs). The results demonstrated that GTE, lut, and lut-7-g attenuated the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in TNF-α-activated HUVECs, and inhibited the adhesion of monocytes to TNF-α-activated HUVECs. The TNF-α-induced mRNA expression of ICAM-1 and VCAM-1 was also suppressed, revealing their inhibitory effects at the transcriptional level. Furthermore, GTE, lut, and lut-7-g blocked the TNF-α-induced degradation of nuclear factor-kB inhibitor (IkB), an indicator of the activation of nuclear factor-kB (NF-kB). In summary, GTE and its bioactive components were effective in preventing the adhesion of monocytes to cytokine-activated endothelium by the inhibition of expression of adhesion molecules, which in turn is mediated through blocking the activation and nuclear translocation of NF-kB. The current results reveal the therapeutic potential of GTE in atherosclerosis. PMID:26393541

  12. Glossogyne tenuifolia Extract Inhibits TNF-α-Induced Expression of Adhesion Molecules in Human Umbilical Vein Endothelial Cells via Blocking the NF-kB Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Chin-Feng Hsuan

    2015-09-01

    Full Text Available Chronic inflammation plays a pivotal role in the development of atherosclerosis, where the pro-inflammatory cytokine-induced expression of endothelial adhesion molecules and the recruitment of monocytes are the crucial events leading to its pathogenesis. Glossogyne tenuifolia ethanol extract (GTE is shown to have potent anti-inflammatory and antioxidant activities. We evaluated the effects of GTE and its major components, luteolin (lut, luteolin-7-glucoside (lut-7-g, and oleanolic acid (OA on TNF-α-induced expression of adhesion molecules in human umbilical vein endothelial cells (HUVECs. The results demonstrated that GTE, lut, and lut-7-g attenuated the expression of intercellular adhesion molecule-1 (ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1 in TNF-α-activated HUVECs, and inhibited the adhesion of monocytes to TNF-α-activated HUVECs. The TNF-α-induced mRNA expression of ICAM-1 and VCAM-1 was also suppressed, revealing their inhibitory effects at the transcriptional level. Furthermore, GTE, lut, and lut-7-g blocked the TNF-α-induced degradation of nuclear factor-kB inhibitor (IkB, an indicator of the activation of nuclear factor-kB (NF-kB. In summary, GTE and its bioactive components were effective in preventing the adhesion of monocytes to cytokine-activated endothelium by the inhibition of expression of adhesion molecules, which in turn is mediated through blocking the activation and nuclear translocation of NF-kB. The current results reveal the therapeutic potential of GTE in atherosclerosis.

  13. Chemical Inhibition of Autophagy

    DEFF Research Database (Denmark)

    Baek, Eric; Lin Kim, Che; Gyeom Kim, Mi;

    2016-01-01

    Chinese hamster ovary (CHO) cells activate and undergo apoptosis and autophagy for various environmental stresses. Unlike apoptosis, studies on increasing the production of therapeutic proteins in CHO cells by targeting the autophagy pathway are limited. In order to identify the effects of chemical...... autophagy inhibitors on the specific productivity (qp), nine chemical inhibitors that had been reported to target three different phases of autophagy (metformin, dorsomorphin, resveratrol, and SP600125 against initiation and nucleation; 3-MA, wortmannin, and LY294002 against elongation, and chloroquine...... significantly increased the qp of DG44-Fc and DUKX-Fc. In contrast, for DG44-Ab, only 3-MA significantly increased the qp. The autophagy-inhibiting activity of the nine chemical inhibitors on the rCHO cell lines was evaluated through Western blot analysis and flow cytometry. Unexpectedly, some chemical...

  14. Proinflammatory Cytokines Induce Endocrine Differentiation in Pancreatic Ductal Cells via STAT3-Dependent NGN3 Activation

    Directory of Open Access Journals (Sweden)

    Ivan Achel Valdez

    2016-04-01

    Full Text Available A major goal of diabetes research is to develop strategies that replenish pancreatic insulin-producing beta cells. One emerging strategy is to harness pancreatic plasticity—the ability of pancreatic cells to undergo cellular interconversions—a phenomenon implicated in physiological stress and pancreatic injury. Here, we investigate the effects of inflammatory cytokine stress on the differentiation potential of ductal cells in a human cell line, in mouse ductal cells by pancreatic intraductal injection, and during the progression of autoimmune diabetes in the non-obese diabetic (NOD mouse model. We find that inflammatory cytokine insults stimulate epithelial-to-mesenchymal transition (EMT as well as the endocrine program in human pancreatic ductal cells via STAT3-dependent NGN3 activation. Furthermore, we show that inflammatory cytokines activate ductal-to-endocrine cell reprogramming in vivo independent of hyperglycemic stress. Together, our findings provide evidence that inflammatory cytokines direct ductal-to-endocrine cell differentiation, with implications for beta cell regeneration.

  15. CRFR1 activation protects against cytokine-induced beta cell death

    DEFF Research Database (Denmark)

    Blaabjerg, Lykke; Christensen, Gitte Lund; Matsumoto, Masahito;

    2014-01-01

    During diabetes development beta cells are exposed to elevated concentrations of proinflammatory cytokines, TNFα and IL-1β which in vitro, induce beta cell death. The class B G-protein-coupled receptors (GPCRs): Corticotropin releasing factor receptor 1 (CRFR1) and CRFR2 are expressed in pancreat...

  16. ATP Is Required and Advances Cytokine-Induced Gap Junction Formation in Microglia In Vitro

    Directory of Open Access Journals (Sweden)

    Pablo J. Sáez

    2013-01-01

    Full Text Available Microglia are the immune cells in the central nervous system. After injury microglia release bioactive molecules, including cytokines and ATP, which modify the functional state of hemichannels (HCs and gap junction channels (GJCs, affecting the intercellular communication via extracellular and intracellular compartments, respectively. Here, we studied the role of extracellular ATP and several cytokines as modulators of the functional state of microglial HCs and GJCs using dye uptake and dye coupling techniques, respectively. In microglia and the microglia cell line EOC20, ATP advanced the TNF-α/IFN-γ-induced dye coupling, probably through the induction of IL-1β release. Moreover, TNF-α/IFN-γ, but not TNF-α plus ATP, increased dye uptake in EOC20 cells. Blockade of Cx43 and Panx1 HCs prevented dye coupling induced by TNF-α/IFN-γ, but not TNF-α plus ATP. In addition, IL-6 prevented the induction of dye coupling and HC activity induced by TNF-α/IFN-γ in EOC20 cells. Our data support the notion that extracellular ATP affects the cellular communication between microglia through autocrine and paracrine mechanisms, which might affect the timing of immune response under neuroinflammatory conditions.

  17. IL-1β Receptor Blockade Protects Islets Against Pro-inflammatory Cytokine Induced Necrosis and Apoptosis

    OpenAIRE

    Schwarznau, Alice; Hanson, Matthew S.; Sperger, Jamie M.; Schram, Brian R; Danobeitia, Juan S.; Greenwood, Krista K.; Vijayan, Ashwanth; Fernandez, Luis A.

    2009-01-01

    Pro-inflammatory cytokines (PIC) impair islet viability and function by activating inflammatory pathways that induce both necrosis and apoptosis. The aim of this study was to utilize an in vitro rat islet model to evaluate the efficacy of a clinically approved IL-1 receptor antagonist (Anakinra) in blocking PIC induced islet impairment. Isolated rat islets were cultured for 48h ± PIC (IL-1β, IFNγ, and TNFα and ±IL-1ra then assayed for cellular integrity by flow cytometry, MAPK phosphorylation...

  18. Effects of Ganoderma lucidum polysaccharides on proliferation and cytotoxicity of cytokine-induced killer cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-ling ZHU; Zhi-bin LIN

    2005-01-01

    Aim: To study the effects (and the mechanisms thereof) of Ganoderma lucidum polysaccharides (Gl-PS) on the proliferation and the anti-tumor activity of cytokineinduced killer (CIK) cells, and to make use of CIK cells as a means to investigate the interactions between Gl-PS and cytokines. Methods: CIK cells were prepared by using the standard protocol as a positive control. Experimental groups also underwent the standard protocol, except that Gl-PS (400 mg/L or 100 mg/L) was added and the dose of anti-CD3 and interleukin-2 they received was reduced by 50% and 75%, respectively. For negative controls, Gl- PS in the experimental protocol was replaced with soluble starch or methylcellulose (400 mg/L or 100 mg/L).CIK cell proliferation, cytotoxicity, and phenotype weredetermined by using the Trypan blue exclusion method, MTT assay, and flow cytometry. Results: By synergizing cytokines, Gl-PS (400 mg/L or 100 mg/L) could decrease the amount of cytokine in lymphokine activated killer (LAK) cells and CIK cells culture, but had no significant effect on the proliferation, cytotoxicity, or phenotype of LAK cells, or CIK cells induced by cytokines at higher doses alone, in which CIK cells expanded about 80-fold and the main effectors, CD3+NK1.1+ cells, expanded by more than 15%. The cytotoxicity of CIK cells in experimental groups was 79.3%±4.7%, 76.9%±6.8% versus the positive control 80.7%±6.8% against P815 (P>0.05)and 88.9%±5.5%, 84.7%±7.9% versus the positive control 89.8%±4.5% against YAC-1 (P>0.05). The activity of Gl-PS could mostly be blocked by anti-CR3.Conclusion: Gl-PS was shown to be a promising biological response modifier and immune potentiator. The effect of Gl-PS on CIK cells is possibly mediated primarily through complement receptor type 3.

  19. Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice

    OpenAIRE

    De Domenico, Ivana; Zhang, Tian Y.; Koening, Curry L.; Branch, Ryan W.; London, Nyall; Lo, Eric; Daynes, Raymond A.; Kushner, James P.; Li, Dean; Ward, Diane M.; Kaplan, Jerry

    2010-01-01

    Hepcidin is a peptide hormone that regulates iron homeostasis and acts as an antimicrobial peptide. It is expressed and secreted by a variety of cell types in response to iron loading and inflammation. Hepcidin mediates iron homeostasis by binding to the iron exporter ferroportin, inducing its internalization and degradation via activation of the protein kinase Jak2 and the subsequent phosphorylation of ferroportin. Here we have shown that hepcidin-activated Jak2 also phosphorylates the trans...

  20. Inflammatory cytokines induce human bronchial smooth muscle cell proliferation via an NCX-1 dependent mechanism

    OpenAIRE

    Yoo, Edwin

    2010-01-01

    Airway smooth muscle hyperplasia is a characteristic of airway remodeling in asthma and this is thought to be, at least in part, cytokine mediated. Because cytosolic free calcium ([Ca²⁺]cyt) plays an important role in smooth muscle proliferation, we chose to examine the role of [Ca²⁺]cyt, focusing on the expression of the Na⁺/Ca²⁺ exchanger 1 (NCX1) protein and its link to human airway smooth muscle proliferation. In vitro studies were done to examine the function and expression of NCX1 prote...

  1. Effect of vitamin E succinate on inflammatory cytokines induced by high-intensity interval training

    Directory of Open Access Journals (Sweden)

    Hadi Sarir

    2015-01-01

    Full Text Available Aim and Scope: The anti-inflammatory effect of vitamin E under moderate exercises has been evaluated. However, the effect of vitamin E succinate, which has more potent anti-inflammatory effect than other isomers of vitamin E has not been evaluated. Therefore, the aim of the present study was to evaluate the effects of vitamin E succinate on tumor necrosis factor alpha (TNF-a and interleukin-6 (IL-6 production induced by high-intensity interval training (HIIT. Materials and Methods: In the present study, 24 rats were randomly divided into control (C, supplementation (S, HIIT, and HIIT + supplementation (HIIT+S groups. HIIT training protocol on a treadmill (at a speed of 40-54 m/min and vitamin E succinate supplementation (60 mg/kg/day was conducted for 6 weeks. Results: Serum IL-6 in the HIIT group significantly increased compared with the C group (350.42 ± 123.31 pg/mL vs 158.60 ± 41.96 pg/mL; P = 0.002. Also, serum TNF-a concentrations significantly enhanced (718.15 ± 133.42 pg/mL vs 350.87 ± 64.93 pg/mL; P = 0.001 in the HIIT group compared with the C group. Treatment of the training group with vitamin E numerically reduced IL-6 and TNF-a when compared with the HIIT group (217.31 ± 29.21 and 510.23 ± 217.88, respectively, P > 0.05. However, no significant changes were observed in serum TNF-a (P = 0.31 and IL-6 (P = 0.52 concentrations in the HIIT + S group compared with the C group. Conclusion: HIIT-induced IL-6 and TNF-α decreased by administration of Vitamin E succinate.

  2. Antitumour activities of cytokine-induced killer cells and dendritic cells in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    ZHANG Song; JIANG Shu-juan; ZHANG Cai-qing; WANG Hong-mei; BAI Chun-xue

    2005-01-01

    @@ Solid tumour cells show a resistance to immunological effector cells in vitro.1 The resistance may be one reason why these tumours withstand immunotherapeutic approaches in humans.Dendritic cells (DC) play an important role in the immune response to tumour associated antigens in humans.DC in the periphery capture and process antigens,express lymphocyte costimulatory molecules,migrate to lymphoid organs and secrete cytokines to initiate immune response.

  3. Effects of NF-κB on COX-2 expression in arsenite exposed SV-HUC-1 cells%NF-κB在砷诱导人正常膀胱上皮细胞COX-2表达中的作用

    Institute of Scientific and Technical Information of China (English)

    席淑华; 王惠惠; 王菲; 刘盛男; 孙贵范

    2011-01-01

    Objective To explore the effects of NF-kB on COX-2 mRNA expression in SV-HUC-1 cells exposed to arse-nite. Methods Cells were cultured in medium contained 0, 1, 2, 4, 8 and 10 )I,mol/L arsenite or PDTC, the inhibitor of NF-kB for 24 h, then the expressions of COX-2 mRNA and nuclear protein NF-kB were determined by RT-PCR and Western blot, respectively. Results Compared with those in control group, the expressions of COX-2 mRNA in cells exposed to 4 and 8 ujnol/L arsenite and the expressions of NF-kB in cells exposed to 4 ujnol/L arsenite were increased significantly ( P < 0. 05 ) , while expressions of NF-kB nuclear proteimim in the cells exposed to 10 u,mol/L arsenite were decreased significantly. On the other hand, expressions of COX-2 mRNA in cells exposed to both 4 ujnol/L arsenite and PDTC were lower significantly than those in the cells only exposed to 4 ujnol/L arsenite ( P < 0.05 ). Conclusion Findings from this study suggested that low dose of arsenic could induce the expression of COX-2 mRNA and NF-kB in SV-HUC-1 cells, while the activation of NF-kB induced by arsenic might play some role in the process mentioned above.%目的 观察NF-κB核转录因子在砷诱导人正常膀胱上皮细胞(SV-HUC-1)环氧化酶-2(COX-2)表达中的作用.方法 在细胞培养液中加入不同浓度的NaAsO2,24h后提取细胞总RNA和核蛋白,用RT-PCR和Western blot方法分别分析COX-2 mRNA表达和NF-κB蛋白水平;选择COX-2高表达的NaAsO2处理组,再用NF-κB抑制剂(PDTC)处理,观察COX-2 mRNA表达水平的变化.结果 4、8μmol/L NaAsO2处理细胞后,COX-2 mRNA表达水平显著高于对照组(P<0.05);4 μmol/L NaAsO2处理组细胞NF-κB蛋白水平也显著提高,高于对照组,而10 μmol/LNaAsO2处理组细胞NF-κB蛋白水平低于对照组(P<0.05);同时用4μ mol/L NaAsO2和PDTC共同处理细胞后,COX-2 mRNA表达水平降低,显著低于单纯用4μoml/L NaAsO2处理细胞的COX-2 mRNA表达水平(P<0.05).结论 低剂

  4. Backward semantic inhibition in toddlers

    OpenAIRE

    Chow, J.; Aimola Davies, AM; Fuentes, LJ; Plunkett, KR

    2016-01-01

    Attention-switching is a crucial ability required in our everyday life, from toddlerhood to adulthood. In adults, shifting attention from one word (e.g., dog) to another (e.g., sea) results in backward semantic inhibition, i.e., the inhibition of the initial word (dog). This study examines whether attention-switching is accompanied by backward semantic inhibition in toddlers using the preferential looking paradigm. The findings demonstrate that a backward inhibitory mechanism operates during ...

  5. Milk-derived tripeptides IPP (Ile-Pro-Pro and VPP (Val-Pro-Pro promote adipocyte differentiation and inhibit inflammation in 3T3-F442A cells.

    Directory of Open Access Journals (Sweden)

    Subhadeep Chakrabarti

    Full Text Available Milk derived tripeptides IPP (Ile-Pro-Pro and VPP (Val-Pro-Pro have shown promise as anti-hypertensive agents due to their inhibitory effects on angiotensin converting enzyme (ACE. Due to the key inter-related roles of hypertension, chronic inflammation and insulin resistance in the pathogenesis of metabolic syndrome, there is growing interest in investigating established anti-hypertensive agents for their effects on insulin sensitivity and inflammation. In this study, we examined the effects of IPP and VPP on 3T3-F442A murine pre-adipocytes, a widely used model for studying metabolic diseases. We found that both IPP and VPP induced beneficial adipogenic differentiation as manifested by intracellular lipid accumulation, upregulation of peroxisome proliferator-activated receptor gamma (PPARγ and secretion of the protective lipid hormone adiponectin by these cells. The observed effects were similar to those induced by insulin, suggesting potential benefits in the presence of insulin resistance. IPP and VPP also inhibited cytokine induced pro-inflammatory changes such as reduction in adipokine levels and activation of the nuclear factor kappa B (NF-κB pathway. Taken together, our findings suggest that IPP and VPP exert insulin-mimetic adipogenic effects and prevent inflammatory changes in adipocytes, which may offer protection against metabolic disease.

  6. The Expression of Human Cytomegalovirus MicroRNA MiR-UL148D during Latent Infection in Primary Myeloid Cells Inhibits Activin A-triggered Secretion of IL-6.

    Science.gov (United States)

    Lau, Betty; Poole, Emma; Krishna, Benjamin; Sellart, Immaculada; Wills, Mark R; Murphy, Eain; Sinclair, John

    2016-08-05

    The successful establishment and maintenance of human cytomegalovirus (HCMV) latency is dependent on the expression of a subset of viral genes. Whilst the exact spectrum and functions of these genes are far from clear, inroads have been made for protein-coding genes. In contrast, little is known about the expression of non-coding RNAs. Here we show that HCMV encoded miRNAs are expressed de novo during latent infection of primary myeloid cells. Furthermore, we demonstrate that miR-UL148D, one of the most highly expressed viral miRNAs during latent infection, directly targets the cellular receptor ACVR1B of the activin signalling axis. Consistent with this, we observed upregulation of ACVR1B expression during latent infection with a miR-UL148D deletion virus (ΔmiR-UL148D). Importantly, we observed that monocytes latently infected with ΔmiR-UL148D are more responsive to activin A stimulation, as demonstrated by their increased secretion of IL-6. Collectively, our data indicates miR-UL148D inhibits ACVR1B expression in latently infected cells to limit proinflammatory cytokine secretion, perhaps as an immune evasion strategy or to postpone cytokine-induced reactivation until conditions are more favourable. This is the first demonstration of an HCMV miRNA function during latency in primary myeloid cells, implicating that small RNA species may contribute significantly to latent infection.

  7. Dose-time effect of sodium arsenite on reactive oxygen species in HaCaT keratinocytes%不同剂量亚砷酸钠暴露不同时间对HaCaT细胞活性氧的影响

    Institute of Scientific and Technical Information of China (English)

    许熙国; 王大朋; 金洹宇; 刘星; 杨旭; 马园; 童建; 安艳

    2013-01-01

    Objective To explore the dose-time effect of sodium arsenite on reactive oxygen species (ROS) in HaCaT cells.Methods HaCaT keratinocytes were divided into non-pretreated group(exposure to a final concentration of 0(control),0.15,0.6,2.5 and 10 μmol/L sodium arsenite for 8,24,72 h),8 h-pretreatment group (exposure to 10 μmol/L of sodium arsenite for 8 h after pretreatment by 0.15 μmol/L sodium arsenite for 8 h),and 24 h-pretreatment group(exposure to 10 μmol/L of sodium arsenite for 8 h after pretreatment by 0.15 μmol/L sodium arsenite for 24 h).The ROS level induced by sodium arsenite in HaCaT cells was detected by FCM (flow cytometry) with DCFH-DA.Results Compared with control group,the intracellular ROS levels in HaCaT cells,treated with various concentrations of sodium arsenite for 8 h and 0.6,2.5,10 μmol/L sodium arsenite for 24 h and 0.6,2.5 μmol/L sodium arsenite for 72 h,were higher,while the ROS levels in HaCaT cells treated with 0.15,10 μmol/L sodium arsenite for 72 h were lower,the difference was statistically significant (P<0.05).With sodium arsenite exposure time prolonged,the intracellular ROS levels in HaCaT cells kept higher,reached peak at the 8th hour,then decreased.But after 24 h-treatment,the ROS level in HaCaT cells treated with 0.15 μmol/L and 0.6 μmol/L sodium arsenite increased again.In 8 h-pretreatment group,the ROS level in HaCaT cells were higher than that in non-pretreated group and 24 h-pretreatment group,whereas the ROS level in HaCaT cells in 24 h-pretreatment group were lower than that in non-pretreated group,the differences were statistically significant (P<0.05).Conclusion Acute sodium arsenite exposure may increase the level of ROS in HaCaT cells with dose-time dependent manner.%目的 探索不同剂量亚砷酸钠暴露不同时间对诱导人永生化角质形成(HaCaT)细胞活性氧(ROS)产生的影响以及低剂量亚砷酸钠预处理HaCaT细胞对诱导ROS水平改变的时间效应.方法 设未预处理

  8. Selective inhibition of human inducible nitric oxide synthase by S-alkyl-L-isothiocitrulline-containing dipeptides.

    Science.gov (United States)

    Park, J M; Higuchi, T; Kikuchi, K; Urano, Y; Hori, H; Nishino, T; Aoki, J; Inoue, K; Nagano, T

    2001-04-01

    The aim of this study was to investigate the structure-activity relationship of S-alkyl-L-isothiocitrulline-containing dipeptides towards three partially purified recombinant human nitric oxide synthase (NOS) isozymes, as well as the effects of these compounds on cytokine-induced NO production by human DLD-1 cells. In an in vitro assay, S-methyl-L-isothiocitrulline (L-MIT) was slightly selective for human neuronal NOS (nNOS) over the inducible (iNOS) or endothelial (eNOS) isozyme, but the combination of a hydrophobic L-amino acid (L-Phe, L-Leu or L-Trp) with L-MIT dramatically altered the inhibition pattern to give selective iNOS inhibitors. Introduction of a hydroxy, nitro, amino or methoxy group at the para position of the aromatic ring of L-MIT-L-Phe (MILF) decreased the selectivity and inhibitory potency. A longer or larger S-alkyl group also decreased the selectivity and potency. Dixon analysis showed that all of the dipeptides were competitive inhibitors of the three isoforms of human NOS. The enzymatic time course curves indicated that MILF was a slow binding inhibitor of human iNOS. These results suggest that the human NOS isozymes have different-sized cavities in the binding site near the position to which the C-terminal of L-arginine binds, and the cavity of iNOS is hydrophobic. Interestingly, L-MIT-D-Phe (MIDF) showed little inhibitory activity or selectivity, suggesting that the cavity of human iNOS is located in a well-defined direction from the alpha carbon atom. NO production in cytokine-stimulated human DLD-1 cells was measured with a fluorescent indicator, DAF-FM. MILF, L-MIT-L-Trp(-CHO) (MILW) and L-MIT-L-Tyr (MILY) showed more potent activity than L-MIT in this whole-cell assay. Thus, S-alkyl-L-isothiocitrulline-containing dipeptides are selective inhibitors of human iNOS, and work efficiently in cell-based assay. PMID:11309260

  9. Chronic fatigue syndrome (CFS) associated with Staphylococcus spp. bacteremia, responsive to potassium arsenite 0.5% in a veterinary surgeon and his coworking wife, handling with CFS animal cases.

    Science.gov (United States)

    Tarello, W

    2001-10-01

    Chronic fatigue syndrome (CFS) in human patients remain a controversial and perplexing condition with emerging zoonotic aspects. Recent advances in human medicine seem to indicate a bacterial etiology and the condition has already been described in horses, dogs, cats and birds of prey in association with micrococci-like organisms in the blood. To evaluate the possibility of a chronic bacteremia, a veterinary surgeon (the author) and his coworking wife, both diagnosed with CFS and meeting the CDC working case definition, were submitted to rapid blood cultures and fresh blood smears investigations. Blood cultures proved Staph-positive and micrococci-like organisms in the blood were repeatedly observed in the 3-year period preceding the arsenical therapy, during which several medicaments, including antibiotics, proved unsuccessful. Following treatment with a low dosage arsenical drug (potassium arsenite 0.5%, im., 1 ml/12 h, for 10 days) both patients experienced complete remission. At the post-treatment control made 1 month later, micrococci had disappeared from the blood, and the CD4/CD8 ratio was raising. PMID:11561958

  10. Cytotoxicity Induced by co-treatment of sodium arsenite and BSO on Chang liver cells%亚砷酸钠联合丁基硫堇亚胺致肝细胞毒性作用

    Institute of Scientific and Technical Information of China (English)

    李冰; 李昕; 荣琳; 王惠惠; 朱博; 张新玉

    2010-01-01

    目的 研究亚砷酸钠(sodium arsenite,NaAsO_2)单独、以及与丁基硫堇亚胺(buthionine sulfoximine,BSO)联合对Chang liver细胞毒性作用.方法 常规培养的Chang liver细胞用NaAsO_2单独或NaAsO_2和BSO联合染毒24 h,倒置相差显微镜采集细胞图像;四甲基偶氮噻唑蓝(MTT)法检测细胞活力.结果 NaAsO_2(0~250μmol/L)明显改变Chang liver细胞的形态并明显降低细胞生存率(P<0.01),且呈剂量-反应关系;NaAsO_2(5,20μmol/L)和BOS(1 mmol/L)联合作用,其细胞生存率明显低于相应浓度的NaAsO_2单独作用组(P<0.01).结论 NaAsO_2具有明显的细胞毒性;NaAsO_2联合BSO能够加重NaAsO_2对Chang liver细胞的毒性.

  11. 亚砷酸钠致雄性大鼠肺损伤机制探讨%Study on mechanism of sodium arsenite-induced lung injury in male rats

    Institute of Scientific and Technical Information of China (English)

    苏鑫; 王素华; 刘建国; 高艳荣; 杨欢

    2016-01-01

    目的:观察亚砷酸钠对雄性大鼠的肺损伤作用,探讨其细胞衰老作用机制。方法无特定病原体级健康成年雄性Wistar大鼠随机分为对照组和低、中、高剂量组,每组8只,对照组大鼠予饮用超纯水,3个剂量组大鼠予饮用质量浓度分别为10、100和1000μg/L的亚砷酸钠溶液,连续染毒4周后处死,进行肺组织病理学检查,并采用酶联免疫吸附实验测定大鼠支气管肺泡灌洗液( BALF )中白细胞介素( IL )-1β、IL-6、IL-10有β-半乳糖苷酶(β-Gal)水平。结果低、中和高剂量组大鼠肺组织均出现肺损伤的早期炎症性病理改变;随着染毒剂量的增加,逐渐出现肺泡间隔增宽、蛋白性水肿液渗出和大量炎症细胞浸润等改变。中和高剂量组大鼠BALF中IL-1β、IL-6和β-Gal水平均高于对照组(P<0.05),低、中和高剂量组大鼠BALF中IL-10水平均低于对照组(P<0.05)。大鼠BALF中β-Gal水平和IL-1β、IL-6水平均呈正相关[相关系数(r)分别为0.691和0.410,P <0.05)];β-Gal水平和IL-10水平不相关( r=-0.117,P>0.05)。结论亚砷酸钠经饮水染毒可导致雄性大鼠发生炎症性肺损伤,其机制可能与细胞衰老激活炎症网络有关。%Objective To observe the effects of lung injury caused by sodium arsenite in male rats, and to explore its cell senescence mechanism.Methods Specific pathogen free healthy adult male Wistar rats were randomly divided into 4 groups with 8 rats in each group: a control group ( given ultrapure water ) and low-, medium-and high-sodium arsenite dose groups (10, 100 and 1 000 μg/L sodium arsenite in drinking water, respectively).The rats were euthanized after 4 weeks of treatment.The pathologic changes in the lung were examined and the levels of interleukin ( IL)-1β, IL-6, IL-10 andβ-galactosidase (β-Gal) in broncho-alveolar lavage fluid

  12. 亚砷酸钠对大鼠外周血淋巴细胞DNA损伤的研究%Effect of sodium arsenite exposure on DNA damage of rat peripheral blood lymphocytes

    Institute of Scientific and Technical Information of China (English)

    田凤(契); 徐媛; 高向东; 张彦宁; 高怡; 裴秋玲

    2011-01-01

    目的 研究亚砷酸钠(NaAsO2)染毒对大鼠外周血淋巴细胞DNA的损伤作用.方法 Wistar大鼠32只,体质量180~200 g,雌雄各半,按体质量随机分为4组,分别为0(对照)、0.05、0.15、0.45 mg/L NaAsO2染毒组,每组8只.大鼠自由饮用含不同剂量NaAsO2的水,每天测量体质量并记录水消耗量.连续染毒30 d后,眼眶静脉采血,应用单细胞凝胶电泳试验评价大鼠外周血淋巴细胞的损伤程度.结果 0.05、0.15、0.45mg/L染砷组大鼠的体质量增长[(121.00±38.57)、(120.62±42.80)、(125.38±48.68)g]和饮水量[(36.9±6.2)、(37.9±5.8)、(39.3±4.2)ml/d]与对照组[(119.25±47.27)g、(38.4±5.1)ml/d]比较,差异无统计学意义(F值分别为0.040、0.828,P均>0.05).0.05、0.15、0.45 mg/L染砷组大鼠的外周血淋巴细胞拖尾率[46.25%(185/400)、57.00%(228/400)、64.00%(256/400)]、彗星尾长[(32.89±17.18)、(58.74±36.28)、(77.55±35.73)μm]、尾矩[(6.29±3.74)、(11.20±9.64)、(17.30±12.60)μm]显著高于对照组[39.25%(157/400)、(18.73±15.83)、(2.61±1.05)μm,P均<0.01];随着染砷剂量的增加,淋巴细胞拖尾率、彗星尾长和尾矩均呈上升趋势.结论 低剂量砷染毒可引起大鼠外周血淋巴细胞DNA的损伤.%Objective To explore the DNA damage in peripheral blood lymphocytes of rats exposed to sodium arsenite. Methods Thirty-two Wistar rats, weighing 180 - 200 g, equal male and female, were randomly divided into 4 groups, 8 in each group. Sodium arsenite 0(control) ,0.05,0.15,0.45 mg/L were given through drinking water for 30 days. Body weight and drinking water consumption were measured every day. Blood were collected and DNA damage in peripheral blood lymphocytes was examined by single cell gel electrophoresis.Results The increase of body mass[( 121.00 ± 38.57), ( 120.62 ± 42.80), ( 125.38 ± 48.68)g]and water intake [(36.9 ± 6.2), (37.9 ± 5.8), (39.3 ± 4.2)ml/d]in 0.05,0.15,0.45 mg/L sodium arsenite groups were compared with the

  13. Can Arousal Modulate Response Inhibition?

    Science.gov (United States)

    Weinbach, Noam; Kalanthroff, Eyal; Avnit, Amir; Henik, Avishai

    2015-01-01

    The goal of the present study was to examine if and how arousal can modulate response inhibition. Two competing hypotheses can be drawn from previous literature. One holds that alerting cues that elevate arousal should result in an impulsive response and therefore impair response inhibition. The other suggests that alerting enhances processing of…

  14. Forcing contact inhibition of locomotion

    OpenAIRE

    Roycroft, A.; Mayor, R.

    2015-01-01

    Contact inhibition of locomotion drives a variety of biological phenomenon, from cell dispersion to collective cell migration and cancer invasion. New imaging techniques have allowed contact inhibition of locomotion to be visualised in vivo for the first time, helping to elucidate some of the molecules and forces involved in this phenomenon.

  15. Potentized homeopathic drug Arsenicum Album 30C inhibits intracellular reactive oxygen species generation and up-regulates expression of arsenic resistance gene in arsenine-exposed bacteria Escherichia coli%顺势疗法药物白砷剂抑制暴露于三氧化二砷的大肠杆菌细胞内活性氧的产生并上调其抗三氧化二砷基因的表达

    Institute of Scientific and Technical Information of China (English)

    Arnab De; Durba Das; Suman Dutta; Debrup Chakraborty; Naoual Boujedaini; Anisur Rahman Khuda-Bukhsh

    2012-01-01

    -treated).A sub-set of untreated E.coli served as the negative control.Glucose uptake,specific activities of hexokinase,lipid peroxidase (LPO),superoxide dismutase (SOD) and catalase,intra- and extra-cellular sodium arsenite content,cell growth,cell membrane potential,DNA damage,intracellular reactive oxygen species (ROS),adenosine triphosphate (ATP) and free glutathione content and expressions of arsB and ptsG gene in normal control,sodium arsenite-treated,drug-treated and placebo-treated E.coli were analyzed.Treatments were blinded and randomized.RESULTS: In sodium arsenite-treated E.coli,glucose uptake,intracellular ROS,LPO and DNA damage increased along with decrease in the specific activities of hexokinase,SOD and catalase,intracellular ATP and free glutathione contents and cell membrane potential and growth,and there were increases in expression levels of arsB gene and ptsG gene.Ars AIb 30C administration reduced arsenic toxicity in E.coli by inhibiting generation of ROS and increasing tolerance to arsenite toxicity and cell growth.CONCLUSION: Ars AIb 30C ameliorated arsenic toxicity and DNA damage,validating efficacy of ultra-highly diluted remedies used in homeopathy.

  16. Balanced feedforward inhibition and dominant recurrent inhibition in olfactory cortex.

    Science.gov (United States)

    Large, Adam M; Vogler, Nathan W; Mielo, Samantha; Oswald, Anne-Marie M

    2016-02-23

    Throughout the brain, the recruitment of feedforward and recurrent inhibition shapes neural responses. However, disentangling the relative contributions of these often-overlapping cortical circuits is challenging. The piriform cortex provides an ideal system to address this issue because the interneurons responsible for feedforward and recurrent inhibition are anatomically segregated in layer (L) 1 and L2/3 respectively. Here we use a combination of optical and electrical activation of interneurons to profile the inhibitory input received by three classes of principal excitatory neuron in the anterior piriform cortex. In all classes, we find that L1 interneurons provide weaker inhibition than L2/3 interneurons. Nonetheless, feedforward inhibitory strength covaries with the amount of afferent excitation received by each class of principal neuron. In contrast, intracortical stimulation of L2/3 evokes strong inhibition that dominates recurrent excitation in all classes. Finally, we find that the relative contributions of feedforward and recurrent pathways differ between principal neuron classes. Specifically, L2 neurons receive more reliable afferent drive and less overall inhibition than L3 neurons. Alternatively, L3 neurons receive substantially more intracortical inhibition. These three features--balanced afferent drive, dominant recurrent inhibition, and differential recruitment by afferent vs. intracortical circuits, dependent on cell class--suggest mechanisms for olfactory processing that may extend to other sensory cortices. PMID:26858458

  17. 亚砷酸钠诱导大鼠胰岛β细胞株INS-1凋亡及其机制的研究%Mechanism of the apoptosis of rat pancreas islet β cell strain (INS-1 cells) induced by sodium arsenite

    Institute of Scientific and Technical Information of China (English)

    潘晓; 姜丽萍; 仲来福; 耿成燕; 孙鲜策

    2012-01-01

    Objective To study mechanism of the apoptosis of rat pancreas islet β cell strain (INS-1cells) induced by sodium arsenite.Methods INS-I cells were exposed to sodium arsenite at the different concentrations.MTr assay was used to detect the viability of INS-1 cells.The potentials on mitochondrial membrane and lysosome membrane of INS-1 cells were determined with the fluorescence spectrophotometer.The apoptotic levels of INS-1 cells exposed to sodium arsenite were observed by a fluorescence microscope and flow cytometry.Results After exposure to sodium araenite,the viability of INS-1 cells significantly decreased with the doses of sodium arsenite.At 24 h after exposure,the OD values of the mitochondrial membrane potentials declined observably with the doses of sodium arsenite (P<0.01).At 48 h after exposure,the OD values of the lysosome membrane potentials significantly increased with the doses of sodium arsenite (P<0.01).At 72 h after exposure,the apoptotic cells were observed under a fluorescence microscope and enhanced with the doses of sodium arsenite.The apoptosis cells with light blue,karyopyknosis,karyorrhexis,apoptotic body and chromatin concentration appeared.The results detected with flow cytometry indicated that after exposure,the apoptotic INS-1 E cells significantly increased with the doses of sodium arsenite.Conclusions The sodium arsenite can induce the apoptosis of INS-1 cells through the mitochondria-lysosome pathway.%目的 研究亚砷酸钠( sodium arsenite)对大鼠胰岛β细胞株INS-1(INS-1细胞)的凋亡作用及其机制.方法 将INS-1细胞暴露于不同浓度的亚砷酸钠,首先进行噻唑蓝(MTT)试验,并用荧光分光光度计测定INS-1细胞线粒体膜电位及溶酶体膜电位的吸光度(A)值;并于亚砷酸钠作用后,应用荧光显微镜和流式细胞仪观察并检测INS-1细胞的凋亡情况.结果 经亚砷酸钠作用后,INS-1细胞的活性明显下降,且细胞活性随着亚砷酸

  18. Protective effect of all-trans retinoic acid on injury of human immortalized hepatocytes induced by sodium arsenite%全反式维甲酸对亚砷酸钠致人肝细胞损伤保护性作用的研究

    Institute of Scientific and Technical Information of China (English)

    孙惠昕; 胡新欣; 张微; 高彦辉; 孙殿军

    2012-01-01

    目的 观察全反式维甲酸(ATRA)对亚砷酸钠致人肝细胞系(HHL)-5细胞损伤的保护性作用,探讨可能机制.方法 采用细胞培养方法,体外培养HHL-5细胞48 h后进行实验,实验分为4组:正常组、ATRA组、亚砷酸钠组、ATRA+亚砷酸钠组.用细胞增殖实验(WST)观察HHL-5细胞的活力;生物化学方法测定各组HHL-5细胞内超氧化物歧化酶(SOD)、谷胱甘肤过氧化物酶(GSH-Px)的活力及丙二醛(MDA)的含量和细胞培养液中谷草转氨酶(AST)的活力;透射电镜观察各组细胞超微结构的变化.结果 亚砷酸钠组HHL-5细胞活力(0.57±0.02)与正常组(0.70±0.01)比较,差异有统计学意义(P< 0.05);SOD、GSH-Px、MDA、AST [(153.84±2.35 )U/mg Prot、(0.08±0.02)U/mg Prot、(4.15±0.50)nmol/mg Prot、(265.43±4.62)×103 U/L]与正常组[(237.41±18.30) U/mg Prot、(0.93±0.02)U/mg Prot、(2.26±0.40)nmol/mg Prot、(177±9.85)×103 U/L]比较,差异有统计学意义(P均.<0.05).ATRA+亚砷酸钠组HHL-5细胞活力(0.65±0.04)与亚砷酸钠组比较,差异有统计学意义(P<0.05);SOD、GSH-Px、MDA、AST[(286.85±3.39)U/mg Prot、(0.56±0.09)U/mg Prot、(3.36±0.37)nmol/mg Prot、(220.02±1.07)×103 U/L]与亚砷酸钠组比较,差异有统计学意义(P均< 0.05).电镜结果显示,亚砷酸钠组同正常组及ATRA组比较,细胞表面微绒毛减少,双层核膜结构不清,胞质内可见空泡样变,肝糖原凝集;ATRA+亚砷酸钠组上述损伤程度减轻.结论 ATRA通过提高HHL-5细胞内抗氧化酶的活力,清除或者减少氧自由基对细胞的损伤,从而发挥保护作用.%Objective To investigate the protective effect of all-trans retinoic acid (ATRA) on injury of human immortalized hepatocytes (HHL-5 cells ) induced by sodium arsenite and possible mechanisms.Methods After cultured for 48 h,HHL-5 cells were divided into four groups:normal group,ATRA group,sodium arsenite group and ATRA + sodium arsenite group.HHL-5 cell viability

  19. Homo Economicus Belief Inhibits Trust

    OpenAIRE

    Ziqiang Xin; Guofang Liu

    2013-01-01

    As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners' benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals' homo economicus belief and inhibit t...

  20. Memory inhibition across the lifespan

    OpenAIRE

    Teale, Julia C.

    2015-01-01

    Age can affect memory performance. This statement is so often heard that it has become almost a truism. When research surrounding memory inhibition – the ability to ignore irrelevant material to aid in the retrieval of a target memory – is examined specifically, a more mixed picture of findings emerges. Whilst some previous work has found evidence of an age-related deficit, other research has rather found intact memory inhibition in older adults. Less often discussed, too, are the effects of ...

  1. The effect of sodium arsenite on the epithelial to mesenchymal transition process%亚砷酸钠对上皮细胞向间充质细胞转变过程的影响

    Institute of Scientific and Technical Information of China (English)

    董雪; 李晓翠; 史艳芬; 范洪学; 李荣贵

    2011-01-01

    目的 研究亚砷酸钠(NaAsO2)对上皮细胞向间质细胞的转变(epithelial to mesenchymal transition,EMT) 过程的影响.方法 ①EMT模型的建立:培养小鼠乳腺上皮细胞(NMuMG),当细胞大约融合50%时,换成3%血清的培养基,24 h后加入5 ng/ml TGF-β,作用24 h后,观察NMuMG形态,细胞染色检测E-ca、Vimentin表达、实时定量RT-PCR检测E-ca,Vimentin mRNAs 表达水平,是否成功的由上皮细胞转变成间质细胞.②加入NaAsO2:以5 ng/ml TGF-β作为阴性对照组,观察组5 ng/ml TGF-β+5 μmol/ml NaAsO2、5 ng/ml TGF-β+10 μmol/ml NaAsO2,再次检测上述指标.结果 ①成功建立EMT模型:细胞形态由立方形的上皮细胞转变成长梭形间质细胞;细胞染色显示,与未诱导组相比,E-ca表达呈阴性,Vimentin表达明显呈阳性;E-ca基因表达水平显著下降,Vimentin基因表达水平显著上调.②NaAsO2对EMT过程的影响:一定浓度范围内,随NaAsO2浓度升高,明显增强了Vimentin表达;E-ca基因水平逐渐降低,Vimentin基因水平明显升高,呈剂量-效应关系.结论 NaAsO2促进了EMT过程,可能是砷中毒引发癌症的发病机制之一.%Objective To explore the effect of sodium arsenite on the epithelial to mesenchymal transition (EMT)process. Methods NMuMGs were cultured, when it grew up to 50% , 3% serous medium were changed, and 5 ng/ml TGF-β was added into medium after 24 hour. When 5 ng/ml TGF-β working on the NMuMGs for 24 hours, the NMuMGs had shown spindle mesenchymal cell. 5 ng/ml TGF-β was as negative control, and 5 ng/ml TGF-β + 5 μmol/ml NaAsO2, 5 ng/ml TGF-β + 10 μmol/ml NaAsO2 were observed. Results The cubical epithelial cell showed on spindal mesenchymal cell, the expression of E-ca in induced group was negative,and the expression of Vimentin was positive; the expression of E-ca mRNA in induced group was reduced, and the expression of Vimentin mRNA was increased. Meanwhile, the mRNA of E-ca was decreased and Vimentin was

  2. 土壤中砷氧化菌的生理生化及转化砷特性研究%Arsenite Transformation Characteristics and Molecular Identification of Arsenic-oxidizing Bacteria Isolated from Soil

    Institute of Scientific and Technical Information of China (English)

    宋卫锋; 罗丽丽; 林梓河; 严明; 邓琪; 莫于婷

    2011-01-01

    [目的]通过外加砷源驯化肇庆市鼎湖山自然保护区土壤中细菌,研究砷氧化菌的生理生化及转化砷特性.[方法]采用富集、稀释平板、硝酸盐漫过、生理生化指标的测定等.[结果]从中分离、鉴定出具有氧化砷功能的产碱杆菌和土壤杆菌2种菌株.[结论]这2种菌株最适氧化砷温度为30℃,最适氧化砷pH为9.培养基中乳酸钠浓度对菌株氧化砷有一定的影响.%[ Objective ] Through domesticated bacteria from the applied arsenic source soil in Dinghushan Nature Reserve of Zhaoqing City,physiological,biochemical and transformation characteristics of arsenic oxide bacteria were studied. [ Method]The methods of concentration,plates serial dilution, silver nitrate overflowed, physiological characteristic were adopted. [ Result ] They were identified as alcaligenes castellani and agrobacterium conn respectively, which were able to oxidize arsenite ( As (Ⅲ) ) into arsenate ( As (Ⅴ) ). [ Conclusion ] The optimal temperature and pH were 30 ℃ and 9 respectively for two bacterial strains. In addition,sodium Lactate medium concentration had a certain impact to arsenicoxidizing.

  3. Effect of sodium arsenite on the gene and protein expression of p53, mdm2 and Kras in islet cells%亚砷酸钠对胰岛细胞中 p53、mdm2和Kras基因及蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    姚晓峰; 孙睿; 姜丽平; 耿成燕; 仲来福; 郑白璐; 杨光; 刘爽; 孙鲜策

    2014-01-01

    Objective To investigate the effect of sodium arsenite on p53, mdm2 and Kras expressions in islet βcells (INS-1) of rat.Methods The levels of wild type p53 (Tp53), mdm2 and Kras in sodium arsenite-treated rat islet βcells were detected by real-time PCR.The expression of mutant p53 and mdm2 protein were detected by western blot. Results After treatment with sodium arsenite, the level of Tp53 decreased, but those of mdm2、Kras increased.The protein expressions of mutant p53 and mdm2 increased.Conclusion Sodium arsenite could induce the transformation of Tp53 to mutant p53, and increase the level of mdm2 and Kras in INS-1 cells.%目的:探讨砷对大鼠胰岛β细胞(INS-1)p53、mdm2和Kras基因和蛋白表达的影响。方法荧光实时定量PCR法检测亚砷酸钠对大鼠胰岛β细胞中野生型p53(Tp53)、mdm2和Kras基因表达的影响,Western blot检测亚砷酸钠对大鼠胰岛β细胞突变型p53和mdm2蛋白表达的影响。结果亚砷酸钠作用于INS-1细胞后,Tp53基因水平降低,mdm2、Kras基因水平升高;突变型p53和mdm2蛋白表达增加。结论亚砷酸钠可使INS-1细胞中抑癌基因Tp53向突变型p53转变,癌基因mdm2和Kras的水平升高。

  4. 亚砷酸治疗急性早幼粒细胞白血病时肝功能损害的特点及保肝药物应用现状%Characteristics of Hepatic Impairment in APL Patients Treated by Arsenite and the Application of Hepatoprotective Drugs

    Institute of Scientific and Technical Information of China (English)

    隋美娟; 张卓(综述); 周晋(审校)

    2015-01-01

    The acute promyelocytic leukemia(APL) is a special kind of acute myelogenous leukemia, 99% of which is characterized with t (15;17)(q22;q12)chromosomal translation,leading to the synthesis of a fusion protein PML-RARα.Since the application of targeted drug like arsenite, the outcome of the APL has improved dramatically .However,arsenite has a toxicity profile that is mainly reflected in liver .In recent years,the increasing attentions are focused on side effects brought by arsenite application especially in liver , the toxicity of which further effects its efficacy .Here is to make a review of the characteristics of hepatic im-pairment and application of hepatoprotective drugs in APL treated by arsenite in order to obtain better thera-peutic effect.%急性早幼粒细胞白血病( APL)是急性髓细胞白血病中的一种特殊类型,99%的 APL有染色体t(15;17)(q22;q12)易位和早幼粒白血病基因与维甲酸受体基因融合基因的形成。近年来,由于亚砷酸等靶向药物的应用,APL的治疗效果大大提高。但亚砷酸应用的同时所带来的不良反应也引起了越来越多的关注,尤其是对肝脏,进而影响着亚砷酸在肝脏转化为活性产物中的疗效。该文针对亚砷酸治疗APL的肝功损害特点以及保肝药物应用的现状进行了综述,旨在合理化监测肝功能及保肝药物的应用,以使亚砷酸的疗效达到最佳。

  5. Synergistic Chondroprotective Effect of α-Tocopherol, Ascorbic Acid, and Selenium as well as Glucosamine and Chondroitin on Oxidant Induced Cell Death and Inhibition of Matrix Metalloproteinase-3—Studies in Cultured Chondrocytes

    Directory of Open Access Journals (Sweden)

    Anne-Christi Graeser

    2009-12-01

    Full Text Available Overproduction of reactive oxygen species and impaired antioxidant defence accompanied by chronic inflammatory processes may impair joint health. Pro-inflammatory cytokines such as interleukin-1β (IL-1β and tumor necrosis factor alpha (TNF-α stimulate the expression of metalloproteinases which degrade the extracellular matrix. Little is known regarding the potential synergistic effects of natural compounds such as α-tocopherol (α-toc, ascorbic acid (AA and selenium (Se on oxidant induced cell death. Furthermore studies regarding the metalloproteinase-3 inhibitory activity of glucosamine sulfate (GS and chondroitin sulfate (CS are scarce. Therefore we have studied the effect of α-toc (0.1–2.5 µmol/L, AA (10–50 µmol/L and Se (1–50 nmol/L on t-butyl hydroperoxide (t-BHP, 100–500 µmol/L-induced cell death in SW1353 chondrocytes. Furthermore we have determined the effect of GS and CS alone (100–500 µmol/L each and in combination on MMP3 mRNA levels and MMP3 secretion in IL-1β stimulated chondrocytes. A combination of α-toc, AA, and Se was more potent in counteracting t-BHP-induced cytotoxicity as compared to the single compounds. Similarly a combination of CS and GS was more effective in inhibiting MMP3 gene expression and secretion than the single components. The inhibition of MMP3 secretion due to GS plus CS was accompanied by a decrease in TNF-α production. Combining natural compounds such as α-toc, AA, and Se as well as GS and CS seems to be a promising strategy to combat oxidative stress and cytokine induced matrix degradation in chondrocytes.

  6. Chikusetsusaponin IVa Butyl Ester (CS-IVa-Be), a Novel IL6R Antagonist, Inhibits IL6/STAT3 Signaling Pathway and Induces Cancer Cell Apoptosis.

    Science.gov (United States)

    Yang, Jie; Qian, Shihui; Cai, Xueting; Lu, Wuguang; Hu, Chunping; Sun, Xiaoyan; Yang, Yang; Yu, Qiang; Gao, S Paul; Cao, Peng

    2016-06-01

    The activation of IL6/STAT3 signaling is associated with the pathogenesis of many cancers. Agents that suppress IL6/STAT3 signaling have cancer-therapeutic potential. In this study, we found that chikusetsusaponin IVa butyl ester (CS-IVa-Be), a triterpenoid saponin extracted from Acanthopanas gracilistylus W.W.Smith, induced cancer cell apoptosis. CS-IVa-Be inhibited constitutive and IL6-induced STAT3 activation, repressed STAT3 DNA-binding activity, STAT3 nuclear translocation, IL6-induced STAT3 luciferase reporter activity, IL6-induced STAT3-regulated antiapoptosis gene expression in MDA-MB-231 cells, and IL6-induced TF-1 cell proliferation. Surprisingly, CS-IVa-Be inhibited IL6 family cytokines rather than other cytokines induced STAT3 activation. Further studies indicated that CS-IVa-Be is an antagonist of IL6 receptor via directly binding to the IL6Rα with a Kd of 663 ± 74 nmol/L and the GP130 (IL6Rβ) with a Kd of 1,660 ± 243 nmol/L, interfering with the binding of IL6 to IL6R (IL6Rα and GP130) in vitro and in cancer cells. The inhibitory effect of CS-IVa-Be on the IL6-IL6Rα-GP130 interaction was relatively specific as CS-IVa-Be showed higher affinity to IL6Rα than to LIFR (Kd: 4,910 ± 1,240 nmol/L) and LeptinR (Kd: 4,990 ± 915 nmol/L). We next demonstrated that CS-IVa-Be not only directly induced cancer cell apoptosis but also sensitized MDA-MB-231 cells to TRAIL-induced apoptosis via upregulating DR5. Our findings suggest that CS-IVa-Be as a novel IL6R antagonist inhibits IL6/STAT3 signaling pathway and sensitizes the MDA-MB-231 cells to TRAIL-induced cell death. Mol Cancer Ther; 15(6); 1190-200. ©2016 AACR.

  7. Homo economicus belief inhibits trust.

    Science.gov (United States)

    Xin, Ziqiang; Liu, Guofang

    2013-01-01

    As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners' benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals' homo economicus belief and inhibit their trust. It seems that people's increasing homo economicus belief may serve as one cause of the worldwide decline of trust. PMID:24146907

  8. Homo economicus belief inhibits trust.

    Directory of Open Access Journals (Sweden)

    Ziqiang Xin

    Full Text Available As a foundational concept in economics, the homo economicus assumption regards humans as rational and self-interested actors. In contrast, trust requires individuals to believe partners' benevolence and unselfishness. Thus, the homo economicus belief may inhibit trust. The present three experiments demonstrated that the direct exposure to homo economicus belief can weaken trust. And economic situations like profit calculation can also activate individuals' homo economicus belief and inhibit their trust. It seems that people's increasing homo economicus belief may serve as one cause of the worldwide decline of trust.

  9. Tunneling inhibition for subwavelength light

    CERN Document Server

    Huang, Changming; Ye, Fangwei; Kartashov, Yaroslav V; Chen, Xianfeng; Torner, Lluis

    2013-01-01

    We show that light tunneling inhibition may take place in suitable dynamically modulated waveguide arrays for light spots whose features are remarkably smaller than the wavelength of light. We found that tunneling between neighboring waveguides can be suppressed for specific frequencies of the out-of-phase refractive index modulation, affording undistorted propagation of the input subwavelength light spots over hundreds of Rayleigh lengths. Tunneling inhibition turns out to be effective only when the waveguide separation in the array is above a critical threshold. Inclusion of a weak focusing nonlinearity is shown to improve localization. We analyze the phenomenon in purely dielectric structures and also in arrays containing periodically spaced metallic layers.

  10. 亚砷酸钠对大耳兔肝脏基质金属蛋白酶抑制因子-1mRNA和蛋白表达的影响%Impact of sodium arsenite on expression of matrix metalloproteinase inhibitor-1 (TIMP-1) mRNA and protein in rabbit liver

    Institute of Scientific and Technical Information of China (English)

    符文慧; 马艳; 牛姜水; 郑玉建

    2013-01-01

    目的 探讨亚砷酸钠对大耳兔肝脏基质金属蛋白酶抑制因子-1(TIMP-1)mRNA和蛋白表达的影响.方法 将30只健康成年清洁级雄性新西兰大耳兔随机分为5组,每组6只,分别为对照(自来水)组及0.15、0.30、0.75、1.5 mg/ml亚砷酸钠染毒组.采用自由饮用方式进行染毒,连续染毒12周.染毒结束后,分别采用酶联免疫吸附(ELISA)法和实时荧光定量PCR(RT-PCR)法检测大耳兔肝组织中TIMP-1蛋白和mRNA的表达水平.结果 与对照组相比,各剂量亚砷酸钠染毒组大耳兔肝组织中TIMP-1蛋白和0.30、0.75、1.5 mg/ml亚砷酸钠染毒组大耳兔肝组织中TIMP-1 mRNA的表达水平均较高,差异有统计学意义(P<0.05);且随着亚砷酸钠染毒剂量的升高,大耳兔肝组织中TIMP-1蛋白及mRNA表达水平均呈上升趋势.结论 基质金属蛋白酶抑制因子-1 (TIMP-1)表达的增高可能是亚砷酸钠肝毒性的易感因素.%Objective To approach the impact of sodium arsenite on the expression of matrix metalloproteinase inhibitor—1 (TIMP-1) mRNA and protein in rabbit liver. Methods A total of 30 male clean grade New Zea-land rabbits were randomly divided into five groups,six in each, and treated with sodium arsenite at the doses of 0,0.15,0.30,0.75,1.5 mg/ml through drinking water, for 12 consecutive weeks. After 12 weeks of treatment, enzyme-linked immunosorbent assay (ELJSA) and RT-PCR were used to detect the level of protein of TIMP—1 and the expression of mRNA of TIMP — 1 in rabbits liver. Results Compared with the control group, the protein of TIMP— 1 in various doses of sodium arsenite exposure group and the mRNA of TIMP—1 in doses of 0.30,0.75,1.5 mg/ml sodium arsenite exposure group rabbits liver were significantly higher (P<0.05); And with sodium arsenite dose increased, TIMP-1 protein and mRNA expression levels in liver tissue showed an upward trend. Conclusion Maybe the up-regulation of TIMP-1 expression is a susceptible factor in

  11. Determination of Arsenite in Water by Anodic Stripping Voltammetry Using Au- Pd Bimetallic Nanoparticles Modified Glassy Carbon Electrode%金-钯双金属纳米颗粒修饰玻碳电极阳极溶出伏安法测定三价砷的方法研究

    Institute of Scientific and Technical Information of China (English)

    蓝月存; 罗汉金; 王灿

    2012-01-01

    An anodic stripping voltammetric method for the determination of arsenite using Au - Pd bimetallic nanoparticles( Au-Pd NPs) modified glassy carbon electrode (Au -Pd/GCE) was developed. The structural information and electrochemical activities of the synthesized Au - Pd nanoparti-cles were investigated with UV - Vis spectroscopy, high resolution transmission electron microscopy ( HRTEM) and cyclic voltammetric ( CV) method. The determination of arsenic was conducted by square wave voltammetric(SWV) method. Effects of deposition potential and SWV parameters (such as frequency, increment and amplitude) on the current intensity of arsenite were investigated. The results showed that Au - Pd bimetallic nanoparticles presented a core - shell structure in shape and the modified electrode exhibited the characteristic peaks of both Au and Pd. A sensitive anodic stripping peak of arsenite appeared at about 0. 30 V, and the peak current was linear with concentration of arsenite in the range of 0. 5-20 μg/L with a limit of detection ( LOD) of 0. 15 μg/L, which is far below the maximum guideline value(10μ/L) set by World Health Organization(WHO). The modified electrode exhibited a good repeatability toward the consecutive determination of arsenite. The interference experiments also showed that except for Cu( II ), the existance of Pb( II ) , Cd( H ) and Zn( II) would not affect the detection of As( 1).%研究了金-钯双金属纳米颗粒修饰电极测定痕量砷的阳极溶出伏安法.采用紫外可见分光光度法、高分辨透射电镜及循环伏安法对颗粒的结构和电化学特性进行表征.采用方波伏安法测定三价砷,探讨了富集电位和方波伏安参数如频率、增幅、波幅以及干扰离子等对测定结果的影响.实验结果表明:金-钯双金属纳米颗粒呈壳-核结构;砷在0.30 V出现灵敏的阳极溶出伏安峰,峰电流与砷质量浓度在0.5~20 μg/L范围内呈良好的线性关系,检出限为0.15 μg/L;

  12. Islam Does Not Inhibit Science.

    Science.gov (United States)

    Shanavas, T. O.

    1999-01-01

    Compares the science/religion relationship in both Christian and Islamic countries. Presents Muslim scholars' ideas about the presence of humans on earth. Presents ideas on active nature, Noah's curse, and the age of the universe. Refutes the notion that Islam inhibited science and advocates the belief that Islam promoted science. (YDS)

  13. Testing of Biologically Inhibiting Surface

    DEFF Research Database (Denmark)

    Bill Madsen, Thomas; Larsen, Erup

    2003-01-01

    The main purpose of this course is to examine a newly developed biologically inhibiting material with regards to galvanic corrosion and electrochemical properties. More in detail, the concern was how the material would react when exposed to cleaning agents, here under CIP cleaning (Cleaning In Pl...

  14. Th2 cytokines inhibit lymphangiogenesis.

    Directory of Open Access Journals (Sweden)

    Ira L Savetsky

    Full Text Available Lymphangiogenesis is the process by which new lymphatic vessels grow in response to pathologic stimuli such as wound healing, inflammation, and tumor metastasis. It is well-recognized that growth factors and cytokines regulate lymphangiogenesis by promoting or inhibiting lymphatic endothelial cell (LEC proliferation, migration and differentiation. Our group has shown that the expression of T-helper 2 (Th2 cytokines is markedly increased in lymphedema, and that these cytokines inhibit lymphatic function by increasing fibrosis and promoting changes in the extracellular matrix. However, while the evidence supporting a role for T cells and Th2 cytokines as negative regulators of lymphatic function is clear, the direct effects of Th2 cytokines on isolated LECs remains poorly understood. Using in vitro and in vivo studies, we show that physiologic doses of interleukin-4 (IL-4 and interleukin-13 (IL-13 have profound anti-lymphangiogenic effects and potently impair LEC survival, proliferation, migration, and tubule formation. Inhibition of these cytokines with targeted monoclonal antibodies in the cornea suture model specifically increases inflammatory lymphangiogenesis without concomitant changes in angiogenesis. These findings suggest that manipulation of anti-lymphangiogenic pathways may represent a novel and potent means of improving lymphangiogenesis.

  15. Conditioned inhibition and reinforcement rate.

    Science.gov (United States)

    Harris, Justin A; Kwok, Dorothy W S; Andrew, Benjamin J

    2014-07-01

    We investigated conditioned inhibition in a magazine approach paradigm. Rats were trained on a feature negative discrimination between an auditory conditioned stimulus (CS) reinforced at one rate versus a compound of that CS and a visual stimulus (L) reinforced at a lower rate. This training established L as a conditioned inhibitor. We then tested the inhibitory strength of L by presenting it in compound with other auditory CSs. L reduced responding when tested with a CS that had been reinforced at a high rate, but had less or even no inhibitory effect when tested with a CS that had been reinforced at a low rate. The inhibitory strength of L was greater if it signaled a decrease in reinforcement from an already low rate than if it signaled an equivalent decrease in reinforcement from a high rate. We conclude that the strength of inhibition is not a linear function of the change in reinforcement that it signals. We discuss the implications of this finding for models of learning (e.g., Rescorla & Wagner, 1972) that identify inhibition with a difference (subtraction) rule.

  16. Inhibition Performance in Children with Math Disabilities

    OpenAIRE

    Winegar, Kathryn Lileth

    2013-01-01

    This study examined the inhibition deficit hypothesis in children with math disabilities (MD). Children with and without MD were compared on two inhibition tasks that included the random generation of numbers and letters. The results addressed three hypotheses. Weak support was found for the first hypothesis which stated difficulties related to inhibition are significantly related to math performance. I found partial support for this hypothesis in that inhibition was related to math problem s...

  17. Intentional inhibition of actions in humans

    OpenAIRE

    Misirlisoy, E.

    2015-01-01

    A crucial component of human behavioural flexibility is the capacity to inhibit actions at the last moment before action execution. This behavioural inhibition is often not an immediate reaction to external stimuli, but rather an endogenous ‘free’ decision. Knowledge about such ‘intentional inhibition’ is currently limited, with most research focused on stimulus-driven inhibition. This thesis will examine intentional inhibition, using several different experimental approaches. The behavioural...

  18. MMP inhibition in prostate cancer.

    Science.gov (United States)

    Lokeshwar, B L

    1999-06-30

    Matrix metalloproteinases (MMPs) play a significant role during the development and metastasis of prostate cancer (CaP). CaP cells secrete high levels of MMPs and low levels of endogenous MMP inhibitors (TIMPs), thus creating an excess balance of MMPs. Established CaP cell lines that express high levels of MMPs frequently metastasize to the bone and the lungs. Drugs such as Taxol and alendronate that reduce cell motility and calcium metabolism reduce bony metastasis of xenografted CaP tumors. We tested several synthetic, nontoxic inhibitors of MMPs that can be administered orally, including doxycycline (DC) and chemically modified tetracyclines (CMTs) on CaP cells in vitro and on a rat CaP model in vivo. Among several anti-MMP agents tested, CMT-3 (6-deoxy, 6-demethyl,4-de-dimethylamino tetracycline) showed highest activity against CaP cell invasion and cell proliferation. Micromolar concentration of CMT-3 and DC inhibited both the secretion and activity of MMPs by CaP cells. When tested for in vivo efficacy in the Dunning rat CaP model by daily oral gavage, CMT-3 and DC both reduced the lung metastases (> 50%). CMT-3, but not DC, inhibited tumor incidence (55 +/- 9%) and also reduced the tumor growth rate (27 +/- 9.3%). More significantly, the drugs showed minimum systemic toxicity. Ongoing studies indicate that CMT-3 may inhibit the skeletal metastases of CaP cells and delay the onset of paraplegia due to lumbar metastases. These preclinical studies provide the basis for clinical trials of CMT-3 for the treatment of metastatic disease. PMID:10415736

  19. PROTECTION OF GLUTATHIONE AGAINST ENDOTHELIAL APOPTOSIS INDUCED BY SODIUM ARSENITE%还原型谷胱甘肽对亚砷酸钠诱导的内皮细胞凋亡的保护作用

    Institute of Scientific and Technical Information of China (English)

    肖南; 刘韧; 田昆仑; 刁有芳; 汪志文

    2000-01-01

    In order to study the protective effect of glutathione(GSH)on endothelial appoptosis, the endothelial cells strain ECV-304was cocultured in vitro with 40,80 and 160 μmol/L sodium arsenite(Ars)alone and with 50μmol/L GSH respectively.Twentyfour hours after culture,endothelial apoptosis, ICAM-1 expression and oxidative state were determined by flow cytom-etry. The results showed that Ars increased endothelial apoptosis with dose-dependent manner, upregulated ICAM-1 expres-sion and suppressed the oxidative state. GSH decreased the endothelial apoptosis induced by 80 and 160 μmol/L Ars by 30.2% and 52.1%,respectively,and down-regulated ICAM-1 expression. As for apoptosis and ICAM-1 expression at 40 μnol/L Ars,GSH did not show significant effects. GSH could also preserve the oxidative state, which was more potent in that in-duced by 40μ M Ars. We concluded that GSH could protect the endothelial apoptosis induced by Ars,and this may associatewith down-regulation of ICAM-1 expression.%本文主要观察还原型谷胱甘肽(GSH)对亚砷酸钠(Ars)诱导的培养内皮细胞凋亡的保护作用。体外培养人内皮细胞株ECV-304,用4×10-5、8×10-5、1.6×10-4mol/LArs及5×10-5mol/LGSH作用,24小时后用流式细胞仪进行凋亡细胞定量、ICAM-1表达及氧化状态的测定。结果Ars以剂量依赖方式引起ECs的凋亡,增加ICAM-1表达,降低氧化状态;GSH可使8×10-5和1.6×10-4mol/LArs引起的凋亡分别降低30.2%和52.1%(P<0.01,P<0.05);GSH还明显降低Ars引起的ECs I-CAM-1的表达,但对4×10-5mol/LArs引起者作用不明显,GSH可升高ECs的氧化状态,而且对4×10-smol/LArs引起者最为明显。结果表明GSH对Ars引起的ECs凋亡有保护作用,且可能与调节ICAM-1表达有关。

  20. Comparison of the total arsenic concentration between saliva and blood after oral administration of sodium arsenite to rats%亚砷酸钠单次染毒大鼠后唾液及血液总砷含量变化比较

    Institute of Scientific and Technical Information of China (English)

    王大朋; 范丽丽; 张利明; 李建; 刘建; 金洹宇; 刘星; 安艳

    2012-01-01

    Objective To compare the total arsenic concentration between blood and saliva after oral administration of sodium arsenite to SD rats. Methods A single oral gavage dose of sodium arsenite (20mg/kg) was administrated to 21 adult male Sprague-Dawley rats. Then collected blood and saliva samples at 0, 1-2, 4-5 , 7-8, 11-12, 17-18, 23-24 hour for total arsenic detection. The blood samples were detected for total arsenic concentration by Atomic Fluorescence Spectrometry ( AFS-230) and the salivary arsenic were detected by inductively coupled plasma mass spectrometry ( ICP-MS). Results After intake of 20mg/kg BW sodium arsenite, the total arsenic concentration in blood of SD rats was increased rapidly, and reached the peak value at the 1-2 hour, then descended gradually. However, there was a second peak value at the 7-8 hour. The upward trend of salivary arsenic was more slowly than blood arsenic, and reached the peak value at the 7-8 hour, then descended gradually. The variation tendency of salivary arsenic and blood arsenic with time were basically the same. Besides, there was an obvious positive association between them, the correlation coefficient was 0.678, P < 0.01. Conclusion The excretion of arsenic in saliva was slower than that of blood samples after administrated a single oral gavage dose of sodium arsenite (20mg/kg) to SD rate, but the metabolism mode of arsenic in saliva was similar with that in blood, suggested that salivary arsenic can also well reflect the exposure level of arsenic in the body.%目的 比较亚砷酸钠单次染毒后大鼠血液及唾液中总砷含量随时间变化情况.方法 健康清洁级SD大鼠21只,适应性饲养一周后一次性灌服亚砷酸钠20mg/kg.于给药前(0 h)和给药后1~2、4~5、7~8、11 ~ 12、17 ~ 18和23 ~ 24 h时间段分别收集血液和唾液,利用原子荧光分光光度计(AFS-230)检测血砷含量,电感耦合-等离子体质谱(ICP-MS)测定唾液砷含量.结果 大鼠摄入亚砷酸

  1. Selective inhibition of human inducible nitric oxide synthase by S-alkyl-L-isothiocitrulline-containing dipeptides

    OpenAIRE

    Park, Jung-Min; Higuchi, Tsunehiko; Kikuchi, Kazuya; Urano, Yasuteru; Hori, Hiroyuki; Nishino, Takeshi; Aoki, Junken; Inoue, Keizo; Nagano, Tetsuo

    2001-01-01

    The aim of this study was to investigate the structure-activity relationship of S-alkyl-L-isothiocitrulline-containing dipeptides towards three partially purified recombinant human nitric oxide synthase (NOS) isozymes, as well as the effects of these compounds on cytokine-induced NO production by human DLD-1 cells.In an in vitro assay, S-methyl-L-isothiocitrulline (L-MIT) was slightly selective for human neuronal NOS (nNOS) over the inducible (iNOS) or endothelial (eNOS) isozyme, but the comb...

  2. Behavioral inhibition and obsessive-compulsive disorder.

    Science.gov (United States)

    Coles, Meredith E; Schofield, Casey A; Pietrefesa, Ashley S

    2006-01-01

    Behavioral inhibition is frequently cited as a vulnerability factor for development of anxiety. However, few studies have examined the unique relationship between behavioral inhibition and obsessive-compulsive disorder (OCD). Therefore, the current study addressed the relationship between behavioral inhibition and OCD in a number of ways. In a large unselected student sample, frequency of current OC symptoms was significantly correlated with retrospective self-reports of total levels of childhood behavioral inhibition. In addition, frequency of current OC symptoms was also significantly correlated with both social and nonsocial components of behavioral inhibition. Further, there was evidence for a unique relationship between behavioral inhibition and OC symptoms beyond the relationship of behavioral inhibition and social anxiety. In addition, results showed that reports of childhood levels of behavioral inhibition significantly predicted levels of OCD symptoms in adulthood. Finally, preliminary evidence suggested that behavioral inhibition may be more strongly associated with some types of OC symptoms than others, and that overprotective parenting may moderate the impact of behavioral inhibition on OC symptoms. The current findings suggest the utility of additional research examining the role of behavioral inhibition in the etiology of OCD. PMID:16621440

  3. Arsenic inhibits hedgehog signaling during P19 cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Jui Tung [Environmental Toxicology Program, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States); Bain, Lisa J., E-mail: lbain@clemson.edu [Environmental Toxicology Program, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States); Department of Biological Sciences, Clemson University, 132 Long Hall, Clemson, SC 29634 (United States)

    2014-12-15

    Arsenic is a toxicant found in ground water around the world, and human exposure mainly comes from drinking water or from crops grown in areas containing arsenic in soils or water. Epidemiological studies have shown that arsenic exposure during development decreased intellectual function, reduced birth weight, and altered locomotor activity, while in vitro studies have shown that arsenite decreased muscle and neuronal cell differentiation. The sonic hedgehog (Shh) signaling pathway plays an important role during the differentiation of both neurons and skeletal muscle. The purpose of this study was to investigate whether arsenic can disrupt Shh signaling in P19 mouse embryonic stem cells, leading to changes muscle and neuronal cell differentiation. P19 embryonic stem cells were exposed to 0, 0.25, or 0.5 μM of sodium arsenite for up to 9 days during cell differentiation. We found that arsenite exposure significantly reduced transcript levels of genes in the Shh pathway in both a time and dose-dependent manner. This included the Shh ligand, which was decreased 2- to 3-fold, the Gli2 transcription factor, which was decreased 2- to 3-fold, and its downstream target gene Ascl1, which was decreased 5-fold. GLI2 protein levels and transcriptional activity were also reduced. However, arsenic did not alter GLI2 primary cilium accumulation or nuclear translocation. Moreover, additional extracellular SHH rescued the inhibitory effects of arsenic on cellular differentiation due to an increase in GLI binding activity. Taken together, we conclude that arsenic exposure affected Shh signaling, ultimately decreasing the expression of the Gli2 transcription factor. These results suggest a mechanism by which arsenic disrupts cell differentiation. - Highlights: • Arsenic exposure decreases sonic hedgehog pathway-related gene expression. • Arsenic decreases GLI2 protein levels and transcriptional activity in P19 cells. • Arsenic exposure does not alter the levels of SHH

  4. Greener Approach towards Corrosion Inhibition

    Directory of Open Access Journals (Sweden)

    Neha Patni

    2013-01-01

    Full Text Available Corrosion control of metals is technically, economically, environmentally, and aesthetically important. The best option is to use inhibitors for protecting metals and alloys against corrosion. As organic corrosion inhibitors are toxic in nature, so green inhibitors which are biodegradable, without any heavy metals and other toxic compounds, are promoted. Also plant products are inexpensive, renewable, and readily available. Tannins, organic amino acids, alkaloids, and organic dyes of plant origin have good corrosion-inhibiting abilities. Plant extracts contain many organic compounds, having polar atoms such as O, P, S, and N. These are adsorbed on the metal surface by these polar atoms, and protective films are formed, and various adsorption isotherms are obeyed. Various types of green inhibitors and their effect on different metals are mentioned in the paper.

  5. Suramin inhibits EV71 infection.

    Science.gov (United States)

    Wang, Yaxin; Qing, Jie; Sun, Yuna; Rao, Zihe

    2014-03-01

    Enterovirus-71 (EV71) is one of the major causative reagents for hand-foot-and-mouth disease. In particular, EV71 causes severe central nervous system infections and leads to numerous dead cases. Although several inactivated whole-virus vaccines have entered in clinical trials, no antiviral agent has been provided for clinical therapy. In the present work, we screened our compound library and identified that suramin, which has been clinically used to treat variable diseases, could inhibit EV71 proliferation with an IC50 value of 40 μM. We further revealed that suramin could block the attachment of EV71 to host cells to regulate the early stage of EV71 infection, as well as affected other steps of EV71 life cycle. Our results are helpful to understand the mechanism for EV71 life cycle and provide a potential for the usage of an approved drug, suramin, as the antiviral against EV71 infection.

  6. Magnetic Catalysis vs Magnetic Inhibition

    CERN Document Server

    Fukushima, Kenji

    2012-01-01

    We discuss the fate of chiral symmetry in an extremely strong magnetic field B. We investigate not only quark fluctuations but also neutral meson effects. The former would enhance the chiral-symmetry breaking at finite B according to the Magnetic Catalysis, while the latter would suppress the chiral condensate once B exceeds the scale of the hadron structure. Using a chiral model we demonstrate how neutral mesons are subject to the dimensional reduction and the low dimensionality favors the chiral-symmetric phase. We point out that this effect, the Magnetic Inhibition, can be a feasible explanation for recent lattice-QCD data indicating the decreasing behavior of the chiral-restoration temperature with increasing B.

  7. Enhanced latent inhibition in high schizotypy individuals

    OpenAIRE

    Granger, Kiri T.; Moran, Paula M.; Buckley, Matthew G.; Haselgrove, Mark

    2016-01-01

    Latent inhibition refers to a retardation in learning about a stimulus that has been rendered familiar by non-reinforced preexposure, relative to a non-preexposed stimulus. Latent inhibition has been shown to be inversely correlated with schizotypy, and abnormal in people with schizophrenia, but these findings are inconsistent. One potential contributing factor to this inconsistency is that many tasks that purport to measure latent inhibition are confounded by alternative effects that also re...

  8. Inhibition of aflatoxin production by selected insecticides.

    OpenAIRE

    Draughon, F A; Ayres, J. C.

    1981-01-01

    The insecticide naled completed inhibition production of aflatoxins B1, B2, G1, and G2 by and growth of Aspergillus parasiticus at a 100-ppm (100 microgram/ml) concentration. The insecticides dichlorvos, Landrin, pyrethrum, Sevin, malathion, and Diazinon significantly (P = 0.05) inhibited production of aflatoxins at a 100-ppm concentration. However, at a concentration of 10 ppm, significant inhibition in production of aflatoxins was found only with naled, dichlorvos, Sevin, Landrin, and pyret...

  9. Cytokines inducing bone marrow SCA+ cells migration into pancreatic islet and conversion into insulin-positive cells in vivo.

    Directory of Open Access Journals (Sweden)

    LuGuang Luo

    Full Text Available We hypothesize that specific bone marrow lineages and cytokine treatment may facilitate bone marrow migration into islets, leading to a conversion into insulin producing cells in vivo. In this study we focused on identifying which bone marrow subpopulations and cytokine treatments play a role in bone marrow supporting islet function in vivo by evaluating whether bone marrow is capable of migrating into islets as well as converting into insulin positive cells. We approached this aim by utilizing several bone marrow lineages and cytokine-treated bone marrow from green fluorescent protein (GFP positive bone marrow donors. Sorted lineages of Mac-1(+, Mac-1(-, Sca(+, Sca(-, Sca(-/Mac-1(+ and Sca(+/Mac-1(- from GFP positive mice were transplanted to irradiated C57BL6 GFP negative mice. Bone marrow from transgenic human ubiquitin C promoter GFP (uGFP, with strong signal C57BL6 mice was transplanted into GFP negative C57BL6 recipients. After eight weeks, migration of GFP positive donor' bone marrow to the recipient's pancreatic islets was evaluated as the percentage of positive GFP islets/total islets. The results show that the most effective migration comes from the Sca(+/Mac(- lineage and these cells, treated with cytokines for 48 hours, were found to have converted into insulin positive cells in pancreatic islets in vivo. This study suggests that bone marrow lineage positive cells and cytokine treatments are critical factors in determining whether bone marrow is able to migrate and form insulin producing cells in vivo. The mechanisms causing this facilitation as well as bone marrow converting to pancreatic beta cells still need to be investigated.

  10. Tumor MICA status predicts the efficacy of immunotherapy with cytokine-induced killer cells for patients with gastric cancer.

    Science.gov (United States)

    Chen, Yu; Lin, Wan-Song; Zhu, Wei-Feng; Lin, Jing; Zhou, Zhi-Feng; Huang, Chuan-Zhong; Chen, Gang; Shi, Yi; Guo, Zeng-Qing; Ye, Yun-Bin

    2016-02-01

    In this study, we determine the relationship between the expression of major histocompatibility complex class I chain-related gene A (MICA) in gastric cancer tumors after D2 gastrectomy and the clinical outcome of a CIK-containing adjuvant therapy. Ninety-five consecutive patients with gastric cancer after D2 gastrectomy who received adjuvant chemotherapy combined with CIK cell therapy were enrolled. The MICA expression of their tumors was determined by immunohistochemistry (IHC). High expression of MICA protein was documented by IHC in 38 of 95 tumor samples (40.0 %). The MICA status was significantly associated with the age and stage, p = 0.008 and 0.023, respectively. Analysis of NKG2D on in vitro expanded CIK cells showed that the percentages of NKG2D+ in CD3+/CD56+, CD3-/CD56+, and CD3+/CD8+ cells populations were 97.2 ± 1.4, 97.9 ± 1.8, and 95.6 ± 2.1 %, respectively. For patient with high MICA-expressing tumors, the median DFS and OS were longer than for the patients with tumors with low expression of MICA; 46.0 versus 41.0 months (p = 0.027), and 48.0 versus 42.0 months (p = 0.031), respectively. In a multivariate analysis, stage and MICA expression were independent prognostic factors for DFS and OS. Our findings show that adjuvant chemotherapy plus CIK therapy treatment is a promising modality for treating gastric cancer patients after D2 gastrectomy. Especially, those who have tumors with high expression of MICA were more likely to benefit from such a treatment strategy. Subsequent studies in clinical trial cohorts will be required to confirm the clinical utility of these markers.

  11. Temporal profiling of cytokine-induced genes in pancreatic β-cells by meta-analysis and network inference

    DEFF Research Database (Denmark)

    Lopes, Miguel; Kutlu, Burak; Miani, Michela;

    2014-01-01

    Type 1 Diabetes (T1D) is an autoimmune disease where local release of cytokines such as IL-1β and IFN-γ contributes to β-cell apoptosis. To identify relevant genes regulating this process we performed a meta-analysis of 8 datasets of β-cell gene expression after exposure to IL-1β and IFN-γ. Two o...

  12. Structural analysis and cytokine-induced activity of gelling sulfated polysaccharide from the cystocarpic plants of Ahnfeltiopsis flabelliformis.

    Science.gov (United States)

    Kravchenko, Anna O; Anastyuk, Stanislav D; Sokolova, Ekaterina V; Isakov, Vladimir V; Glazunov, Valery P; Helbert, William; Yermak, Irina M

    2016-10-20

    Gelling sulfated polysaccharide from the cystocarpic plants of Ahnfeltiopsis flabelliformis was studied. According to FT-IR and NMR spectroscopy data, the polysaccharide was found to be iota/kappa-carrageenan with iota- and kappa-type units in a 2:1 ratio containing beta-carrageenan units and minor amounts of nu- and mu-carrageenans. The HPLC and ESI MS/MS data of enzymatic hydrolysis products revealed that the main components of the polymer chain are iota-carrabiose, iota-carratetraose and hybrid tetra- and hexasaccharides consisting of kappa- and iota-units. Xylose was a substituent of a hydroxyl group at C-6 of 1,3-linked β-d-galactose in the total polysaccharides. It was shown that the ability of carrageenans to increase the synthesis of cytokines depended on their molecular weight. The polysaccharide induced the synthesis of the anti-inflammatory cytokine IL-10, whereas oligosaccharides increased the synthesis of both pro- and anti-inflammatory cytokines at high concentrations. PMID:27474596

  13. HDAC Inhibitor-Mediated Beta-Cell Protection Against Cytokine-Induced Toxicity Is STAT1 Tyr701 Phosphorylation Independent

    DEFF Research Database (Denmark)

    Dahllöf, Mattias Salling; Christensen, Dan P; Harving, Mette;

    2015-01-01

    regulates IFN-γ signaling at the level of STAT1 Tyr701 phosphorylation. Using different small molecule HDAC inhibitors with varying class selectivity, INS-1E wild type and stable HDAC1-3 knockdown pancreatic INS-1 cell lines, we show that IFN-γ-induced Cxcl9 and iNos expression as well as Cxcl9 and GAS...

  14. Cytokine-induced impairment of short-chain fatty acid oxidation and viability in human colonic epithelial cells

    DEFF Research Database (Denmark)

    Pedersen, G; Saermark, T; Horn, T;

    2000-01-01

    Pro-inflammatory cytokines may directly influence the viability and metabolic function of colonic epithelial cells (CEC) as an early event in the development of inflammatory bowel disease. We report here that TNF-alpha+IFN-gamma induced a synergistic, concentration-dependent decline in butyrate...... oxidation, an essential energy supply, in HT-29 and DLD-1 cells. TNF-alpha+IFN-gamma induced a parallel profound decline in cell viability in HT-29 cells, but not in DLD-1 cells, where impairment of butyrate oxidation seemed to precede later occurrence of cell damage. TNF-alpha+INF-gamma induced CEC damage...

  15. Astrocyte-derived proinflammatory cytokines induce hypomyelination in the periventricular white matter in the hypoxic neonatal brain.

    Directory of Open Access Journals (Sweden)

    Yiyu Deng

    Full Text Available Hypoxic exposure in the perinatal period causes periventricular white matter damage (PWMD, a condition associated with myelination abnormalities. Under hypoxic conditions, glial cells were activated and released a large number of inflammatory mediators in the PWM in neonatal brain, which may result in oligodendrocyte (OL loss and axonal injury. This study aims to determine if astrocytes are activated and generate proinflammatory cytokines that may be coupled with the oligodendroglial loss and hypomyelination observed in hypoxic PWMD. Twenty-four 1-day-old Wistar rats were exposed to hypoxia for 2 h. The rats were then allowed to recover under normoxic conditions for 7 or 28 days before being killed. Another group of 24 rats kept outside the chamber was used as age-matched controls. Upregulated expression of TNF-α and IL-1β was observed in astrocytes in the PWM of P7 hypoxic rats by double immunofluorescence, western blotting and real time RT-PCR. This was linked to apoptosis and enhanced expression of TNF-R1 and IL-1R1 in APC(+ OLs. PLP expression was decreased significantly in the PWM of P28d hypoxic rats. The proportion of myelinated axons was markedly reduced by electron microscopy (EM and the average g-ratios were higher in P28d hypoxic rats. Upregulated expression of TNF-α and IL-1β in primary cultured astrocytes as well as their corresponding receptors in primary culture APC(+ oligodendrocytes were detected under hypoxic conditions. Our results suggest that following a hypoxic insult, astrocytes in the PWM of neonatal rats produce inflammatory cytokines such as TNF-α and IL-1β, which induce apoptosis of OLs via their corresponding receptors associated with them. This results in hypomyelination in the PWM of hypoxic rats.

  16. Gamma c-signaling cytokines induce a regulatory T cell phenotype in malignant CD4+ T lymphocytes

    DEFF Research Database (Denmark)

    Kasprzycka, Monika; Zhang, Qian; Witkiewicz, Agnieszka;

    2008-01-01

    CD25 and TGF-beta, the expression of FOXP3 and, to a lesser degree, IL-10 was restricted to two CTCL cell lines that are dependent on exogenous IL-2. IL-2, IL-15, and IL-21, all of which signals through receptors containing the common gamma chain, induced expression of IL-10 in the IL-2-dependent...... that the T regulatory cell features are induced in CTCL T cells by common gamma chain signaling cytokines such as IL-2 and do not represent a fully predetermined, constitutive phenotype independent of the local environmental stimuli to which these malignant mature CD4(+) T cells become exposed....

  17. The glycolipid sulfatide protects insulin-producing cells against cytokine-induced apoptosis, a possible role in diabetes

    DEFF Research Database (Denmark)

    Roeske-Nielsen, A; Dalgaard, L T; Månsson, Sven-Erik;

    2010-01-01

    these is NO production. The glycosphingolipid sulfatide is present in ß-cells in the secretory granules in varying amounts and is secreted together with insulin. We now investigate whether sulfatide is able to protect insulin-producing cells against the pro-apoptotic effect of interleukin-1ß, interferon-¿ and tumour...

  18. HIV-1 DNA vaccine with adjuvant cytokines induces specific immune responses against HIV-1 infection in mice

    Institute of Scientific and Technical Information of China (English)

    WANG Fu-xiang; SUN Yong-tao; WANG Lin-xu; LIU Juan

    2006-01-01

    @@ There is mounting evidence that the induction of strong mucosal and cell-mediated immune responses is key element to consider in constructing efficacious HIV-1 vaccine. Therapeutic vaccines that induce high levels of CTL specific to HIV are currently being developed worldwide.

  19. Cytokines induce upregulation of vascular P2Y(2) receptors and increased mitogenic responses to UTP and ATP

    DEFF Research Database (Denmark)

    Hou, M; Möller, S; Edvinsson, L;

    2000-01-01

    . Because released cytokines in atherosclerotic lesions mediate multiple effects on gene transcription in VSMCs, we speculated that cytokines could be involved in the regulation of P2Y(2) receptor expression. Using a competitive reverse transcription-polymerase chain reaction, we detected that interleukin......-activated protein kinase inhibitor SB20358 alone nor its combination with PD098059 blocked the effect of IL-1beta on the expression of P2Y(2) receptor mRNA. Our results demonstrate that inflammatory mediators upregulate vascular P2Y(2) receptors at the transcriptional and at the functional level through protein...

  20. Protective effect of trichostatin A and 5-azacitidine on cytokine-induced toxicity in pancreatic β-cells

    Institute of Scientific and Technical Information of China (English)

    候粲

    2014-01-01

    Objective To investigate the effect of trichostatin A(TSA)and 5-azacitidine(5-Aza C)on pancreaticβ-cells impaired by cytokine,via measuring the proliferation,apoptosis,and function of pancreaticβ-cells.Methods RIN-m5f was impaired by interleukin-1βand interferon-γin vitro,and treated with TSA and 5-Aza C.Experiment groups included blank control group,cytokine induction group,0.05/0.10μmol/L TSA group,0.63/1.25μmol/L 5-Aza C group,and 0.10μmol/L TSA

  1. Nardostachys jatamansi extract protects against cytokine-induced β-cell damage and streptozotocin-induced diabetes

    Institute of Scientific and Technical Information of China (English)

    Mi-Young; Song; Ui-Jin; Bae; Bong-Hee; Lee; Kang-Beom; Kwon; Eun-A; Seo; Sung-Joo; Park; Min-Sun; Kim; Ho-Joon; Song; Keun-Sang; Kwon; Jin-Woo; Park; Do-Gon; Ryu; Byung-Hyun; Park

    2010-01-01

    AIM: To investigate the anti-diabetogenic mechanism of Nardostachys jatamansi extract (NJE). METHODS: Mice were injected with streptozotocin viaa tail vein to induce diabetes. Rat insulinoma RINm5F cells and isolated rat islets were treated with interleukin1β and interferon-γ to induce cytotoxicity. RESULTS: Treatment of mice with streptozotocin resulted in hyperglycemia and hypoinsulinemia, which was conf irmed by immunohistochemical staining of the islets. The diabetogenic effects of streptozotocin were c...

  2. Reduced surround inhibition in musicians.

    Science.gov (United States)

    Shin, Hae-Won; Kang, Suk Y; Hallett, Mark; Sohn, Young H

    2012-06-01

    To investigate whether surround inhibition (SI) in the motor system is altered in professional musicians, we performed a transcranial magnetic stimulation (TMS) study in 10 professional musicians and 15 age-matched healthy non-musicians. TMS was set to be triggered by self-initiated flexion of the index finger at different intervals ranging from 3 to 1,000 ms. Average motor evoked potential (MEP) amplitudes obtained from self-triggered TMS were normalized to average MEPs of the control TMS at rest and expressed as a percentage. Normalized MEP amplitudes of the abductor digiti minimi (ADM) muscles were compared between the musicians and non-musicians with the primary analysis being the intervals between 3 and 80 ms (during the movement). A mixed-design ANOVA revealed a significant difference in normalized ADM MEPs during the index finger flexion between groups, with less SI in the musicians. This study demonstrated that the functional operation of SI is less strong in musicians than non-musicians, perhaps due to practice of movement synergies involving both muscles. Reduced SI, however, could lead susceptible musicians to be prone to develop task-specific dystonia.

  3. Expression of Nrf2 induced by sodium arsenite in mouse pancreatic β cells%Nrf2在急性亚砷酸钠暴露的小鼠胰岛β细胞中的表达

    Institute of Scientific and Technical Information of China (English)

    杨蓓; 陈雪; 丁金兰

    2013-01-01

    Objective To test the expressions of Nrf2 and phase II detoxifying enzyme genes induced by sodium arsenite (NaAsO2) in mouse pancreatic β-cell MIN6.Methods MIN6 cells were exposed to 4μmol/L NaAsO2 for 2,6,12,18,24hours.Nrf2 protein levels in Nuclear factions,cytosolic factions and whole-cell of MIN6 cells were measured with Western blotting.mRNA exprcssions of Nrf2 and phase Ⅱ detoxifying enzyme genes were measured by Real-time PCR.Results Expression of Nrf2 protein was significantly increased after 4μmol/L NaAsO2 exposure did reached the peak at 2hours,then decreased gradually.Nrf2 protein expressions in nuclear factions were consistent with Nrf2 levels of the whole MIN6 cell in the time-dependent fasion.But 4μmol/L NaAsO2 exposure did not induce a robust increase in Nrf2 mRNA.The induction of some phase Ⅱ detoxification enzyme genes,including NAD (P) H:quinone oxidoreductase 1 (Nqo1),heme oxygenase 1 (Homx-1),were time-dependently increased in MIN6 cells.Nqo1 and Homx-1 mRNA expressions were obviously increased after 2hours NaAsO2 exposure and went higher at 6hours,then decreased gradually.Conclusions Upon exposure to NaAsO2,Nrf2 is stabilized and translocated into the nucleus,and then activates transcription of various detoxification enzyme genes in mouse pancreatic β-cells.%目的 检测急性亚砷酸钠作用小鼠胰岛β细胞的Nrf2及其调控的Ⅱ相解毒酶的表达情况.方法 4μmol/L亚砷酸钠(NaAsO2)作用于MIN6细胞2、6、12、18、24h;利用Western blotting检测亚砷酸钠暴露不同时间点细胞核、细胞质和细胞总的Nrf2蛋白表达;应用Real-time PCR检测不同时间点Nrf2及其调控的Ⅱ相解毒酶NAD(P)H:醌氧化还原酶1(Nqo1)和血红素氧化酶1(Hmox-1)mRNA表达.结果 亚砷酸钠暴露2h,Nrf2蛋白表达增多并达到高峰,之后随时间的延长Nrf2蛋白表达逐渐降低.Nrf2核蛋白表达的时间效应性与细胞总的Nrf2表达完全一致.但不同时间

  4. Contour Detection Operators Based on Surround Inhibition

    NARCIS (Netherlands)

    Grigorescu, Cosmin; Petkov, Nicolai; Westenberg, Michel A.

    2003-01-01

    We propose a biologically motivated computational step, called non-classical receptive field (non-CRF) inhibition, to improve contour detection in images of natural scenes. We augment a Gabor energy operator with non-CRF inhibition. The resulting contour operator responds strongly to isolated lines,

  5. Quorum Sensing Inhibition, Relevance to Periodontics

    OpenAIRE

    Yada, Sudheer; B Kamalesh; Sonwane, Siddharth; Guptha, Indra; Swetha, R K

    2015-01-01

    Quorum sensing helps bacteria to communicate with each other and in coordinating their behavior. Many diseases of human beings, plants, and animals are mediated by quorum sensing. Various approaches are being tried to inhibit this communication to control the diseases caused by bacteria. Periodontal pathogens also communicate through quorum sensing and new approaches to treat periodontal disease using quorum sensing inhibition need to explored.

  6. Cortisol involvement in mechanisms of behavioral inhibition

    NARCIS (Netherlands)

    Tops, Mattie; Boksem, Maarten A. S.

    2011-01-01

    We studied whether baseline cortisol is associated with post-error slowing, a measure that depends upon brain areas involved in behavioral inhibition. Moreover, we studied whether this association holds after controlling for positive associations with behavioral inhibition scores and error-related n

  7. Inhibition: Mental Control Process or Mental Resource?

    Science.gov (United States)

    Im-Bolter, Nancie; Johnson, Janice; Ling, Daphne; Pascual-Leone, Juan

    2015-01-01

    The current study tested 2 models of inhibition in 45 children with language impairment and 45 children with normally developing language; children were aged 7 to 12 years. Of interest was whether a model of inhibition as a mental-control process (i.e., executive function) or as a mental resource would more accurately reflect the relations among…

  8. A Qualitative Approach to Enzyme Inhibition

    Science.gov (United States)

    Waldrop, Grover L.

    2009-01-01

    Most general biochemistry textbooks present enzyme inhibition by showing how the basic Michaelis-Menten parameters K[subscript m] and V[subscript max] are affected mathematically by a particular type of inhibitor. This approach, while mathematically rigo