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Sample records for benzopyrene-diol-epoxide bpde-induced bax

  1. Attenuation of BPDE-induced p53 accumulation by TPA is associated with a decrease in stability and phosphorylation of p53 and down-regulation of NF-κB activation: Role of p38 MAP kinase

    Science.gov (United States)

    Mukherjee, Jagat J.; Sikka, Harish C.

    2005-01-01

    DNA damage caused by benzo[a]pyrene (BP) or other PAHs induce p53 protein as a protective measure to eliminate the possibility of mutagenic fixation of the DNA damage. 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibits p53 response induced by BP and other DNA-damaging agents and may cause tumor promotion. The molecular mechanism of attenuation of BP-induced p53 response by TPA is not known. We investigated the effect of TPA on p53 response in BPDE-treated mouse epidermal JB6(P+) Cl 41 cells. BPDE treatment induced p53 accumulation which was attenuated significantly by TPA. Cells treated with BPDE and TPA showed increased ratio of Mdm2 to p53 proteins in p53 immunoprecipitate and decreased p53 life span compared to BPDE-treated cells indicating p53 destabilization by TPA. TPA also inhibited BPDE-induced p53 phosphorylation at serine15. Activation of both ERKs and p38 MAPK by BPDE and attenuation of BPDE-induced p53 accumulation by U0126 or SB202190, specific inhibitor of MEK1/2 or p38 MAPK, indicate the role of ERKs and p38 MAPK in p53 accumulation. Interestingly, TPA potentiated BPDE-induced activation of ERKs whereas p38 MAPK activation was significantly inhibited by TPA, suggesting that inhibition of p38 MAPK is involved in p53 attenuation by TPA. Furthermore SB202190 treatment caused decreased p53 stability and inhibition of phosphorylation of p53 at serine 15 in BPDE-treated cells. We also observed that TPA or SB202190 attenuated BPDE-induced NF-κB activation in JB6 (Cl 41) cells harboring NF-κB reporter plasmid. To our knowledge this is the first report that TPA inhibits chemical carcinogen-induced NF-κB activation. Interference of TPA with BPDE-induced NF-κB activation implicates abrogation of p53 function which has been discussed. Overall our data suggest that abrogation of BPDE-induced p53 response and of NF-κB activation by TPA is mediated by impairment of signaling pathway involving p38 MAPK. PMID:16244358

  2. BAX supports the mitochondrial network, promoting bioenergetics in nonapoptotic cells

    Science.gov (United States)

    Boohaker, Rebecca J.; Zhang, Ge; Carlson, Adina Loosley; Nemec, Kathleen N.

    2011-01-01

    The dual functionality of the tumor suppressor BAX is implied by the nonapoptotic functions of other members of the BCL-2 family. To explore this, mitochondrial metabolism was examined in BAX-deficient HCT-116 cells as well as primary hepatocytes from BAX-deficient mice. Although mitochondrial density and mitochondrial DNA content were the same in BAX-containing and BAX-deficient cells, MitoTracker staining patterns differed, suggesting the existence of BAX-dependent functional differences in mitochondrial physiology. Oxygen consumption and cellular ATP levels were reduced in BAX-deficient cells, while glycolysis was increased. These results suggested that cells lacking BAX have a deficiency in the ability to generate ATP through cellular respiration. This conclusion was supported by detection of reduced citrate synthase activity in BAX-deficient cells. In nonapoptotic cells, a portion of BAX associated with mitochondria and a sequestered, protease-resistant form was detected. Inhibition of BAX with small interfering RNAs reduced intracellular ATP content in BAX-containing cells. Expression of either full-length or COOH-terminal-truncated BAX in BAX-deficient cells rescued ATP synthesis and oxygen consumption and reduced glycolytic activity, suggesting that this metabolic function of BAX was not dependent upon its COOH-terminal helix. Expression of BCL-2 in BAX-containing cells resulted in a subsequent loss of ATP measured, implying that, even under nonapoptotic conditions, an antagonistic interaction exists between the two proteins. These findings infer that a basal amount of BAX is necessary to maintain energy production via aerobic respiration. PMID:21289292

  3. Ernest Belfort Bax: Marxist, Idealist, Positivist

    OpenAIRE

    Bevir, Mark

    1993-01-01

    Bax was the leading philosopher of the socialist revival in Britain during the 1880s. He saw Marxism as an economic and historical science that lacked a philosophical and ethical basis. Consequently, he tried to justify the Marxian dialectic by using a philosophy indebted to German idealism to show that the dialectic was a fact about reality itself, and he also tried to provide an ethical defence of Marxism in terms of a positivist ethic enshrining the goals of the French Revolution. Such ...

  4. Small molecules reveal an alternative mechanism of Bax activation.

    Science.gov (United States)

    Brahmbhatt, Hetal; Uehling, David; Al-Awar, Rima; Leber, Brian; Andrews, David

    2016-04-15

    The pro-apoptotic protein Bax commits a cell to death by permeabilizing the mitochondrial outer membrane (MOM). To obtain small-molecule probes for elucidating the molecular mechanism(s) of Bax activation, we screened for compounds that induced Bax-mediated liposome permeabilization. We identified five structurally different small molecules that promoted both Bax targeting to and oligomerization at membranes. All five compounds initiated Bax oligomerization in the absence of membranes by a mechanism unlike Bax activation by Bcl-2 homology 3 domain (BH3) proteins. Some of the compounds induced Bax/Bak-dependent apoptosis in cells. Activation of Bax by the most active compound was poorly inhibited by the anti-apoptotic protein Bcl-XL and requires a cysteine residue at position 126 of Bax that is not required for activation by BH3 proteins. Our results reveal a novel pathway for Bax activation independent of pro-apoptotic BH3 proteins that may have important implications for the regulation of Bax activity in cells. PMID:26916338

  5. PUMA and Bax-induced Autophagy Contributes to Apoptosis

    OpenAIRE

    Yee, Karen S.; Wilkinson, Simon; James, John; Ryan, Kevin M.; Vousden, Karen H.

    2009-01-01

    The p53-inducible BH3-only protein PUMA is a key mediator of p53-dependent apoptosis, and PUMA has been shown to function by activating Bax and mitochondrial outer membrane permeabilization. In this study we describe an ability of PUMA to induce autophagy that leads to the selective removal of mitochondria. This function of PUMA depends on Bax/Bak and can be reproduced by overexpression of Bax. The induction of autophagy coincides with cytochrome c release, and taken together the results sugg...

  6. PUMA- and Bax-induced autophagy contributes to apoptosis

    OpenAIRE

    Yee, K S; Wilkinson, S; James, J; Ryan, K M; Vousden, K H

    2009-01-01

    The p53-inducible BH3-only protein PUMA is a key mediator of p53-dependent apoptosis, and PUMA has been shown to function by activating Bax and mitochondrial outer membrane permeabilization. In this study, we describe an ability of PUMA to induce autophagy that leads to the selective removal of mitochondria. This function of PUMA depends on Bax/Bak and can be reproduced by overexpression of Bax. The induction of autophagy coincides with cytochrome c release, and taken together the results sug...

  7. A novel plant glutathione S-transferase/peroxidase suppresses Bax lethality in yeast

    DEFF Research Database (Denmark)

    Kampranis, S C; Damianova, R; Atallah, M;

    2000-01-01

    The mammalian inducer of apoptosis Bax is lethal when expressed in yeast and plant cells. To identify potential inhibitors of Bax in plants we transformed yeast cells expressing Bax with a tomato cDNA library and we selected for cells surviving after the induction of Bax. This genetic screen allo...

  8. The apoptotic response in HCT116BAX-/- cancer cells becomes rapidly saturated with increasing expression of a GFP-BAX fusion protein

    International Nuclear Information System (INIS)

    Many chemotherapeutic agents promote tumor cell death by activating the intrinsic pathway of apoptosis. Intrinsic apoptosis involves permeabilization of the mitochondrial outer membrane and the release of cytochrome c, a process that is controlled by proteins of the BCL2 gene family. Chemoresistance is often associated with abnormalities in concentrations of BCL2 family proteins. Although stoichiometirc interactions between anti-apoptotic and BH3-only BCL2 family proteins have been well documented as affecting cell death, the association between changes in BAX concentration and intrinsic apoptosis are poorly understood. Exogenous GFP-murine Bax fusion constructs were transfected into BAX-deficient HCT116 cells. To titrate the expression of the fusion protein, GFP-BAX was cloned into a tetracycline sensitive expression cassette and cotransfected with a plasmid expressing the rtTA transcription factor into HCT116BAX-/- cells. Linear expression of the fusion gene was induced with doxycycline and monitored by quantitative PCR and immunoblotting. Cell death was assayed by DAPI staining cells after exposure to indomethacin, and scoring nuclei for condensed chromatin and fragmented nuclei. HCT116BAX-/- cells were resistant to indomethacin, but susceptibility could be recovered in cells expressing a GFP-BAX fusion protein. Titration of GFP-BAX expression revealed that the concentration of BAX required to induce a saturating apoptosis response from baseline, was rapidly achieved. Increased levels of GFP-BAX were unable to stimulate higher levels of cell death. Examination of GFP-BAX distribution before and after indomethacin treatment indicated that BAX protein did not form aggregates when present at sub-lethal concentrations. Within the limitations of this experimental system, BAX-dependent apoptosis in HCT116 cells exhibits an all-or-none response depending on the level of BAX protein present. The lack of BAX aggregation at sub-saturation levels suggests that the

  9. Spatial and temporal changes in Bax subcellular localization during NPe6-PDT-induced apoptosis

    Science.gov (United States)

    Liu, Lei; Xing, Da; Chen, Wei R.; Wan, Qingling; Zhou, Feifan

    2008-02-01

    Photodynamic therapy (PDT) employing photosensiter N-aspartyl chlorin e6 (NPe6) can induce lysosome disruption and initiate the intrinsic apoptotic pathway. Bax, a member of the Bcl-2 family of proteins, is an essential regulator of apoptosis. Bax is normally found in the cytosol of healthy cells, and translocates to mitochondria in response to many apoptotic stimuli. In this study, using real-time single-cell analysis, we have investigated the kinetics of Bax distribution during NPe6-induced apoptosis in ASTC-a-1 cells. In order to monitor Bax subcellular distribution, cells were stained with GFP-Bax and Mito Tracker Red. The results show that Bax redistribution occurred at about 170 min after treated with NPe6-PDT, and then sequestered into clusters associated with the mitochondira within 30 min. Our data clearly showed the spatial and temporal changes in Bax distribution in living cells during NPe6-induced apoptosis.

  10. Overexpression of Bax induces apoptosis and enhances drug sensitivity of hepatocellular cancer-9204 cells

    Institute of Scientific and Technical Information of China (English)

    Jian-Yong Zheng; Guang-Shun Yang; Wei-Zhong Wang; Jiang Li; Kai-Zong Li; Wen-Xian Guan; Wen-Liang Wang

    2005-01-01

    AIM: To investigate the role of overexpression of Bax in apoptotic pathways and the response of human hepatocellular cancer (HCC)-9204 cells to cell death induced by adriamycin.METHODS: The whole length of Bax cDNA was transfectrd into human HCC-9204 cells by the method of lipofectamine transfection. An inducible MT-Ⅱ regulatory system was constructed, which allowed controlled expression of protein upon addition of ZnSO4 (100 μmol/L) as an external inducer. Stable transfecting inducible expression vector containing Bax gene was performed. Expression of Bax in protein was analyzed by immunohistochemistry and Western blotting. TUNEL and flow cytometry were used to assess the effect of Bax on apoptosis. Colony assay and tetrazolium blue (MTT) assay were used to evaluate the difference in drug sensitivity of HCC-9204 cells after Bax-transfection.RESULTS: Immunohistochemistry and Western blotting demonstrated that the expression of Bax protein markedly increased in Bax-transfected cells 4 h after the addition cytoplasm and perinuclear region of HCC-9404 cells, and there was ectopic expression in cells with marked condensation of chromatin and cytoplasm (apoptotic cells). Apoptotic index significantly increased in Bax-transfected HCC-9204/Bax cells (3.6 vs 27.2, 4.2 vs 32.3, P<0.05).Flow cytometry analysis showed a significant sub-G1 peak and apoptosis in 15.4% HCC-9204/Bax cells 24 h after treatment. Furthermore, colony survival rate decreased from 66% (HCC-9204/pMD) to 45% (HCC-9204/Bax) 2 dafter ADR withdrawal. MTT assay result showed that the effects of Bax on cell viability following ADR exposure were significant as compared to the vehicle-transfected HCC-9204/pMD cells (21% vs 44%, P<0.01).CONCLUSION: Overexpression of Bax not only induces apoptosis, but also sensitizes HCC-9204 cells to cell death induced by adriamycin.

  11. Clinicopathological significance of Bcl-2 and Bax protein expression in human pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Ming Dong; Jian-Ping Zhou; Hao Zhang; Ke-Jian Guo; Yu-Lin Tian; Yu-Ting Dong

    2005-01-01

    AIM: To assess the clinicopathological significance of the expression of the apoptosis-inhibitory Bcl-2 protein (pBcl-2) and the apoptosis-promoting Bax protein (pBax) in human invasive ductal carcinomas (IDCs) of the pancreas. METHODS: Fifty-nine surgical specimens of IDCs of the pancreas were stained immunohistochemically to detectpBcl-2 and pBax expressions whose correlation to tumor classification, staging, and prognosis was analyzed by univariate and multivariate analyses. RESULTS: The expression of pBcl-2 and pBax was detected in 21 of 59 (35.6%) and in 29 of 59 (49.2%) patients with IDCs of the pancreas, respectively. Neither pBcl-2 nor pBax alone was correlated to TNM staging and differentiation degree of IDCs of the pancreas according to univariate analysis. By Mantel-Cox test, the median survival time after surgery for pBcl-2(+) and pBcl-2(-) groups were 14.3 and 7.3 mo, respectively (χ2= 9.357, P = 0.002) and that for pBax(+) and pBax(-) groups were 12.9 and 10.2 mo, respectively (χ2= 0.285, P>0.05).Contingency coefficient between pBd-2 and pBax expression was 0.298, indicating that there was correlation between them (χ2= 5.74, P<0.05). The median survival time after surgery for pBd-2(+)pBax(+) and pBcl-2(+)pBax(-) groups were 14.3 and 14.1 mo, respectively, and that for pBcl-2 (-)pBax(+) and pBcl-2(-)pBax(-) groups were 5.9 and 9.9 mo, respectively. There was a significant difference between pBcl-2(+)pBax(+) and pBcl-2(-)pBax(+) (χ2 = 5.06,P<0.05), such was the case for pBcl-2(+)pBax(+) andpBcl-2(-)pBax(-) (χ2= 7.18, P<0.01). Cox proportional hazards model for multivariate analysis was applied, indicating that pBcl-2, TNM staging, age and pBax were high risk factors of post-surgical survival time. CONCLUSION: Both pBcl-2 and pBax have high expression in IDCs of the pancreas, indicating that co-expression of pBcl-2 and pBax is a good indicator of favorable prognosis in IDCs of the pancreas.

  12. Expression of Bax in yeast affects not only the mitochondria but also vacuolar integrity and intracellular protein traffic

    DEFF Research Database (Denmark)

    Dimitrova, Irina; Toby, Garabet G; Tili, Esmerina;

    2004-01-01

    Bax-induced lethality in yeast is accompanied by morphological changes in mitochondria, giving rise to a reduced number of swollen tubules. Although these changes are completely abolished upon coexpression of the Bax inhibitor, Bcl-2, coexpression of Bax with Bax inhibiting-glutathione S-transfer...

  13. Bax function in the absence of mitochondria in the primitive protozoan Giardia lamblia.

    Directory of Open Access Journals (Sweden)

    Adrian B Hehl

    Full Text Available Bax-induced permeabilization of the mitochondrial outer membrane and release of cytochrome c are key events in apoptosis. Although Bax can compromise mitochondria in primitive unicellular organisms that lack a classical apoptotic machinery, it is still unclear if Bax alone is sufficient for this, or whether additional mitochondrial components are required. The protozoan parasite Giardia lamblia is one of the earliest branching eukaryotes and harbors highly degenerated mitochondrial remnant organelles (mitosomes that lack a genome. Here we tested whether human Bax expressed in Giardia can be used to ablate mitosomes. We demonstrate that these organelles are neither targeted, nor compromised, by Bax. However, specialized compartments of the regulated secretory pathway are completely ablated by Bax. As a consequence, maturing cyst wall proteins that are sorted into these organelles are released into the cytoplasm, causing a developmental arrest and cell death. Interestingly, this ectopic cargo release is dependent on the carboxy-terminal 22 amino acids of Bax, and can be prevented by the Bax-inhibiting peptide Ku70. A C-terminally truncated Bax variant still localizes to secretory organelles, but is unable to permeabilize these membranes, uncoupling membrane targeting and cargo release. Even though mitosomes are too diverged to be recognized by Bax, off-target membrane permeabilization appears to be conserved and leads to cell death completely independently of mitochondria.

  14. Bax function in the absence of mitochondria in the primitive protozoan Giardia lamblia.

    Science.gov (United States)

    Hehl, Adrian B; Regos, Attila; Schraner, Elisabeth; Schneider, André

    2007-01-01

    Bax-induced permeabilization of the mitochondrial outer membrane and release of cytochrome c are key events in apoptosis. Although Bax can compromise mitochondria in primitive unicellular organisms that lack a classical apoptotic machinery, it is still unclear if Bax alone is sufficient for this, or whether additional mitochondrial components are required. The protozoan parasite Giardia lamblia is one of the earliest branching eukaryotes and harbors highly degenerated mitochondrial remnant organelles (mitosomes) that lack a genome. Here we tested whether human Bax expressed in Giardia can be used to ablate mitosomes. We demonstrate that these organelles are neither targeted, nor compromised, by Bax. However, specialized compartments of the regulated secretory pathway are completely ablated by Bax. As a consequence, maturing cyst wall proteins that are sorted into these organelles are released into the cytoplasm, causing a developmental arrest and cell death. Interestingly, this ectopic cargo release is dependent on the carboxy-terminal 22 amino acids of Bax, and can be prevented by the Bax-inhibiting peptide Ku70. A C-terminally truncated Bax variant still localizes to secretory organelles, but is unable to permeabilize these membranes, uncoupling membrane targeting and cargo release. Even though mitosomes are too diverged to be recognized by Bax, off-target membrane permeabilization appears to be conserved and leads to cell death completely independently of mitochondria. PMID:17534438

  15. Expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia

    Institute of Scientific and Technical Information of China (English)

    Sheng-Mian Li; Shu-Kun Yao; Nobuyoshi Yamamura; Toshitsugu Nakamura

    2003-01-01

    AIM: To compare the difference of expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia, and to analyze the role of Bcl-2 and Bax proteins in the progression from dysplasia to carcinoma and to evaluate the correlation of Bcl-2/Bax protein expression with the biological behaviors.METHODS: Expressions of Bcl-2 and Bax were examined immunohistochemically in 27 cases of extrahepatic biliary tract carcinomas (bile duct carcinoma: n=21, carcinoma of ampulla of Vater: n=6), and 10 cases of atypical dysplasia.Five cases of normal biliary epithelial tissues were used as controls. A semiquantitative scoring system was used to assess the Bcl-2 and Bax reactivity.RESULTS: The expression of Bd-2 was observed in 10 out of 27 (37.0 %) invasive carcinomas, 1 out of 10 clysplasias, none out of 5 normal epithelial tissues. Bax expression rate was 74.1% (20/27) in invasive carcinoma, 30 % (3/10) in dysplasia,and 40 % (2/5) in normal biliary epithelium. Bcl-2 and Bax activities were more intense in carcinoma than in dysplasia,with no significant difference in Bcl-2 expression (P=0.1:10),and significant difference in Bax expression (P=0.038). Level of Bax expression was higher in invasive carcinoma than in dysplasia and normal tissue (P=0.012). Bcl-2 expression was correlated to Bax expression (P=0.0059). However, Bcl-2/Bax expression had no correlation with histological subtype,grade of differentiation, or level of invasion.CONCLUSION: Increased Bcl-2/Bax expression from dysplasia to invasive tumors supports the view that this is the usual route for the development of extrahepatic biliary tract carcinoma. Bcl-2/Bax may be involved, at least in part,in the apoptotic activity in extrahepatic biliary carcinoma.

  16. Evidence that inhibition of BAX activation by BCL-2 involves its tight and preferential interaction with the BH3 domain of BAX

    Institute of Scientific and Technical Information of China (English)

    Bonsu Ku; Chengyu Liang; Jae U Jung; Byung-Ha Oh

    2011-01-01

    Interactions between the BCL-2 family proteins determine the cell's fate to live or die. How they interact with each other to regulate apoptosis remains as an unsettled central issue. So far, the antiapoptotic Bc1-2 proteins are thought to interact with BAX weakly, but the physiological significance of this interaction has been vague.Herein, we show that recombinant BCL-2 and BCL-w interact potently with a BCL-2 homology (BH) 3 domain-containing peptide derived from BAX, exhibiting the dissociation constants of 15 and 23 nM, respectively. To clarify the basis for this strong interaction, we determined the three-dimensional structure of a complex of BCL-2 with a BAX peptide spanning its BH3 domain. It revealed that their interactions extended beyond the canonical BH3 domain and involved three nonconserved charged residues of BAX. A novel BAX variant, containing the alanine substitution of these three residues, had greatly impaired affinity for BCL-2 and BCL-w, hut was otherwise indistinguishable from wild-type BAX. Critically, the apoptotic activity of the BAX variant could not be restrained by BCL-2 and BCL-w, pointing that the observed tight interactions are critical for regulating BAX activation. We also comprehensively quantified the binding affinities between the three BCL-2 subfamily proteins. Collectively, the data show that due to the high affinity of BAX for BCL-2, BCL-w and A1, and of BAK for BCL-XL, MCL-1 and A1, only a subset of BH3-only proteins, commonly including BIM, BID and PUMA, could he expected to free BAX or BAK from the antiapoptotic BCL-2 proteins to elicit apoptosis.

  17. The oxidized phospholipid PazePC promotes permeabilization of mitochondrial membranes by Bax.

    Science.gov (United States)

    Lidman, Martin; Pokorná, Šárka; Dingeldein, Artur P G; Sparrman, Tobias; Wallgren, Marcus; Šachl, Radek; Hof, Martin; Gröbner, Gerhard

    2016-06-01

    Mitochondria play a crucial role in programmed cell death via the intrinsic apoptotic pathway, which is tightly regulated by the B-cell CLL/lymphoma-2 (Bcl-2) protein family. Intracellular oxidative stress causes the translocation of Bax, a pro-apoptotic family member, to the mitochondrial outer membrane (MOM) where it induces membrane permeabilization. Oxidized phospholipids (OxPls) generated in the MOM during oxidative stress directly affect the onset and progression of mitochondria-mediated apoptosis. Here we use MOM-mimicking lipid vesicles doped with varying concentrations of 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazePC), an OxPl species known to significantly enhance Bax-membrane association, to investigate three key aspects of Bax's action at the MOM: 1) induction of Bax pores in membranes without additional mediator proteins, 2) existence of a threshold OxPl concentration required for Bax-membrane action and 3) mechanism by which PazePC disturbs membrane organization to facilitate Bax penetration. Fluorescence leakage studies revealed that Bax-induced leakage, especially its rate, increased with the vesicles' PazePC content without any detectable threshold neither for OxPl nor Bax. Moreover, the leakage rate correlated with the Bax to lipid ratio and the PazePC content. Solid state NMR studies and calorimetric experiments on the lipid vesicles confirmed that OxPl incorporation disrupted the membrane's organization, enabling Bax to penetrate into the membrane. In addition, 15N cross polarization (CP) and insensitive nuclei enhanced by polarization transfer (INEPT) MAS NMR experiments using uniformly (15)N-labeled Bax revealed dynamically restricted helical segments of Bax embedded in the membrane, while highly flexible protein segments were located outside or at the membrane surface. PMID:26947183

  18. A sandwich ELISA for the conformation-specific quantification of the activated form of human Bax.

    Science.gov (United States)

    Teijido, Oscar; Ganesan, Yogesh Tengarai; Llanos, Raul; Peton, Ashley; Urtecho, Jean-Baptiste; Soprani, Adauri; Villamayor, Aimee; Antonsson, Bruno; Manon, Stéphen; Dejean, Laurent

    2016-03-15

    Bcl-2 family proteins are critical regulators of mitochondrial outer membrane permeabilization (MOMP), which represents the point of no return of apoptotic cell death. The exposure of the Bax N-terminus at the mitochondria reflects Bax activation; and this activated configuration of the Bax protein is associated with MOMP. N-terminal exposure can be detected using specific monoclonal and/or polyclonal antibodies, and the onset of activated Bax has extensively been used as an early marker of apoptosis. The protocols of immunoprecipitation and/or immunocytochemistry commonly used to detect activated Bax are long and tedious, and allow semiquantification of the antigen at best. The sandwich ELISA protocol we developed has a 5 ng/mL detection limit and is highly specific for the activated conformation of Bax. This ELISA allows a rapid quantification of activated human Bax in whole cells and isolated mitochondria protein extracts. These properties grant this assay the potential to further clarify the prognostic and diagnostic value of activated Bax in disorders associated with deregulated apoptotic pathways such as degenerative diseases or cancer. PMID:26748144

  19. Effect of Helicobacter pylori infection on Bax protein expression in patients with gastric precancerous lesions

    Institute of Scientific and Technical Information of China (English)

    Hai-Feng Liu; Wei-Wen Liu; Guo-An Wang; Xiao-Chun Teng

    2005-01-01

    AIM: To investigate the effect of Helicobacter pylori (H pylori) infection on Bax protein expression, and explore the role of H pylori in gastric carcinogenesis.METHODS: H pylori was assessed by rapid urease test and Warthin-Starry method, and expression of Bax protein was examined immunohistochemically in 72 patients with pre-malignant lesions.RESULTS: Bax protein was differently expressed in intestinal metaplasia and gastric dysplasia, and showed 63.99% positivity. The positivity of Bax protein expression in H pylori-positive gastric precancerous lesions (72.3%) was significantly higher than that in H pylori-negative gastric precancerous lesions (48.0%, χ2 = 4.191, P<0.05).H pylori infection was well correlated with the expression of Bax protein in gastric precancerous lesions (r = 0.978,P<0.01). After eradication of H pylori, the positivity of Bax protein expression significantly decreased in H pylori-positive gastric precancerous lesions (χ2= 5.506,P<0.05). In the persisting H pylori-infected patients,the positivity of Bax protein expression was not changed.CONCLUSION: H pylori infection may be involved in the upregulation of Bax gene, which might be one of the mechanisms of H pylori infection-induced gastric epithelial cell apoptosis. H pylori might act as a tumor promoter in the genesis of gastric carcinoma and eradication of H pylori could inhibit gastric carcinogenesis.

  20. Involvement of nitric oxide signaling in mammalian Bax-induced terpenoid indole alkaloid production of Catharanthus roseus cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Bax, a mammalian pro-apoptotic member of the Bcl-2 family, has been demonstrated to be a potential regulatory factor for plant secondary metabolite biosynthesis recently. To investigate the molecular mechanism of Bax-induced secondary metabolite biosynthesis, we determined the contents of nitric oxide (NO) of the transgenic Catharanthus roseus cells overexpressing a mouse Bax protein and checked the effects of NO specific scavenger 2,4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1- oxyl-3-oxide (cPITO) on Bax-induced terpenoid indole alkaloid (TIA) production of the cells. The data showed that overexpression of the mouse Bax in C. roseus cells triggered NO generation of the cells. Treatment of cPITO not only inhibited the Bax-triggered NO burst but also suppressed the Bax-induced TIA production. The results indicated that the mouse Bax might activate the NO signaling in C. roseus cells and induce TIA production through the NO-dependent signal pathway in the cells. Furthermore, the activities of nitric oxide synthase (NOS) were significantly increased in the transgenic Bax cells as compared to those in the control cells, showing that the mouse Bax may induce NOS of C. roseus cells. Treatment of the transgenic Bax cells with NOS inhibitor PBITU blocked both Bax-induced NO generation and TIA production, which suggested that the mouse Bax might trigger NO generation and TIA production through NOS. However, the NOS-like activities and NO generation in the transgenic Bax cells did not match kinetically and the Bax-induced NOS-like activity was much later and lower than NO production. Moreover, the Bax-induced NO generation and TIA production were only partially inhibited by PBITU. Thus, our results suggested that the Bax-induced NO production and secondary metabolite biosynthesis in C. roseus cells was not entirely dependent on NOS or NOS-like enzymes.

  1. Overexpression of Bax sensitizes prostate cancer cells to TGF-β induced apoptosis

    Institute of Scientific and Technical Information of China (English)

    Pei Hui LIN; Zui PAN; Lin ZHENG; Na LI; David DANIELPOUR; Jian Jie MA

    2005-01-01

    NRP-154 is a tumorigenic epithelial cell line derived from the preneoplastic dorsal-lateral prostate of rats. These cells are exquisitely sensitive to TGF-β induced apoptosis. In contrast, we find that NRP-154 cells can sustain overexpression of exogenous Bax protein, which is different from non-tumor cells where Bax functions as a ubiquitous stimulator of apoptosis. NRP-154 cells stably overexpressing Bax show increased sensitivity to TGF-β induced apoptosis. The degree of TGF-β induced apoptosis displays high correlation with cleavage of Bax at the amino-terminus. Our data indicate that prostate cancer cells can host high levels of latent Bax which can be activated through post-translational modification.

  2. Bax/Bak activation in the absence of Bid, Bim, Puma, and p53.

    Science.gov (United States)

    Zhang, J; Huang, K; O'Neill, K L; Pang, X; Luo, X

    2016-01-01

    How BH3-only proteins activate Bax/Bak, the two gateway proteins of the mitochondria-dependent apoptotic pathway, remains incompletely understood. Although all pro-apoptotic BH3-only proteins are known to bind/neutralize the anti-apoptotic Bcl-2 proteins, the three most potent ones, Bid (tBid), Bim, and Puma, possess an additional activity of directly activating Bax/Bak in vitro. This latter activity has been proposed to be responsible for triggering Bax/Bak activation following apoptotic stimulation. To test this hypothesis, we generated Bid(-/)(-)Bim(-/)(-)Puma(-/)(-) (TKO), TKO/Bax(-/)(-)/Bak(-/)(-) (PentaKO), and PentaKO/Mcl-1(-/-) (HexaKO) HCT116 cells through gene editing. Surprisingly, although the TKO cells were resistant to several apoptotic stimuli, robust apoptosis was induced upon the simultaneous inactivation of Bcl-xL and Mcl-1, two anti-apoptotic Bcl-2 proteins known to suppress Bax/Bak activation and activity. Importantly, such apoptotic activity was completely abolished in the PentaKO cells. In addition, ABT-737, a BH3 mimetic that inhibits Bcl-xL/Bcl-w/Bcl-2, induced Bax activation in HexaKO cells reconstituted with endogenous level of GFP-Bax. Further, by generating TKO/p53(-/-) (QKO) cells, we demonstrated that p53, a tumor suppressor postulated to directly activate Bax, is not required for Bid/Bim/Puma-independent Bax/Bak activation. Together, these results strongly suggest that the direct activation activities of Bid (tBid), Bim, Puma, and p53 are not essential for activating Bax/Bak once the anti-apoptotic Bcl-2 proteins are neutralized. PMID:27310874

  3. Molecular Basis for Membrane Pore Formation by Bax Protein Carboxyl Terminus

    Science.gov (United States)

    Tatulian, Suren A.; Garg, Pranav; Nemec, Kathleen N.; Chen, Bo; Khaled, Annette R.

    2015-01-01

    Bax protein plays a key role in mitochondrial membrane permeabilization and cytochrome c release upon apoptosis. Our recent data have indicated that the 20-residue C-terminal peptide of Bax (BaxC-KK; VTIFVAGVL-TASLTIWKKMG), when expressed intracellularly, translocates to the mitochondria and exerts lethal effect on cancer cells. Moreover, the BaxC-KK peptide, as well as two mutants where the two lysines are replaced with glutamate (BaxC-EE) or leucine (BaxC-LL), have been shown to form relatively large pores in lipid membranes, composed of up to eight peptide molecules per pore. Here the pore structure is analyzed by polarized Fourier transform infrared, circular dichroism, and fluorescence experiments on the peptides reconstituted in phospholipid membranes. The peptides assume an α/β-type secondary structure within membranes. Both β-strands and α-helices are significantly (by 30–60 deg) tilted relative to the membrane normal. The tryptophan residue embeds into zwitterionic membranes at 8–9 Å from the membrane center. The membrane anionic charge causes a deeper insertion of tryptophan for BaxC-KK and BaxC-LL but not for BaxC-EE. Combined with the pore stoichiometry determined earlier, these structural constraints allow construction of a model of the pore where eight peptide molecules form an “α/β-ring” structure within the membrane. These results identify a strong membranotropic activity of Bax C-terminus and propose a new mechanism by which peptides can efficiently perforate cell membranes. Knowledge on the pore forming mechanism of the peptide may facilitate development of peptide-based therapies to kill cancer or other detrimental cells such as bacteria or fungi. PMID:23110300

  4. PUMA promotes Bax translocation by competitive binding to Bcl-Xl during UV-induced apoptosis

    Science.gov (United States)

    Zhang, Yingjie; Xing, Da; Wu, Yinyuan; Liu, Lei

    2008-02-01

    Ultraviolet (UV) irradiation can induce apoptosis through both the membrane death receptor and the intrinsic apoptotic signaling pathways as DNA-damaging agents. PUMA, a BH3-only Bcl-2 family protein, plays an essential role in DNA damage-induced apoptosis. Bax, also a Bcl-2 family member, translocates from the cytosol to the mitochondrial membrane during UV-induced apoptosis. However, the regulation of Bax activation induced by UV irradiation remains poorly understood. In this study, the FRET (fluorescence resonance energy transfer) technique was used to study the interactions of Bax, Bcl-Xl, and PUMA in ASTC-a-1 cells. The results show that Bax translocated from the cytosol to the mitochondrial membrane at about 7 h after UV irradiation, and the translocation can not be blocked completely when overexpressed Bcl-xl. Moreover, The interaction of Bax and Bcl-Xl weakened markedly. In addition, Co-immunoprecipitation shows that PUMA released Bax by directly binding to Bcl-XL after UV irradiation in ASTC-a-1 cells. Taken together, these results indicated that PUMA can promote Bax translocation by binding to Bcl-Xl during UV-induced apoptosis.

  5. GSH depletion enhances adenoviral bax-induced apoptosis in lung cancer cells.

    Science.gov (United States)

    Honda, Tsuyoshi; Coppola, Simona; Ghibelli, Lina; Cho, Song H; Kagawa, Shunsuke; Spurgers, Kevin B; Brisbay, Shawn M; Roth, Jack A; Meyn, Raymond E; Fang, Bingliang; McDonnell, Timothy J

    2004-04-01

    The utility of dominant acting proapoptotic molecules to induce cell death in cancer cells is being evaluated in preclinical studies and clinical trials. We recently developed a binary adenoviral expression system to enable the efficient gene transfer of Bax and other proapoptotic molecules. Using this system, overexpression of Bax protein in four non-small-cell lung cancer (NSCLC) cell lines, H1299, A549, H226 and H322, was evaluated. The H322 line exhibited significant resistance to Bax-induced cell death compared to the other cell lines. H322 cells had the highest level of glutathione (GSH). GSH levels were significantly decreased following buthionine sulfoximine treatment and this coincided with enhanced apoptosis induction by Ad-Bax in H322 cells. GSH depletion enhanced Bax protein translocation to mitochondrial membranes. These findings suggest that the redox status may be a determinant of Bax-mediated cell death and that manipulation of intracellular thiols may sensitize cells to apoptosis by facilitating Bax insertion into mitochondrial membranes. PMID:15002033

  6. Insights into the structural stability of Bax from molecular dynamics simulations at high temperatures

    Science.gov (United States)

    Rosas-Trigueros, Jorge Luis; Correa-Basurto, José; Guadalupe Benítez-Cardoza, Claudia; Zamorano-Carrillo, Absalom

    2011-01-01

    Bax is a member of the Bcl-2 protein family that participates in mitochondrion-mediated apoptosis. In the early stages of the apoptotic pathway, this protein migrates from the cytosol to the outer mitochondrial membrane, where it is inserted and usually oligomerizes, making cytochrome c-compatible pores. Although several cellular and structural studies have been reported, a description of the stability of Bax at the molecular level remains elusive. This article reports molecular dynamics simulations of monomeric Bax at 300, 400, and 500 K, focusing on the most relevant structural changes and relating them to biological experimental results. Bax gradually loses its α-helices when it is submitted to high temperatures, yet it maintains its globular conformation. The resistance of Bax to adopt an extended conformation could be due to several interactions that were found to be responsible for maintaining the structural stability of this protein. Among these interactions, we found salt bridges, hydrophobic interactions, and hydrogen bonds. Remarkably, salt bridges were the most relevant to prevent the elongation of the structure. In addition, the analysis of our results suggests which conformational movements are implicated in the activation/oligomerization of Bax. This atomistic description might have important implications for understanding the functionality and stability of Bax in vitro as well as within the cellular environment. PMID:21936009

  7. Bax-PGAM5L-Drp1 complex is required for intrinsic apoptosis execution.

    Science.gov (United States)

    Xu, Wenjuan; Jing, Linlin; Wang, Quanshi; Lin, Chung-Chih; Chen, Xiaoting; Diao, Jianxin; Liu, Yuanliang; Sun, Xuegang

    2015-10-01

    Intrinsic apoptosis eliminates cells with damaged DNA and cells with dysregulated expression of oncogene. PGAM5, a member of the phosphoglycerate mutase family, has two splicing variants: PGAM5L (the long form) and PGAM5S (the short form). It has been well established that PGAM5 is at the convergent point of multiple necrosis pathways. However, the role of PGAM5 in intrinsic apoptosis is still controversial. Here we report that the PGAM5L, but not PGAM5S is a prerequisite for the activation of Bax and dephosphorylation of Drp1 in arenobufagin and staurosporine induced intrinsic apoptosis. Knockdown of PGAM5L inhibits the translocation of Bax to the mitochondria and reduces mitochondrial fission. The interaction between PGAM5L and Drp1 was observed in both arenobufagin and staurosporine treated HCT116 cells, but not in HCT116 Bax(-/-) cells. Bax transfection rescues the formation of the triplex in both arenobufagin and staurosporine stimulated HCT116 Bax(-/-) cells. Arenobufagin shows remarkable anti-cancer effects both in orthotropic and heterotropic CRC models and demonstrates less toxic effects as compared with that of cisplatin. Bax-PGAM5L-Drp1 complex is detected in arenobufagin and staurosporine treated CRC cells in vitro and in arenobufagin and cisplatin treated tumor in vivo as well. In summary, our results demonstrate that Bax-PGAM5L-Drp1 complex is required for intrinsic apoptosis execution. PMID:26356820

  8. The effect of radiation on bcl-2 and bax in hyperplastic prostatic tissues

    International Nuclear Information System (INIS)

    Aim: To investigate the expressions of bcl-2 and bax in benign prostatic hyperplasia (BPH) and the effect of β-rays on bcl-2 and bax. Methods: The expressions of bcl-2 and bax are studied by means of immunohistochemical method in 9 normal prostate (NP) and 15 BPH and 35 patients treated with 90Sr/90Y Prostatic Hyperplasia Applicator. Results: The expressions of bcl-2 in epithelia of NP and BPH are higher than that in stroma P<0.01=. The expressions of bcl-2 in epithelia and stroma of BPH are higher than that in NP P<0.01=. The expressions of bax in epithelia of NP are higher than that in BPH P<0.05=. However ,the expressions of bcl-2 in epithelia and stroma of BPH are higher than bax P<0.01 =. Compared with the control group, the expressions of bcl-2 in epithelia and stroma of BPH treated with 90Sr/90Y Prostatic Hyperplasia Applicator decreased and the expressions of bax increased P<0.01=. Conclusion: bcl-2 gene and bax gene play an important role in the regulation of prostatic apoptosis and the treatment of β-rays can accelerate the apoptosis of prostatic tissues. (authors)

  9. Enhancing terpenoid indole alkaloid production by inducible expression of mammalian Bax in Catharanthus roseus cells

    Institute of Scientific and Technical Information of China (English)

    XU MaoJun; DONG JuFang

    2007-01-01

    Bax, a mammalian pro-apoptotic member of the Bcl-2 family, triggers hypersensitive reactions when expressed in plants. To investigate the effects of Bax on the biosynthesis of clinically important natural products in plant cells, we generate transgenic Catharanthus roseus cells overexpressing a mouse Bax protein under the β-estradiol-inducible promoter. The expression of Bax in transgenic Catharanthus roseus cells is highly dependent on β-estradiol concentrations applied. Contents of catharanthine and total terpenoid indole alkaloid of the transgenic cells treated with 30 μmol/L β-estradiol are 5.0- and 5.5-fold of the control cells. Northern and Western blotting results show that expression of mammalian Bax induces transcriptional activation of Tdc and Str, two key genes in terpenoid indole alkaloid biosynthetic pathway of Catharanthus roseus cells, and stimulates the accumulation of defense-related protein PR1 in the cells, showing that the mouse Bax triggers the defense responses of Catharanthus roseus cells and activates the terpenoid indole alkaloid biosynthetic pathway. Thus, our data suggest that the mammalian Bax might be a potential regulatory factor for secondary metabolite biosynthesis in plant cells and imply a new secondary metabolic engineering strategy for enhancing the metabolic flux to natural products by activating the whole biosynthetic pathway rather than by engineering the single structural genes within the pathways.

  10. Enhancing terpenoid indole alkaloid production by inducible expression of mammalian Bax in Catharanthus roseus cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Bax,a mammalian pro-apoptotic member of the Bcl-2 family,triggers hypersensitive reactions when expressed in plants.To investigate the effects of Bax on the biosynthesis of clinically important natural products in plant cells,we generate transgenic Catharanthus roseus cells overexpressing a mouse Bax protein under the β-estradiol-inducible promoter.The expression of Bax in transgenic Catharanthus roseus cells is highly dependent on β-estradiol concentrations applied.Contents of catharanthine and total terpenoid indole alkaloid of the transgenic cells treated with 30 μmol/L β-estradiol are 5.0-and 5.5-fold of the control cells.Northern and Western blotting results show that expression of mammalian Bax induces transcriptional activation of Tdc and Str,two key genes in terpenoid indole alkaloid bio-synthetic pathway of Catharanthus roseus cells,and stimulates the accumulation of defense-related protein PR1 in the cells,showing that the mouse Bax triggers the defense responses of Catharanthus roseus cells and activates the terpenoid indole alkaloid biosynthetic pathway.Thus,our data suggest that the mammalian Bax might be a potential regulatory factor for secondary metabolite biosynthesis in plant cells and imply a new secondary metabolic engineering strategy for enhancing the metabolic flux to natural products by activating the whole biosynthetic pathway rather than by engineering the single structural genes within the pathways.

  11. A Novel Mechanism for CTCF in the Epigenetic Regulation of Bax in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Claudia Fabiola Méndez-Catalá

    2013-08-01

    Full Text Available We previously reported the association of elevated levels of the multifunctional transcription factor, CCCTC binding factor (CTCF, in breast cancer cells with the specific anti-apoptotic function of CTCF. To understand the molecular mechanisms of this phenomenon, we investigated regulation of the human Bax gene by CTCF in breast and non-breast cells. Two CTCF binding sites (CTSs within the Bax promoter were identified. In all cells, breast and non-breast, active histone modifications were present at these CTSs, DNA harboring this region was unmethylated, and levels of Bax mRNA and protein were similar. Nevertheless, up-regulation of Bax mRNA and protein and apoptotic cell death were observed only in breast cancer cells depleted of CTCF. We proposed that increased CTCF binding to the Bax promoter in breast cancer cells, by comparison with non-breast cells, may be mechanistically linked to the specific apoptotic phenotype in CTCF-depleted breast cancer cells. In this study, we show that CTCF binding was enriched at the Bax CTSs in breast cancer cells and tumors; in contrast, binding of other transcription factors (SP1, WT1, EGR1, and c-Myc was generally increased in non-breast cells and normal breast tissues. Our findings suggest a novel mechanism for CTCF in the epigenetic regulation of Bax in breast cancer cells, whereby elevated levels of CTCF support preferential binding of CTCF to the Bax CTSs. In this context, CTCF functions as a transcriptional repressor counteracting influences of positive regulatory factors; depletion of breast cancer cells from CTCF therefore results in the activation of Bax and apoptosis.

  12. Isatin decreases Bax protein expression in the substantia nigra of a mouse model of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    Jiguo Zhang; Fang Zhang; Yanlong Qiu; Wang Yue

    2011-01-01

    The present study observed the action of 1H-indole-2, 3-dione (isatin) on Bax protein expression in the substantia nigra of a Parkinson's disease animal model. Parkinson's disease-like behaviors were induced in C57BL/6J mice treated with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). Bax protein expression was significantly reduced in isatin (100, 200 mg/kg)-pretreated mice. Results demonstrate that isatin plays a neuroprotective role in mice treated with MPTP by down-regulating Bax protein expression.

  13. bax, but not bcl-2, influences the prognosis of human pancreatic cancer

    OpenAIRE

    Friess, H; Lu, Z; H. Graber; Zimmermann, A.; Adler, G.; Korc, M.; Schmid, R; Buchler, M

    1998-01-01

    Background—bcl-2 and bax belong to the bcl-2-related gene family, which marks a new class of genes that influence apoptosis. The bcl-2 oncogene acts as a broad antiapoptotic factor and extends both normal and tumour cell survival. In contrast, the bax gene is a promoter of apoptosis. 
Aims—To analyse the expression of bcl-2 and bax in pancreatic cancer and correlate the results with clinical parameters. 
Patients—Pancreatic cancer tissue samples were obtained fro...

  14. Bax translocation into mitochondria during dihydroartemisinin(DHA)-induced apoptosis in human lung adenocarcinoma cells

    Science.gov (United States)

    Lu, Ying-ying; Chen, Tong-sheng; Qu, Jun-Le

    2009-02-01

    Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, isolated from the traditional Chinese herb Artemisia annua, has been shown to possess promising anticancer activities and induce cancer cell death through apoptotic pathways. However, the molecular mechanisms are not well understood. This study was investigated in human lung adenocarconoma ASTC-a-1 cell line and aimed to determine whether the apoptotic process was mediated by Bax activation and translocation during DHA-induced apoptosis. In this study, DHA induced a time-dependent apoptotic cell death, which was assayed by Cell Counting Kit (CCK-8) and Hoechst 33258 staining. Detection of Bax aggregation and translocation to mitochondria was observed in living cells which were co-transfected with GFP-Bax and Dsred-mito plasmid using confocal fluorescence microscope technique. Overall, these results demonstrated that Bax activation and translocation to mitochondria occurred during DHA-induced apoptosis.

  15. Driving p53 Response to Bax Activation Greatly Enhances Sensitivity to Taxol by Inducing Massive Apoptosis

    Directory of Open Access Journals (Sweden)

    Paola De Feudis

    2000-05-01

    Full Text Available The proapoptotic gene bax is one of the downstream effectors of p53. The p53 binding site in the bax promoter is less responsive to p53 than the one in the growth arrest mediating gene p21. We introduced the bax gene under the control of 13 copies of a strong p53 responsive element into two ovarian cancer cell lines. The clones expressing bax under the control of p53 obtained from the wild-type (wt p53-expressing cell line A2780 were much more sensitive (500- to 1000-fold to the anticancer agent taxol than the parent cell line, with a higher percentage of cells undergoing apoptosis after drug treatment that was clearly p53-dependent and bax-mediated. Xenografts established in nude mice from one selected clone (A2780/C3 were more responsive to taxol than the parental line and the apoptotic response of A2780/C3 tumors was also increased after treatment. Introduction of the same plasmid into the p53 null SKOV3 cell line did not alter the sensitivity to taxol or the induction of apoptosis. In conclusion, driving the p53 response (after taxol treatment by activating the bax gene rather than the p21 gene results in induction of massive apoptosis, in vitro and in vivo, and greatly enhances sensitivity to the drug.

  16. THE EXPRESSION AND CLINICAL VALUE OF APOPTOSIS CONTROL GENE Bcl-2 AND Bax IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    ZHENG Jun; YAO Zhen-xiang; ZHANG Jing

    1999-01-01

    Objective: To study the expression and clinical value of apoptosis control gene bcl-2 and bax in breast cancer.Methods: Protein bax and bcl-2 in 41 breast cancers obtained from operations in our hospital in 1996 were detected using ABC immunohistochemical stain assay and compared with 10 cases with normal breast tissues.Results: The positive rate of bax in normal breast tissue was 90% and in breast cancer was 59%, with a significant statistical difference between them (P<0.05), but there was no statistical difference in bcl-2 protein expression. Among the 41 breast cancer, the group with lymph node metastasis (21 cases) had obviously low bax expression (43%) and high bcl-2 expression (76%), showing significant difference to the group without lymph node metastasis (P<0.05).Conclusion: The antiapoptosis function of bcl-2 was stronger than bax in breast cancer. Protein bax and bcl-2 assay may be useful in understanding the biological behaviors of breast cancer.

  17. A New Fungal Diterpene Induces VDAC1-dependent Apoptosis in Bax/Bak-deficient Cells.

    Science.gov (United States)

    Huang, Li; Han, Junjie; Ben-Hail, Danya; He, Luwei; Li, Baowei; Chen, Ziheng; Wang, Yueying; Yang, Yanlei; Liu, Lei; Zhu, Yushan; Shoshan-Barmatz, Varda; Liu, Hongwei; Chen, Quan

    2015-09-25

    The pro-apoptotic Bax and Bak proteins are considered central to apoptosis, yet apoptosis occurs in their absence. Here, we asked whether the mitochondrial protein VDAC1 mediates apoptosis independently of Bax/Bak. Upon screening a fungal secondary metabolite library for compounds inducing apoptosis in Bax/Bak-deficient mouse embryonic fibroblasts, we identified cyathin-R, a new cyathane diterpenoid compound able to activate apoptosis in the absence of Bax/Bak via promotion of the VDAC1 oligomerization that mediates cytochrome c release. Diphenylamine-2-carboxilic acid, an inhibitor of VDAC1 conductance and oligomerization, inhibited cyathin-R-induced VDAC1 oligomerization and apoptosis. Similarly, Bcl-2 overexpression conferred resistance to cyathin-R-induced apoptosis and VDAC1 oligomerization. Silencing of VDAC1 expression prevented cyathin-R-induced apoptosis. Finally, cyathin-R effectively attenuated tumor growth and induced apoptosis in Bax/Bak-deficient cells implanted into a xenograft mouse model. Hence, this study identified a new compound promoting VDAC1-dependent apoptosis as a potential therapeutic option for cancerous cells lacking or presenting inactivated Bax/Bak.

  18. A New Fungal Diterpene Induces VDAC1-dependent Apoptosis in Bax/Bak-deficient Cells*

    Science.gov (United States)

    Huang, Li; Han, Junjie; Ben-Hail, Danya; He, Luwei; Li, Baowei; Chen, Ziheng; Wang, Yueying; Yang, Yanlei; Liu, Lei; Zhu, Yushan; Shoshan-Barmatz, Varda; Liu, Hongwei; Chen, Quan

    2015-01-01

    The pro-apoptotic Bax and Bak proteins are considered central to apoptosis, yet apoptosis occurs in their absence. Here, we asked whether the mitochondrial protein VDAC1 mediates apoptosis independently of Bax/Bak. Upon screening a fungal secondary metabolite library for compounds inducing apoptosis in Bax/Bak-deficient mouse embryonic fibroblasts, we identified cyathin-R, a new cyathane diterpenoid compound able to activate apoptosis in the absence of Bax/Bak via promotion of the VDAC1 oligomerization that mediates cytochrome c release. Diphenylamine-2-carboxilic acid, an inhibitor of VDAC1 conductance and oligomerization, inhibited cyathin-R-induced VDAC1 oligomerization and apoptosis. Similarly, Bcl-2 overexpression conferred resistance to cyathin-R-induced apoptosis and VDAC1 oligomerization. Silencing of VDAC1 expression prevented cyathin-R-induced apoptosis. Finally, cyathin-R effectively attenuated tumor growth and induced apoptosis in Bax/Bak-deficient cells implanted into a xenograft mouse model. Hence, this study identified a new compound promoting VDAC1-dependent apoptosis as a potential therapeutic option for cancerous cells lacking or presenting inactivated Bax/Bak. PMID:26253170

  19. Bcl-xS and Bax induce different apoptotic pathways in PC12 cells.

    Science.gov (United States)

    Lindenboim, L; Yuan, J; Stein, R

    2000-03-30

    Apoptosis is regulated by the action of the Bcl-2 family of proteins, which includes anti- and pro-apoptotic members such as Bcl-xS and Bax. These proteins may differ from each other in structure, mechanism of action and interactions with anti-apoptotic signaling. The mechanism whereby Bax induces cell death has been studied in some cellular systems, but the mechanism of Bcl-xS-induced apoptosis is largely unknown. In this study we investigated and compared the apoptotic effects of Bcl-xS and Bax in the pheochromocytoma cell line, PC12 (a useful model system for studying neuronal apoptosis), and the extent to which they are protected by the survival factor, nerve growth factor (NGF). PC12 cells express endogenous Bcl-xS, Bax and Bcl-xL proteins. Subcellular fractionation revealed that Bax is presented mainly in the cytosolic and the heavy membrane fractions, Bcl-xS is present only in the cytosol, and the anti-apoptotic protein Bcl-xL is located mainly in the heavy membrane fraction. In contrast to the cytosolic localization of endogenous Bcl-xS, the exogenously overexpressed Bcl-xS is localized to the mitochondria. Overexpression of Bcl-xS or Bax induces cell death in the transfected cells. The cell death induced by overexpression of Bcl-xS was inhibited by coexpression of Bcl-xS with Bcl-2 or Bcl-xL, or by treatment with the broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoro-methylketone (Z-VAD-FMK) or with NGF. The Bcl-2 mutants deltaC22, which lacks the transmembrane domain, and G145A (mI-3) were able to inhibit the death-inducing effect of Bcl-xS. These results therefore suggest that the apoptotic pathway induced by overexpression of Bcl-xS in PC12 cells can be controlled by Bcl-2 and Bcl-xL, is mediated by caspases, and can be inhibited by the NGF signaling pathway. The Bax-induced cell death was inhibited by co-expression of Bax with Bcl-2 or Bcl-xL, but was not inhibited by Z-VAD-FMK, NGF, or the Bcl-2 ml-3 or deltaC22 mutants. These

  20. Dynamic interaction between 14-3-3zeta and bax during TNF-α-induced apoptosis in living cells

    Science.gov (United States)

    Gao, Xuejuan; Xing, Da; Chen, Tongsheng

    2006-09-01

    Bax, a proapoptotic member of the Bcl-2 family, localizes largely in the cytoplasm but redistributes to mitochondria and undergoes oligomerization to induce the release of apoptogenic factors such as cytochrome c in response to apoptotic stimuli. Cytoplasmic protein 14-3-3zeta binds to Bax and, upon apoptotic stimulation, releases Bax by a caspase-independent mechanism. However, the direct interaction of the cytoplasmic 14-3-3zeta and Bax in living cells has not been observed. In present study, to monitor the dynamic interaction between 14-3-3zeta and Bax in living cells in real time during apoptosis induced by tumor necrosis factor (TNF-α), DsRed-14-3-3zeta plasmid is constructed. By cotransfecting DsRed- 14-3-3zeta and GFP-Bax plasmids into human lung adenocarcinoma cells (ASTC-a-1), we observe the dynamic interaction between Bax and 14-3-3zeta using fluorescence resonance energy transfer (FRET) technique on laser scanning confocal microscope. The results show that 14-3-3zeta remains in the cytoplasm but GFP-Bax translocates to mitochondria completely after TNF-α stimulation. These results reveal that 14-3-3zeta binds directly to Bax in healthy cells, and that 14-3-3zeta negatively regulates Bax translocation to mitochondria during TNF-α-induced apoptosis.

  1. Effect of β Radiation on Bcl-2 and Bax Expressions in Benign Prostate Hyperplasia Tissues

    Institute of Scientific and Technical Information of China (English)

    MA Qing-jie; GAO Shi; ZHAO Jie; GU Xin-quan; CAI Shan-yu; ZHAO Guo-qing

    2008-01-01

    The authors chose specimens from nine normal prostate tissues(NP group),15 benign prostate hyperplasia(BPH) prostates(BPH group),and 35 BPH prostates that had been treated with 90Sr/90Y Prostatic Hyperplasia Applicator(exposure group),The expressions of bcl-2 and bax in stroma and epithelia of prostate tissues were demonstrated by means of immunohistochemical staining,and the staining positive rate was semiquantatively determined,so as to observe the expression of bcl-2 and bax genes in the prostate tissues of normal individuals and BPH patients,before and after β radiation,and to evaluate the influence of β radiation on bcl-2 and bax expressions,The expressions of gene bcl-2 in the prostate epithelia of NP and BPH are significantly higher than those in the prostate stroma(P<0.01),However,the expressions of bcl-2 in the prostate epithelia and stroma of the BPH group are obviously higher than those in the NP group(P<0.01),The expression of gene bax in the prostate epithelia of the NP group is higher than that in the BPH group(P<0.05),However,bcl-2 expressions in the prostate epithelia and stroma of the BPH group are significantly higher than the bax expressions(P<0.01),Compared with those of the NP group,the expressions of bcl-2 in the prostate epithelia and stroma of the exposure group decrease remarkably,even as the expressions of the bax notably increase(P<0.01),Thus,the administration of β radiation can remarkably affect bcl-2 and bax gene expressions,to regulate cell apoptosis,in the prostate tissues of BPH.

  2. Bax expression measured by AQUAnalysis is an independent prognostic marker in oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Bose Pinaki

    2012-08-01

    Full Text Available Abstract Background Resistance to apoptosis is a hallmark of cancer and proteins regulating apoptosis have been proposed as prognostic markers in several malignancies. However, the prognostic impact of apoptotic markers has not been consistently demonstrated in oral squamous cell carcinoma (OSCC. This inconsistency in reported associations between apoptotic proteins and prognosis can be partly attributed to the intrinsic low resolution and misclassification associated with manual, semi-quantitative methods of biomarker expression measurement. The aim of this study was to examine the association between apoptosis-regulating proteins and clinical outcomes in oral squamous cell carcinoma (OSCC using the quantitative fluorescence immunohistochemistry (IHC based AQUAnalysis technique. Methods Sixty-nine OSCC patients diagnosed between 1998–2005 in Calgary, Alberta, Canada were included in the study. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs were assembled from triplicate cores of formalin-fixed paraffin embedded pre-treatment tumour tissue. Bax, Bcl-2 and Bcl-XL protein expression was quantified using fluorescent IHC and AQUA technology in normal oral cavity squamous epithelium (OCSE and OSCC tumour samples. Survival was analyzed using Kaplan-Meier plots and the Cox proportional hazard model. Results Bax expression was predominantly nuclear in OCSE and almost exclusively cytoplasmic in OSCC. No similar differences in localization were observed for Bcl-2 or Bcl-XL. Only Bax expression associated with disease-specific survival (DSS, with 5-year survival estimates of 85.7% for high Bax versus 50.3% for low Bax (p = 0.006, in univariate analysis. High Bax expression was also significantly associated with elevated Ki67 expression, indicating that increased proliferation might lead to an improved response to radiotherapy in patients with elevated Bax expression. In multivariate analyses

  3. Bax expression measured by AQUAnalysis is an independent prognostic marker in oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Resistance to apoptosis is a hallmark of cancer and proteins regulating apoptosis have been proposed as prognostic markers in several malignancies. However, the prognostic impact of apoptotic markers has not been consistently demonstrated in oral squamous cell carcinoma (OSCC). This inconsistency in reported associations between apoptotic proteins and prognosis can be partly attributed to the intrinsic low resolution and misclassification associated with manual, semi-quantitative methods of biomarker expression measurement. The aim of this study was to examine the association between apoptosis-regulating proteins and clinical outcomes in oral squamous cell carcinoma (OSCC) using the quantitative fluorescence immunohistochemistry (IHC) based AQUAnalysis technique. Sixty-nine OSCC patients diagnosed between 1998–2005 in Calgary, Alberta, Canada were included in the study. Clinical data were obtained from the Alberta Cancer Registry and chart review. Tissue microarrays (TMAs) were assembled from triplicate cores of formalin-fixed paraffin embedded pre-treatment tumour tissue. Bax, Bcl-2 and Bcl-XL protein expression was quantified using fluorescent IHC and AQUA technology in normal oral cavity squamous epithelium (OCSE) and OSCC tumour samples. Survival was analyzed using Kaplan-Meier plots and the Cox proportional hazard model. Bax expression was predominantly nuclear in OCSE and almost exclusively cytoplasmic in OSCC. No similar differences in localization were observed for Bcl-2 or Bcl-XL. Only Bax expression associated with disease-specific survival (DSS), with 5-year survival estimates of 85.7% for high Bax versus 50.3% for low Bax (p = 0.006), in univariate analysis. High Bax expression was also significantly associated with elevated Ki67 expression, indicating that increased proliferation might lead to an improved response to radiotherapy in patients with elevated Bax expression. In multivariate analyses, Bax protein expression remained an independent

  4. Identification of Bax-interacting proteins in oligodendrocyte progenitors during glutamate excitotoxicity and perinatal hypoxia–ischemia

    Directory of Open Access Journals (Sweden)

    Sopio Simonishvili

    2013-12-01

    Full Text Available OPC (oligodendrocyte progenitor cell death contributes significantly to the pathology and functional deficits following hypoxic-ischemic injury in the immature brain and to deficits resulting from demyelinating diseases, trauma and degenerative disorders in the adult CNS. Glutamate toxicity is a major cause of oligodendroglial death in diverse CNS disorders, and previous studies have demonstrated that AMPA/kainate receptors require the pro-apoptotic protein Bax in OPCs undergoing apoptosis. The goal of the present study was to define the pro-apoptotic and anti-apoptotic effectors that regulate Bax in healthy OPCs and after exposure to excess glutamate in vitro and following H–I (hypoxia–ischemia in the immature rat brain. We show that Bax associates with a truncated form of Bid, a BH3-only domain protein, subsequent to glutamate treatment. Furthermore, glutamate exposure reduces Bax association with the anti-apoptotic Bcl family member, Bcl-xL. Cell fractionation studies demonstrated that both Bax and Bid translocate from the cytoplasm to mitochondria during the early stages of cell death consistent with a role for Bid as an activator, whereas Bcl-xL, which normally complexes with both Bax and Bid, disassociates from these complexes when OPCs are exposed to excess glutamate. Bax remained unactivated in the presence of insulin-like growth factor-1, and the Bcl-xL complexes were protected. Our data similarly demonstrate loss of Bcl-xL–Bax association in white matter following H–I and implicate active Bad in Bax-mediated OPC death. To identify other Bax-binding partners, we used proteomics and identified cofilin as a Bax-associated protein in OPCs. Cofilin and Bax associated in healthy OPCs, whereas the Bax–cofilin association was disrupted during glutamate-induced OPC apoptosis.

  5. Immunohistochemical localization of Bcl-2 and Bax proteins in in situ and invasive duct breast carcinomas.

    Science.gov (United States)

    Kapucuoglu, N; Losi, L; Eusebi, V

    1997-01-01

    Bcl-2 and Bax proteins are coded by a family of genes that take part in the manteinance of the balance between cell proliferation rate and programmed cell death in multicellular organisms. The Bax gene acts as promoter of cell death by opposing the death protector effect of the Bcl-2 gene. Expression of the Bcl-2 and Bax proteins has been investigated in 58 cases of duct carcinoma in situ (DCIS) and duct invasive and invasive lobular carcinomas (IC) of the breast. While both proteins were expressed at the same time in normal and benign epithelium, different staining patterns were observed according to the degree of differentiation of the neoplastic epithelium. In well-differentiated DCIS and grade I IC there was a predominance of Bcl-2 protein staining. Grade II lesions co-expressed both proteins. Poorly differentiated DCIS displayed a predominantly Bax protein staining pattern. Therefore, it appears that Bax protein expression, especially in DCIS, relates to more aggressive neoplasms while Bcl-2 protein expression is associated with less aggressive malignant lesions.

  6. Apoptosis of human tumor cells by chemotherapeutic anthracyclines is enhanced by Bax overexpression.

    Science.gov (United States)

    Lu, Y; Yagi, T

    1999-09-01

    One of the major factors for efficacy of a chemotherapeutic drug is its activity to induce apoptosis of tumor cells. Doxorubicin and daunorubicin, radiomimetic anthracycline-group drugs, have been used for chemotherapy for about 30 years. Here we established the colorectal tumor and osteosarcoma cells in which Bax expression can be induced by the treatment of isopropyl-beta-D-thiogalactopyranoside, and examined the effect of the Bax overexpression on the cell death caused by these drugs. While the Bax overexpression neither affected growth nor morphology of the undamaged cells, it enhanced the cell death caused by these drugs. Increase in cellular nucleus fragmentation and DNA ladder formation indicates that the Bax-enhanced cell death is due to enhanced apoptosis of the drug-treated cells. The enhanced cell death was not observed when the cells were irradiated with X-ray or treated with other chemotherapeutic agents we examined. These results indicate that Bax may have a specific role to enhance the efficacy of chemotherapy with anthracycline-group agents.

  7. BAX OVEREXPRESSION ENHANCES APOPTOSIS INDUCED BY ADRIAMYCIN IN HCC-9204 CELLS

    Institute of Scientific and Technical Information of China (English)

    郑建勇; 李江; 李开宗; 王文亮; 王为忠

    2004-01-01

    Objective: To investigate the effect of overexpression of Bax to the sensitivity of human HCC-9204 cells to adriamycin (ADR). Methods: Human cultured hepatocellular carcinoma cell line HCC-9204 was exposed in vitro to adriamycin for various time. An inducible vector containing Bax gene, with ZnSO4 as external inducer was constructed. Cell apoptosis was ascertained by morphological criteria, detection of apoptotic DNA fragmentation by TUNEL assay and flow cytometry. Tetrazolium blue (MTT) assay was used to evaluate the differences in drug sensitivity of HCC-9204 cells after Bax-transfection. Results: HCC-9204 cells treated with adriamycin at 20μmol/L showed extensive cell death. TUNEL assay showed nucleus fragmentation. And apoptotic peak was also shown by flow cytometry. FACS analyses showed a significant sub-G1 peak and apoptosis in 31% cells at 24h after treatment. Furthermore, the time-course of cell viability following exposure of HCC-9204/Bax cells to adriamycin showed that Bax was able to significantly decrease cell survival following exposure to adriamycin.

  8. Eucommia ulmoides cortex, geniposide and aucubin regulate lipotoxicity through the inhibition of lysosomal BAX.

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    Geum-Hwa Lee

    Full Text Available In this study we examined the inhibition of hepatic dyslipidemia by Eucommia ulmoides extract (EUE. Using a screening assay for BAX inhibition we determined that EUE regulates BAX-induced cell death. Among various cell death stimuli tested EUE regulated palmitate-induced cell death, which involves lysosomal BAX translocation. EUE rescued palmitate-induced inhibition of lysosomal V-ATPase, α-galactosidase, α-mannosidase, and acid phosphatase, and this effect was reversed by bafilomycin, a lysosomal V-ATPase inhibitor. The active components of EUE, aucubin and geniposide, showed similar inhibition of palmitate-induced cell death to that of EUE through enhancement of lysosome activity. Consistent with these in vitro findings, EUE inhibited the dyslipidemic condition in a high-fat diet animal model by regulating the lysosomal localization of BAX. This study demonstrates that EUE regulates lipotoxicity through a novel mechanism of enhanced lysosomal activity leading to the regulation of lysosomal BAX activation and cell death. Our findings further indicate that geniposide and aucubin, active components of EUE, may be therapeutic candidates for non-alcoholic fatty liver disease.

  9. Apoptosis repressor with a CARD domain (ARC restrains Bax-mediated pathogenesis in dystrophic skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Jennifer Davis

    Full Text Available Myofiber wasting in muscular dystrophy has largely been ascribed to necrotic cell death, despite reports identifying apoptotic markers in dystrophic muscle. Here we set out to identify the contribution of canonical apoptotic pathways to skeletal muscle degeneration in muscular dystrophy by genetically deleting a known inhibitor of apoptosis, apoptosis repressor with a card domain (Arc, in dystrophic mouse models. Nol3 (Arc protein genetic deletion in the dystrophic Sgcd or Lama2 null backgrounds showed exacerbated skeletal muscle pathology with decreased muscle performance compared with single null dystrophic littermate controls. The enhanced severity of the dystrophic phenotype associated with Nol3 deletion was caspase independent but dependent on the mitochondria permeability transition pore (MPTP, as the inhibitor Debio-025 partially rescued skeletal muscle pathology in Nol3 (-/- Sgcd (-/- double targeted mice. Mechanistically, Nol3 (-/- Sgcd (-/- mice showed elevated total and mitochondrial Bax protein levels, as well as greater mitochondrial swelling, suggesting that Arc normally restrains the cell death effects of Bax in skeletal muscle. Indeed, knockdown of Arc in mouse embryonic fibroblasts caused an increased sensitivity to cell death that was fully blocked in Bax Bak1 (genes encoding Bax and Bak double null fibroblasts. Thus Arc deficiency in dystrophic muscle exacerbates disease pathogenesis due to a Bax-mediated sensitization of mitochondria-dependent death mechanisms.

  10. Bax is not involved in the resveratrol-induced apoptosis in human lung adenocarcinoma cells

    Science.gov (United States)

    Zhang, Wei-wei; Wang, Zhi-ping; Chen, Tong-sheng

    2010-02-01

    Resveratrol (RV) is a natural plant polyphenol widely present in foods such as grapes, wine, and peanuts. Previous studies indicate that RV has an ability to inhibit various stages of carcinogenesis and eliminate preneoplastic cells in vitro and in vivo. However, little is known about the molecular mechanism of RV-induced apoptosis in human lung adenocarcinoma (ASTC-a-1) cell. In this report, we analyzed whether Bax translocation from cytoplasm to mitochondria during RV-induced apoptosis in single living cell using onfocal microscopey. Cells were transfected with GFP-Bax plasmid. Cell counting kit (CCK-8) assay was used to assess the inhibition of RV on the cells viability. Apoptotic activity of RV was detected by Hoechst 33258 and propidium iodide (PI) staining. Our results showed that RV induced a dose-dependent apoptosis in which Bax did not translocate to mitochondrias.

  11. Influence of Apoptin on Up-regulation of the Expression of Bad and Bax

    Institute of Scientific and Technical Information of China (English)

    GUO Tai; YANG Qian

    2005-01-01

    The chicken anemia virus protein, apoptin, which manifests selectivity and specificity to tumor cells, induces a p53-independent and Bcl-2-insensitive type of apoptosis in various human tumor cells. In this study, the apoptin gene was cloned from the total DNA of chicken anemia virus, and the recombinant vector was constructed. We used oligonucleotide microarray to study the changes of four genes, including Bcl-2, Bcl-xL, Bad and Bax. The post-transfection with the recombinant was also studied. The pro-apoptotic genes(Bad and Bax) and anti-apoptosis genes(Bcl-2 and Bcl-xL) were up-regulated in contrast to the controls. According to the published data, either Bcl-2 or Bcl-xL can form non-functional heterodimers by Bad and Bax binding together, resulting in blocking partly the release of cytochrome c from mitochondria. However, apoptosis could be inhibited by neither the endogenous Bcl-xL nor Bcl-2 over-expression. The experiments show that the apoptin-induced apoptotic pathway is related to the up-regulation of Bad and Bax. Bad was up-regulated by apoptin; then this up-regulated product of Bad was in favor of displacing Bax from binding to Bcl-xL or Bcl-2. Consequently, Bax exerted a pro-apoptotic dysfunction to mitochondria, thereby inducing the release of cytochrome c. Finally, apoptin induced the apoptosis of HHCC cells. These results indicate that the oligonucleotide microarray can reveal the genes related to the apoptosis induced by apoptin in HHCC cells.

  12. PUMA Promotes Bax Translocation by Both Directly Interacting with Bax and by Competitive Binding to Bcl-XL during UV-induced Apoptosis

    OpenAIRE

    Zhang, Yingjie; Xing, Da; Liu, Lei

    2009-01-01

    Cell apoptosis induced by UV irradiation is a highly complex process in which different molecular signaling pathways are involved. p53 up-regulated modulator of apoptosis (PUMA) has been proposed as an important regulator in UV irradiation-induced apoptosis. However, the molecular mechanism through which PUMA regulates apoptosis, especially how PUMA activates Bcl-2-associated X protein (Bax) in response to UV irradiation is still controversial. In this study, by using real-time single-cell an...

  13. Differential expression of Bcl-2 and Bax during gastric ischemia-reperfusion of rats

    Institute of Scientific and Technical Information of China (English)

    Wei-Li Qiao; Guang-Ming Wang; Yue Shi; Jin-Xia Wu; You-Jian Qi; Jian-Fu Zhang; Hong Sun; Chang-Dong Yan

    2011-01-01

    AIM: To investigate expression of Bcl-2 and Bax in gastric ischemia-reperfusion (GI-R) and involvement of extracellular signal-regulated kinase (ERK) 1/2 activation.METHODS: The GI-R model was established by ligature of the celiac artery for 30 min and reperfusion in Sprague-Dawley rats. Rats were assigned to groups in accordancewith their evaluation period: control, 0, 0.5, 1, 3, 6, 24,48, and 72 h. Expression and distribution of Bcl-2 and Bax proteins were analyzed by immunohistochemistry and western blotting in gastric tissue samples after sacrifice.RESULTS: Compared with controls, the percentage of positive cells and protein levels of Bcl-2 decreased in the early phases of reperfusion, reached its minimumat 1 h (P < 0.05); it then increased, reaching its peak at 24 h of reperfusion (P < 0.05). The pattern of Bax expression was opposite to that of Bcl-2. Bax expressionincreased after reperfusion, with its peak at 1 h of reperfusion (P < 0.05), and then it decreased gradually to a minimum at 24 h after reperfusion (P < 0.05).On the other hand, inhibition of activation of ERK1/2 induced by PD98059, a specific upstream MEK inhibitor,had significant effects on Bcl-2 and Bax in GI-R.Compared with GI-R treatment only at 3 h of reperfusion,PD98059 reduced the number of Bcl-2 positive cells (0.58% of R3h group, P < 0.05) and Bcl-2 proteinlevel (74% of R3h group, P < 0.05) but increased the number of Bax-positive cells (1.33-fold vs R3h group, P< 0.05) and Bax protein level (1.35-fold of R3h group,P < 0.05).CONCLUSION: These results indicated that the Bcl-2 and Bax played a pivotal role in the gastric mucosal I-R injury and repair by activation of ERK1/2.

  14. 杏仁核点燃鼠海马不同亚区Bax mRNA的表达%The expression of Bax mRNA in the hippocampus-subareas in amygdala-kindled rats

    Institute of Scientific and Technical Information of China (English)

    梁代义; 伍国锋; 庞成

    2006-01-01

    目的:观察细胞凋亡调控基因Bax mRNA在癫(癎)鼠海马不同亚区的表达.方法:利用电极植入鼠脑杏仁核的方法建立点燃癫(癎)模型,采用原位杂交法检测鼠脑海马CA1、CA2、CA3及齿状回(DGL)区Bax mRNA的表达.结果:正常大鼠海马各区少见Bax mRNA阳性细胞表达,杏仁核植入电极大鼠及其点燃后海马各区Bax mRNA表达阳性细胞数增多,点燃鼠Bax mRNA阳性细胞平均光密度高于仅仅植入电极鼠,海马不同亚区Bax mRNA阳性细胞平均光密度值不同.结论:杏仁核点燃癫(癎)模型鼠的海马不同亚区均存在Bax mRNA表达增强,但不同亚区对Bax mRNA表达敏感性不同,以DGL区为最高.

  15. NDV-induced apoptosis in absence of Bax; evidence of involvement of apoptotic proteins upstream of mitochondria

    Directory of Open Access Journals (Sweden)

    Molouki Aidin

    2012-08-01

    Full Text Available Abstract Background Recently it was shown that following infection of HeLa cells with Newcastle disease virus (NDV, the matrix (M protein binds to Bax and subsequently the intrinsic pathway of apoptosis is activated. Moreover, there was very little alteration on mRNA and protein levels of Bax and Bcl-2 after infection with NDV. Finding In order to further investigate the role of members of the Bcl-2 family, Bax-knockout and wild-type HCT116 cells were infected with NDV strain AF2240. Although both cells underwent apoptosis through the activation of the intrinsic pathway and the release of cytochrome c from mitochondria, the percentage of dead Bax-knockout cells was significantly lower than wt cells (more than 10% at 48 h post-infection. In a parallel experiment, the effect of NDV on HT29 cells, that are originally Bcl-2-free, was studied. Apoptosis in HT29 cells was associated with Bax redistribution from cytoplasm to mitochondria, similar to that of HeLa and wt HCT116 cells. Conclusion Although the presence of Bax during NDV-induced apoptosis contributes to a faster cell death, it was concluded that other apoptotic protein(s upstream of mitochondria are also involved since cancer cells die whether in the presence or absence of Bax. Therefore, the classic Bax/Bcl-2 ratio may not be a major determinant in NDV-induced apoptosis.

  16. A BAX/BAK and cyclophilin D-independent intrinsic apoptosis pathway.

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    Sebastián Zamorano

    Full Text Available Most intrinsic death signals converge into the activation of pro-apoptotic BCL-2 family members BAX and BAK at the mitochondria, resulting in the release of cytochrome c and apoptosome activation. Chronic endoplasmic reticulum (ER stress leads to apoptosis through the upregulation of a subset of pro-apoptotic BH3-only proteins, activating BAX and BAK at the mitochondria. Here we provide evidence indicating that the full resistance of BAX and BAK double deficient (DKO cells to ER stress is reverted by stimulation in combination with mild serum withdrawal. Cell death under these conditions was characterized by the appearance of classical apoptosis markers, caspase-9 activation, release of cytochrome c, and was inhibited by knocking down caspase-9, but insensitive to BCL-X(L overexpression. Similarly, the resistance of BIM and PUMA double deficient cells to ER stress was reverted by mild serum withdrawal. Surprisingly, BAX/BAK-independent cell death did not require Cyclophilin D (CypD expression, an important regulator of the mitochondrial permeability transition pore. Our results suggest the existence of an alternative intrinsic apoptosis pathway emerging from a cross talk between the ER and the mitochondria.

  17. Effect of Bcl-2 and Bax on survival of side population cells from hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To understand the role and significance of side population (SP) cells from hepatocellular carcinoma (HCC) in hepatocarcinogenesis, development, relapse and metastasis, we simulated the denutrition conditions that cancer cells experience in clinical therapy, observed the different anti-apoptosis ability of SP cells and non-SP cells under such conditions, and established the possible effects of P53, Bcl-2 and Bax on survival of SP cells.METHODS: We used flow cytometry to analyze and sort the SP and non-SP cells in established HCC lines MHCC97and hHCC. We evaluated cell proliferation by methyl thiazolyl tetrazolium (MTT) assay and investigated the expression of p53, bd-2 and bax genes during denutrition,by RT-PCR and immunofluorescence staining.RESULTS: The percentage of SP cells in the two established HCC lines was 0.25% and 0.5%, respectively.SP cells had greater anti-apoptosis and proliferation ability than non-SP cells. Expression of Bcl-2 and Bax in SP and non-SP cells differed during denutrition. The former was up-regulated in SP cells, and the latter was up-regulated in non-SP cells.CONCLUSION: It may be that different upstream molecules acted and led to different expression levels of Bcl-2 and Bax in these two cell lines. There was a direct relationship between up-regulation of Bcl-2 and down-regulation of Bax and higher anti-apoptosis ability in SP cells. It may be that the existence and activity of SP cells are partly responsible for some of the clinical phenomena which are seen in HCC, such as relapse or metastasis. Further research on SP cells may have potential applications in the field of anticancer therapy.

  18. WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zeilstra, Jurrit; Joosten, Sander P.J. [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Wensveen, Felix M. [Department of Experimental Immunology, Academic Medical Center, Amsterdam (Netherlands); Dessing, Mark C.; Schuetze, Denise M. [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Eldering, Eric [Department of Experimental Immunology, Academic Medical Center, Amsterdam (Netherlands); Spaargaren, Marcel [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands); Pals, Steven T., E-mail: s.t.pals@amc.uva.nl [Department of Pathology, Academic Medical Center, University of Amsterdam (Netherlands)

    2011-03-04

    Research highlights: {yields} Intestinal adenomas initiated by aberrant activation of the WNT pathway displayed an increased sensitivity to apoptosis. {yields} Expression profiling of apoptosis-related genes in Apc{sup Min/+} mice revealed the differential expression of pro-apoptotic Bok and Bax. {yields} APC-mutant adenomatous crypts in FAP patients showed strongly increased BAX immunoreactivity. {yields} Blocking of {beta}-catenin/TCF-4-mediated signaling in colon cancer cells reduced the expression of BOK and BAX. -- Abstract: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or {beta}-catenin causes constitutively active {beta}-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the Apc{sup Min/+} mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of {beta}-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which

  19. WNT signaling controls expression of pro-apoptotic BOK and BAX in intestinal cancer

    International Nuclear Information System (INIS)

    Research highlights: → Intestinal adenomas initiated by aberrant activation of the WNT pathway displayed an increased sensitivity to apoptosis. → Expression profiling of apoptosis-related genes in ApcMin/+ mice revealed the differential expression of pro-apoptotic Bok and Bax. → APC-mutant adenomatous crypts in FAP patients showed strongly increased BAX immunoreactivity. → Blocking of β-catenin/TCF-4-mediated signaling in colon cancer cells reduced the expression of BOK and BAX. -- Abstract: In a majority of cases, colorectal cancer is initiated by aberrant activation of the WNT signaling pathway. Mutation of the genes encoding the WNT signaling components adenomatous polyposis coli or β-catenin causes constitutively active β-catenin/TCF-mediated transcription, driving the transformation of intestinal crypts to cancer precursor lesions, called dysplastic aberrant crypt foci. Deregulated apoptosis is a hallmark of adenomatous colon tissue. However, the contribution of WNT signaling to this process is not fully understood. We addressed this role by analyzing the rate of epithelial apoptosis in aberrant crypts and adenomas of the ApcMin/+ mouse model. In comparison with normal crypts and adenomas, aberrant crypts displayed a dramatically increased rate of apoptotic cell death. Expression profiling of apoptosis-related genes along the crypt-villus axis and in Apc mutant adenomas revealed increased expression of two pro-apoptotic Bcl-2 family members in intestinal adenomas, Bok and Bax. Analysis of the colon of familial adenomatous polyposis (FAP) patients along the crypt-to-surface axis, and of dysplastic crypts, corroborated this expression pattern. Disruption of β-catenin/TCF-4-mediated signaling in the colorectal cancer cell line Ls174T significantly decreased BOK and BAX expression, confirming WNT-dependent regulation in intestinal epithelial cells. Our results suggest a feedback mechanism by which uncontrolled epithelial cell proliferation in the stem

  20. Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio

    Directory of Open Access Journals (Sweden)

    Azimahtol Hawariah LP

    2007-04-01

    Full Text Available Abstract Background Zerumbone is a cytotoxic component isolated from Zingiber zerumbet Smith, a herbal plant which is also known as lempoyang. This new anticancer bioactive compound from Z. zerumbet was investigated for its activity and mechanism in human liver cancer cell lines. Results Zerumbone significantly showed an antiproliferative activity upon HepG2 cells with an IC50 of 3.45 ± 0.026 μg/ml. Zerumbone was also found to inhibit the proliferation of non-malignant Chang Liver and MDBK cell lines. However the IC50 obtained was higher compared to the IC50 for HepG2 cells (> 10 μg/ml. The extent of DNA fragmentation was evaluated by the Tdt-mediated dUTP nick end labelling assay which showed that, zerumbone significantly increased apoptosis in HepG2 cells in a time-course manner. In detail, the apoptotic process triggered by zerumbone involved the up-regulation of pro-apoptotic Bax protein and the suppression of anti-apoptotic Bcl-2 protein expression. The changes that occurred in the levels of this antagonistic proteins Bax/Bcl-2, was independent of p53 since zerumbone did not affect the levels of p53 although this protein exists in a functional form. Western blotting analysis for Bax protein was further confirmed qualitatively with an immunoassay that showed the distribution of Bax protein in zerumbone-treated cells. Conclusion Therefore, zerumbone was found to induce the apoptotic process in HepG2 cells through the up and down regulation of Bax/Bcl-2 protein independently of functional p53 activity.

  1. IMPORTANCE OF APOPTOSIS MARKERS (MDM2, BCL-2 AND Bax) IN CONVENTIONAL RENAL CELL CARCINOMA.

    Science.gov (United States)

    Saker, Z; Tsintsadze, O; Jiqia, I; Managadze, L; Chkhotua, A

    2015-12-01

    The goal of the current study was to analyze the expression of Bcl-2, MDM2 and Bax in benign and malignant renal tissue samples and assess their possible association with different clinical parameters. Prognostic significance of the markers in recurrence-free and cancer-specific survivals has also been evaluated. Activity of MDM2, Bcl-2 and Bax was evaluated in: 24 normal human kidney tissues resected from the patients of different ages (range: 21-80 years), and in 52 conventional RCC samples. Intensity of the markers' expression was compared between the groups and correlation was analyzed with different clinical parameters. Activity of anti-apoptotic MDM2 and Bcl-2 was significantly elevated while activity of pro-apoptotic Bax was decreased in RCC as compared with normal kidney tissues. Bax expression was positively correlated with patient age. Significant association has been detected between the evaluated markers and cancer clinical parameters like: tumor stage, grade, lymph node and distant metastases. The markers' activity was associates with the tumor morphological features, in particular: presence of tumor necrosis and microvascular invasion. Disease recurrence and 5-year patient survival were associated with the markers' activity. Cox regression analyses have shown that tumor size, pathological stage and grade are the risk factors for disease recurrence and patient death. Expression of MDM2 and Bcl-2 is significantly up-regulated, while Bax is down-regulated in RCC as compared with normal kidney tissue. Intensity of the markers'activities is associated with the tumor pathological and clinical parameters (stage, grade, lymph node and distant metastases, tumor recurrence and patient survival). Further studies with more patients and longer follow-up will uncover the clinical importance of the evaluated markers in RCC. PMID:26719546

  2. Loss of anti-Bax function in Gerstmann-Straussler-Scheinker syndrome-associated prion protein mutants.

    Directory of Open Access Journals (Sweden)

    Julie Jodoin

    Full Text Available Previously, we have shown the loss of anti-Bax function in Creutzfeldt Jakob disease (CJD-associated prion protein (PrP mutants that are unable to generate cytosolic PrP (CyPrP. To determine if the anti-Bax function of PrP modulates the manifestation of prion diseases, we further investigated the anti-Bax function of eight familial Gerstmann-Sträussler-Scheinker Syndrome (GSS-associated PrP mutants. These PrP mutants contained their respective methionine ((M or valine ((V at codon 129. All of the mutants lost their ability to prevent Bax-mediated chromatin condensation or DNA fragmentation in primary human neurons. In the breast carcinoma MCF-7 cells, the F198S(V, D202N(V, P102L(V and Q217R(V retained, whereas the P102L(M, P105L(V, Y145stop(M and Q212P(M PrP mutants lost their ability to inhibit Bax-mediated condensed chromatin. The inhibition of Bax-mediated condensed chromatin depended on the ability of the mutants to generate cytosolic PrP. However, except for the P102L(V, none of the mutants significantly inhibited Bax-mediated caspase activation. These results show that the cytosolic PrP generated from the GSS mutants is not as efficient as wild type PrP in inhibiting Bax-mediated cell death. Furthermore, these results indicate that the anti-Bax function is also disrupted in GSS-associated PrP mutants and is not associated with the difference between CJD and GSS.

  3. Low levels of Bax inhibitor-1 gene expression increase tunicamycin-induced apoptosis in human neuroblastoma SY5Y cells

    Institute of Scientific and Technical Information of China (English)

    Dan Wu; Peirong Wang; Shiyao Wang

    2012-01-01

    A human SH-SY5Y neuroblastoma cell line with a low level of Bax inhibitor-1 expression was established by lentivirus-mediated RNA interference and fluorescence-activated cell sorting. In control SH-SY5Y cells, tunicamycin treatment induced endoplasmic reticulum stress-mediated apoptosis; however, after Bax inhibitor-1 gene knockdown, cell survival rates were significantly decreased and the degree of apoptosis was significantly increased following tunicamycin treatment. In addition, chromatin condensation and apparent apoptotic phenomena, such as marginalization and cytoplasmic vesicles, were observed. Our findings indicate that Bax inhibitor-1 can delay apoptosis induced by endoplasmic reticulum stress.

  4. Conformational Heterogeneity of Bax Helix 9 Dimer for Apoptotic Pore Formation

    Science.gov (United States)

    Liao, Chenyi; Zhang, Zhi; Kale, Justin; Andrews, David W.; Lin, Jialing; Li, Jianing

    2016-07-01

    Helix α9 of Bax protein can dimerize in the mitochondrial outer membrane (MOM) and lead to apoptotic pores. However, it remains unclear how different conformations of the dimer contribute to the pore formation on the molecular level. Thus we have investigated various conformational states of the α9 dimer in a MOM model — using computer simulations supplemented with site-specific mutagenesis and crosslinking of the α9 helices. Our data not only confirmed the critical membrane environment for the α9 stability and dimerization, but also revealed the distinct lipid-binding preference of the dimer in different conformational states. In our proposed pathway, a crucial iso-parallel dimer that mediates the conformational transition was discovered computationally and validated experimentally. The corroborating evidence from simulations and experiments suggests that, helix α9 assists Bax activation via the dimer heterogeneity and interactions with specific MOM lipids, which eventually facilitate proteolipidic pore formation in apoptosis regulation.

  5. Conformational Heterogeneity of Bax Helix 9 Dimer for Apoptotic Pore Formation.

    Science.gov (United States)

    Liao, Chenyi; Zhang, Zhi; Kale, Justin; Andrews, David W; Lin, Jialing; Li, Jianing

    2016-01-01

    Helix α9 of Bax protein can dimerize in the mitochondrial outer membrane (MOM) and lead to apoptotic pores. However, it remains unclear how different conformations of the dimer contribute to the pore formation on the molecular level. Thus we have investigated various conformational states of the α9 dimer in a MOM model - using computer simulations supplemented with site-specific mutagenesis and crosslinking of the α9 helices. Our data not only confirmed the critical membrane environment for the α9 stability and dimerization, but also revealed the distinct lipid-binding preference of the dimer in different conformational states. In our proposed pathway, a crucial iso-parallel dimer that mediates the conformational transition was discovered computationally and validated experimentally. The corroborating evidence from simulations and experiments suggests that, helix α9 assists Bax activation via the dimer heterogeneity and interactions with specific MOM lipids, which eventually facilitate proteolipidic pore formation in apoptosis regulation. PMID:27381287

  6. Bax translocation mediated mitochondrial apoptosis and caspase dependent photosensitizing effect of Ficus religiosa on cancer cells.

    Directory of Open Access Journals (Sweden)

    Jazir Haneef

    Full Text Available The main aim of the present work was to investigate the potential effect of acetone extract of Ficus religosa leaf (FAE in multiple apoptosis signalling in human breast cancer cells. FAE treatment significantly induced dose and time dependent, irreversible inhibition of breast cancer cell growth with moderate toxicity to normal breast epithelial cells. This observation was validated using Sulforhodamine B assay. Cell cycle analysis by Flow cytometry showed cell cycle arrest in G1 phase and induction of sub-G0 peak. FAE induced chromatin condensation and displayed an increase in apoptotic population in Annexin V-FITC/PI (Fluorescein isothiocyanate/Propidium iodide double staining. FAE stimulated the loss of mitochondrial membrane potential in multiple breast cancer cell lines when compared to normal diploid cells. To understand the role of Bax in FAE induced apoptosis, we employed a sensitive cell based platform of MCF-7 cells expressing Bax-EGFP. Bax translocation to mitochondria was accompanied by the disruption of mitochondrial membrane potential and marked elevation in LEHDase activity (Caspase 9. Consistent with this data, FAE induced Caspase activation as evidenced by ratio change in FRET Caspase sensor expressing MCF-7 cell line and cleavage of prominent Caspases and PARP. Interestingly, FAE accelerated cell death in a mitochondrial dependent manner in continuous live cell imaging mode indicating its possible photosensitizing effect. Intracellular generation of reactive oxygen species (ROS by FAE played a critical role in mediating apoptotic cell death and photosensitizing activity. FAE induced dose and time dependent inhibition of cancer cell growth which was associated with Bax translocation and mitochondria mediated apoptosis with the activation of Caspase 9 dependent Caspase cascade. FAE also possessed strong photosensitizing effect on cancer cell line that was mediated through rapid mitochondrial transmembrane potential loss and

  7. Bax translocation mediated mitochondrial apoptosis and caspase dependent photosensitizing effect of Ficus religiosa on cancer cells.

    Science.gov (United States)

    Haneef, Jazir; Parvathy, Muraleedharan; M, Parvathy; Thankayyan R, Santhosh Kumar; Sithul, Hima; Sreeharshan, Sreeja

    2012-01-01

    The main aim of the present work was to investigate the potential effect of acetone extract of Ficus religosa leaf (FAE) in multiple apoptosis signalling in human breast cancer cells. FAE treatment significantly induced dose and time dependent, irreversible inhibition of breast cancer cell growth with moderate toxicity to normal breast epithelial cells. This observation was validated using Sulforhodamine B assay. Cell cycle analysis by Flow cytometry showed cell cycle arrest in G1 phase and induction of sub-G0 peak. FAE induced chromatin condensation and displayed an increase in apoptotic population in Annexin V-FITC/PI (Fluorescein isothiocyanate/Propidium iodide) double staining. FAE stimulated the loss of mitochondrial membrane potential in multiple breast cancer cell lines when compared to normal diploid cells. To understand the role of Bax in FAE induced apoptosis, we employed a sensitive cell based platform of MCF-7 cells expressing Bax-EGFP. Bax translocation to mitochondria was accompanied by the disruption of mitochondrial membrane potential and marked elevation in LEHDase activity (Caspase 9). Consistent with this data, FAE induced Caspase activation as evidenced by ratio change in FRET Caspase sensor expressing MCF-7 cell line and cleavage of prominent Caspases and PARP. Interestingly, FAE accelerated cell death in a mitochondrial dependent manner in continuous live cell imaging mode indicating its possible photosensitizing effect. Intracellular generation of reactive oxygen species (ROS) by FAE played a critical role in mediating apoptotic cell death and photosensitizing activity. FAE induced dose and time dependent inhibition of cancer cell growth which was associated with Bax translocation and mitochondria mediated apoptosis with the activation of Caspase 9 dependent Caspase cascade. FAE also possessed strong photosensitizing effect on cancer cell line that was mediated through rapid mitochondrial transmembrane potential loss and partial Caspase

  8. Influence of neurotrophin-3 on Bcl-2 and Bax expressions in spinal cord injury of rats

    Institute of Scientific and Technical Information of China (English)

    GUO Shu-zhang; JIANG Tao; REN Xian-jun

    2007-01-01

    Objective:To study the protective mechanisms of neurotrophin-3 (NT-3) on the spinal cord injury.Methods:Totally 105 SD rats were randomly divided into 3 groups:control group,experimental group and sham operation group.Rats from the former 2 groups were inflicted to animal model of acute spinal cord injury according to Allen's (WD) by situating a thin plastic tube in the subarachnoid space below the injury level for perfusion.Rats in experimental group received 20μl NT-3 (200 ng) from the tube at 0,4,8,12,24 h and 3,7 d after injury,and those in control group got an equal volume of normal saline at the same time.The animals in sham operation group only received opening vertebral plate and tube was put in subarachnoid space.The rats were sacrificed at 4,8,12,24 h and 3,7,14 d post injury (n=5).The expression levels of Bcl-2 and Bax proteins in spinal cord of rats were detected by immunohistochemistry assay.Results:The level of Bax protein in control group significantly increased as compared with those in sham operation group, and the peak reached at 8 h after spinal cord injury.The Bcl-2 proteins were always weakly positive.The Bax proteins in NT-3 group significantly decreased but the Bcl-2 proteins obviously increased as compared with those in control group.Conclusion:NT-3 can protect spinal cord from injury in vivo.One of the mechanisms is that NT-3 can inhibit abnormal expression of Bax protein,and increase the expression of Bcl-2 protein,then inhibit apoptosis after spinal cord injury.

  9. Effects of apoptosis-related proteins caspase-3, Bax and Bcl-2 on cerebral ischemia rats

    OpenAIRE

    Liu, Guangyi; Tao WANG; WANG, TINGING; Song, Jinming; Zhou, Zhen

    2013-01-01

    Neuron apoptosis is known to mediate a change of ethology following cerebral ischemia-reperfusion injury in rats. Additionally, Bcl-2, Bax and caspase-3 proteins may exert a significant effect on neuron injury. The aim of this study was to investigate the role, mechanism of action and clinical significance of these proteins in neuron apoptosis and functional impairment following cerebral ischemia-reperfusion injury in rats. Sixty male healthy adult Wistar rats were randomly assigned into cont...

  10. Effect of Exercise Training on Bcl-2 and Bax Gene Expression in the Rat Heart

    OpenAIRE

    Jafari; Pourrazi; Nikookheslat; Baradaran

    2015-01-01

    Background Apoptosis or programmed cell death plays an important role in the development of cardiovascular diseases, particularly heart failure. Current evidence suggests that exercise training may alter apoptosis-related signaling in sensitive somatic tissues such as the myocardium. Objectives The aim of this study was to assess the effect of exercise training on Bcl-2 and Bax genes expression as key molecules involved in intrins...

  11. Electrical conductivity and defect chemistry of BaxSr1 - xCoyFe1 - yO3 - dBaxSr1−xCoyFe1−yO3− perovskites

    NARCIS (Netherlands)

    Yáng, Z.; Harvey, A.S.; Infortuna, A.; Schoonman, J.; Gauckler, L.J.

    2010-01-01

    Bulk BaxSr1 - xCoyFe1 - yO3 - dBaxSr1−xCoyFe1−yO3− compositions (BSCF) were synthesized by the solid-state reaction method. The electrical conductivity of ceramic bars was measured using a dc four-probe method as a function of temperature in air up to 970 °C. All compositions showed thermally activa

  12. AxBAxB… pulsed atomic layer deposition: Numerical growth model and experiments

    Science.gov (United States)

    Muneshwar, Triratna; Cadien, Ken

    2016-02-01

    Atomic layer deposition (ALD) is widely used for the fabrication of advanced semiconductor devices and related nanoscale structures. During ALD, large precursor doses (>1000 L per pulse) are often required to achieve surface saturation, of which only a small fraction is utilized in film growth while the rest is pumped from the system. Since the metal precursor constitutes a significant cost of ALD, strategies to enhance precursor utilization are essential for the scaling of ALD processes. In the precursor reaction step, precursor physisorption is restricted by steric hindrance (mA1) from ligands on the precursor molecules. On reaction, some of these ligands are removed as by-products resulting in chemisorbed species with reduced steric hindrance (mA1 → mA2, where mA2 1, x ∈ I) short-pulses rather than a single pulse. A numerical first-order surface reaction kinetics growth model is presented and applied to study the effect of AxBAxB… pulsed ALD on the growth per cycle (GPC). The model calculations predict higher GPC for AxBAxB… pulsing than with ABAB… deposition. In agreement with the model predictions, with AxBAxB… pulsed deposition, the GPC was found to increase by ˜46% for ZrN plasma enhanced ALD (PEALD), ˜49% for HfO2 PEALD, and ˜8% for thermal Al2O3 ALD with respect to conventional ABAB… pulsed growth.

  13. The Expression of Apoptosis-Related Genes Bcl-2 and Bax Protein and Apoptosis Positivity in Cervical Carcinoma during Irradiation

    Institute of Scientific and Technical Information of China (English)

    ZHAODongli; SHIJingsen; LIMingzhong; SONGLiping; WANGShuwen

    2005-01-01

    Objective: To evaluate the apoptosis positivity, the expression of Bcl-2. bax proteins in 30 patients with squamous cell cervix carcinoma before and after radiotherapy. Methods: By using immunohistochemical and TDT-dUTP nick end labelling techniques. 30 cases of squamous cell cervical carcinoma were analyzed. Results: The apoptosis positivity before and after irradiation was 76.7%, and 100% respectively, with the difference being significant (P<0.05); The positive rates of Bcl-2 protein before and after irradiation were 73.3% and 46.7% respectively, with the difference being significant (P<0.05): The positive rates of bax protein before and after irradiation were 86% and 100 respectively, with the difference being significant (P<0.05). Conclusion: bax and Bcl-2 protein play an important role in apoptosis induced by fractionated radiation therapy. Apoptosis induced by irradiation is contributed to upregulation of bax protein or downregulation of Bcl-2 protein.

  14. Expression and Significance of Bcl-2, Bax, Fas and Caspase-3 in Different Phases of Human Hemangioma

    Institute of Scientific and Technical Information of China (English)

    YANG Hong; DENG Chenguo; SHEN Shengguo; ZHANG Duanlian; YUYing

    2006-01-01

    The relationship between Bcl-2, Bax, Fas, caspase-3 and development of hemangioma and the molecular mechanism was investigated. By using immunohistochemical S-P method, proliferating cell nuclear antigen was detected. According to the classification of Mulliken in combination with PCNA expression, 27 cases were identified as proliferating hemangioma and 22 cases as involutive hemangioma. Five normal skin tissues around the tumor tissue served as controls. By using immunohistochemical technique, the expression of Bcl-2, Bax, Fax and Caspase-3 was detected. The cells expressing Bcl-2, Bax, Fax and cappase-3 were identified as hemangioma endothelia by immunohistochemical staining of Ⅷ factor. The average absorbance (A) and average positive area rate of Bcl-2, Bax, Fas and caspase-3 expression were measured by using HPIAS-2000 imaging analysis system. The results showed that the expression of Bcl-2 in the endothelia of proliferating hemangioma was significantly higher that in involutive degenerative hemangioma endothelia and vascular endothelia of normal skin tissue (P<0.01). The expression of Bax, Fas and Caspase-3 in the endothelia of involutive hemangioma was obviously higher than in the endothelia of proliferating hemangioma and normal skin tissue (P<0.01). The expression of BAx and Fas in endothelia of proliferating hemangioma was higher than in those of normal skin tissue (P<0.05). It was suggested that Bcl-2,Bax, Fas and caspase-3 might be involved in the development and involution of hemangioma. Bcl-2 could promote the growth of hemangioma by inhibiting apoptosis of endothelia. Bax, Fas and caspase-3 promote the switch of hemangioma from proliferation to involution by inducing the apoptosis of hemangioma endothelia.

  15. Bax-induced apoptosis shortens the life span of DNA repair defect Ku70-knockout mice by inducing emphysema.

    Science.gov (United States)

    Matsuyama, Shigemi; Palmer, James; Bates, Adam; Poventud-Fuentes, Izmarie; Wong, Kelvin; Ngo, Justine; Matsuyama, Mieko

    2016-06-01

    Cells with DNA damage undergo apoptosis or cellular senescence if the damage cannot be repaired. Recent studies highlight that cellular senescence plays a major role in aging. However, age-associated diseases, including emphysema and neurodegenerative disorders, are caused by apoptosis of lung alveolar epithelial cells and neurons, respectively. Therefore, enhanced apoptosis also promotes aging and shortens the life span depending on the cell type. Recently, we reported that ku70(-) (/) (-)bax(-) (/) (-) and ku70(-) (/) (-)bax(+/) (-) mice showed significantly extended life span in comparison with ku70(-) (/) (-)bax(+/+) mice. Ku70 is essential for non-homologous end joining pathway for DNA double strand break repair, and Bax plays an important role in apoptosis. Our study suggests that Bax-induced apoptosis has a significant impact on shortening the life span of ku70(-) (/) (-) mice, which are defective in one of DNA repair pathways. The lung alveolar space gradually enlarges during aging, both in mouse and human, and this age-dependent change results in the decrease of respiration capacity during aging that can lead to emphysema in more severe cases. We found that emphysema occurred in ku70(-) (/) (-) mice at the age of three-months old, and that Bax deficiency was able to suppress it. These results suggest that Bax-mediated apoptosis induces emphysema in ku70(-) (/) (-) mice. We also found that the number of cells, including bronchiolar epithelial cells and type 2 alveolar epithelial cells, shows a higher DNA double strand break damage response in ku70 KO mouse lung than in wild type. Recent studies suggest that non-homologous end joining activity decreases with increased age in mouse and rat model. Together, we hypothesize that the decline of Ku70-dependent DNA repair activity in lung alveolar epithelial cells is one of the causes of age-dependent decline of lung function resulting from excess Bax-mediated apoptosis of lung alveolar epithelial cells (and their

  16. A single nucleotide polymorphism in the Bax gene promoter affects transcription and influences retinal ganglion cell death

    Directory of Open Access Journals (Sweden)

    Sheila J Semaan

    2010-03-01

    Full Text Available Pro-apoptotic Bax is essential for RGC (retinal ganglion cell death. Gene dosage experiments in mice, yielding a single wild-type Bax allele, indicated that genetic background was able to influence the cell death phenotype. DBA/2JBax+/− mice exhibited complete resistance to nerve damage after 2 weeks (similar to Bax−/− mice, but 129B6Bax+/− mice exhibited significant cell loss (similar to wild-type mice. The different cell death phenotype was associated with the level of Bax expression, where 129B6 neurons had twice the level of endogenous Bax mRNA and protein as DBA/2J neurons. Sequence analysis of the Bax promoters between these strains revealed a single nucleotide polymorphism (T129B6 to CDBA/2J at position −515. A 1.5- to 2.5-fold increase in transcriptional activity was observed from the 129B6 promoter in transient transfection assays in a variety of cell types, including RGC5 cells derived from rat RGCs. Since this polymorphism occurred in a p53 half-site, we investigated the requirement of p53 for the differential transcriptional activity. Differential transcriptional activity from either 129B6 or DBA/2J Bax promoters were unaffected in p53−/− cells, and addition of exogenous p53 had no further effect on this difference, thus a role for p53 was excluded. Competitive electrophoretic mobility-shift assays identified two DNA–protein complexes that interacted with the polymorphic region. Those forming Complex 1 bound with higher affinity to the 129B6 polymorphic site, suggesting that these proteins probably comprised a transcriptional activator complex. These studies implicated quantitative expression of the Bax gene as playing a possible role in neuronal susceptibility to damaging stimuli.

  17. Associations of MMP-2, BAX, and Bcl-2 mRNA and Protein Expressions with Development of Atrial Fibrillation.

    Science.gov (United States)

    Diao, Shu-Ling; Xu, Hui-Pu; Zhang, Bei; Ma, Bao-Xin; Liu, Xian-Liang

    2016-01-01

    BACKGROUND To examine changes of mRNA and protein expressions of MMP-2, Bcl-2, and BAX in atrial fibrillation (AF) patients, and investigate the correlations among these 3 biomarkers. MATERIAL AND METHODS Rheumatic heart disease patients (n=158) undergoing cardiac surgical procedures for mitral valve repair or replacement were included as the AF group (n=123), containing paroxysmal AF (n=42), persistent AF (n=36), and permanent AF (n=45). Rheumatic heart disease patients with sinus rhythm (SR) (n=35) were enrolled as the SR group (control group). Immunohistochemistry, Western blot, and real-time polymerase chain reaction (PCR) were applied to detect the protein and mRNA expression levels of MMP-2, Bcl-2, and BAX. Apoptosis was observed with light and electron microscopes and detected by TdT-mediated dUTP nick-end labeling (TUNEL). RESULTS Compared with the SR group, the left atrial diameters (LADs), protein and mRNA expression levels of MMP-2 and BAX, apoptotic index (AI), and Bcl-2/BAX ratio were evidently increased in the 3 AF groups, but protein and mRNA expression levels of Bcl-2 decreased in the AF groups (all P<0.05). Correlation analysis found that MMP-2 protein expression levels was positively correlated with BAX expression, but negatively correlated with Bcl-2 expression levels. CONCLUSIONS Our study results suggest that elevated MMP-2 expression and disturbance balance of Bcl-2/BAX expressions may be associated with the development and maintenance of AF. MMP-2 may be involved in the development of AF through promoting BAX expressions and inhibiting Bcl-2. PMID:27141955

  18. Enhancing survival of mouse oocytes following chemotherapy or aging by targeting Bax and Rad51.

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    Loro L Kujjo

    Full Text Available BACKGROUND: Therapeutic approaches to preserve fertility in females undergoing cancer treatments are currently ineffective. This is partly due to limited knowledge of the molecular mechanisms that injured germ cells elicit to repair damage and survive or to abort repair and activate biochemical pathways leading to death. So far, we know that following spontaneously occurring or drug-induced DNA damage, the efficiency of DNA repair is a critical determinant of the cell's fate. The protein encoded by the Rad51 gene is one of several components recruited for homologous recombination-dependent DNA double-strand break repair in both somatic cells and germ cells. Recently, we showed that microinjection of recombinant Rad51 into AKR/J mouse oocytes decreased the extent of spontaneous DNA double-strand breaks, suppressed apoptosis, and restored the developmental competence in AKR/J embryos. Herein we characterized the nature of chemotherapy-induced lesions in oocytes, and the associated individual components of the DNA damage sensor and repair apparatus. For comparison, we also assessed parallel spontaneous changes in aging oocytes. METHODS: Data collected were derived from: analysis of apoptosis; immunodepletion; oocyte microinjections; immunocytochemistry; immunofluorescence; and CHIP-like assays. RESULTS: Our data show that: (i DNA damage in oocytes can be induced by both chemotherapy and spontaneously by the aging process; (ii oocytes possess the machinery and capability for repairing such DNA damage; (iii Rad51 is a critical player in the repair of both chemotherapy-induced and spontaneously-sustained DNA damage; and (iv in response to damage, oocytes exhibit an inverse functional relationship between presence of Bax and activity of Rad51. CONCLUSION/SIGNIFICANCE: Our results establish Rad51 and/or Bax as potential candidates that can be targeted for development of individualized chemotherapeutic interventions that are effective, but minimal in

  19. BAX and tumor suppressor TRP53 are important in regulating mutagenesis in spermatogenic cells in mice.

    Science.gov (United States)

    Xu, Guogang; Vogel, Kristine S; McMahan, C Alex; Herbert, Damon C; Walter, Christi A

    2010-12-01

    During the first wave of spermatogenesis, and in response to ionizing radiation, elevated mutant frequencies are reduced to a low level by unidentified mechanisms. Apoptosis is occurring in the same time frame that the mutant frequency declines. We examined the role of apoptosis in regulating mutant frequency during spermatogenesis. Apoptosis and mutant frequencies were determined in spermatogenic cells obtained from Bax-null or Trp53-null mice. The results showed that spermatogenic lineage apoptosis was markedly decreased in Bax-null mice and was accompanied by a significantly increased spontaneous mutant frequency in seminiferous tubule cells compared to that of wild-type mice. Apoptosis profiles in the seminiferous tubules for Trp53-null were similar to control mice. Spontaneous mutant frequencies in pachytene spermatocytes and in round spermatids from Trp53-null mice were not significantly different from those of wild-type mice. However, epididymal spermatozoa from Trp53-null mice displayed a greater spontaneous mutant frequency compared to that from wild-type mice. A greater proportion of spontaneous transversions and a greater proportion of insertions/deletions 15 days after ionizing radiation were observed in Trp53-null mice compared to wild-type mice. Base excision repair activity in mixed germ cell nuclear extracts prepared from Trp53-null mice was significantly lower than that for wild-type controls. These data indicate that BAX-mediated apoptosis plays a significant role in regulating spontaneous mutagenesis in seminiferous tubule cells obtained from neonatal mice, whereas tumor suppressor TRP53 plays a significant role in regulating spontaneous mutagenesis between postmeiotic round spermatid and epididymal spermatozoon stages of spermiogenesis. PMID:20739667

  20. Upregulation of Bax and Bcl-2 following prenatal cocaine exposure induces apoptosis in fetal rat brain

    Directory of Open Access Journals (Sweden)

    DaLiao Xiao, Lubo Zhang

    2008-01-01

    Full Text Available Cocaine abuse during pregnancy has been associated with numerous adverse perinatal outcomes. Aims: The present study was to determine whether prenatal cocaine exposure induced apoptosis and the possible role of Bcl-2 family genes in the programming cell death in fetal rat brain. Main methods: Pregnant rats were treated with cocaine subcutaneously (30 & 60 mg/kg/day from day 15 to 21 of gestation. Then the fetal and maternal brains were isolated. Key findings: Cocaine produced a dose-dependent decrease in fetal brain weight and brain/body weight ratio (P<0.05. Apoptotic nuclei in fetal brain were increased from 2.6 ± 0.1 (control to 8.1± 0.6 (low dose and 10.4 ± 0.2% (high dose (P<0.05. In accordance, cocaine dose dependently increased activities of caspase-3, caspase-8, and caspase-9 (% of control in the fetal brain by 177%, 155%, 174%, respectively, at 30 mg/kg/day, and by 191%, 176%, 274%, respectively, at 60 mg/kg/day. In contrast, cocaine showed no effect on caspase activities in the maternal brain. Cocaine produced a dose-dependent increase in both Bcl-2 and Bax protein expression in the fetal brain, and increased the ratio of Bax/Bcl-2 at dose of 30 mg/kg/day (P<0.05. Significance: Our study has demonstrated that prenatal cocaine exposure induces apoptosis in the fetal brain, and suggested that up-regulating Bax/Bcl-2 gene expression may be involved in cocaine-induced apoptosis. The increased apoptosis of neuronal cells in the fetal brain is likely to play a key role in cocaine-induced neuronal defects during fetal development.

  1. Expression of Ki-67, Bcl-2 and Bax in the First Trimester Abortion Materials

    Directory of Open Access Journals (Sweden)

    Ender DÜZCAN

    2010-01-01

    Full Text Available Objective: The aim of this study was to investigate possible similar or different mechanisms in recurrent and spontaneous abortion by evaluating immunohistochemical correlation between proliferation marker Ki-67, and apoptosis markers Bcl-2 and Bax in the fetal trophoblasts and maternal deciduas from abortion material.Material and Method: Eighty samples of curettage materials from 65 abortion patients histopathologically diagnosed “decidua showing Arias-Stella reaction and chorionic villi” or only “decidua showing Arias-Stella reaction” were included in the study. Hematoxylin&Eosin stained sections from all cases were re-evaluated and further stained immunohistochemically using antibodies against Ki-67, Bcl-2 and Bax.Results: Proliferation rate evaluated by Ki-67 expression both in the cytotrophoblastic cells and decidua was found to be significantly lower in spontaneous and recurrent abortions compared to evacuation abortion. The extent of Bcl-2 expression in syncytiotrophoblastic cells covering villous stroma was also decreased in spontaneous abortion. There were no significant differences between spontaneous and recurrent abortions in terms of Bcl-2 expression in syncytiotrophoblasts and Ki-67 proliferation index in cytotrophoblastic cells or decidua. Bax staining showed minimal decidual expression in a few spontaneous and recurrent abortions.Conclusion: We concluded that proliferation rate was decreased in fetal villous cytotrophoblasts and maternal deciduas in spontaneous and recurrent abortions. We also proposed that loss of Bcl-2 expression in syncytiotrophoblasts may cause abortion in a subset of cases. However, the data from spontaneous and recurrent abortions did not not support the presence of different mechanisms in both groups.

  2. Proteomic Profiling of Differentially Expressed Proteins from Bax inhibitor-1 Knockout and Wild Type Mice

    OpenAIRE

    Li, Bo; John C Reed; Kim, Hyung-Ryong; Chae, Han-Jung

    2012-01-01

    Bax inhibitor-1 (BI-1) is an anti-apoptotic protein located in the endoplasmic reticulum (ER). The role of BI-1 has been studied in different physiopathological models including ischemia, diabetes, liver regeneration and cancer. However, fundamental knowledge about the effects of BI-1 deletion on the proteome is lacking. To further explore this protein, we compared the levels of different proteins in bi-1−/− and bi-1+/+ mouse tissues by two-dimensional electrophoresis (2-DE) and mass spectrom...

  3. NFAT2 mediates high glucose-induced glomerular podocyte apoptosis through increased Bax expression

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ruizhao, E-mail: liruizhao1979@126.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Zhang, Li, E-mail: Zhanglichangde@163.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Southern Medical University, Guangzhou, Guangdong (China); Shi, Wei, E-mail: shiwei.gd@139.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Zhang, Bin, E-mail: zhangbinyes@yahoo.com.cn [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Liang, Xinling, E-mail: xinlingliang@yahoo.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Liu, Shuangxin, E-mail: mplsxi@yahoo.com.cn [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China); Wang, Wenjian, E-mail: wwjph@yahoo.com [Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan No. 2 Road, Guangzhou, 510080 (China)

    2013-04-15

    Background: Hyperglycemia promotes podocyte apoptosis and plays a key role in the pathogenesis of diabetic nephropathy. However, the mechanisms that mediate hyperglycemia-induced podocyte apoptosis is still far from being fully understood. Recent studies reported that high glucose activate nuclear factor of activated T cells (NFAT) in vascular smooth muscle or pancreatic β-cells. Here, we sought to determine if hyperglycemia activates NFAT2 in cultured podocyte and whether this leads to podocyte apoptosis. Meanwhile, we also further explore the mechanisms of NFAT2 activation and NFAT2 mediates high glucose-induced podocyte apoptosis. Methods: Immortalized mouse podocytes were cultured in media containing normal glucose (NG), or high glucose (HG) or HG plus cyclosporine A (a pharmacological inhibitor of calcinerin) or 11R-VIVIT (a special inhibitor of NFAT2). The activation of NFAT2 in podocytes was detected by western blotting and immunofluorescence assay. The role of NFAT2 in hyperglycemia-induced podocyte apoptosis was further evaluated by observing the inhibition of NFAT2 activation by 11R-VIVIT using flow cytometer. Intracellular Ca{sup 2+} was monitored in HG-treated podcocytes using Fluo-3/AM. The mRNA and protein expression of apoptosis gene Bax were measured by real time-qPCR and western blotting. Results: HG stimulation activated NFAT2 in a time- and dose-dependent manner in cultured podocytes. Pretreatment with cyclosporine A (500 nM) or 11R-VIVIT (100 nM) completely blocked NFAT2 nuclear accumulation. Meanwhile, the apoptosis effects induced by HG were also abrogated by concomitant treatment with 11R-VIVIT in cultured podocytes. We further found that HG also increased [Ca{sup 2+}]i, leading to activation of calcineurin, and subsequent increased nuclear accumulation of NFAT2 and Bax expression in cultured podocytes. Conclusion: Our results identify a new finding that HG-induced podocyte apoptosis is mediated by calcineurin/NFAT2/Bax signaling pathway

  4. Temporal Alterations in Cellular Bax:Bcl-2 Ratio following Traumatic Brain Injury in the Rat

    OpenAIRE

    Raghupathi, Ramesh; Strauss, Kenneth I.; Zhang, Chen; Krajewski, Stanislaw; Reed, John C.; McIntosh, Tracy K.

    2003-01-01

    Cell death/survival following CNS injury may be a result of alterations in the intracellular ratio of death and survival factors. Using immunohistochemistry, Western analysis and in situ hybridization, the expression of the anti-cell death protein, Bcl-2, and the pro-cell death protein, Bax, was evaluated following lateral fluid-percussion (FP) brain injury of moderate severity (2.3–2.6 atm) in adult male Sprague-Dawley rats. By 2 h post-injury, a marked reduction of cellular Bcl-2-immunoreac...

  5. Effects of Chronic Mild Stress in Female Bax Inhibitor-1-Gene Knockout Mice

    OpenAIRE

    Sui, Zhi-Yan; Chae, Han-Jung; Huang, Guang-Biao; Zhao, Tong; Shrestha Muna, Sushma; Chung, Young-Chul

    2012-01-01

    Objective The anti-apoptotic protein Bax inhibitor-1 (BI-1) is a regulator of apoptosis linked to endoplasmic reticulum (ER) stress, and BI-1-/- mice exhibit increased sensitivity to tissue damage. The purpose of this study was to investigate the role of BI-1 in the pathogenesis of chronic mild stress (CMS)-induced depression-like behaviors in BI-1-/- mice. Methods We delivered CMS for 2 or 6 weeks in BI-1-knockout and wild-type mice. Control groups of BI-1-knockout and wild-type mice were le...

  6. Effect of Flunarizine on the Expression of Bax mRNA in Hippocampus of Amygdala Kindling Seizures Rat%氟桂利嗪对杏仁核点燃鼠海马Bax mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    梁代义; 伍国锋; 董佑忠; 庞成

    2005-01-01

    目的:观察氟桂利嗪对杏仁核点燃鼠癎性发作及海马促凋亡基因Bax mRNA表达的影响.方法:建立杏仁核点燃模型,予不同剂量氟桂利嗪灌喂点燃鼠.原位杂交法检测鼠脑海马Bax mRNA表达,图像分析软件测量阳性细胞平均吸光度.结果:正常大鼠海马存在少量Bax mRNA表达阳性细胞,点燃鼠海马各区Bax mRNA表达阳性细胞数及平均吸光度增加,氟桂利嗪处理后平均吸光度下降与剂量有关.结论:氟桂利嗪具有抗癫癎效应和拮抗点燃鼠海马Bax mRNA表达的作用.

  7. NOXA-induced alterations in the Bax/Smac axis enhance sensitivity of ovarian cancer cells to cisplatin.

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    Chao Lin

    Full Text Available Ovarian cancer is the most common cause of death from gynecologic malignancy. Deregulation of p53 and/or p73-associated apoptotic pathways contribute to the platinum-based resistance in ovarian cancer. NOXA, a pro-apoptotic BH3-only protein, is identified as a transcription target of p53 and/or p73. In this study, we found that genetic variants of Bcl-2 proteins exist among cisplatin-sensitive and -resistant ovarian cancer cells, and the responses of NOXA and Bax to cisplatin are regulated mainly by p53. We further evaluated the effect of NOXA on cisplatin. NOXA induced apoptosis and sensitized A2780s and SKOV3 cells to cisplatin in vitro and in vivo. The effects were mediated by elevated Bax expression, enhanced caspase activation, release of Cyt C and Smac into the cytosol. Furthermore, gene silencing of Bax or Smac significantly attenuated NOXA and/or cisplatin-induced apoptosis in chemosensitive A2780s cells, whereas overexpression of Bax or addition of Smac-N7 peptide significantly increased NOXA and/or cisplatin-induced apoptosis in chemoresistant SKOV3 cells. To our knowledge, these data suggest a new mechanism by which NOXA chemosensitized ovarian cancer cells to cisplatin by inducing alterations in the Bax/Smac axis. Taken together, our findings show that NOXA is potentially useful as a chemosensitizer in ovarian cancer therapy.

  8. Killing of Brain Tumor Cells by Hypoxia-Responsive Element Mediated Expression of BAX

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    Hangjun Ruan

    1999-11-01

    Full Text Available The presence of radioresistant hypoxic cells in human brain tumors limits the overall effectiveness of conventional fractionated radiation therapy. Tumor-specific therapies that target hypoxic cells are clearly needed. We have investigated the expression of suicide genes under hypoxia by a hypoxia-responsive element (HRE, which can be activated through hypoxia-inducible factor-1 (HIF-1. We transfected plasmids containing multiple copies of HIRE into U-87 MG and U-251 MG-NCI human brain tumor cells and tested their ability to induce LacZ gene expression under anoxia. Gene expression under anoxia versus oxia was increased about 12-fold for U-87 MG cells and about fourfold for U-251 MG-NCI cells. At intermediate hypoxic conditions, increased LacZ gene expression in U-87 MG cells was induced by the plasmid that contained three HREs, but not by the plasmid with two HREs. Lastly, when we placed a suicide gene BAX under the control of HREs, cells transfected with the BAX plasmids were preferentially killed through apoptosis under anoxia. Our studies demonstrate that HRE-regulated gene expression is active in brain tumor cells, and that the amount of increased gene expression obtained is dependent on the cell line, the HIRE copy number, and the degree of hypoxia.

  9. PUMA promotes Bax translocation in FOXO3a-dependent pathway during STS-induced apoptosis

    Science.gov (United States)

    Zhang, Yingjie; Chen, Qun

    2009-08-01

    PUMA (p53 up-regulated modulator of apoptosis, also called Bbc3) was first identified as a BH3-only Bcl-2 family protein that is transcriptionally up-regulated by p53 and activated upon p53-dependent apoptotic stimuli, such as treatment with DNA-damaging drugs or UV irradiation. Recently studies have been shown that Puma is also up-regulated in response to certain p53-independent apoptotic stimuli, such as growth factor deprivation or treatment with glucocorticoids or STS (staurosporine). However, the molecular mechanisms of PUMA up-regulation and how PUMA functions in response to p53-independent apoptotic stimuli remain poorly understood. In this study, based on real-time single cell analysis, flow cytometry and western blotting technique, we investigated the function of PUMA in living human lung adenocarcinoma cells (ASTC-a-1) after STS treatment. Our results show that FOXO3a was activated by STS stimulation and then translocated from cytosol to nucleus. The expression of PUMA was up-regulated via a FOXO3a-dependent manner after STS treatment, while p53 had little function in this process. Moreover, cell apoptosis and Bax translocation induced by STS were not blocked by Pifithrin-α (p53 inhibitor), which suggested that p53 was not involved in this signaling pathway. Taken together, these results indicate that PUMA promoted Bax translocation in a FOXO3a-dependment pathway during STS-induced apoptosis, while p53 was dispensable in this process.

  10. HIV-1 Vpr-induced apoptosis is cell cycle dependent and requires Bax but not ANT.

    Directory of Open Access Journals (Sweden)

    Joshua L Andersen

    2006-12-01

    Full Text Available The HIV-1 accessory protein viral protein R (Vpr causes G2 arrest and apoptosis in infected cells. We previously identified the DNA damage-signaling protein ATR as the cellular factor that mediates Vpr-induced G2 arrest and apoptosis. Here, we examine the mechanism of induction of apoptosis by Vpr and how it relates to induction of G2 arrest. We find that entry into G2 is a requirement for Vpr to induce apoptosis. We investigated the role of the mitochondrial permeability transition pore by knockdown of its essential component, the adenine nucleotide translocator. We found that Vpr-induced apoptosis was unaffected by knockdown of ANT. Instead, apoptosis is triggered through a different mitochondrial pore protein, Bax. In support of the idea that checkpoint activation and apoptosis induction are functionally linked, we show that Bax activation by Vpr was ablated when ATR or GADD45alpha was knocked down. Certain mutants of Vpr, such as R77Q and I74A, identified in long-term nonprogressors, have been proposed to inefficiently induce apoptosis while activating the G2 checkpoint in a normal manner. We tested the in vitro phenotypes of these mutants and found that their abilities to induce apoptosis and G2 arrest are indistinguishable from those of HIV-1NL4-3 vpr, providing additional support to the idea that G2 arrest and apoptosis induction are mechanistically linked.

  11. CO-EXPRESSIONS OF SURVIVIN GENE,BCL-2 AND BAX PROTEINS IN OVARIAN CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    林蓓; 张淑兰; 赵长清

    2004-01-01

    Objective To characterize the cellular properties of ovarian cancer, we examined the correlation between the expression of apoptosis-related gene survivin and those of Bcl-2 and Bar proteins. Methods Expressions of survivin mRNA, and Bcl-2 and Bax proteins in 35 cases of ovarian carcinoma, 10 cases of borderline carcinoma, 10 cases of benign tumors and 10 cases of normal tissue were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry SABC method, respectively. Results Expression of survivin gene was detected in a significantly greater proportion in ovarian carcinoma and borderline carcinoma than those in benign tumors and normal tissues. Although there was no relationship between expression of survivin gene and FIGO stage, histologic grade, pathological type and lymphatic metastasis, expressions of Bcl-2 and Bar proteins were positively and negatively correlated with that of survivin gene, respectively. Conclusion Survivin may play an important role in pathogenesis of ovarian carcinoma, with a synergistic role of apoptosis-related gene Bcl-2protein and an antagonistic role of Bax protein in formation and progression of ovarian carcinoma.

  12. Effects of curcumin on hippocampal Bax and Bcl-2 expression and cognitive function of a rat model of Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Yunliang Wang; Honglei Yin; Jiyu Lou; Bing Han; Xinyue Qin; Fanchao Meng; Shuang Geng; Yajun Liu

    2011-01-01

    We tested the effects of curcumin treatment on a rat model of Alzheimer's disease induced by beta-amlyoid (Aβ1-40) expression. We investigated alterations in the expression of the apoptosis-related genes Bax and Bcl-2 in the hippocampus, as well as changes in the spatial memory and cognitive function of the rats. Reverse transcription-polymerase chain reaction and immunohistochemistry results showed that Bax expression was remarkably decreased and Bcl-2 expression was increased in the rat Alzheimer's disease model after curcumin treatment. Morris water maze results showed that the average time of escape latency was shortened in the curcumin treated model rats. Our study shows that curcumin can significantly improve spatial learning and memory functions in rats with Aβ1-40-induced Alzheimer's disease by modulating Bax and Bcl-2 expression.

  13. Exhaustive Training Increases Uncoupling Protein 2 Expression and Decreases Bcl-2/Bax Ratio in Rat Skeletal Muscle

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    W. Y. Liu

    2013-01-01

    Full Text Available This work investigates the effects of oxidative stress due to exhaustive training on uncoupling protein 2 (UCP2 and Bcl-2/Bax in rat skeletal muscles. A total of 18 Sprague-Dawley female rats were randomly divided into three groups: the control group (CON, the trained control group (TC, and the exhaustive trained group (ET. Malondialdehyde (MDA, superoxide dismutase (SOD, xanthine oxidase (XOD, ATPase, UCP2, and Bcl-2/Bax ratio in red gastrocnemius muscles were measured. Exhaustive training induced ROS increase in red gastrocnemius muscles, which led to a decrease in the cell antiapoptotic ability (Bcl-2/Bax ratio. An increase in UCP2 expression can reduce ROS production and affect mitochondrial energy production. Thus, oxidative stress plays a significant role in overtraining.

  14. BAX and BAK1 are dispensable for ABT-737-induced dissociation of the BCL2-BECN1 complex and autophagy.

    Science.gov (United States)

    Pedro, Jose Manuel Bravo-San; Wei, Yongjie; Sica, Valentina; Maiuri, Maria Chiara; Zou, Zhongju; Kroemer, Guido; Levine, Beth

    2015-01-01

    Disruption of the complex of BECN1 with BCL2 or BCL2L1/BCL-XL is an essential switch that turns on cellular autophagy in response to environmental stress or treatment with BH3 peptidomimetics. Recently, it has been proposed that BCL2 and BCL2L1/BCL-XL may inhibit autophagy indirectly through a mechanism dependent on the proapoptotic BCL2 family members, BAX and BAK1. Here we report that the BH3 mimetic, ABT-737, induces autophagy in parallel with disruption of BCL2-BECN1 binding in 2 different apoptosis-deficient cell types lacking BAX and BAK1, namely in mouse embryonic fibroblasts cells and in human colon cancer HCT116 cells. We conclude that the BH3 mimetic ABT-737 induces autophagy through a BAX and BAK1-independent mechanism that likely involves disruption of BECN1 binding to antiapoptotic BCL2 family members.

  15. Effects of genistein on neuronal apoptosis, and expression of Bcl-2 and Bax proteins in the hippocampus of ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    Yun Peng; Bo Jiang; Huiling Wu; Ruchun Dai; Liming Tan

    2012-01-01

    Genistein is one of several isoflavones that has a structure similar to 17β-estradiol, has a strong antioxidant effect, and a high affinity to estrogen receptors. At 15 weeks after ovariectomy, the expression of Bcl-2 in the hippocampus of rats decreased and Bax expression increased, with an obvious upregulation of apoptosis. However, intraperitoneal injection of genistein or 17β-estradiol for 15 consecutive weeks from the second day after operation upregulated Bcl-2 protein expression, downregulated Bax protein expression, and attenuated hippocampal neuron apoptosis. Our experimental findings indicate that long-term intervention with genistein can lead to a decrease in apoptosis in hippocampal neurons following ovariectomy, upregulate the expression of Bcl-2, and downregulate the expression of Bax. In addition, genistein and 17β-estradiol play equal anti-apoptotic and neuroprotective roles.

  16. The bcl-2, bax gene expression and apoptosis of continuous low-dose-rate irradiation on PC-3 transplanting tumor

    International Nuclear Information System (INIS)

    Objective: The aim of this study was to investigate bcl-2, bax expression and apoptosis of continuous low-dose-rate irradiation on prostate cancer (PC)-3 transplanting tumor. Methods: The expression of bcl-2 and bax associated with apoptosis between experiment and control groups were analyzed using immunohistochemistry at 48, 96 and 192 h after two 125I seed sources implanting model. The correlation between apoptosis and the ratio of bax/bcl-2 was analyzed using Bi-variable linear correlation. SPSS 11.0 was used to analyse the data. Results: The bcl-2 expression in experiment group began to down-regulated significantly after 125I seed irradiation for 48 h as compared with control(t=2.500, P=0.067), though it was not reached to statistical significance. At 96 and 192 h after irradiation, significantly low expression of bcl- 2 were noted (t=4.950, 3.464; P=0.008 and 0.026). In contrast, significantly over expression of bax was noted at 48, 96 and 192 h after 12si irradiation (t=3.334,4.025,5.292;P=0.029, 0.016 and 0.006). The apoptotic index (AI) for PC-3 at 48, 96 and 192 h after 125I irradiation were 22.3%, 21.7% and 30.7%, which was significantly higher than controls when at 96 and 192 h after 125I irradiation (P= 0.016 and 0.036). Moreover, positive correlation was noted between AI and bax/bcl-2 ratio (r=0.784, P= 0.012). Conclusion: Low-dose-rate irradiation could down-regulate the expression of bcl-2, up-regulate the expression of bax and induced PC-3 cells apoptosis. (authors)

  17. Recombinant factor IX (BAX326) in previously treated paediatric patients with haemophilia B: a prospective clinical trial.

    Science.gov (United States)

    Urasinski, T; Stasyshyn, O; Andreeva, T; Rusen, L; Perina, F G; Oh, M S; Chapman, M; Pavlova, B G; Valenta-Singer, B; Abbuehl, B E

    2015-03-01

    A newly developed recombinant factor IX (BAX326(1) ) was investigated for prophylactic use in paediatric patients aged 96% of bleeds (100% of minor, 88.9% of moderate and 100% of major bleeds); the majority (88.5%) resolved after 1-2 infusions. Longer T1/2 and lower IR were observed in younger children (<6 years) compared to those aged 6 to 12 years. BAX326 administered as prophylactic treatment as well as for controlling bleeds is efficacious and safe in paediatric patients aged <12 years with haemophilia B. PMID:25495591

  18. Attenuation of p53 expression and Bax down-regulation during phorbol ester mediated inhibition of apoptosis

    OpenAIRE

    Meßmer, Udo K; Brüne, Bernhard

    1997-01-01

    Nitric oxide (NO) caused apoptotic cell death in murine RAW 264.7 macrophages. Associated with apoptotic morphology we observed p53 up-regulation and increased Bax expression. 12-O-tetradecanoylphorbol-13-acetate (TPA), a protein kinase C (PKC) activator potently blocked NO-induced apoptosis. To gain insights into the mechanisms involved we investigated the effect of TPA on apoptotic conveying proteins such as p53 and Bax.TPA (100 nM) attentuated p53 up-regulation elicited by the NO-releasing...

  19. E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation

    International Nuclear Information System (INIS)

    PUMA is a pro-apoptotic Bcl-2 family member that has been shown to be involved in apoptosis in many cell types. We sought to ascertain whether induction of PUMA plays a crucial role in E2F-1-induced apoptosis in melanoma cells. PUMA gene and protein expression levels were detected by real-time PCR and Western blot in SK-MEL-2 and HCT116 cell lines after Ad-E2F-1 infection. Activation of the PUMA promoter by E2F-1 overexpression was detected by dual luciferase reporter assay. E2F-1-induced Bax translocation was shown by immunocytochemistry. The induction of caspase-9 activity was measured by caspase-9 colorimetric assay kit. Up-regulation of the PUMA gene and protein by E2F-1 overexpression was detected by real-time PCR and Western blot analysis in the SK-MEL-2 melanoma cell line. In support of this finding, we found six putative E2F-1 binding sites within the PUMA promoter. Subsequent dual luciferase reporter assay showed that E2F-1 expression could increase the PUMA gene promoter activity 9.3 fold in SK-MEL-2 cells. The role of PUMA in E2F-1-induced apoptosis was further investigated in a PUMA knockout cell line. Cell viability assay showed that the HCT116 PUMA-/- cell line was more resistant to Ad-E2F-1-mediated cell death than the HCT116 PUMA+/+ cell line. Moreover, a 2.2-fold induction of the PUMA promoter was also noted in the HCT116 PUMA+/+ colon cancer cell line after Ad-E2F-1 infection. Overexpression of a truncated E2F-1 protein that lacks the transactivation domain failed to up-regulate PUMA promoter, suggesting that PUMA may be a transcriptional target of E2F-1. E2F-1-induced cancer cell apoptosis was accompanied by Bax translocation from the cytosol to mitochondria and the induction of caspase-9 activity, suggesting that E2F-1-induced apoptosis is mediated by PUMA through the cytochrome C/Apaf-1-dependent pathway. Our studies strongly demonstrated that E2F-1 induces melanoma cell apoptosis via PUMA up-regulation and Bax translocation. The signaling

  20. Comparison of automated BAX polymerase chain reaction and standard culture methods for detection of Listeria monocyogenes in blue crab meat (Callinectus sapidus) and blue crab processing plants

    Science.gov (United States)

    This study compared the BAX Polymerase Chain Reaction method (BAX PCR) with the Standard Culture Method (SCM) for detection of L. monocytogenes in blue crab meat and crab processing plants. The aim of this study was to address this data gap. Raw crabs, finished products and environmental sponge samp...

  1. Laquinimod decreases Bax expression and reduces caspase-6 activation in neurons.

    Science.gov (United States)

    Ehrnhoefer, Dagmar E; Caron, Nicholas S; Deng, Yu; Qiu, Xiaofan; Tsang, Michelle; Hayden, Michael R

    2016-09-01

    Laquinimod is an immunomodulatory compound that has shown neuroprotective benefits in clinical trials for multiple sclerosis. Laquinimod ameliorates both white and gray matter damage in human patients, and prevents axonal degeneration in animal models of multiple sclerosis. Axonal damage and white matter loss are a common feature shared between different neurodegenerative diseases. Caspase-6 activation plays an important role in axonal degeneration on the molecular level. Increased activity of caspase-6 has been demonstrated in brain tissue from presymptomatic Huntington disease mutation carriers, and it is an early marker of axonal dysfunction. Since laquinimod is currently undergoing a clinical trial in Huntington disease (LEGATO-HD, clinicaltrials.gov ID: NCT02215616), we set out to evaluate its impact on neuronal caspase-6 activation. We find that laquinimod ameliorates DNA-damage induced activation of caspase-6 in primary neuronal cultures. This is an indirect effect that is not mediated by direct inhibition of the enzyme. The investigation of potential caspase-6 activating mechanisms revealed that laquinimod reduces the expression of Bax, a pro-apoptotic molecule that causes mitochondrial cytochrome c release and caspase activation. Bax expression is furthermore increased in striatal tissues from the YAC128 mouse model of HD in an age-dependent manner. Our results demonstrate that laquinimod can directly downregulate neuronal apoptosis pathways relevant for axonal degeneration in addition to its known effects on astrocytes and microglia in the CNS. It targets a pathway that is relevant for the pathogenesis of HD, supporting the hypothesis that laquinimod may provide clinical benefit. PMID:27296315

  2. Effect of Exercise Training on Bcl-2 and Bax Gene Expression in the Rat Heart

    Directory of Open Access Journals (Sweden)

    Jafari

    2015-10-01

    Full Text Available Background Apoptosis or programmed cell death plays an important role in the development of cardiovascular diseases, particularly heart failure. Current evidence suggests that exercise training may alter apoptosis-related signaling in sensitive somatic tissues such as the myocardium. Objectives The aim of this study was to assess the effect of exercise training on Bcl-2 and Bax genes expression as key molecules involved in intrinsic pathway of apoptosis in the rat heart. Materials and Methods This study was conducted with a two-group experimental design (animal model and sixteen three-month-old male rats were selected and randomly divided to two groups of exercise training (n = 8 and control (n = 8. Rats in the trained group participated in an exercise training program for 12 weeks (10 – 60 m min-1, 24 – 33 min d-1, 15%. The rat hearts were removed forty-eight hours after the last training session. RNA extraction and synthesis of cDNA was done, and Bax and Bcl2 genes expression was analyzed through the Real Time-Polymerase Chain Reaction (RT-PCR. Kolmogorov-Smirnov and independent t-test were applied for statistical analysis of the data (P 0.05. However, Bcl2 expression was higher in the trained group compared to the control group (11%. Conclusions In general, it seems that three-month exercise training was effective in reducing cardiac mitochondrial pro-apoptotic protein. However, considering the results of the Bcl2 gene expression, more researches are needed to identify effects of exercise trainings on indices of myocardial apoptosis.

  3. EXPRESSION OF BAX AND BCL-2 IN MOUSE OFFSPRING BRAIN AFTER MATERNAL ORAL ADMINIS TRATION OF MONOSODIUM GLUTAMATE

    Institute of Scientific and Technical Information of China (English)

    徐磊; 赵晏; 展淑琴; 王会生; 史文春

    2002-01-01

    Objective To analyze the excitotoxicity of monoso dium glutamate (MSG) in the offspring cerebral cortex and hippocampal subregions after maternal oral administration of MSG. Methods Kunming mi ce were given per os MSG ( 4.0 g/kg ) at 17~21 days of pregnancy and their offs pring behaviors were studied at 10, 20 , 30 days postnatally. By using immunohis tochemical means, the involvement of Bcl-2 and Bax in the glutamate-induced c ell death in cortical and hippocampal neur ons were examined. Cell damage was assessed by direct cell counting. Res ults Administration of monosodium glutamate during the fetal period in mice resulted in a moderate increase in the expression of Bax in principal neuro ns in CA1, CA2, CA3, CA4 and in the cerebral cortex at postpartum 10, 20, 30 day s in the offspring mice, whereas Bcl-2 protein expressions were reduced signif icantly in the same regions as compared with those of controls. Conclusi on These findings suggest that glutamate toxicity results in cellular d eath via an apoptotic mechanism in which the Bcl-2/Bax-alpha molecular comple x may be involved. The glutamate-induced apoptosis appears to be related to the modulation of Bcl-2 family gene products such as Bcl-2 and Bax.

  4. EXPRESSION OF BAX AND BCL-2 IN MOUSE OFFSPRING BRAIN AFIER MATERNAL ORAL ADMINISTRATION OF MONOSODIUM GLUTAMATE

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective:To analyze the excitotoxicity of monosodium glutamate(MSG)in the offspring crebral cortex and hippocampal subresions after maternal oral administration of MSG.Methods:Kunming mice were given per os MSG(4.0g/kg)at 17-21 days of pregnancy and their offspring behaviors were studied at 10,20,30days postnatally.By using inmunohistochemical means,the involvment of Bcl-2 and bax in the glutamate-induced cell death in cortical and hippocampal neurons were examined.Cell damage was assessed by direct cell counting.Results:administration of monosodium glutamate during the fetal period in mice resulted in a moderate increase in the expression of Bax in principal neurons in CA1,CA2,CA3,CA4 and in the cerebral cortex at postpartum 10,20,30 days in the offspring mice,whereas Bcl-2 protein expressions were reduced significantly in the same regions as compared with those of controls.Conclusion:These findings suggest that glutamate toxicity results in cellular death via an apoptotic mechanism in which the Bcl-2/Bax-alpha molecular complex may be involved.The glutamate-induced apoptosis appears to be related to the modulation of Bcl-2 family gene products such as Bcl-2 and Bax.

  5. Relationship between expression of Bax and Bcl-2 proteins and apoptosis in radiation compound wound healing of rats

    Institute of Scientific and Technical Information of China (English)

    崔玉芳; 夏国伟; 付小兵; 杨红; 彭瑞云; 张莹; 谷庆阳; 高亚兵; 崔雪梅; 胡文华

    2003-01-01

    Objective: To study the relationship between the expression of Bax, Bcl-2 proteins, and apoptosis in radiation compound wound healing of rats.Methods: Apoptosis, Bax and Bcl-2 proteins were estimated by in situ terminal labeling (TUNEL) and immunohistochemical methods. Results: (1) Changes of the apoptosis in wound healing showed three typical characteristics: early occurrence, high frequency and delayed disappearance after radiation to rats when compared with those of simple wound group, which might be an important reason for radiation-induced delayed wound healing. (2) The expression of Bax protein increased evidently with the increment of apoptosis and showed a good corresponding relationship with the apoptotic frequency in the process of wound healing. While the expression of Bcl-2 protein decreased obviously as the apoptosis reached a maximum and showed increasing tendency up to normal level when the apoptosis decreased distinctively. Conclusions: Bax and Bcl-2 proteins play an important role in the apoptotic regulation of radiation compound wound healing in rats.

  6. Apoptosis and Bax expression are increased by coal dust in the polycyclic aromatic hydrocarbon-exposed lung

    Energy Technology Data Exchange (ETDEWEB)

    Ghanem, M.M.; Battelli, L.A.; Mercer, R.R.; Scabilloni, J.F.; Kashon, M.L.; Ma, J.Y.C.; Nath, J.; Hubbs, A.F.

    2006-09-15

    Miners inhaling respirable coal dust (CD) frequently develop coal workers' pneumoconiosis. Many coal miners are also exposed to polycyclic aromatic hydrocarbon (PAH) components of diesel engine exhaust and cigarette smoke, which may contribute to lung disease in these workers. Recently, apoptosis was reported to play a critical role in the development of another pneumoconiosis of miners, silicosis. In addition, CID was reported to suppress cytochrome P450 1A1 (CYP1A1) induction by PAHs. We exposed rats intratracheally to 0.0, 2.5, 10.0, 20.0, or 40.0 mg/rat CD and, 11 days later, to intraperitoneal P-naphthoflavone (BNF), a PAH. In another group of rats exposed to CD and BNF, caspase activity was inhibited by injection of the pan-caspase inhibitor Q-VD-OPH (quinoline-Val-Asp (OMe)-CH{sub 2}-OPH). In rats exposed to BNF, CD exposure increased alveolar expression of the proapoptotic mediator Bax but decreased CYP1A1 induction relative to BNF exposure alone. Pan-caspase inhibition decreased CD-associated Bax expression and apoptosis but did not restore CYP1A1 activity. Further, CD-induced lung inflammation and alveolar epithelial cell hypertrophy and hyperplasia were not suppressed by caspase inhibition. It is concluded that combined BNF and CD exposure increased Bax expression and apoptosis in the lung, but Bax and apoptosis were not the major determinants of early lung injury in this model.

  7. Immunohistochemical study of epidermal and dermal expression of Bcl-X, Bcl-2 and bax in psoriasis.

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To investigate the regulation of cell proliferation and apoptosis in psoriasis. Methods: The expressions of Bcl-X, Bcl-2 and Bax were studied with immunohistochemical technique (SP) in the lesional and non-lesional psoriatic skin. Results: There were significant overexpressions of Bcl-X in all layers of epidermis, inflammatory cells and vascular endothelia in dermis;

  8. EGR-1 forms a complex with YAP-1 and upregulates Bax expression in irradiated prostate carcinoma cells.

    Science.gov (United States)

    Zagurovskaya, M; Shareef, M M; Das, A; Reeves, A; Gupta, S; Sudol, M; Bedford, M T; Prichard, J; Mohiuddin, M; Ahmed, M M

    2009-02-26

    In this study, we investigated the functional role of early growth response-1 (Egr1 gene) in the regulation of radiation-induced clonogenic inhibition and apoptosis in p53 wild-type and mutant prostate cancer cells 22Rv1 and DU145, respectively. 22Rv1 cells were more sensitive to irradiation compared with DU145 cells, and the sensitivity was enhanced by overexpression of EGR-1 in both cells. Dominant-negative EGR-1 mutant (dnEGR-1) or repressor of EGR-1, NGFIA binding protein 1 (NAB1), increased radioresistance of these cells. Significant activation of caspases 3 and 9 and Bcl2-associated X (Bax) with increased poly(ADP-ribose) polymerase (PARP) cleavage and cytochrome c release was observed in radiation-exposed EGR-1 overexpressing cells. Gel shift analysis and chloramphenicol acetyl transferase (CAT) reporter assays indicate that EGR-1 transactivates the promoter of the Bax gene. Interaction of EGR-1 and Yes kinase-associated protein 1 (YAP-1) through the WW domain of YAP-1 enhances the transcriptional activity of EGR-1 on the Bax promoter as shown by chromatin immunoprecipitation and reporter assays. Irradiation of PC3 cell xenografts that were treated with adenoviral EGR-1 showed significant regression in tumor volume. These findings establish the radiation-induced pro-apoptotic action of EGR-1, in a p53-independent manner, by directly transactivating Bax, and prove that alters the B-cell CLL/lymphoma 2 (Bcl-2)/Bax ratio as one of the mechanisms resulting in significant activation of caspases, leading to cell death through the novel interaction of EGR-1 with YAP-1. PMID:19137013

  9. Experession of Bax in Lung Cancer Cell Apoptosis Induced by Peroxisome Proliferator-activated Receptor-γ Anoists

    Institute of Scientific and Technical Information of China (English)

    ZAHNGMin; BAIMing; 等

    2002-01-01

    Objective:To discuss the relationship between Bax expression level and lung cancer cell apoptosis induced by peroxisome proliferator-activated receptor-γ(PPAR-γ) agonists.Methods:RT-PCR and Western blot analyis were used to detect PPAR-γ expression in the lung cancer cells,and TUNEL was used to detect apoptosis induced by PPAR-γ agnoists,while in situ hybridization and immunohistochemistry were used to monitor the changes of Bax mRNA and protein expression levels after apoptosis induced.Results PPAR-γ expression was detectable in two kinds lung cancer cells (including Non-small cell lung cancer and small cell lung cancer) ,and PPAR-γ agonists could inhibit lung cancer growth through inducing apoptosis.The apoptostic rates in control group,15d-PGJ2 group and cilitazone group were (1.86±0.49)%,(25.8±2.9)±,and (17.3±1.9)%,(P<0.01)respectively;Bax mRNA expression rates in the three groups were (8.75± 1.36)%,(66.2±12.86)%,and(29.5±6.5)%(P<0.01)respectively;Bax protein expression rates in the three groups were(9.2±1.45)%,(63±10.4)%,and (34.5±6.0)%(P<0.05) respectively.Conclusion PPAR-y is predicted to be a new targes in treating lung cancer in the future,and Bax is most likely to work in treating lung cancer apoptosis induced by PPAR-y agnoists as a factor to induce apoptosis.

  10. Erythropoietin can promote survival of cerebral cells by downregulating Bax gene after traumatic brain injury in rats

    Directory of Open Access Journals (Sweden)

    Liao Z

    2009-01-01

    Full Text Available Background : Traumatic brain injury (TBI is an important cause of adult mortality and morbidity. Erythropoietin (Epo has been shown to promote the viability of cerebral cells by upregulating Bcl-2 gene; however, Epo may exert its antiapoptotic effect via the differential regulation of the expression of genes involved in the apoptotic process. Aim : The present study examined the neuroprotective effect of Epo as a survival factor through the regulation of the Bax. Materials and Methods : Wistar rats were randomly divided into three groups: Recombinant human EPO treated (rhEPO TBI, vehicle-treated TBI, and sham-operated. Traumatic brain injury was induced by the Feeney free-falling model. Rats were killed 5, 12, 24, 72, 120, or 168 h after TBI. Regulation of Bcl-2 was detected by reverse transcription-polymerase chain reaction (RT-PCR, western blotting and immunofluorescence. Results : Bax mRNA and protein levels were lower in the rhEPO-treated rat brains than in the vehicle-treated rat brains. Induction of Bax expression peaked at 24 h and remained stable for 72-120 h in vehicle-treated rat brains, whereas induction of Bax expression was only slightly elevated in rhEPO-treated rat brains. The number of TdT-mediated dUTP Nick-End Labeling(TUNEL-positive cells in the rhEPO-treated rat brains was far fewer than in the vehicle-treated rat brains. Conclusions : Epo exerts neuroprotective effect against traumatic brain injury via reducing Bax gene expression involved in inhibiting TBI-induced neuronal cell death.

  11. Boron neutron capture therapy induces apoptosis of glioma cells through Bcl-2/Bax

    Directory of Open Access Journals (Sweden)

    Mao Xinggang

    2010-12-01

    Full Text Available Abstract Background Boron neutron capture therapy (BNCT is an alternative treatment modality for patients with glioma. The aim of this study was to determine whether induction of apoptosis contributes to the main therapeutic efficacy of BNCT and to compare the relative biological effect (RBE of BNCT, γ-ray and reactor neutron irradiation. Methods The neutron beam was obtained from the Xi'an Pulsed Reactor (XAPR and γ-rays were obtained from [60Co] γ source of the Fourth Military Medical University (FMMU in China. Human glioma cells (the U87, U251, and SHG44 cell lines were irradiated by neutron beams at the XAPR or [60Co] γ-rays at the FMMU with different protocols: Group A included control nonirradiated cells; Group B included cells treated with 4 Gy of [60Co] γ-rays; Group C included cells treated with 8 Gy of [60Co] γ-rays; Group D included cells treated with 4 Gy BPA (p-borono-phenylalanine-BNCT; Group E included cells treated with 8 Gy BPA-BNCT; Group F included cells irradiated in the reactor for the same treatment period as used for Group D; Group G included cells irradiated in the reactor for the same treatment period as used for Group E; Group H included cells irradiated with 4 Gy in the reactor; and Group I included cells irradiated with 8 Gy in the reactor. Cell survival was determined using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium (MTT cytotoxicity assay. The morphology of cells was detected by Hoechst33342 staining and transmission electron microscope (TEM. The apoptosis rate was detected by flow cytometer (FCM. The level of Bcl-2 and Bax protein was measured by western blot analysis. Results Proliferation of U87, U251, and SHG44 cells was much more strongly inhibited by BPA-BNCT than by irradiation with [60Co] γ-rays (P 60Co] γ-rays (P P Conclusions Compared with ��-ray and reactor neutron irradiation, a higher RBE can be achieved upon treatment of glioma cells with BNCT. Glioma cell apoptosis induced by

  12. Effect of Achyranthes bidentata polysaccharides on the expression of BCL-2 and bax in hepatic tissues after exhaustive exercise in rats.

    Science.gov (United States)

    Lin, Jinyang; Zhang, Zhuoying; Shan, Ying

    2010-01-01

    This study aims to assess the effects of Achyranthes bidentata polysaccharides (ABPS) on the expression of bcl-2 and bax in hepatic tissues after exhaustive exercise in order to provide theoretical support for the application of ABPS in the field of sports nutrition. Thirty male Sprague-Dawley rats were randomized into three groups, each consisting of 10 rats: Normal control group (NCG), Exhausting exercises control group (EECG), ABPS treated group (ATG). ABPS were fed orally by gastric intubation to rats of ABPS treated group (ATG) once daily for 7 days. Control animals (EECG and NCG) received the same amount of isotonic sodium chloride solution. Exhaustive exercise was performed on a rodent treadmill. The SP (streptavidin peroxidase) method for immunohistochemical staining was adopted to test the protein expression of bax and bcl-2 in the hepatic tissues of the rats. Exhausting exercises increased bax protein expression of hepatic tissues of rats and bax/bcl-2 ratio dramatically, but a decreased bcl-2 protein expression. In the rats fed ABPS orally by gastric intubation, the bax protein expression and bax/bcl-2 ratio obviously decreased, while bcl-2 protein expression increased. The result indicated that bax and bcl-2 co-regulated the exercise-induced hepatocyte apoptosis. Feeding ABPS orally by gastric intubation to rats can inhibit the hepatocyte apoptosis in exhaustive exercise. PMID:21731162

  13. BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized α helix of BCL2) not always convinces BAX (BCL-2-associated X protein) for apoptosis.

    Science.gov (United States)

    Verma, Sharad; Goyal, Sukriti; Tyagi, Chetna; Jamal, Salma; Singh, Aditi; Grover, Abhinav

    2016-06-01

    The interaction of BAX (BCL-2-associated X protein) with BIM (BCL-2 interacting mediator of cell death) SAHB (stabilized α helix of BCL2) directly initiates BAX-mediated mitochondrial apoptosis. This molecular dynamics study reveals that BIM SAHB forms a stable complex with BAX but it remains in a non-functional conformation. N terminal of BAX folds towards the core which has been reported exposed in the functional monomer. The α1-α2 loop, which has been reported in open conformation in functional BAX, acquires a closed conformation during the simulation. BH3/α2 remains less exposed as compared to initial structure. The hydrophobic residues of BIM accommodates in the rear pocket of BAX during the simulation. A steep decrease in radius of gyration and solvent accessible surface area (SASA) indicates the complex folding to acquire a more stable but inactive conformation. Further the covariance matrix reveals that the backbone atoms' motions favour the inactive conformation of the complex. This is the first report on the non-functional BAX-BIM SAHB complex by molecular dynamics simulation in the best of our knowledge. PMID:27262527

  14. Titanium dioxide induces apoptotic cell death through reactive oxygen species-mediated Fas upregulation and Bax activation

    Directory of Open Access Journals (Sweden)

    Yoon TH

    2012-03-01

    Full Text Available Ki-Chun Yoo1, Chang-Hwan Yoon1, Dongwook Kwon2, Kyung-Hwan Hyun1, Soo Jung Woo1, Rae-Kwon Kim1, Eun-Jung Lim1, Yongjoon Suh1, Min-Jung Kim1, Tae Hyun Yoon2, Su-Jae Lee11Laboratory of Molecular Biochemistry, 2Laboratory of Nanoscale Characterization and Environmental Chemistry, Department of Chemistry, Hanyang University, Seoul, Republic of KoreaBackground: Titanium dioxide (TiO2 has been widely used in many areas, including biomedicine, cosmetics, and environmental engineering. Recently, it has become evident that some TiO2 particles have a considerable cytotoxic effect in normal human cells. However, the molecular basis for the cytotoxicity of TiO2 has yet to be defined.Methods and results: In this study, we demonstrated that combined treatment with TiO2 nanoparticles sized less than 100 nm and ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-dependent upregulation of Fas and conformational activation of Bax in normal human cells. Treatment with P25 TiO2 nanoparticles with a hydrodynamic size distribution centered around 70 nm (TiO2P25–70 together with ultraviolet A irradiation-induced caspase-dependent apoptotic cell death, accompanied by transcriptional upregulation of the death receptor, Fas, and conformational activation of Bax. In line with these results, knockdown of either Fas or Bax with specific siRNA significantly inhibited TiO2-induced apoptotic cell death. Moreover, inhibition of reactive oxygen species with an antioxidant, N-acetyl-L-cysteine, clearly suppressed upregulation of Fas, conformational activation of Bax, and subsequent apoptotic cell death in response to combination treatment using TiO2P25–70 and ultraviolet A irradiation.Conclusion: These results indicate that sub-100 nm sized TiO2 treatment under ultraviolet A irradiation induces apoptotic cell death through reactive oxygen species-mediated upregulation of the death receptor, Fas, and activation of the preapoptotic protein

  15. Effects of erythropoietin on the expression of tumor necrosis factor-alpha and Bax after facial nerve axotomy in rats

    Institute of Scientific and Technical Information of China (English)

    Wei Zhang; Shengyu Lü; Ziying Yu; Ming Bi; Bin Sun

    2011-01-01

    This study sought to evaluate the effect of high-dose erythropoietin (EPO; 5 000 IU/kg) on the expression of tumor necrosis factor-alpha (TNF-α) and Bax in the facial nucleus after facial nerve transection in rats. A total of 42 Wistar rats of both genders were used in this study, and 40 rats were randomly divided into 2 groups: EPO group and model group. The EPO group was treated with EPO once a day for 5 days at a dose of 5 000 IU/kg body weight. The model group was treated with saline of the same amount. At day 3 after EPO (or saline) treatment, the right facial nerves of the 40 rats were transected at the level of the stylomastoid foramen, with the left sides untreated. The remaining 2 rats that did not undergo axotomy served as the control group. The surviving motor neurons in operated rats were counted in coronal paraffin sections of the facial nucleus. The expression of TNF-α and Bax in the facial nucleus was detected by immunohistochemical staining at days 3, 7, 14, 21, and 28 after axotomy. At days 14, 21, and 28 after facial nerve axotomy, a significantly greater proportion of facial motor neurons survived in the EPO group than in the model group. After axotomy, the expression of TNF-α and Bax increased in motor neurons in both the EPO and the model groups. TNF-α expression reached its peak level at day 14 after axotomy, while Bax expression reached its peak level at day 21. TNF-α expression was much lower in the EPO group than in the model group at all time points. No significant difference in Bax expression was found between the EPO and the model groups. These results indicate that high-dose EPO treatment attenuates the increase in TNF-α expression in the facial nucleus and reduces the loss of motor neurons after facial nerve transection in rats. However, high-dose EPO treatment has little effect on Bax expression.

  16. Bcl-2 and bax expression and prostate cancer outcome in men treated with radiotherapy in Radiation Therapy Oncology Group protocol 86-10

    International Nuclear Information System (INIS)

    Purpose: Bcl-2 and bax are proteins with opposing roles in apoptosis regulation; yet abnormal expression of either has been associated with failure after radiotherapy (RT). In this study we examined bcl-2 and bax expression as predictive markers in men treated with radiotherapy ± androgen deprivation on Radiation Therapy Oncology Group (RTOG) protocol 86-10. Experimental Design: Suitable archival diagnostic tissue was obtained from 119 (26%) patients for bcl-2 analysis and 104 (23%) patients for bax analysis. Cox proportional hazards multivariate analysis was used to determine the relationship of abnormal bcl-2 and bax expression to the end points of local failure, distant metastasis, cause-specific mortality, and overall mortality. Bcl-2 overexpression was classified as any tumor cell cytoplasmic staining and altered bax expression was classified as greater or lesser cytoplasmic staining intensity of tumor cells as compared with adjacent normal prostate epithelium. Results: The study cohort exhibited bcl-2 overexpression in 26% (n = 30) of cases and abnormal bax expression in 47% (n = 49) of cases. A borderline significant relationship was observed between abnormal bax expression and higher Gleason score (p = 0.08). In univariate and multivariate analyses, there was no statistically significant relationship seen between abnormal bcl-2 or bax expression and outcome. Conclusions: Abnormal bcl-2 and bax expression were not related to any of the end points tested. The cohort examined was comprised of patients with locally advanced disease and it is possible that these markers may be of greater value in men with earlier-stage prostate cancer

  17. Direct proof of static charge stripe correlations in La2-xBaxCuO4

    Science.gov (United States)

    Chen, X. M.; Thampy, V.; Mazzoli, C.; Barbour, A.; Gu, G.; Hill, J. P.; Tranquada, J. M.; Dean, M. P. M.; Wilkins, S. B.

    The nature of charge stripe order in the cuprates, and in particular whether the stripes are static or dynamic, is a key issue in understanding the relationship between stripes and superconductivity. In La2-xBaxCuO4 (LBCO) a low temperature structural distortion is widely believed to pin stripes into fixed, static domains, but such an assertion has never been directly verified. We performed resonant soft x-ray photon correlation spectroscopy (XPCS) to probe the charge order Bragg peak of 1/8 doped LBCO. At low temperatures, we observe time-independent x-ray speckle patterns persisting for more than three hours, proving the static nature of the stripes and we go on to discuss how stripe order melts with increasing temperature. Our results demonstrate that the combination of XPCS with diffraction limited light sources such as the National Synchrotron Light Source II can probe the dynamics of even subtle order parameters such as stripes in the cuprates. Work performed at Brookhaven National Laboratory was supported by the US Department of Energy, Division of Materials Science, under Contract No. DE-AC02-98CH10886. Use of the National Synchrotron Light Source II was supported under Contract No. DE-SC0012704.

  18. Infrared Spectra of La0.65BaxMnO3-δ Oxides

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The infrared spectra of La0.65BaxMnO3-d (x = 0.35, 0.33 and 0.30) were investigated experimentally. The result shows that the sample La0.65Ba0.33MnO3-d has the largest Curie temperature and the smallest resistivity and wave number of the stretching vibration mode of MnO6 octahedron at 300 K among the investigated samples. However, the absorption strength for the stretching vibration mode of MnO6 octahedron in La0.65Ba0.35MnO3-d is stronger for paramagnetic phase than that for ferromagnetic phase, which may be connected with the reducing of the dynamic incoherent Jahn-Teller distortion below Curie temperature. In addition, the large shift of wave number for the stretching mode at the temperatures from 293 to 423 K has been observed in La0.65Ba0.35MnO3-d, which may be due to the increase of the Mn-O bond length with temperature increasing.

  19. Expression of Arabidopsis Bax Inhibitor-1 in transgenic sugarcane confers drought tolerance.

    Science.gov (United States)

    Ramiro, Daniel Alves; Melotto-Passarin, Danila Montewka; Barbosa, Mariana de Almeida; Santos, Flavio Dos; Gomez, Sergio Gregorio Perez; Massola Júnior, Nelson Sidnei; Lam, Eric; Carrer, Helaine

    2016-09-01

    The sustainability of global crop production is critically dependent on improving tolerance of crop plants to various types of environmental stress. Thus, identification of genes that confer stress tolerance in crops has become a top priority especially in view of expected changes in global climatic patterns. Drought stress is one of the abiotic stresses that can result in dramatic loss of crop productivity. In this work, we show that transgenic expression of a highly conserved cell death suppressor, Bax Inhibitor-1 from Arabidopsis thaliana (AtBI-1), can confer increased tolerance of sugarcane plants to long-term (>20 days) water stress conditions. This robust trait is correlated with an increased tolerance of the transgenic sugarcane plants, especially in the roots, to induction of endoplasmic reticulum (ER) stress by the protein glycosylation inhibitor tunicamycin. Our findings suggest that suppression of ER stress in C4 grasses, which include important crops such as sorghum and maize, can be an effective means of conferring improved tolerance to long-term water deficit. This result could potentially lead to improved resilience and yield of major crops in the world. PMID:26872943

  20. Human ribosomal protein L9 is a Bax suppressor that promotes cell survival in yeast.

    Science.gov (United States)

    Eid, Rawan; Sheibani, Sara; Gharib, Nada; Lapointe, Jason F; Horowitz, Avital; Vali, Hojatollah; Mandato, Craig A; Greenwood, Michael T

    2014-05-01

    The identification of a human ribosomal protein L9 (hRPL9) cDNA as a sequence capable of suppressing the lethal effects of heterologously expressed murine Bax in yeast led us to investigate its antiapoptotic potential. Using growth and viability assays, we show that yeast cells heterologously expressing hRPL9 are resistant to the growth inhibitory and lethal effects of exogenously supplied copper, indicating that it has pro-survival properties. To explore potential mechanisms, we used yeast mutants defective in all three types of programmed cell death (apoptosis, necrosis, and autophagy). The ability to retain pro-survival function in all the mutants suggests that hRPL9 may regulate a common pro-death process. In contrast, the yeast RPL9 orthologues, RPL9A and RPL9B, have opposite effects when overexpressed in yeast. In effect, instead of showing resistance to stress, RPL9A and RPL9B overexpressing cells show reduced cell growth. Further analysis indicates that the effects of overexpressed RPL9A and RPL9B are not in themselves lethal, instead, they serve to increase cell doubling time. Thus, yeast RPL9s are more representative of RPs whose extra-ribosomal function is similar to that of tumor suppressors. Taken together, our results demonstrate that RPL9 represents a species- and sequence-specific regulator of cell growth and survival. PMID:24305165

  1. Interaction between Hsp60 and Bax in normal human myocardium and in myocardium affected by dilated cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Tykhonkova I. O.

    2009-04-01

    Full Text Available The main functional compartments of molecular chaperone Hsp60 are mitochondria and cytoplasm. Up to 30 % of Hsp60 are located in cytoplasm of cardiomyocytes. The interaction between molecular chaperone Hsp60 and proapoptotic Bax protein in the cytoplasmic fraction from normal human heart tissue has been revealed by co-immunoprecipitation in contrast to myocardium affected by dilated cardiomyopathy, where this interaction has not been observed

  2. BAX and Tumor Suppressor TRP53 Are Important in Regulating Mutagenesis in Spermatogenic Cells in Mice1

    OpenAIRE

    Xu, Guogang; Vogel, Kristine S.; McMahan, C. Alex; Herbert, Damon C.; Walter, Christi A.

    2010-01-01

    During the first wave of spermatogenesis, and in response to ionizing radiation, elevated mutant frequencies are reduced to a low level by unidentified mechanisms. Apoptosis is occurring in the same time frame that the mutant frequency declines. We examined the role of apoptosis in regulating mutant frequency during spermatogenesis. Apoptosis and mutant frequencies were determined in spermatogenic cells obtained from Bax-null or Trp53-null mice. The results showed that spermatogenic lineage a...

  3. The effect of octreotide and bromocriptine on expression of a pro-apoptotic Bax protein in rat prolactinoma.

    Directory of Open Access Journals (Sweden)

    Jolanta Kunert-Radek

    2004-03-01

    Full Text Available It is well established that disruption of apoptosis may lead to tumor initiation, progression or metastasis. It is also well documented that many anticancer drugs induce apoptosis. In the earlier studies, the dopamine D2 receptor agonist bromocriptine (BC and somatostatin analog octreotide (OCT were found to inhibit the growth of the estrogen-induced rat prolactinoma. Our previous investigations, applying the TUNEL method showed the involvement of the pro-apoptotic effect in the action of BC, and to a lesser degree, in the action of OCT. The aim of the present study was to investigate whether the pro-apoptotic action of these drugs involves the increased expression of Bax--a member of Bcl-2 protein family which is known to play an important role in the regulation of apoptosis. Male four-week Fisher 344 rats were used in the experiment. Capsules containing diethylstilboestrol (DES were implanted subcutaneously. Six weeks after the implantation the rats were given OCT (2 x 25 microg/animal/24, BC (3 mg/kg b.w./24 h or OCT and BC at the above doses for 10 days. Bax expression was detected by immunohistochemistry. Prolactin (PRL in blood serum was measured by radioimmunoassay (RIA. It has been found that both OCT and BC, alone or in combination, significantly reduce the tumor weight. Both OCT and BC suppressed PRL levels, but the inhibitory effect of BC was stronger than that of OCT. It has been found that the treatment with OCT and BC, alone or in combination, causes a significant increase in Bax expression in the rat prolactinoma cells. Our findings indicate that anti-tumoral action of bromocriptine and to some extent the action of octreotide in the experimental rat prolactinoma is connected with the induction of apoptosis and is associated with increased Bax expression.

  4. Evaluation of Bax and Bcl-2 Proteins Expression in the Rat Hippocampus due to Childhood Febrile Seizure

    OpenAIRE

    SAEEDI BORUJENI, Mohammad Javad; Hami, Javad; Haghir, Hossein; Rastin, Maryam; Sazegar, Ghasem

    2016-01-01

    Objective Simple Febrile Seizure (SFS) is the most common seizure disorder in childhood, and is frequently described as inoffensive disorder. Nevertheless, there is evidence suggesting the association between neonatal febrile seizures and hippocampal abnormalities in adulthood. This study was conducted at evaluating the hippocampal expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins following SFS induction in rat neonates. Materials & Methods Febrile seizure was modeled by hyper...

  5. Melatonin restores normal Bax and Bcl-2 protein expression in the subgranular zone of the dentate gyrus in pinealectomized rats

    Institute of Scientific and Technical Information of China (English)

    Shengchang Zhang; Shuang Zhao; Lu Bai; Mingming Guan; Jielin Mo; Ling Lan

    2011-01-01

    In this study, we sought to elucidate the effects of melatonin on learning and memory as well as apoptosis and expression of the Bax or Bcl-2 proteins in the subgranular zone of the dentate gyrus in pinealectomized rats. Using the Morris water maze and the olfactory memory tests, we found that the average escape latency in pinealectomized rats was clearly increased compared with sham-operated rats. Moreover, the average escape latency in the melatonin-treated and pinealectomized rats was longer than that in the sham-operated rats and shorter than that in the pinealectomized and untreated rats. Immunohistochemistry and terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) showed that there were fewer Bax immunoreactive cells and TUNEL-positive (apoptotic) cells but more Bcl-2 immunoreactive cells in the melatonin-treated rats compared with the pinealectomized rats. The sham-operated rats showed numbers of these cells similar to the melatonin-treated rats. These experimental findings demonstrate that melatonin treatment may reduce abnormal apoptosis by promoting gene expression of Bax and suppressing gene expression of Bcl-2 in the subgranular zone of the dentate gyrus in pinealectomized rats. These effects appear to result in the inhibition of cellular apoptosis and the improvement of spatial learning and memory in pinealectomized rats.

  6. Schiff Base Metal Derivatives Enhance the Expression of HSP70 and Suppress BAX Proteins in Prevention of Acute Gastric Lesion

    Directory of Open Access Journals (Sweden)

    Shahram Golbabapour

    2013-01-01

    Full Text Available Schiff base complexes have appeared to be promising in the treatment of different diseases and disorders and have drawn a lot of attention to their biological activities. This study was conducted to evaluate the regulatory effect of Schiff base metal derivatives on the expression of heat shock proteins (HSP 70 and BAX in protection against acute haemorrhagic gastric ulcer in rats. Rats were assigned to 6 groups of 6 rats: the normal control (Tween 20 5% v/v, 5 mL/kg, the positive control (Tween 20 5% v/v, 5 mL/kg, and four Schiff base derivative groups named Schiff_1, Schiff_2, Schiff_3, and Schiff_4 (25 mg/kg. After 1 h, all of the groups received ethanol 95% (5 mL/kg but the normal control received Tween 20 (Tween 20 5% v/v, 5 mL/kg. The animals were euthanized after 60 min and the stomachs were dissected for histology (H&E, immunohistochemistry, and western blot analysis against HSP70 and BAX proteins. The results showed that the Schiff base metal derivatives enhanced the expression of HSP70 and suppressed the expression of BAX proteins during their gastroprotection against ethanol-induced gastric lesion in rats.

  7. Emodin inhibits LOVO colorectal cancer cell proliferation via the regulation of the Bcl-2/Bax ratio and cytochrome c.

    Science.gov (United States)

    Ma, Liang; Li, Wusheng

    2014-10-01

    In this study, the effect of emodin and its mechanism of action were investigated in LOVO colorectal cancer cells. Cell growth was determined using a Cell Counting kit-8 assay, and the results demonstrated that emodin significantly inhibited the growth of LOVO cells in a concentration-dependent manner. In order to investigate the anticancer mechanism of emodin, reverse transcription polymerase chain reaction assays were performed to determine the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax) expression ratio in LOVO colorectal cancer cells following treatment with emodin. The results showed that emodin induced a significant increase in the Bax expression level and a marked reduction of the Bcl-2 expression level in LOVO cells. In addition, emodin was found to have an inhibitory effect on the mitochondrial membrane potential and the results from the western blot analysis revealed that cytochrome c was released from the mitochondria to the cytoplasm. In combination, these results suggest that emodin inhibits cancer cell growth via the regulation of the Bcl-2/Bax ratio and by its effect on the mitochondrial apoptosis pathway.

  8. Melatonin promotes Bax sequestration to mitochondria reducing cell susceptibility to apoptosis via the lipoxygenase metabolite 5-hydroxyeicosatetraenoic acid

    KAUST Repository

    Radogna, Flavia

    2015-03-01

    Extra-neurological functions of melatonin include control of the immune system and modulation of apoptosis. We previously showed that melatonin inhibits the intrinsic apoptotic pathway in leukocytes via stimulation of high affinity MT1/MT2 receptors, thereby promoting re-localization of the anti-apoptotic Bcl-2 protein to mitochondria. Here we show that Bcl-2 sequesters pro-apoptotic Bax into mitochondria in an inactive form after melatonin treatment, thus reducing cell propensity to apoptosis. Bax translocation and the anti-apoptotic effect of melatonin are strictly dependent on the presence of Bcl-2, and on the 5-lipoxygenase (5-LOX) metabolite 5-hydroxyeicosatetraenoic acid (5-HETE), which we have previously shown to be produced as a consequence of melatonin binding to its low affinity target calmodulin. Therefore, the anti-apoptotic effect of melatonin requires the simultaneous, independent interaction with high (MT1/MT2) and low (calmodulin) affinity targets, eliciting two independent signal transduction pathways converging into Bax sequestration and inactivation. MT1/MT2 vs. lipoxygenase pathways are activated by 10-9 vs. 10-5M melatonin, respectively; the anti-apoptotic effect of melatonin is achieved at 10-5M, but drops to 10-9M upon addition of exogenous 5-HETE, revealing that lipoxygenase activation is the rate-limiting pathway. Therefore, in areas of inflammation with increased 5-HETE levels, physiological nanomolar concentrations of melatonin may suffice to maintain leukocyte viability.

  9. Preparation and Photocatalytic Properties of Sr2−xBaxTa3O10−yNz Nanosheets

    Directory of Open Access Journals (Sweden)

    Tatsumi Ishihara

    2013-01-01

    Full Text Available Sr2−xBaxTa3O10−yNz (x = 0.0, 0.5, 1.0 nanosheets were prepared by exfoliating layered perovskite compounds (CsSr2−xBaxTa3O10−yNz. The Sr1.5Ba0.5Ta3O9.7N0.2 nanosheet showed the highest photocatalytic activity for H2 production from the water/methanol system among the Sr2−xBaxTa3O9.7N0.2 nanosheets prepared. In addition, Rh-loaded Sr1.5Ba0.5Ta3O9.6N0.3 nanosheet showed the photocatalytic activity for oxygen and hydrogen production from water. The ratio of hydrogen to oxygen evolved was around two. These results indicate that the Rh-loaded Sr1.5Ba0.5Ta3O9.6N0.3 nanosheet is a potential catalyst for photocatalytic water splitting.

  10. Effects of fluoride on liver apoptosis and Bcl-2, Bax protein expression in freshwater teleost, Cyprinus carpio.

    Science.gov (United States)

    Cao, Jinling; Chen, Jianjie; Wang, Jundong; Jia, Ruhui; Xue, Wenjuan; Luo, Yongju; Gan, Xi

    2013-05-01

    Fish take up fluoride directly from water and are the target organisms for fluoride pollution in the aquatic ecosystems. This study was conducted to evaluate oxidative stress, histopathological changes, apoptosis and Bcl-2, Bax expression in the livers of the common carp (Cyprinus carpio) chronically exposed to fluoride. Our results showed that after 90 d of exposure, the inhibition of SOD, GSH activities and a dose-dependent stimulation of MDA levels in the liver tissues indicated that fluoride caused oxidative stress in the fish. Microscopic examinations showed that damages to the liver tissues and cell organelles in the liver tissues increased with exposure concentration. A positive correlation was observed between the apoptosis index and fluoride levels in the livers (r=0.995). There was a negative correlation between the fluoride concentration of water and the expression of Bcl-2, Bcl-2/Bax (r=-0.98, r=-0.96). A positive correlation was showed between the fluoride concentration of water and the expression of Bax (r=0.96) after 90 d of exposure. Our results suggested that the common carp could tolerate relatively high levels of fluoride but adverse effects of fluoride occurred in the livers of the fish after 90 d of exposure. The apoptosis of liver cells had an important causative role in the process of fluoride-induced pathological changes of liver. PMID:23415306

  11. p53's mitochondrial translocation and MOMP action is independent of Puma and Bax and severely disrupts mitochondrial membrane integrity

    Institute of Scientific and Technical Information of China (English)

    Sonja Wolff; Susan Erster; Gustavo Palacios; Ute M Moll

    2008-01-01

    p53's apoptotic program consists of transcription-dependent and transcription-independent pathways. In the latter, physical interactions between mitochondrial p53 and anti-and pro-apoptotic members of the Bcl2 family of mitochondrial permeability regulators are central. Using isogenic cell systems with defined deficiencies, we characterize in detail how mitochondrial p53 contributes to mitochondrial permeabilization, to what extent its action depends on other key Bcl2 family members and define its release activity. We show that mitochondrial p53 is highly efficient in inducing the release of soluble and insoluble apoptogenic factors by severely disrupting outer and inner mitochondrial membrane integrity. This action is associated with wild-type p53-induced oligomerization of Bax, Bak and VDAC and the formation of a stress-induced endogenous complex between p53 and cyclophilin D, normally located at the inner membrane. Tumor-derived p53 mutants are deficient in activating the Bax/Bak lipid pore. These actions are independent of Puma and Bax. Importantly, the latter distinguishes the mitochondrial from the cytosolic p53 death pathway.

  12. Exogenous phosphatidylethanolamine induces apoptosis of human hepatoma HepG2 cells via the bcl-2/bax pathway

    Institute of Scientific and Technical Information of China (English)

    Yu Yao; Chen Huang; Zong-Fang Li; Ai-Ying Wang; Li-Ying Liu; Xiao-Ge Zhao; Yu Luo; Lei Ni; Wang-Gang Zhang; Tu-Sheng Song

    2009-01-01

    AIM: To investigate the signaling pathways implicated in phosphatidylethanolamine (PE)-induced apoptosis of human hepatoma HepG2 cells. METHODS: Inhibitory effects of PE on human hepatoma HepG2 cells were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle, apoptosis and mitochondrial transmembrane potential (ΔΨm) were analyzed by flow cytometry. Immunocytochemical assay and Western blotting were used to examine Bcl-2, Bax and caspase-3 protein levels in HepG2 cells treated with PE. RESULTS: PE inhibited the growth of HepG2 cells in a dose- and time- dependent manner. It did not affect the cell cycle, but induced apoptosis. PE significantly decreased ΔΨm at 0.25, 0.5 and 1 mmol/L, respectively, suggesting that PE induces cell apoptosis by decreasing the mitochondrial transmembrane potential. The Bcl-2 expression level induced by different concentrations of PE was lower than that in control groups. However, the Bax expression level induced by PE was higher than that in the control group. Meanwhile, PE increased the caspase-3 expression in a dose- and time-dependent manner. CONCLUSION: Exogenous PE induces apoptosis of human hepatoma HepG2 cells via the bcl-2/bax pathway.

  13. Virosecurinine induces apoptosis by affecting Bcl-2 and Bax expression in human colon cancer SW480 cells.

    Science.gov (United States)

    Chen, Chuan-Rong; Xia, Yong-Hui; Yao, Shu-Yan; Zhang, Qing; Wang, Ying; Ji, Zhao-Ning

    2012-04-01

    Virosecurinine, the major alkaloid isolated from Securinega suffruticosa Pall Rehd was found to exhibit growth inhibition and cytotoxicity against huaman colon cancer SW480 cells via the microculture tetrazolium (MTT) assay. Due to its greater cytotoxic potency and selectivity towards SW480 cells, flow cytometry was used to analyze the cell cycle distribution of control and treated SW480 cells whereas Annexin V-FITC/PI flow cytometry analysis was carried out to confirm apoptosis induced by virosecurinine in SW480 cells. Apoptotic regulatory genes were determined by RT-PCR analysis. Virosecurinine was found to induce G1/S cell cycle arrest which led to predominantly apoptotic mode of cell death. Mechanistically, virosecurinine was found to up-regulated the Bax gene expression and down-regulated the Bcl-2 expression in SW480, The ratio of Bcl-2 to Bax was significantly decreased. Hence, we suggest that virosecurinine induced apoptosis in SW480 cells by affecting the expression of bcl-2 and bax. PMID:22570942

  14. Bak compensated for Bax in p53-null cells to release cytochrome c for the initiation of mitochondrial signaling during Withanolide D-induced apoptosis.

    Directory of Open Access Journals (Sweden)

    Susmita Mondal

    Full Text Available The goal of cancer chemotherapy to induce multi-directional apoptosis as targeting a single pathway is unable to decrease all the downstream effect arises from crosstalk. Present study reports that Withanolide D (WithaD, a steroidal lactone isolated from Withania somnifera, induced cellular apoptosis in which mitochondria and p53 were intricately involved. In MOLT-3 and HCT116p53+/+ cells, WithaD induced crosstalk between intrinsic and extrinsic signaling through Bid, whereas in K562 and HCT116p53-/- cells, only intrinsic pathway was activated where Bid remain unaltered. WithaD showed pronounced activation of p53 in cancer cells. Moreover, lowered apoptogenic effect of HCT116p53-/- over HCT116p53+/+ established a strong correlation between WithaD-mediated apoptosis and p53. WithaD induced Bax and Bak upregulation in HCT116p53+/+, whereas increase only Bak expression in HCT116p53-/- cells, which was coordinated with augmented p53 expression. p53 inhibition substantially reduced Bax level and failed to inhibit Bak upregulation in HCT116p53+/+ cells confirming p53-dependent Bax and p53-independent Bak activation. Additionally, in HCT116p53+/+ cells, combined loss of Bax and Bak (HCT116Bax-Bak- reduced WithaD-induced apoptosis and completely blocked cytochrome c release whereas single loss of Bax or Bak (HCT116Bax-Bak+/HCT116Bax+Bak- was only marginally effective after WithaD treatment. In HCT116p53-/- cells, though Bax translocation to mitochondria was abrogated, Bak oligomerization helped the cells to release cytochrome c even before the disruption of mitochondrial membrane potential. WithaD also showed in vitro growth-inhibitory activity against an array of p53 wild type and null cancer cells and K562 xenograft in vivo. Taken together, WithaD elicited apoptosis in malignant cells through Bax/Bak dependent pathway in p53-wild type cells, whereas Bak compensated against loss of Bax in p53-null cells.

  15. Early apoptosis and cell death induced by ATX-S10Na ( Ⅱ)-mediated photodynamic therapy are Bax- and p53-dependent in human colon cancer cells

    Institute of Scientific and Technical Information of China (English)

    Makoto Mitsunaga; Akihito Tsubota; Kohichi Nariai; Yoshihisa Namiki; Makoto Sumi; Tetsuya Yoshikawa; Kiyotaka Fujise

    2007-01-01

    AIM: To investigate the roles of Bax and p53 proteins in photosensitivity of human colon cancer cells by using lysosome-localizing photosensitizer, ATX-S10Na (Ⅱ).METHODS: HCT116 human colon cancer cells and Bax-null or p53-null isogenic derivatives were irradiated with a diode laser. Early apoptosis and cell death in response to photodynamic therapy were determined by MTT assays, annexin V assays, transmission electron microscopy assays, caspase assays and western blotting.RESULTS: Induction of early apoptosis and cell death was Bax- and p53-dependent. Bax and p53 were required for caspase-dependent apoptosis. The levels of anti-apoptotic Bcl-2 family proteins, Bcl-2 and Bcl-XL,were decreased in Bax- and p53-independent manner.CONCLUSION: Our results indicate that early apoptosis and cell death of human colon cancer cells induced by photodynamic therapy with lysosome-localizingphotosensitizer ATX-S10Na (Ⅱ) are mediated by p53-Bax network and Iow levels of Bcl-2 and Bcl-XL proteins.Our results might help in formulating new therapeutic approaches in photedynamic therapy.

  16. In-house validation study of the DuPont Qualicon BAX system Q7 instrument with the BAX system PCR Assay for Salmonella (modification of AOAC Official Method 2003.09 and AOAC Research Institute Performance-Tested Method 100201).

    Science.gov (United States)

    Tice, George; Andaloro, Bridget; White, H Kirk; Bolton, Lance; Wang, Siqun; Davis, Eugene; Wallace, Morgan

    2009-01-01

    In 2006, DuPont Qualicon introduced the BAX system Q7 instrument for use with its assays. To demonstrate the equivalence of the new and old instruments, a validation study was conducted using the BAX system PCR Assay for Salmonella, AOAC Official Method 2003.09, on three food types. The foods were simultaneously analyzed with the BAX system Q7 instrument and either the U.S. Food and Drug Administration Bacteriological Analytical Manual or the U.S. Department of Agriculture-Food Safety and Inspection Service Microbiology Laboratory Guidebook reference method for detecting Salmonella. Comparable performance between the BAX system and the reference methods was observed. Of the 75 paired samples analyzed, 39 samples were positive by both the BAX system and reference methods, and 36 samples were negative by both the BAX system and reference methods, demonstrating 100% correlation. Inclusivity and exclusivity for the BAX system Q7 instrument were also established by testing 50 Salmonella strains and 20 non-Salmonella isolates. All Salmonella strains returned positive results, and all non-Salmonella isolates returned a negative response. PMID:19610394

  17. Engineering of the Curie temperature of epitaxial Sr1-xBaxTiO3 films via strain

    Science.gov (United States)

    Dai, Y.; Schubert, J.; Hollmann, E.; Mussler, G.; Wördenweber, R.

    2016-09-01

    The impact of strain on the structural and electrical properties of epitaxial Sr1-xBaxTiO3 films grown on single crystalline DyScO3 (110), TbScO3 (110), and GdScO3 (110) substrates is presented. X-ray diffraction measurements demonstrate that all films are grown epitaxially. The tensile in-plane strain is only partially compensated by a contraction of the out-of-plane lattice parameter. As a result, the volume of the unit cell of the Sr1-xBaxTiO3 film increases due to the tensile strain, and the resulting Poisson ratio of the film is ν ≈ 0.33, which is larger than but still close to the literature values of ν ≈ 0.23 for unstrained defect-free SrTiO3. The Curie temperature derived from the temperature dependence of the in-plane dielectric response leads to a strain-temperature phase diagram for the epitaxial Sr1-xBaxTiO3 films. The experimental data show a deviation from the linear dependence predicted by the Landau thermodynamic theory for large strain (>1.2%). However, using the equilibrium thermodynamic analysis, we can demonstrate that this deviation arises from the relaxation of the strain due to defect formation in the film. The result reveals that in addition to the nominal misfit strain, the defect formation strongly affects the effective strain and, thus, the dielectric response of epitaxially grown ferroelectric films.

  18. First Principles Calculations of Structural, Electronic, Thermodynamic and Thermal Properties of BaxSr1-xTe Ternary Alloys

    Science.gov (United States)

    Chelli, S.; Meradji, H.; Amara Korba, S.; Ghemid, S.; El Haj Hassan, F.

    2014-12-01

    The structural, electronic thermodynamic and thermal properties of BaxSr1-xTe ternary mixed crystals have been studied using the ab initio full-potential linearized augmented plane wave (FP-LAPW) method within density functional theory (DFT). In this approach, the Perdew-Burke-Ernzerhof-generalized gradient approximation (PBE-GGA) was used for the exchange-correlation potential. Moreover, the recently proposed modified Becke Johnson (mBJ) potential approximation, which successfully corrects the band-gap problem was also used for band structure calculations. The ground-state properties are determined for the cubic bulk materials BaTe, SrTe and their mixed crystals at various concentrations (x = 0.25, 0.5 and 0.75). The effect of composition on lattice constant, bulk modulus and band gap was analyzed. Deviation of the lattice constant from Vegard's law and the bulk modulus from linear concentration dependence (LCD) were observed for the ternary BaxSr1-xTe alloys. The microscopic origins of the gap bowing were explained by using the approach of Zunger and co-workers. On the other hand, the thermodynamic stability of these alloys was investigated by calculating the excess enthalpy of mixing, ΔHm as well as the phase diagram. It was shown that these alloys are stable at high temperature. Thermal effects on some macroscopic properties of BaxSr1-xTe alloys were investigated using the quasi-harmonic Debye model, in which the phononic effects are considered.

  19. Changes of bcl-xL and bax mRNA expression following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    骆纯; 卢亦成; 江基尧; 朱诚

    2002-01-01

    Objective: To investigate the changes of bcl-2 gene family and the molecular mechanism of neuronal apoptosis following traumatic brain injury (TBI) in rats.Methods: Male Sprague-Dawley (SD) rats were subjected to lateral fluid percussion brain injury (FPBI) of moderate severity. The bcl-xL and bax mRNA expression was detected by reverse transcription polymerase chain reaction (RT-PCR). In addition to morphological evidence of apoptosis, terminal deoxynucleotide transferase-mediated dUTP-biotin nick-end labeling (TUNEL) histochemistry was used to identify the DNA fragmentation in situ at both light and electron microscope levels, whereas characteristic internucleosomal DNA fragmentation of apoptosis was demonstrated by DNA gel electrophoresis.Results: The apoptotic response to trauma was regionally distinct and may be involved in both acute and delayed cell death. The bcl-xL mRNA expression of the impact site was significantly lower (67.42%±7.54%) than that of the ipsilateral hemisphere at 6 hours after injury (P<0.01). The decrease of bcl-xL mRNA expression preceded apoptosis at 24 hours after injury. The bax mRNA expression rose slowly, doubled at 3 days after injury and returned to the sham level slowly.Conclusions: Decreased expression of bcl-xL mRNA and increased expression of bax mRNA coincides with apoptosis following brain injury. The bcl-2 gene family is involved in neuronal apoptosis after TBI, and the changes of mRNA expression of the family members lead the neuronal cells to apoptosis.

  20. Intermittent hypoxia attenuates ischemia/reperfusion induced apoptosis in cardiac myocytes via regulating Bcl-2/Bax expression

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Intermittent hypoxia has been shown to provide myocardial protection against ishemia/reperfusion-induced injury.Cardiac myocyte loss through apoptosis has been reported in ischemia/reperfusion injury. Our aim was to investigate whether intermittent hypoxia could attenuate ischemia/reperfusion-induced apoptosis in cardiac myocytes and its potential mechanisms. Adult male Sprague-Dawley rats were exposed to hypoxia simulated 5000 m in a hypobaric chamber for 6 h/day, lasting 42 days. Normoxia group rats were kept under normoxic conditions. Isolated perfused hearts from both groups were subjected to 30 min of global ischemia followed by 60 min reperfusion.Incidence of apoptosis in cardiac myocytes was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DNA agarose gel electrophoresis. Expressions of apoptosis related proteins,Bax and Bcl-2, in cytosolic and membrane fraction were detected by Western Blotting. After ischemia/reperfusion,enhanced recovery of cardiac function was observed in intermittent hypoxia hearts compared with normoxia group.Ischemia/reperfusion-induced apoptosis, as evidenced by TUNEL-positive nuclei and DNA fragmentation, was significantly reduced in intermittent hypoxia group compared with normoxia group. After ischemia/reperfusion,expression of Bax in both cytosolic and membrane fractions was decreased in intermittent hypoxia hearts compared with normoxia group. Although ischemia/reperfusion did not induce changes in the level of Bcl-2 expression in cytosolic fraction between intermittent hypoxia and normoxia groups, the expression of Bcl-2 in membrane fraction was upregulated in intermittent hypoxia group compared with normoxia group. These results indicated that the cardioprotection of intermittent hypoxia against ischemia/reperfusion injury appears to be in part due to reduce myocardial apoptosis. Intermittent hypoxia attenuated ischemia/reperfusion-induced apoptosis via increasing the ratio of Bcl

  1. Involvement of P53 and Bax/Bad triggering apoptosis in thioacetamide-induced hepatic epithelial cells

    Institute of Scientific and Technical Information of China (English)

    Li-Hsuen Chen; Chia-Yu Hsu; Ching-Feng Weng

    2006-01-01

    AIM: Thioacetamide (TAA) has been used in studying liver fibrosis and cirrhosis, however, the mechanisms of TAA-induced apoptosis in liver are still unclear. The hepatic epithelial cell line clone 9 was cultured and treated with TAA to investigate the causes of cell death. METHODS: The cell viability of TAA-induced clone 9 cells was determined using MTT assay. Total cellular GSH in TAA-induced clone 9 cells was measured using a slight modification of the Tietze assay. The activity of caspase 3 in TAA-induced clone 9 cells was monitored by the cleavage of DEVD-p-nitroanaline. TUNEL assay and flow cytometry were applied for the determination of DNA fragmentation and the proportion of apoptosis in TAAinduced clone 9 cells, respectively. The alterations of caspase 3, Bad, Bax and Phospho-P53 contents in TAAinduced clone 9 cells were measured by Western blot. RESULTS: The experimental data indicated that TAA caused rat hepatic epithelial cell line clone 9 cell death in a dose-and time-dependent manner; 60% of the cells died (MTT assay) within 24 h after 100 mg/L TAA was applied. Apoptotic cell percentage (TUNEL assay) and caspase 3 activities were highest after 100 mg/L TAA was added for 8 h. The release of GSH and the elevation in caspase content after TAA treatment resulted in clone 9 cell apoptosis via oxidative stress and a caspasedependent mechanism. The phospho-p53, Bax and Bad protein expressions in clone 9 cells were increased after TAA treatment.CONCLUSION: These results reveal that TAA activates p53, increases caspase 3, Bax and Bad protein contents,perhaps causing the release of cytochrome c from mitochondria and the disintegration of membranes, leading to apoptosis of cells.

  2. On the moment of inertia in deformed Ba-Xe nuclei as deduced from gamma-gamma energy correlation experiments

    International Nuclear Information System (INIS)

    The γ-rays following reactions induced by bombarding targets of 114,116,118,120,122Sn with 118 MeV 12C ions were investigated using six NaI(Tl) detectors in a two-dimensional coincidence arrangement. Experimental energy-correlation spectra were extracted from the original coincidence matrices. The energy-correlation spectra exhibit the features expected for rotational nuclei and were used to deduce information on the moment of inertia Isup((2)) = ΔI/Δω. The gross properties of the behaviour of Isup((2)) in the Ba-Xe region are discussed together with their interpretation within the cranked shell model (CSM). (orig.)

  3. Retinoids cause apoptosis in pancreatic cancer cells via activation of RAR-γ and altered expression of Bcl-2/Bax

    OpenAIRE

    Pettersson, F; Dalgleish, A G; Bissonnette, R P; Colston, K W

    2002-01-01

    All-trans-retinoic acid and 9-cis-retinoic acid have been reported to have inhibitory effects on pancreatic adenocarcinoma cells and we have shown that this is partly due to induction of apoptosis. In this study, the mechanisms whereby 9-cis-retinoic acid induces apoptosis in these cells were investigated. An involvement of the Bcl-2 family of proteins was shown, such that 9-cis-retinoic acid causes a decrease in the Bcl-2/Bax ratio. Overexpression of Bcl-2 also resulted in inhibition of apop...

  4. The protective role of Bax Inhibitor-1 against chronic mild stress through the inhibition of monoamine oxidase A

    OpenAIRE

    Hwa-Young Lee; Geum-Hwa Lee; Anu Marahatta; Shun-Mei Lin; Mi-Rin Lee; Kyu Yun Jang; Kyung Min Kim; Hee Jae Lee; Jae-Won Lee; Tarique Rajasaheb Bagalkot; Young-Chul Chung; Yong-Chul Lee; Hyung-Ryong Kim; Han-Jung Chae

    2013-01-01

    The anti-apoptotic protein Bax inhibitor-1 (BI-1) is a regulator of apoptosis linked to endoplasmic reticulum (ER) stress. It has been hypothesized that BI-1 protects against neuron degenerative diseases. In this study, BI-1−/− mice showed increased vulnerability to chronic mild stress accompanied by alterations in the size and morphology of the hippocampi, enhanced ROS accumulation and an ER stress response compared with BI-1+/+ mice. BI-1−/− mice exposed to chronic mild stress showed signif...

  5. Molecular cloning, characterization and expression analysis of (B-cell lymphoma-2 associated X protein) Bax in the orange-spotted grouper (Epinephelus coioides) after the Vibrio alginolyticus challenge.

    Science.gov (United States)

    Luo, Sheng-Wei; Wang, Wei-Na; Sun, Zuo-Ming; Xie, Fu-Xing; Kong, Jing-Rong; Liu, Yuan; Cheng, Chang-Hong

    2016-07-01

    Bax is a pro-apoptotic member of Bcl-2 like superfamily, playing an important role in regulating the apoptosis. In this study, the full-length Bax (EcBax) was obtained, containing a 5'UTR of 64 bp, an ORF of 579 bp and a 3'UTR of 1021 bp. The EcBax gene encoded a polypeptide of 192 amino acids with an estimated molecular mass of 21.55 KDa and a predicted isoelectric point (pI) of 6.75. The deduced amino acid sequence analysis showed that EcBax comprised the conserved residues and the characteristic domains known to the critical function of Bax. qRT-PCR analysis revealed that EcBax mRNA was broadly expressed in all of the examined tissues, while the highest expression level was observed in blood, followed by the expression in liver, gill, spleen, kidney, heart, muscle and intestine. A sharp increase of EcBax expression was observed in the vibrio challenge group by comparing with those in the control. Subcellular localization analysis revealed that EcBax was predominantly localized in the cytoplasm. EcBax exerted a regulatory role in modulating the mitochondrial membrane potential, promoting the cytochrome c release, and then activating the downstream caspase signaling. Moreover, the overexpression of EcBax can decrease the cell viability and antagonize NF-kB, AP-1, Stat3 promoter activity in Hela cells. These results indicate that EcBax containing the conserved domain of pro-apoptotic member of Bcl-2 family may disrupt the mammalian signaling and play a regulative role in the apoptotic process.

  6. The Impact of Adenosine Fast Induction of Myocardial Arrest during CABG on Myocardial Expression of Apoptosis-Regulating Genes Bax and Bcl-2

    Directory of Open Access Journals (Sweden)

    Ahmed Shalaby

    2009-01-01

    Full Text Available Background. We studied the effect of fast induction of cardiac arrest with denosine on myocardial bax and bcl-2 expression. Methods and Results. 40 elective CABG patients were allocated into two groups. The adenosine group (n=20 received 250 μg/kg adenosine into the aortic root followed by blood potassium cardioplegia. The control group received potassium cardioplegia in blood. Bcl-2 and bax were measured. Bax was reduced in the postoperative biopsies (1.38 versus 0.47, P=.002 in the control group. Bcl-2 showed a reducing tendency (0.14 versus 0.085, P=.07. After the adenosine treatment, the expression of both bax (0.52 versus 0.59, P=.4 and bcl-2 (0.104 versus 0.107, P=.4 remained unaltered after the operation. Conclusion. Open heart surgery is associated with rapid reduction in the expression of apoptosis regulating genes bax and bcl-2. Fast Adenosine induction abolished changes in their expression.

  7. BaP-induced DNA damage initiated p53-independent necroptosis via the mitochondrial pathway involving Bax and Bcl-2.

    Science.gov (United States)

    Jiang, Y; Chen, X; Yang, G; Wang, Q; Wang, J; Xiong, W; Yuan, J

    2013-12-01

    Benzo(a)pyrene (BaP), a typical environmental carcinogen, can induce cell death both by protein 53 or tumor protein 53 (p53)-independent and -dependent pathways. However, little is known about the molecular mechanisms of p53-independent pathways in BaP-induced cell death. In this study, cells with different genetic background (including p53-proficient human fetal lung fibroblast cell lines (MRC-5), p53-deficient human non-small-cell lung carcinoma cell lines (H1299), and p53-knockdown cell lines (MRC-5(p53-/-))) were used to establish models of BaP-induced cell death. The results showed that BaP (8, 16, 32, and 64 μM) induced necroptotic cell death in the cell lines. The necroptotic cell death and DNA damage were concurrently observed. In the three cell lines, at 24 h after treatment, BaP (8-64 μM) upregulated expressions of BAX, BCL-2, and cleaved caspase-3 proteins, but not their messenger RNA levels. The findings suggested that BaP-induced necroptosis was modulated by the p53-independent pathway, which was related to the induction of BAX, decreased expression of BCL-2, and activation of caspase-3.

  8. Bcl-2, Bax, and c-Fos expression correlates to RPE cell apoptosis induced by UV-light and daunorubicin

    DEFF Research Database (Denmark)

    Liang, Y G; Jorgensen, A G; Kaestel, C G;

    2000-01-01

    PURPOSE. The aim of this study was to determine the role of Bcl-2, Bcl-X L, Bax, and c-Fos in regulation of apoptosis, induced by ultraviolet-light A (UV-A) and daunorubicin (DNR), in retinal pigment epithelium (RPE) cells grown on bovine extracellular matrix (ECM)-coated or uncoated plastic dishes....... METHODS. Apoptosis in confluent RPE cells cultured on ECM-coated or uncoated dishes was induced by UV-A or DNR. Apoptosis was detected by 7-amino-actinomycin D labeling followed by flow cytometry and by terminal deoxy-transferase mediated X-dUTP nick end labeling (TUNEL). Cellular expression of Bcl-2, Bcl......-X L, Bax, and c-Fos was determined by the use of antibodies and flow cytometry, Western blot analysis, and immunocytochemical staining. RESULTS. Both UV-A and DNR induce apoptosis in human RPE cells in vitro. Human fetal RPE cells grown on ECM-coated dishes were significantly more resistant to UV...

  9. Expression of p53, Bax and Bcl-2 proteins in hepatocytes in non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    Anatol Panasiuk; Janusz Dzieciol; Bozena Panasiuk; Danuta Prokopowicz

    2006-01-01

    AIM: To analyze the protein expression essential for apoptosis in liver steatosis.METHODS: The expression of proapoptotic proteinsp53, Bax, and antiapoptotic Bcl-2 in hepatocytes with steatosis (SH) and without steatosis (NSH) was evaluated in 84 patients at various stages of non-alcoholic fatty liver disease (NAFLD).RESULTS: Immunohistochemical staining of liver tissue showed the activation of p53 protein in SH and NSH with increased liver steatosis, diminished Bcl-2 and slightly decreased Bax protein. Positive correlation was found between the stage of liver steatosis with p53 expression in SH (r = 0.54, P < 0.01) and NSH (r = 0.49,P < 0.01).The antiapoptotic protein Bcl-2 was diminished together with the advancement of liver steatosis, especially in non-steatosed hepatocytes (r =0.43, P < 001).CONCLUSION: Apoptosis is one of the most important mechanisms leading to hepatocyte elimination in NAFLD. The intensification of inflammation in NAFLD induces proapoptotic protein p53 with the inhibition of antiapoptotic Bcl-2.

  10. (-)-Anonaine induces apoptosis through Bax- and caspase-dependent pathways in human cervical cancer (HeLa) cells.

    Science.gov (United States)

    Chen, Chung-Yi; Liu, Tsan-Zon; Tseng, Wei-Chang; Lu, Fung-Jou; Hung, Ray-Ping; Chen, Chi-Hung; Chen, Ching-Hsein

    2008-08-01

    (-)-Anonaine has been shown to have some anticancer activities, but the mechanisms of (-)-anonaine inducing cell death of human cancer cells is not fully understood. We investigated the mechanisms of apoptosis induced by (-)-anonaine in human HeLa cancer cells. Treatment with (-)-anonaine induces dose-dependent DNA damage that is correlated with increased intracellular nitric oxide, reactive oxygen species, glutathione depletion, disruptive mitochondrial transmembrane potential, activation of caspase 3, 7, 8, and 9, and poly ADP ribose polymerase cleavage. Our data indicate that (-)-anonaine up-regulated the expression of Bax and p53 proteins in HeLa cancer cells. The apoptosis and expression of Bax induced by (-)-anonaine could be inhibited when the HeLa cells were pretreated with Boc-Asp(OMe)-fmk, which is a broad caspases inhibitor. There was no obvious DNA damage in the (-)-anonaine-treated Madin-Darby canine kidney and Vero cell lines. Both Madin-Darby canine kidney and Vero cell lines are kidney epithelial cellular morphology. These results suggest that (-)-anonaine might be considered a potent compound for chemotherapy against cervical cancer or a health food supplement for cancer chemoprevention.

  11. JNK-Bcl-2/Bcl-xL-Bax/Bak Pathway Mediates the Crosstalk between Matrine-Induced Autophagy and Apoptosis via Interplay with Beclin 1

    Directory of Open Access Journals (Sweden)

    Jiong Yang

    2015-10-01

    Full Text Available Autophagy is associated with drug resistance which has been a threat in chemotherapy of hepatocellular carcinoma (HCC. The interconnected molecular regulators between autophagy and apoptosis serve as switching points critical to the ultimate outcome of the cell. Our study was performed to investigate the crosstalk between autophagy and apoptosis in HCC after the treatment of matrine. Flow cytometry and TUNEL (terminal dexynucleotidyl transferase (TdT-mediated dUTP nick end labeling assay were used to detect apoptosis in vitro and in vivo, respectively. Bax oligomerization and Cytochrome c release assay were performed. Immunoprecipitation and siRNA transfection were used to detect the interplay between Bcl-2/Bcl-xL,Bax, and Beclin 1. Our results showed that: (1 matrine not only activated caspase and PARP (poly ADP-ribose polymerase cleavage, but also triggered autophagy as shown by the increased levels of LC3II, Beclin 1, and PI3KC3, and the decreased level of p62; (2 matrine treatment promoted the JNK-Bcl-2/ Bcl-xL-Bax/Bak pathway; (3 Bax was oligomerized, the mitochondrial membrane potential altered, and Cytochrome c was released subsequently; (4 Bax interacts with Beclin 1 and inhibits autophagy, which may be a new crosstalk point; and (5 finally, we showed that matrine suppressed the growth of a MHCC97L xenograft in vivo for the first time. In conclusion, the JNK-Bcl-2/Bcl-xL-Bax/Bak pathway mediates the crosstalk between matrine-induced autophagy and apoptosis via interplay with Beclin 1.

  12. JNK-Bcl-2/Bcl-xL-Bax/Bak Pathway Mediates the Crosstalk between Matrine-Induced Autophagy and Apoptosis via Interplay with Beclin 1.

    Science.gov (United States)

    Yang, Jiong; Yao, Shukun

    2015-10-27

    Autophagy is associated with drug resistance which has been a threat in chemotherapy of hepatocellular carcinoma (HCC). The interconnected molecular regulators between autophagy and apoptosis serve as switching points critical to the ultimate outcome of the cell. Our study was performed to investigate the crosstalk between autophagy and apoptosis in HCC after the treatment of matrine. Flow cytometry and TUNEL (terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling) assay were used to detect apoptosis in vitro and in vivo, respectively. Bax oligomerization and Cytochrome c release assay were performed. Immunoprecipitation and siRNA transfection were used to detect the interplay between Bcl-2/Bcl-xL,Bax, and Beclin 1. Our results showed that: (1) matrine not only activated caspase and PARP (poly ADP-ribose polymerase) cleavage, but also triggered autophagy as shown by the increased levels of LC3II, Beclin 1, and PI3KC3, and the decreased level of p62; (2) matrine treatment promoted the JNK-Bcl-2/ Bcl-xL-Bax/Bak pathway; (3) Bax was oligomerized, the mitochondrial membrane potential altered, and Cytochrome c was released subsequently; (4) Bax interacts with Beclin 1 and inhibits autophagy, which may be a new crosstalk point; and (5) finally, we showed that matrine suppressed the growth of a MHCC97L xenograft in vivo for the first time. In conclusion, the JNK-Bcl-2/Bcl-xL-Bax/Bak pathway mediates the crosstalk between matrine-induced autophagy and apoptosis via interplay with Beclin 1.

  13. Bax and Bak expression in cervical smears of women with low-and high-risk HPV types: A study of 120 cases

    Directory of Open Access Journals (Sweden)

    Eirini Klapsinou

    2015-01-01

    Full Text Available Background: Human papillomavirus (HPV is known to be involved in the carcinogenesis of squamous cells in uterine cervix cancer, mostly by binding and inactivating the p53 and pRb tumor suppressor genes. Lately, evidence has emerged suggesting that HPV oncoproteins may interact with proteins involved in cellular apoptosis as well. Aim: This study aimed to investigate the expression of proapoptotic proteins Bax and Bak in women with low-risk and high-risk HPV types as opposed to HPV-negative women, and in women with normal pap smear compared to women with abnormal Papanicolau test (Pap smear. Materials and Methods: A total of 120 liquid-based cervical samples were subtyped for HPV types with microarray hybridization and then stained and evaluated immunocytochemically for Bax and Bak expression. Statistical analysis was performed on the Bax and Bak scores (percentage of positive cells × staining intensity, the overall percentage of positive cells, and the most prevalent staining intensity group found in each sample. Results: A weak association between negative Bax staining and cytologically normal Pap smears was discovered, whereas cytologically abnormal samples tended to stain weakly or moderately positive. No other statistically significant difference was found in the other analyzed parameters. Conclusion: Cytologically normal pap smears seem to have a slight tendency to stain negative for Bax as opposed to cytologically abnormal pap smears. Although the association is weak, it is an indication that there might be a connection between the expression of Bax and the development of cervical intraepithelial dysplasia, which warrants further investigation in larger-scale studies.

  14. Effects of L-Tetrahydropalmatine on the Expressions of bcl-2 and bax in Rat after Acute Global Cerebral Ischemia and Reperfusion

    Institute of Scientific and Technical Information of China (English)

    刘彬; 杨光田

    2004-01-01

    To investigate the effects of L-Tetrahydropalmatine (L-THP) on the expressions of bcl2, bax and neuronal apoptosis after cerebral ischemia and reperfusion, 60 Wistars rats were randomly divided into 3 groups: sham-operation group (group S, n = 20), ischemic-reperfusion group treated with saline (group I, n=20) and ischemia-reperfusion group treated with L-THP (group T, n=20) . The rat model of global cerebral ischemia and reperfusion was induced by Pulsinelli's four-vessel occlusion method. The expression of bcl-2 and bax mRNA was detected by in situ hybridization and reverse transcriptional polymerase chain reaction (RT-PCR). The number of apoptotic neurons was examined by terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP nick end-labeling (TUNEL) method. Compared with group S, the expression of bcl-2 and bax mRNA in group I was increased significantly (P<0.01), and the number of apoptotic neurons increased either (P<0.01). After L-THP treatment, the expression of bcl-2 mRNA was up-regulated (P<0.01) and that of bax mRNA was down-regulated (P<0.01); the number of apoptotic neurons was decreased (P<0.01). Our results indicated that bcl-2 may suppress apoptosis and bax promote apoptosis after cerebral ischemia and reperfusion. L-THP could ameliorate cerebral ischemia and reperfusion damage by reducing the apoptosis through regulating bcl-2 and bax.

  15. Apoptosis and the activity of ceramide, Bax and Bcl-2 in the lungs of neonatal rats exposed to limited and prolonged hyperoxia

    Directory of Open Access Journals (Sweden)

    Bitar Fadi F

    2006-07-01

    Full Text Available Abstract Background The aim of the study is to examine the effect of limited and prolonged hyperoxia on neonatal rat lung. This is done by examining the morphologic changes of apoptosis, the expression of ceramide, an important mediator of apoptosis, the expression of inflammatory mediators represented by IL-1β and the expression of 2 proto-oncogenes that appear to modulate apoptosis (Bax and Bcl-2. Methods Newborn rats were placed in chambers containing room air or oxygen above 90% for 7 days. The rats were sacrificed at 3, 7 or 14 days and their lungs removed. Sections were fixed, subjected to TUNEL, Hoechst, and E-Cadherin Staining. Sections were also incubated with anti-Bcl-2 and anti-Bax antisera. Bcl-2 and Bax were quantitated by immunohistochemistry. Lipids were extracted, and ceramide measured through a modified diacylglycerol kinase assay. RT-PCR was utilized to assess IL-1β expression. Results TUNEL staining showed significant apoptosis in the hyperoxia-exposed lungs at 3 days only. Co-staining of the apoptotic cells with Hoechst, and E-Cadherin indicated that apoptotic cells were mainly epithelial cells. The expression of Bax and ceramide was significantly higher in the hyperoxia-exposed lungs at 3 and 14 days of age, but not at 7 days. Bcl-2 was significantly elevated in the hyperoxia-exposed lungs at 3 and 14 days. IL-1β expression was significantly increased at 14 days. Conclusion Exposure of neonatal rat lung to hyperoxia results in early apoptosis documented by TUNEL assay. The early rise in Bax and ceramide appears to overcome the anti-apoptotic activity of Bcl-2. Further exposure did not result in late apoptotic changes. This suggests that apoptotic response to hyperoxia is time sensitive. Prolonged hyperoxia results in acute lung injury and the shifting balance of ceramide, Bax and Bcl-2 may be related to the evolution of the inflammatory process.

  16. Hypoxia-mediated down-regulation of Bid and Bax in tumors occurs via hypoxia-inducible factor 1-dependent and -independent mechanisms and contributes to drug resistance

    DEFF Research Database (Denmark)

    Erler, Janine Terra; Cawthorne, Christopher J; Williams, Kaye J;

    2004-01-01

    of the Bcl-2 protein family. Oxygen deprivation of human colon cancer cells in vitro provoked decreased mRNA and protein levels of proapoptotic Bid and Bad. Hypoxia-inducible factor 1 (HIF-1) was dispensable for the down-regulation of Bad but required for that of Bid, consistent with the binding of HIF-1......alpha to a hypoxia-responsive element (positions -8484 to -8475) in the bid promoter. Oxygen deprivation resulted in proteosome-independent decreased expression of Bax in vitro, consistent with a reduction in global translation efficiency. The physiological relevance of Bid and Bax down...

  17. Determination of stoichiometry and concentration of trace elements in thin BaxSr1-xTiO3 perovskite layers.

    Science.gov (United States)

    Becker, J S; Boulyga, S F

    2001-07-01

    This paper describes an analytical procedure for determining the stoichiometry of BaxSr1-xTiO3 perovskite layers using inductively coupled plasma mass spectrometry (ICP-MS). The analytical results of mass spectrometry measurements are compared to those of X-ray fluorescence analysis (XRF). The performance and the limits of solid-state mass spectrometry analytical methods for the surface analysis of thin BaxSr1-xTiO3 perovskite layers sputtered neutral mass spectrometry (SNMS)--are investigated and discussed. PMID:11496982

  18. Immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 proteins in nephroblastomas A expressão imuno-histoquímica das proteínas p53, BCL-2, BAX e VEGFR1 em nefroblastomas

    Directory of Open Access Journals (Sweden)

    Ana Paula Percicote

    2013-02-01

    Full Text Available INTRODUCTION: Nephroblastoma or Wilms' tumor is the most frequent renal cancer in children. Although its prognosis is favorable for most patients, it may relapse or have a fatal outcome. The characterization of risk groups by applying immunohistochemical biomarkers aims to adapt the treatment to its corresponding group as well as to reduce relapses and fatal outcome. p53, B-cell lymphoma 2 (BCL-2, BCL-2 associated protein X (BAX and vascular endothelial growth factor receptor 1 (VEGFR1 are among the most widely studied biomarkers, which are related to the apoptotic pathway, DNA repair and neovascularization. OBJECTIVE: The objective of this study is to assess the immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 in samples of human nephroblastoma and to correlate them with clinicopathological prognostic factors. MATERIAL AND METHODS: Twenty-nine surgical specimens of nephroblastoma diagnosed from 1994 to 2007 were selected from the Anatomopathological Service of two hospitals in Curitiba. The immunohistochemical analysis of tissue microarrays was performed through immunoperoxidase staining and the yielded results were compared with clinicopathological prognostic factors. RESULTS: The major immunohistochemical expression of VEGFR1 in blastema and epithelium presented positive association with the risk group. Hence this may be related to higher vascular neoplastic invasion apparently caused by the endothelial growth factor, which maximizes the chances of metastasis and ultimately changes tumor staging, risk group and clinical evolution. CONCLUSIONS: The immunohistochemical expression of VEGFR1 substantiated a directly proportional association with the nephroblastoma risk group.INTRODUÇÃO: O nefroblastoma, ou tumor de Wilms, é a neoplasia renal mais frequente na infância. Embora o prognóstico seja favorável para a maioria dos pacientes, muitos evoluem para recidiva ou óbito. A caracterização de grupos de risco por meio de

  19. Curcuma purpurascens BI. rhizome accelerates rat excisional wound healing: involvement of Hsp70/Bax proteins, antioxidant defense, and angiogenesis activity

    Directory of Open Access Journals (Sweden)

    Rouhollahi E

    2015-10-01

    Full Text Available Elham Rouhollahi,1 Soheil Zorofchian Moghadamtousi,2 Fatemeh Hajiaghaalipour,3 Maryam Zahedifard,2 Faezeh Tayeby,2 Khalijah Awang,4 Mahmood Ameen Abdulla,3 Zahurin Mohamed1 1Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, 2Institute of Biological Sciences, Faculty of Science, 3Department of Biomedical Science, Faculty of Medicine, 4Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia Purpose: Curcuma purpurascens BI. is a member of Zingiberaceae family. The purpose of this study is to investigate the wound healing properties of hexane extract of C. purpurascens rhizome (HECP against excisional wound healing in rats.Materials and methods: Twenty four rats were randomly divided into 4 groups: A negative control (blank placebo, acacia gum, B low dose of HECP, C high dose of HECP, and D positive control, with 6 rats in each group. Full-thickness incisions (approximately 2.00 cm were made on the neck area of each rat. Groups 1–4 were treated two-times a day for 20 days with blank placebo, HECP (100 mg/kg, HECP (200 mg/kg, and intrasite gel as a positive control, respectively. After 20 days, hematoxylin and eosin and Masson’s trichrome stainings were employed to investigate the histopathological alterations. Protein expressions of Bax and Hsp70 were examined in the wound tissues using immunohistochemistry analysis. In addition, levels of enzymatic antioxidants and malondialdehyde representing lipid peroxidation were measured in wound tissue homogenates.Results: Macroscopic evaluation of wounds showed conspicuous elevation in wound contraction after topical administration of HECP at both doses. Moreover, histopathological analysis revealed noteworthy reduction in the scar width correlated with the enhanced collagen content and fibroblast cells, accompanied by a reduction of inflammatory cells in the granulation tissues. At the molecular level, HECP facilitates wound-healing process

  20. Study of BaxSr1-xTiO3 thin films using transverse-field Ising model

    Institute of Scientific and Technical Information of China (English)

    Tao Yong-Mei; Jiang Qing

    2004-01-01

    In this paper, the effects of doping on the thermodynamic properties of BaxSr1-xTiO3 (BST) thin film are investigated, based on the transverse-field Ising model (TIM) within the framework of mean field theory. We apply the double-peak distribution model of related parameters to mimic doping. The lattice expansion arising from doping with large Ba2+ was also taken into account. We concentrate on the doping concentration dependence of peak temperature (Tm), spontaneous polarization and dielectric susceptibility. It is found that the doping concentration has great influence on the dielectric properties and phase transition properties of BST thin films. We also discuss the quantum effect arising from doping.

  1. Effects of aspartame on hsp70, bcl-2 and bax expression in immune organs of Wistar albino rats

    Science.gov (United States)

    Choudhary, Arbind Kumar; Devi, Rathinasamy Sheela

    2016-01-01

    Abstract Aspartame, a “first generation sweetener”, is widely used in a variety of foods, beverages, and medicine. The FDA has determined the acceptable daily intake (ADI) value of aspartame to be 50 mg/kg·day, while the JECFA (Joint FAO/WHO Expert Committee on Food Additives) has set this value at 40 mg/kg of body weight/day. Safety issues have been raised about aspartame due to its metabolites, specifically toxicity from methanol and/or its systemic metabolites formaldehyde and formic acid. The immune system is now recognized as a target organ for many xenobiotics, such as drugs and chemicals, which are able to trigger unwanted apoptosis or to alter the regulation of apoptosis. Our previous studies has shown that oral administration of aspartame [40 mg/(kg·day)] or its metabolites for 90 days increased oxidative stress in immune organs of Wistar albino rats. In this present study, we aimed to clarify whether aspartame consumption over a longer period (90-days) has any effect on the expression of hsp70, bcl-2 and bax at both mRNA transcript and protein expression levels in immune organs. We observed that oral administration of aspartame for 90 days did not cause any apparent DNA fragmentation in immune organs of aspartame treated animals; however, there was a significant increase in hsp70 expression, apart from significant alteration in bcl-2 and bax at both mRNA transcript and protein expression level in the immune organs of aspartame treated animals compared to controls. Hence, the results indicated that hsp70 levels increased in response to oxidative injury induced by aspartame metabolites; however, these metabolites did not induce apoptosis in the immune organs. Furthermore, detailed analyses are needed to elucidate the precise molecular mechanisms involved in these changes.

  2. Changes of bcl—XL and bax mRNA expression following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    骆纯; 卢亦成; 等

    2002-01-01

    Objective:To investigate the changes of bcl-2 gene family and the molecular mechanism of neuromal apoptosis following traumatic brain injury(TBI)in rats.Methods:Male Sprague-Dawley(SD)rats were subjected to lateral fluid percussion brain injury(FPBI)of moderate severity.Thebcl-XLand baxmRNA expression was detected by reverse transcription polymerase chain reaction(RT-PCR)bax mRNA expression rose slowly,doubled at 3days after injury and returned to the sham level slowly.Conclusions:Decreased expression of bcl-XLmRNA and increased expression of bax mRNA coincides tith apoptosis followwin brain injury.The bcl-2gene family is involved in neuronal apoptosis after TBI,and the changes of mRNA expression of the family members lead the neuronal cells to apoptosis.

  3. Ganoderma lucidum spore powder modulates Bcl-2 and Bax expression in the hippocampus and cerebral cortex, and improves learning and memory in pentylenetetrazole-kindled rats

    Institute of Scientific and Technical Information of China (English)

    Shuang Zhao; Shengchang Zhang; Shuqiu Wang

    2011-01-01

    We studied the effects of Ganoderma lucidum spore powder on Bax and Bcl-2 expression and neuronal apoptosis in pentylenetetrazole-kindled epileptic rats. Sixty adult rats were randomly divided into a control group, an epileptic group (kindled) and three medication groups ( 150, 300,450 mg/kg given to kindled rats). Bax and Bcl-2 immunohistochemistry and TUNEL labeling show ed that the number of Bax- and TUNEL-positive cells in the hippocampus and cerebral cortex decreased significantly in the high-dose medication group, while the number of Bcl-2immunoreactive cells increased. The Morris water maze test showed that high-dose treatment significantly shortened escape latency and increased spatial probe trial performance. Our findings indicate that a high dose of Ganoderma lucidum spore powder upregulates the expressionof antiapoptotic Bcl-2 protein in the hippocampus and cerebral cortex, inhibits proapoptotic Bax expression, and decreases seizure-induced neuronal apoptosis. Further,Ganoderma lucidum appears to protect against epilepsy-related learning and memory impairments.

  4. BaxSr1−xTi1.02O3 metal–insulator–metal capacitors on planarized alumina substrates

    NARCIS (Netherlands)

    Tiggelman, M.P.J.; Reimann, K.; Klee, M.; Mauczok, R.; Keur, W.; Hueting, R.J.E.

    2010-01-01

    Nanocrystalline barium strontium titanate (BaxSr1−xTi1.02O3) thin films with a barium content of x=0.8, 0.9 and 1 have been fabricated in a metal–insulator–metal configuration on glass-planarized alumina substrates. Cost-effective processing measures have been utilized by using poly-crystalline alum

  5. The trade-off between tuning ratio and quality factor of BaxSr1-xTiO3 MIM capacitors on alumina substrates

    NARCIS (Netherlands)

    Tiggelman, M.P.J.; Reimann, K.; Liu, J.; Klee, M.; Mauczok, R.; Keur, W.; Schmitz, J.; Hueting, R.J.E.

    2008-01-01

    Barium strontium titanate with different compositions is deposited using wet-chemical processing on a glass planarization layer, on top of alumina substrates. Three samples were fabricated with BaxSr1-xTiO3 (BST) with the barium content x varying between 0.8 and 1. The poly-crystalline films are 530

  6. Effect of compound preparation Tongqiao Jiannao capsules on neural cell apoptosis and Bcl-2 and Bax protein levels in a rat model of brain ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Rui Wang; Guanglai Li; Wei Wang; Huanying Li

    2008-01-01

    BACKGROUND: Pharmacological studies have demonstrated that compound preparation Tongqiao Jiannao capsules composed of Zexie, Baizhu, Honghua, Danshen, and Shexiang can supplement qi,activate blood circulation, relieve blood stasis, induce resuscitation for alleviating pain, relieve pain, anddilate blood vessels.OBJECTIVE: To observe the effects of Tongqiao Jiannao capsules on the levels of the anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax, and verify the mechanism of action.DESIGN, TIME AND SETTING: Randomized, controlled animal experiment, performed in the Laboratory of Biochemistry and Molecular Biology, Shanxi Medical University between June 2001 and December 2002.MATERIALS: The right middle cerebral arteries of 24 healthy adult Sprague Dawley rats were occluded by the suture method. The primary Chinese herbal medicinal ingredients of Tongqiao Jiannao capsules are Zexie. Baizhu, Honghua, Danshen, and Shexiang, which were purchased from Shanxi Provincial Medicinal Material Company, China, and prepared into condensed granules in the Room for Chinese Herbal Medicine Preparation, Second Hospital, Shanxi Medical University. Bcl-2 and Bax immunohistochemical staining kits, a 3,3-diaminobenzidine(DAB) kit, and an in situ apoptosis detection kit were purchased from Wuhan Boster Bioengineering Co., Ltd., China.METHODS: Twenty-four rats were randomly and evenly divided into three groups: (1) sham-operated rats in which sutures were inserted and immediately pulled out; (2) Tongqiao Jiannao capsule-treated rats that were intragastrically administered 6.5 g/kg/d Tongqiao Jiannao capsule preparation for seven successive days prior to middle cerebral artery occlusion (MCAO); and (3) MCAO rats without any other treatments.MAIN OUTCOME MEASURES: The levels of neural cell apoptosis and Bcl-2 and Bax proteins at 24 hours post-surgery.RESULTS: In the MCAO group, the numbers of apoptotic cells and Bax-positive cells were significantly increased, while the numbers of

  7. Runx3 Expression Inhibits Proliferation and Distinctly Alters mRNA Expression of Bax in AGS and A549 Cancer Cells

    Science.gov (United States)

    Torshabi, Maryam; Faramarzi, Mohammad Ali; Tabatabaei Yazdi, Mojtaba; Ostad, Seyyed Naser; Gharemani, Mohammad Hosein

    2011-01-01

    Runx3, a member of Runt-related transcription factor (Runx) proteins with tumor suppressor effect, is a tissue–restricted and cancer related transcription factor that regulate cell proliferation and growth, as well as differentiation. In the present study, exogenous Run3 was transiently expressed in AGS (human gastric adenocarcinoma), with undetectable Runx3 protein and in A549 (human lung carcinoma) with low levels of endogenous Runx3 protein. The GFP tagged Runx3 was transfected into AGS and A549 cells using fugene6 and PolyFect and Runx3 expression was confirmed by fluorescent microscopy and RT-PCR. The effect of Runx3 transfection on cell proliferation was determined by MTT assay and the results were confirmed by the trypan blue dye exclusion method. The effect of Runx3 expression on mRNA expression of BCL2-associated X protein (Bax) was evaluated using RT-PCR. In AGS and A549 cells, Runx3 expression inhibited cell proliferation (p < 0.01). The growth inhibition was less in A549 cells. We show that Runx3 expression increases Bax mRNA expression in AGS cells when compared with control (p < 0.05), but no significant differences in mRNA expression was observed in both examined cells. Runx3 expression has antiproliferative effect in AGS cell perhaps via increase in expression of Bax. The effect of Runx3 on A549 cells’ viability which has endogenous level of Runx3 is not related to Bax. These findings implicate a complex regulation by Runx3 in inhibition of cell proliferation utilizing Bax. PMID:24250365

  8. Study on Apoptosis and Expression of P53, Bcl-2, Bax in Cardiac Myocytys of Congestive Heart Failure Induced by Ventricular Pacing

    Institute of Scientific and Technical Information of China (English)

    QI; Benling; CAO; Linsheng; WANG; Lin; ZHOU; Jingqun

    2001-01-01

    The apoptosis and the expression of p53, bcl-2 and Bax in myocytes of chronic rapid ventricular pacing-induced congestive heart failure (CHF) in rabbits were investigated. The CHF rabbit model (P, n= 7) was established by chronic rapid ventricular pacing for 3 weeks. By using TUNEL technique the apoptosis in the myocytes in the rabbit model was studied and the expression of p53,bcl-2 and Bax in myocytes was detected by using immunohistochemical method. Sham-operated (C,n = 9) group served as control group. The results showed that there were about 4033± 884.56 apoptotic cells/106 myocytes in P group, but no apoptotic cells were found in C group. Myocytes positive for p53 immunoreactivity (18. 86±8. 48 vs 5. 06±0. 87, P<0.01) and positive for Bax immunoreactivity (7. 15±1.91 vs 0. 43±0. 09, P<0.01) were increased in P group as compared with those in C group, while the myocytes positive for bcl-2 immunoreactivity (7. 08±1.05 vs 14. 97±4.47,P<0. 01) and the ratio of bcl-2/Bax were decreased in P group as compared with those in C group.Apoptosis was involved in the development of CHF induced by continuously rapid ventricular pacing in rabbit. The expression of p53 and Bax was increased, while the expression of bcl-2 was inhibited.These might play an important role in the acceleration of the apoptosis.

  9. Photobiomodulation on Bax and Bcl-2 Proteins and SIRT1/PGC-1α Axis mRNA Expression Levels of Aging Rat Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Fang-Hui Li

    2014-01-01

    Full Text Available Objective. This study aimed to analyze the effects of low level laser irradiation (LLLI on Bax and IGF-1 and Bcl-2 protein contents and SIRT1/PGC-1α axis mRNA expression levels to prevent sarcopenia in aged rats. Material and Methods. Twenty female Sprague Dawley rats (18 months old were randomly divided into two groups (n=10 per group: control (CON and LLLI groups. The gallium-aluminum-arsenium (GaAlAs laser irradiation at 810 nm was used in the single point contact mode (3.75 J/cm2; 0.4 cm2; 125 mW/cm2; 30 s. Bax, Bcl-2, and IGF-1 proteins and SIRT1/PGC-1α axis mRNA expression were assessed 24 h after LLLI on gastrocnemius in aged rat. Results. Gastrocnemius muscle weights, gastrocnemius mass/body mass, Bcl-2/BAX ratio, Bcl-2 protein, IGF-1 protein, and the mRNA contents in SIRT1, PGC-1α, NRF1, TMF, and SOD2 were significantly (P<0.05 increased by LLLI compared to CON group without LLLI. However, levels of BAX protein and caspase 3 mRNA were significantly attenuated by LLLI compared to CON group (P<0.05. Conclusion. LLLI at 810 nm inhibits sarcopenia associated with upregulation of Bcl-2/BAX ratio and IGF-1 and SIRT1/PGC-1α axis mRNA expression in aged rats. This indicates that LLLI has potential to decrease progression of myocyte apoptosis in sarcopenic muscles.

  10. Identification of Novel Pepper Genes Involved in Bax- or INF1-Mediated Cell Death Responses by High-Throughput Virus-Induced Gene Silencing

    Directory of Open Access Journals (Sweden)

    Jeong Hee Lee

    2013-11-01

    Full Text Available Hot pepper is one of the economically important crops in Asia. A large number of gene sequences, including expressed sequence tag (EST and genomic sequences are publicly available. However, it is still a daunting task to determine gene function due to difficulties in genetic modification of a pepper plants. Here, we show the application of the virus-induced gene silencing (VIGS repression for the study of 459 pepper ESTs selected as non-host pathogen-induced cell death responsive genes from pepper microarray experiments in Nicotiana benthamiana. Developmental abnormalities in N. benthamiana plants are observed in the 32 (7% pepper ESTs-silenced plants. Aberrant morphological phenotypes largely comprised of three groups: stunted, abnormal leaf, and dead. In addition, by employing the combination of VIGS and Agrobacterium-mediated transient assays, we identified novel pepper ESTs that involved in Bax or INF1-mediated cell death responses. Silencing of seven pepper ESTs homologs suppressed Bax or INF1-induced cell death, five of which suppressed both cell death responses in N. benthamiana. The genes represented by these five ESTs encode putative proteins with functions in endoplasmic reticulum (ER stress and lipid signaling. The genes represented by the other two pepper ESTs showing only Bax-mediated cell death inhibition encode a CCCH-type zinc finger protein containing an ankyrin-repeat domain and a probable calcium-binding protein, CML30-like. Taken together, we effectively isolated novel pepper clones that are involved in hypersensitive response (HR-like cell death using VIGS, and identified silenced clones that have different responses to Bax and INF1 exposure, indicating separate signaling pathways for Bax- and INF1-mediated cell death.

  11. Melatonin may play a role in modulation of bax and bcl-2 expression levels to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Mohseni, Mehran [Department of Radiology and Medical Physics, Faculty of Paramedicine, Kashan University of Medical Sciences, Kashan (Iran, Islamic Republic of); Mihandoost, Ehsan, E-mail: mihandoost.e@gmail.com [Department of Medical Radiation Engineering, Science and Research Branch, Islamic Azad University, Tehran (Iran, Islamic Republic of); Shirazi, Alireza [Department of Medical Physics and Biomedical Engineering, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Sepehrizadeh, Zargham [Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Bazzaz, Javad Tavakkoly [Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Ghazi-khansari, Mahmoud [Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of)

    2012-10-15

    The close relationship between free radicals effects and apoptosis process has been proved. Melatonin has been reported as a direct free radical scavenger. We investigated the capability of melatonin in the modification of radiation-induced apoptosis and apoptosis-associated upstream regulators expression in rat peripheral blood lymphocytes. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 8 Gy at a dose rate of 101 cGy/min with or without melatonin pretreatments at different concentrations of 10 and 100 mg/kg body weight. The rats were divided into eight groups of control, irradiation-only, vehicle-only, vehicle plus irradiation, 10 mg/kg melatonin alone, 10 mg/kg melatonin plus irradiation, 100 mg/kg melatonin alone and 100 mg/kg melatonin plus irradiation. Rats were given an intraperitoneal (IP) injection of melatonin or the same volume of vehicle alone 1 h prior to irradiation. Blood samples were taken 4, 24, 48 and 72 h after irradiation for evaluation of flow cytometric analysis of apoptotic lymphocytes using Annexin V/PI assay and measurement of bax and bcl-2 expression using quantitative real-time PCR (RT{sup 2}qPCR). Irradiation-only and vehicle plus irradiation showed an increase in the percentage of apoptotic lymphocytes significantly different from control group (P < 0.01), while melatonin pretreatments in a dose-dependent manner reduced it as compared with the irradiation-only and vehicle plus irradiation groups (P < 0.01) in all time points. This reduced apoptosis by melatonin was related to the downregulation of bax, upregulation of bcl-2, and therefore reduction of bax/bcl-2 ratio. Our results suggest that melatonin in these doses may provide modulation of bax and bcl-2 expression as well as bax/bcl-2 ratio to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis.

  12. Lack of association between Bax promoter (-248G>A single nucleotide polymorphism and susceptibility towards cancer: evidence from a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Sushil Kumar Sahu

    Full Text Available BACKGROUND: The Bcl-2-associated X protein (Bax is a proapoptotic member of the Bcl-2 family known to be activated and upregulated during apoptosis. Single nucleotide polymorphisms (SNPs in Bax promoter may participate in the process of carcinogenesis by altering its own expression and the cancer related genes. Bax-248G>A polymorphism has been implicated to alter the risk of cancer, but the listed results are inconsistent and inconclusive. In the present study, we performed a meta-analysis to systematically summarize the possible association of this polymorphism with the risk of cancer. METHODOLOGY: We conducted a search of case-control studies on the associations of Bax-248G>A polymorphism with susceptibility to cancer in Pub Med, Science Direct, Wiley Online Library and hand search. Data from all eligible studies based on some key search terms, inclusion and exclusion criteria were extracted for this meta-analysis. Hardy-Weinberg equilibrium (HWE in controls, power calculation, heterogeneity analysis, Begg's funnel plot, Egger's linear regression test, forest plot and sensitivity analysis were performed in the present study. RESULTS: Cancer risk associated with Bax-248G>A polymorphism was estimated by pooled odds ratios (ORs and 95% confidence intervals (95% CIs. The pooled ORs were calculated in allele contrast, homozygous comparison, heterozygous comparison, dominant and recessive model. Statistical significance was checked through Z and p-value in forest plot. A total of seven independent studies including 1772 cases and 1708 controls were included in our meta-analysis. Our results showed that neither allele frequency nor genotype distributions of this polymorphism were associated with risk for cancer in any of the genetic model. Furthermore, Egger's test did not show any substantial evidence of publication bias. CONCLUSIONS/SIGNIFICANCE: This meta-analysis suggests that the Bax-248G>A polymorphism is not an important cancer risk factor

  13. BaxSr1−xTiO3 thin films prepared by OTS monomolecular film reverse induction and liquid phase self-assembly method

    International Nuclear Information System (INIS)

    Highlights: • OTS-SAMs were prepared on the substrate by self-assembled monomolecular technique. • After UV-light irradiation, OTS-SAMs became hydrophilic monolayers in 1 nm thickness. • Ferroelectric BaxSr1−xTiO3 film can be prepared on substrate by the reverse LPD-SAMs. -- Abstract: Octadecyl-trichlorosilane self-assembled monolayers (OTS-SAMs) were prepared on the ITO glass substrate surface by self-assembled monomolecular film technique and BaxSr1−xTiO3 thin film was prepared by the reverse induction and adsorption on the functionalized substrate surface. The morphologies of OTS-SAMs before and after UV-light irradiation, the variation of the contact angles, and the microstructure and electrical property of BaxSr1−xTiO3 thin film were investigated. The results show that after UV-light irradiation, the hydrophilic film of OTS-SAMs with the thickness of 1 nm and the contact angle of 5° can be used to prepare the homogeneous BaxSr1−xTiO3 thin film by the reverse induction method. As the increase of Ba content, the diffraction peaks corresponding to SrTiO3 crystal plane is shifted to small angles. The grains of the thin film are decreased as the increase of Ba doping content. When Sr/Ba is between 9/1 and 8/2, the dielectric constant of BaxSr1−xTiO3 thin film is higher while the dielectric loss is smaller. At 10 kHz, the dielectric constant of Ba0.2Sr0.8TiO3 thin film is 880 and the dielectric loss is 0.04. The remnant polarization of BaxSr1−xTiO3 thin film prepared by the reverse induction and adsorption and liquid phase self-assembly method is 0.64 μC/cm2 and the coercivity is 13.84 kV/cm

  14. Cyclophilin A affects Bcl-2 and Bax expression following beta-amyloid fragment 25-35-induced injury to PC12 cells

    Institute of Scientific and Technical Information of China (English)

    Li Cheng; Chaodong Zhang

    2008-01-01

    BACKGROUND: Cyclophilin A can protect neurons against oxidative stress.OBJECTIVE: To investigate the effect of cyclophilin A on Bcl-2 and Bax protein expression in pheochromocytoma (PCI2) cells treated with beta-amyloid fragment 25-35 (A β25-35), and to verify the protection pathway ofcyclophilin A.DESIGN, TIME AND SETTING: The initial experiment was performed at the Laboratory of Department of Neurology, First Clinical College, China Medical University from November 2006 to July 2007.MATERIALS: PCI2 cells were cultured at the Cell Center of Peking Union Medical College. A β25-35 (Sigma, USA), antibodies of Bcl-2 and Bax (Wuhan Boster, China), and recombinant human cyclophilin A (Biomol, USA) were used in this study.METHODS: PC12 cells were divided into three groups. Cells in the control group were incubated in culture medium. Cells in the Aβ25-35 injury group were incubated in medium containing a final concentration of 10 μ mol/L of Aβ25-35. Cells in the cyclophilin A group were incubated in medium containing a final concentration of 10 nmol/L of cyclophilin A for 30 minutes, and then treated with 10 μmol/L Aβ25-35. MAIN OUTCOME MEASURES: After 24 hours of culture, immunohistochemistry was used to detect Bcl-2 and Bax expression in PC12 cells. Annexin-V flow cytometry was employed to measure the apoptosis rate of PC12 cells. The MTT method was applied to examine the survival rate of PC12 cells.RESULTS: Bcl-2 expression decreased, whereas Bax expression increased in PCI2 cells treated with Aβ25-35 (t = 2.277, 5.957, P<0.05). However, in PC12 cells treated with Aβ25-35 and cyclophilin A, Bcl-2 expression increased and Bax expression decreased (t = 4.497, 2.531, P < 0.05). The survival rate of PC12 cells significantly decreased and the apoptosis rate increased (t=8.509, 22.886, P < 0.05) following Aβ25-35 treatment. Cyclophilin A enhanced the survival rate of PC12 cells to Aβ25-35-induced apoptosis (t = 4.895, 10.042, P< 0.05).CONCLUSION: Cyclophilin A can

  15. EXPRESSIONS OF survivin, bax AND caspase-3 IN MISSED ABORTION PATIENTS%稽留流产病人survivin、bax及caspase-3的表达

    Institute of Scientific and Technical Information of China (English)

    张娟; 王蓁

    2011-01-01

    目的 探讨survivin、bax及caspase-3的表达与稽留流产的关系.方法 以35例稽留流产病人为病例组,30例正常妊娠者为对照组.采用免疫组织化学sP法检测绒毛细胞滋养细胞和合体滋养细胞及蜕膜组织蜕膜细胞中survivin、bax和caspase-3的表达.结果 病例组妊娠组织中survivin的表达明显低于对照组,bax及caspase-3的表达明显高于对照组(u=2.87~5.29,P<0.01).病例组survivin与bax及caspase-3的表达均呈负相关(r=-0.59、-0.71,P<0.05、0.01),bax与caspase-3的表达呈正相关(r=0.79,P<0.01).结论 survivin的低表达、bax及caspase-3的高表达在稽留流产的发生中起重要作用.%Objective To study the relationship of expressions of survivin, bax and caspase-3 with missed abortion.Methods Thirty-five missed abortion patients were assigned as study group, and 30 with normal pregnancy as controls. Immunohistochemistry technique was employed to detect the expressions of survivin, bax and caspase-3 in cytotrophoblast and syncytiotrophoblast of villi and decidual cells of decidua. Results Compared with that of the controls, the expression of survivin in the study group was significantly lower, while the expressions of bax and caspase-3 were higher (uc = 2. 87-5.29, P<0.01 ). In the study group, the survivin expression was negatively correlated wit h t he expressions of bax and caspase-3 (r = - 0. 59,0. 71; P< 0. 05,0.01), respectively, and the expression of bax was found to be positively correlated with caspase-3 (r=0. 79,P<0.01). Conclusion Low expression of survivin and high expressions of bax and caspase-3 play an important role in the occurrence of missed abortion.

  16. Role of the lattice dynamics in La2-xBaxCuO4 superconductor based on DFT method

    Directory of Open Access Journals (Sweden)

    A Tavana

    2010-09-01

    Full Text Available Electron-phonon coupling parameters are calculated for La2-x BaxCuO4 cuprate superconductor in a wide range of dopings, from undoped to overdoped compounds. In this study we aim to study the quality of such calculations based on DFT method so, the results of σ GGA+U electronic structure calculations are also investigated. The obtained value for electron-phonon coupling is in the same order of previous calculations but, the value obtained for the Hubbard U parameter shows that, such methods are poor in the estimation of electronic correlations to decide about the role of phonons in these compounds based on their results. Moreover, existence of several structural phase transitions with temperature and doping, lead to larger error in these calculations. Based on the calculated phonon dispersions, structural phase transitions can be resulted which shows the ability of DFT in the study of structural properties and the weakness of the strongly correlations in this properties.

  17. Grape Seed Procyanidin Extract Improves Insulin Production but Enhances Bax Protein Expression in Cafeteria-Treated Male Rats

    Directory of Open Access Journals (Sweden)

    Lídia Cedó

    2013-01-01

    Full Text Available In a previous study, the administration of a grape seed procyanidin extract (GSPE in female Wistar rats improved insulin resistance, reduced insulin production, and modulated apoptosis biomarkers in the pancreas. Considering that pharmacokinetic and pharmacodynamic parameters in females are different from these parameters in males, the aim of the present study was to evaluate the effects of GSPE on male Wistar cafeteria-induced obese rats. The results have confirmed that the cafeteria model is a robust model mimicking a prediabetic state, as these rats display insulin resistance, increased insulin synthesis and secretion, and increased apoptosis in the pancreas. In addition, GSPE treatment (25 mg/kg of GSPE for 21 days in male rats improves insulin resistance and counteracts the cafeteria-induced effects on insulin synthesis. However, the administration of the extract enhances the cafeteria-induced increase in Bax protein levels, suggesting increased apoptosis. This result contradicts previous results from cafeteria-fed female rats, in which GSPE seemed to counteract the increased apoptosis induced by the cafeteria diet.

  18. Spectroscopic studies of the ferroelectric and magnetic phase transitions in multiferroic Sr1-xBaxMnO3.

    Science.gov (United States)

    Goian, V; Kadlec, F; Kadlec, C; Dabrowski, B; Kolesnik, S; Chmaissem, O; Nuzhnyy, D; Kempa, M; Bovtun, V; Savinov, M; Hejtmánek, J; Prokleška, J; Kamba, S

    2016-05-01

    Dielectric response of perovskite Sr1-xBaxMnO3 (x = 0.43 and 0.45) ceramics was investigated using microwave, THz and infrared spectroscopic techniques in order to study the ferroelectric and antiferromagnetic phase transitions with critical temperatures TC ≈ 350 K and TN ≈ 200 K, respectively. The two lowest-frequency polar phonons are overdamped above TN and they exhibit pronounced softening on heating towards TC. Nevertheless, permittivity ε' in the THz range shows only a small anomaly at TC because the phonon contribution to ε' is rather small. The phonons are coupled with a central mode which provides the main contribution to the dielectric anomaly at TC. Thus, the ferroelectric phase transition has characteristics of a crossover from displacive to order-disorder type. At the same time, the intrinsic THz central peak is partially screened by conductivity and related Maxwell-Wagner relaxation, which dominates the microwave and lower-frequency spectra. Below TN, the ferroelectric distortion markedly decreases, which has an influence on the frequencies of both the central and soft modes. Therefore, ε' in the THz range increases at TN on cooling. In spite of the strong spin-phonon coupling near TN, surprisingly no magnetodielectric effect was observed in the THz spectra upon applying magnetic field of up to 7 T, which is in contradiction with the theoretically expected huge magnetoelectric coupling. We explain this fact as due to the insensitivity of TN to magnetic field. PMID:27023160

  19. Plumbagin reduces chronic lymphocytic leukemia cell survival by downregulation of Bcl-2 but upregulation of the Bax protein level.

    Science.gov (United States)

    Fu, Chunling; Gong, Yanqing; Shi, Xuanxuan; Sun, Zengtian; Niu, Mingshan; Sang, Wei; Xu, Linyan; Zhu, Feng; Wang, Ying; Xu, Kailin

    2016-09-01

    Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western countries, and mainly originates from an accumulation of abnormal B cells caused by the dysregulation of cell proliferation and apoptosis rates. The aberration of apoptosis-related genes in CLL cells results in defective apoptosis of CLL cells in response to traditional therapeutic medicine. Plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), a natural compound from Plumbago zeylinica, has been shown to exhibit pro-apoptotic activities in tumor cells. In the present study, we report that plumbagin effectively inhibited CLL cell viability with a lower dose compared to fludarabine, and inhibited cell proliferation in a dose-dependent manner. In addition, plumbagin promoted accumulation of MEC-1 cells in the S phase, and blocked cell cycle transition of HG3 cells from G0/G1 to S phase. Molecularly, plumbagin markedly induced CLL cell apoptosis through reduction of Bcl-2, but through an increase in the Bax protein level. These results suggest that plumbagin may be considered as a potential anticancer agent for CLL therapy. PMID:27461100

  20. The N-terminus and alpha-5, alpha-6 helices of the pro-apoptotic protein Bax, modulate functional interactions with the anti-apoptotic protein Bcl-xL

    Directory of Open Access Journals (Sweden)

    Sowdhamini R

    2007-05-01

    Full Text Available Abstract Background Bcl-2 family proteins are key regulators of mitochondrial integrity and comprise both pro- and anti-apoptotic proteins. Bax a pro-apoptotic member localizes as monomers in the cytosol of healthy cells and accumulates as oligomers in mitochondria of apoptotic cells. The Bcl-2 homology-3 (BH3 domain regulates interactions within the family, but regions other than BH3 are also critical for Bax function. Thus, the N-terminus has been variously implicated in targeting to mitochondria, interactions with BH3-only proteins as well as conformational changes linked to Bax activation. The transmembrane (TM domains (α5-α6 helices in the core and α9 helix in the C-terminus in Bax are implicated in localization to mitochondria and triggering cytotoxicity. Here we have investigated N-terminus modulation of TM function in the context of regulation by the anti-apoptotic protein Bcl-xL. Results Deletion of 29 amino acids in the Bax N-terminus (Bax 30–192 caused constitutive accumulation at mitochondria and triggered high levels of cytotoxicity, not inhibited by Bcl-xL. Removal of the TM domains (Bax 30–105 abrogated mitochondrial localization but resulted in Bcl-xL regulated activation of endogenous Bax and Bax-Bak dependent apoptosis. Inclusion of the α5-α6 helices/TMI domain (Bax 30–146 phenocopied Bax 30–192 as it restored mitochondrial localization, Bcl-xL independent cytotoxicity and was not dependent on endogenous Bax-Bak. Inhibition of function and localization by Bcl-xL was restored in Bax 1–146, which included the TM1 domain. Regardless of regulation by Bcl-xL, all N-terminal deleted constructs immunoprecipitated Bcl-xLand converged on caspase-9 dependent apoptosis consistent with mitochondrial involvement in the apoptotic cascade. Sub-optimal sequence alignments of Bax and Bcl-xL indicated a sequence similarity between the α5–α6 helices of Bax and Bcl-xL. Alanine substitutions of three residues (T14A-S15A-S16A in

  1. Ab-initio study of structural, elastic, electronic and thermodynamic properties of BaxSr1−xS ternary alloys

    Directory of Open Access Journals (Sweden)

    Chelli S.

    2015-12-01

    Full Text Available The structural, elastic, electronic and thermodynamic properties of BaxSr1−xS ternary alloys have been investigated using the full-potential (linearized augmented plane wave method. The ground state properties, such as lattice constant, bulk modulus and elastic constants, are in good agreement with numerous experimental and theoretical data. The dependence of the lattice parameters, bulk modulus and band gap on the composition x was analyzed. Deviation of the lattice constant from Vegard’s law and the bulk modulus from linear concentration dependence (LCD was observed. The microscopic origins of the gap bowing were explained by using the approach of Zunger et al. The thermodynamic stability of BaxSr1−xS alloy was investigated by calculating the excess enthalpy of mixing, ΔHm and the calculated phase diagram showed a broad miscibility gap with a critical temperature.

  2. Injury of mitochondria and the expressions of fas and bax mRNA in the hip-pus of epileptic rats of different latency

    Institute of Scientific and Technical Information of China (English)

    Shuhai Tang; Jianying Sun; Xiaojun Pan; Li Zhang

    2006-01-01

    BACKGROUND: It has been confirmed that Fas and Bax respectively mediate the exogenous and endogenous pathways of neuronal apoptosis, and then mediate the neuronal injury after status epilepticus.OBJECTIVE: To comparatively observe the injury of mitochondrial ultrastructure and the expressions of fas and bax in hippocampal tissue of rats with status epilepticus of different latency.DESIGN: A randomized control study.SETTING: Department of Anesthesiology and Department of Neurology, Qilu Hospital of Shandong University.MATERIALS: Totally 110 male adult SD rats of 260-300 g were used. Kainic acid was purchased from American Sigma Company.METHODS: The experiment was carried out in the Pathological Laboratory of Shandong Academy of Medical Sciences between March and July 2005.① Totally 100 SD rats were divided into two groups according to the random number table method:intraperitoneal injection group and caudal venous injection group.The rats were given kainic acid injected intraperitoneally(12 mg/kg)and through caudal vein (10 mg/kg) respectively. Each group was observed at 3, 6, 24, 48 and 72 hours after status epilepticus respectively.Ten rats were selected for each time point, including 2 for examination of electron microscope and 8 for the diction of the fas and bax mRNA expressions. The time and manifestations of seizure were observed, and the seizure was lasted for 2 hours, and then it was terminated by intraperitoneal injection of diazepam (10 mg/kg). Another 10 rats were used as the normal control group, and the materials were taken at 24 hours after status epilepticus, 2 of rats for the examination of electron microscope and 8 of them for the reverse transcription-polymerase chain reaction (RT-PCR). ② The ultrastructure of hippocampal neurons and its mitochondria were observed with transmission electron microscope. ③ The fas and bax mRNA expressions were detected with reverse transcription-polymerase chain reaction (RT-PCR).MAIN OUTCOME MEASURES: The

  3. Titanium Dioxide (TiO2) Nanoparticles Preferentially Induce Cell Death in Transformed Cells in a Bak/Bax-Independent Fashion

    OpenAIRE

    Yanglong Zhu; Eaton, John W.; Chi Li

    2012-01-01

    While the cytotoxic effects of titanium dioxide (TiO(2)) nanoparticles have been under intense investigation, the molecular mechanisms of this cytotoxicity remain unknown. Here we investigated the influence of oncogenic transformation and a major apoptotic signaling pathway on cellular responses to TiO(2) nanoparticles. Isogenic wild-type (WT) and apoptosis-resistant (Bak(-/-)Bax(-/-)) cell lines with and without tumorigenic transformation were examined. TiO(2) nanoparticles preferentially re...

  4. Effect of Achyranthes Bidentata Polysaccharides on the Expression of BCL-2 and Bax in Hepatic Tissues after Exhaustive Exercise in Rats

    OpenAIRE

    Lin, Jinyang; Zhang, Zhuoying; Shan, Ying

    2010-01-01

    This study aims to assess the effects of Achyranthes bidentata polysaccharides (ABPS) on the expression of bcl-2 and bax in hepatic tissues after exhaustive exercise in order to provide theoretical support for the application of ABPS in the field of sports nutrition. Thirty male Sprague-Dawley rats were randomized into three groups, each consisting of 10 rats: Normal control group (NCG), Exhausting exercises control group (EECG), ABPS treated group (ATG). ABPS were fed orally by gastric intub...

  5. An Assay of Bax and Bcl2 Expression in Mice Hippocampus Following Ischemia-Reperfusion Treatment with CoQ10

    Directory of Open Access Journals (Sweden)

    Jalal Hassanshahi

    2013-10-01

    Full Text Available Introduction: Preliminary studies confirmed reduction of cell death following treatment with antioxidants. According to this finding we investigated the relationship between consumption of CoQ10 and expression of bax and bcl2 in hippocampus ischemia that this expression related to cell programmed death.Material and Methods: We studied the protective role of CoQ10 against ischemia-reperfusion. Experimental design includes four groups: intact (N=7, ischemic control (N=7, sham control (N=7 and treatment groups with CoQ10 (N=7. The mice (treatment group treated with CoQ10 as Pre-Treatment for a week. Then, ischemia induced by common carotid artery ligation and following the reduction in inflammation (a week the treatment group post-treated with CoQ10 for a week. Nissl staining applied to counting necrotic cells of hippocampus and the western blotting performed to measurement the bax and bcl2 expression. Tunnel kit was used to quantify apoptotic cell death while to short term memory scale, we apply Y-maze.Results: Cell death was significantly lower when mice treated with CoQ10. Bax expression was significantly high in ischemic group but in treatment group was less and reversely the bcl2 expression in ischemic group was lower than treatment and vehicle groups. The memory test results were consistent with cell death results. Conclusion: Ischemia for 15 minutes induced cell death in hippocampus with more potent effect on CA1. CoQ10 intake significantly reduced cell death and decreased memory loss. with prevent of expression of bax and increase in expression of bcl2.

  6. Angiotensin II-Induced Apoptosis of Human Umbilical Vein Endothelial Cells was Inhibited by Blueberry Anthocyanin Through Bax- and Caspase 3-Dependent Pathways.

    Science.gov (United States)

    Du, Jian; Leng, Jiyan; Zhang, Li; Bai, Guangxin; Yang, Di; Lin, Huan; Qin, Junjie

    2016-01-01

    BACKGROUND This study aimed to investigate the inhibitory effect of blueberry anthocyanin (BBA) on Angiotensin II (Ang II)-induced apoptosis of human umbilical vein endothelial cells (HUVECs), and its regulation mechanisms involving Bax and Caspase 3. MATERIAL AND METHODS HUVECs were first treated by different concentrations of Ang II (10-9, 10-8, 10-7, 10-6, 10-5, and 10-4 mol/L) and BBA (80, 40, 20, 10, 5, and 2.5 μg/ml). After 24 h and 48 h of treatment, MTT was performed to detect the viability of HUVECs. Then, HUVECs were randomly divided into the Ang II group (10-6 mol/L Ang II) and Ang II + BBA group (10-6 mol/L Ang II and 20 μg/ml BBA), and the apoptosis rate was detected by flow cytometry. Western blot analysis was performed to detect the expression of Bax and Caspase 3 in these 2 groups. During the whole process, HUVECs without any treatments served as the control group. RESULTS The cell viability of HUVECs was significantly reduced by Ang II in a time- and concentration-dependent manner (P<0.05), while BBA significantly elevated the cell viability of HUVECs until a peak of 20.0 μg/ml. The apoptosis rate of HUVECs was significantly increased by Ang II (P<0.01) and reduced by the BBA intervention (P<0.05). Ang II significantly elevated the expression of Bax and Caspase 3 in HUVECs, but their expression was significantly inhibited by BBA. CONCLUSIONS BBA increased cell viability and reduced apoptosis rate of HUVECs induced by Ang II through Bax- and Caspase 3-dependent pathways. PMID:27616275

  7. Expression of bax and bcl2 Genes in MDMA-induced Hepatotoxicity on Rat Liver Using Quantitative Real-Time PCR Method through Triggering Programmed Cell Death

    OpenAIRE

    2015-01-01

    Background: 3-4methylenedioxymethamphetamine (MDMA) is a synthetic and psychoactive drug, which is known popularly as Ecstasy and has toxic effects on human organs. Objectives: Considering the potential toxic interaction, this study was performed to quantify the expression of bax and bcl2 genes in MDMA-induced hepatotoxicity on rat liver. Subsequently, we evaluated pentoxifylline as a possible protective drug on hepatotoxicity. Materials and Methods: Adult male Wistar rats weighting 250 - 300...

  8. Oridonin induces apoptosis of HeLa cells via altering expres sion of Bcl-2/Bax and activating caspase-3/ICAD pathway

    Institute of Scientific and Technical Information of China (English)

    Chun-ling ZHANG; Li-jun WU; Shin-ichi TASHIRO; Satoshi ONODERA; Takashi IKEJIMA

    2004-01-01

    AIM: To study the mechanisms by which oridonin inhibited HeLa cell growth in vitro. METHODS: Viability of oridonin-induced HeLa cells was measured by MTT assay. Apoptotic cells with condensed nuclei were visualized by phase contrast microscopy. Nucleosomal DNA fragmentation was assayed by agarose gel electrophoresis.Caspase activity was assayed using fiuorometric protease assay. ICAD, Bcl-2, and Bax proteins expression were detected by Western blot analysis. RESULTS: Oridonin induced oligonucleosomal fragmentation of DNA and increased caspase-3 activity, on the other hand, reduced the expression of inhibitor of caspase-3-activated DNase (ICAD), a caspase-3 substrate, at 12 h in HeLa cells. Oridonin-induced DNA fragmentation, caspase-3 activation and down-regulation of ICAD expression were effectively inhibited by a caspase-3 inhibitor, z-DEVD-fmk (z-AspGlu-Val-Asp-fmk). However, pretreatment with an inhibitor of poly (ADP-ribose) polymerase (PARP), 3, 4-dihydro5-[4-(1-piperidinyl)butoxy]-1 (2H)-isoquinolinone (DPQ), did not suppress oridonin-induced HeLa cell death. In addition, oridonin-induced apoptosis was associated with an increase in the expression of the apoptosis inducer Bax, and a significant reduction in expression of the apoptosis suppressor Bcl-2 in mitochondria. CONCLUSION:Oridonin induces HeLa cells apoptosis by altering balance of Bcl-2 and Bax protein expression and activation of caspase-3/ICAD pathway.

  9. Gambogic acid induces mitochondria-dependent apoptosis by modulation of Bcl-2 and Bax in mantle cell lymphoma JeKo-1 cells

    Institute of Scientific and Technical Information of China (English)

    Jingyan Xu; Min Zhou; Jian Ouyang; Jing Wang; Qiguo Zhang; Yong Xu; Yueyi Xu

    2013-01-01

    Objective:To study the mechanisms in gambogic acid (GA)-induced JeKo-1 human Mantle Cell Lymphoma cell apoptosis in vitro.Methods:The proliferation of GA-treated JeKo-1 cells was measured by CCK-8 assay and Ki-67 immunocytochemical detection.Apoptosis,cell cycle and mitochondrial membrane potential were measured by flow cytometric analysis.Caspase-3,-8 and-9 were detected by colorimetric assay.Bcl-2 and Bax were analyzed by Western blotting.Results:GA inhibited cell growth in a time-and dose-dependent manner.GA induces apoptosis in JeKo-1 cells but not in normal bone marrow cells,which was involved in reducing the membrane potential of mitochondria,activating caspases-3,-8 and-9 and decreasing the ratio of Bcl-2 and Bax without cell cycle arresting.Conclusions:GA induced apoptosis in human MCL JeKo-1 cells by regulating Bcl-2/Bax and activating caspase-3,-8 and-9 via mitochondrial pathway without affecting cell cycle.

  10. Effect of Hypoxic Preconditioning on Neural Cell Apoptosis and Expression of Bcl-2 and Bax in Cerebral Ischemia-Reperfusion in Rats

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to investigate the protective effect of hypoxic preconditioning on the cerebral ischemia-reperfusion injury, the expression of Bcl-2 and Bax was detected by using immunohistochemical staining after 3 h cerebral ischemia followed by 1, 6, 12, 24 and 48 h reperfusion respectively in rats treated with or without hypoxic preconditioning before cerebral ischemia. In addition,the apoptosis of neural cells and the behavioral scores for neurological functions recovery were evaluated by TUNEL staining and "crawvling method", respectively. Compared with control group (cerebral ischemia-reperfusion without hypoxic preconditioning), the expression of Bcl-2 was significantly increased, but that of Bax decreased in the hypoxic preconditioning group (cerebral ischemiareperfusion with hypoxic preconditioning), both P<0. 05. The pre-treatment with hypoxic preconditioning could reduce the apoptosis of neural cells and promote the neurological function recovery as compared to control group. It was suggested that hypoxic preconditioning may have protective effects on the cerebral ischemia-reperfusion injury by inhibiting the apoptosis of neural cells, increase the expression of Bcl-2 and decrease the expression of Bax.

  11. Curcumin induces the expression of NF-κB and Bcl-2/Bax in human renal cell carcinoma cell line ACHN

    Institute of Scientific and Technical Information of China (English)

    Gang Li; Tie Chong; Ziming Wang

    2009-01-01

    Objective: To explore the in vitro effects of curcumin on the proliferation and apoptosis of the human renal cell carcinoma cell line ACHN, and to investigate its mechanisms of action. Methods: The human renal cell carcinoma cell line ACHN was treated with different concentrations of curcumin for 24 h. The MTT assay was used to evaluate the cytotoxic effects of curcumin and flow cytometry was utilized to observe and detect the apoptosis of ACHN cells induced by curcumin. The expression levels of Bcl-2, Bax and NF-κBP65 mRNA were evaluated by Reverse Transcription-Polymerase Chain Reaction (RT-PCR), while the expression of Bcl-2, Bax, NF-κBP65 and IkB proteins was evaluated by Western blot. Results: The concentrations of curcumin used significantly inhibited the proliferation of ACHN human renal cell carcinoma cells in vitro in a dose and time-dependent manner (Ftime=5.55, P < 0.05; Fdose=110.05, P < 0.05). Obvious apoptosis of cells treated with different concentrations of curcumin could be observed by FCM. Compared with the control group, the apoptosis rates of curcumin-treated cells were markedly increased (F=96.35, P < 0.05). Lower dose of curcumin significantly induced the apoptosis of ACHN cells. With intervention of different concentrations of curcumin (0, 10, 20 and 40 μmol/L) for 24 h, the expression levels of Bcl-2 and NF-κBP65 mRNA in ACHN cells were decreased while the expression level of Bax mRNA was increased (P < 0.05), and Bcl-2, and NF-κBP65 protein decreased, while Bax and IκB protein increased compared with those in the untreated group. Conclusion: Curcumin inhibited proliferation and increased apoptosis of the human renal cell carcinoma cell line ACHN. These curcumin effects appear to involve up-regulating IκB, down-regulating NF-κB, and regulating the expression of the apoptosis genes Bcl-2/Bax.

  12. Gastroprotective activity of Annona muricata leaves against ethanol-induced gastric injury in rats via Hsp70/Bax involvement.

    Science.gov (United States)

    Moghadamtousi, Soheil Zorofchian; Rouhollahi, Elham; Karimian, Hamed; Fadaeinasab, Mehran; Abdulla, Mahmood Ameen; Kadir, Habsah Abdul

    2014-01-01

    The popular fruit tree of Annona muricata L. (Annonaceae), known as soursop and graviola, is a widely distributed plant in Central and South America and tropical countries. Leaves of A. muricata have been reported to possess antioxidant and anti-inflammatory activities. In this study, the gastroprotective effects of ethyl acetate extract of A. muricata leaves (EEAM) were investigated against ethanol-induced gastric injury models in rats. The acute toxicity test of EEAM in rats, carried out in two doses of 1 g/kg and 2 g/kg, showed the safety of this plant, even at the highest dose of 2 g/kg. The antiulcer study in rats (five groups, n=6) was performed with two doses of EEAM (200 mg/kg and 400 mg/kg) and with omeprazole (20 mg/kg), as a standard antiulcer drug. Gross and histological features showed the antiulcerogenic characterizations of EEAM. There was significant suppression on the ulcer lesion index of rats pretreated with EEAM, which was comparable to the omeprazole effect in the omeprazole control group. Oral administration of EEAM to rats caused a significant increase in the level of nitric oxide and antioxidant activities, including catalase, glutathione, and superoxide dismutase associated with attenuation in gastric acidity, and compensatory effect on the loss of gastric wall mucus. In addition, pretreatment of rats with EEAM caused significant reduction in the level of malondialdehyde, as a marker for oxidative stress, associated with an increase in prostaglandin E2 activity. Immunohistochemical staining also demonstrated that EEAM induced the downregulation of Bax and upregulation of Hsp70 proteins after pretreatment. Collectively, the present results suggest that EEAM has a promising antiulcer potential, which could be attributed to its suppressive effect against oxidative damage and preservative effect toward gastric wall mucus.

  13. Effects of in vitro fertilization and embryo culture on TRP53 and Bax expression in B6 mouse embryos

    Directory of Open Access Journals (Sweden)

    Chami Omar

    2006-11-01

    Full Text Available Abstract In the mouse, embryo culture results in a characteristic phenotype of retarded embryo preimplantation development and reduced numbers of cells within embryos. The expression of TRP53 is central to the regulation of the cell's capacity to proliferate and survive. In this study we found that Trp53 mRNA is expressed throughout the preimplantation stage of development. Levels of TRP53 protein expression were low during the cleavage stages and increased at the morula and blastocyst stages in B6 embryos collected from the reproductive tract. Embryos collected at the zygote stage and cultured for 96 h also showed low levels of TRP53 expression at precompaction stages. There were higher levels of TRP53 in cultured morula and the level in cultured blastocysts was clearly increased above blastocysts collected directly from the uterus. Immunolocalization of TRP53 showed that its increased expression in cultured blastocysts corresponded with a marked accumulation of TRP53 within the nuclei of embryonic cells. This pattern of expression was enhanced in embryos produced by in vitro fertilization and subjected to culture. The TRP53 was transcriptionally active since culture also induced increased expression of Bax, yet this did not occur in embryos lacking Trp53 (Trp53-/-. The rate of development of Trp53-/- zygotes to the blastocyst stage was not different to wildtype controls when embryos were cultured in groups of ten but was significantly faster when cultured individually. The results show that zygote culture resulted in the accumulation of transcription activity of TRP53 in the resulting blastocysts. This accounts for the adverse effects of culture of embryos individually, but does not appear to be the sole cause of the retarded preimplantation stage growth phenotype associated with culture in vitro.

  14. Expression of anti-apoptotic protein Bcl-2 and pro-apoptotic protein Bax after delayed paraplegia induced by ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Bibo Liu; Miao Liu; Duoning Wang; Wei Ma; Shengli Dang

    2006-01-01

    BACKGROUND:Operation of spine does not involve in spinal cord;however,spinal cord injury occurs at post-operation induced by unclear factors.Meanwhile,after decompression of lumbar spinal canal,symptoms are severer and severer.In addition,during extirpation of oervical and lumbar intervertabral disc,spinal cord and its vessels are not damaged,but spinal cord injury is also suffered from patients with partial improvement.All statuses mentioned above are related to expressed changes of bc/-2 gene inhibiting apoptosis and bax gene accelerating apoptosis.OBJECTIVE:To observe motor function of hindlimbs of ischemia/reperfusion model in rabbits at various time points after reperfusion and expressions of apoptosis correlated protein Bcl-2 and Bax.DESIGN:Completely randomized grouping design and contrast study.SEITING:Department of Orthopedics,the First Affiliated Hospital of Medical School,Xi'an Jiao Tong University.MATERIALS:Forty-eight New Zealand white rabbits of both genders were randomly divided into sham operation group(n=24) and model group(n=24),and then,rabbits in each group were observed at four time points:8,24,72 and 168 hours after reperfusion,with 6 in each time point.Rabbit-anti-rabbit Bcl-2 antibody and rabbit-anti-rabbit Bax antibody were provided by Boster Company.The procedures were accordant to the METHODS:The experiment was carried out at Laboratory of Orthopaedics of First Affiliated Hospital of Medical School,Xi'an Jiao Tong University from April to August 2005.①Delayed paralysis models of spinal cord after ischemia/reperfusion were established based on method of Zivin et al.Animals in sham operation group underwent an exposure of abdominal aorta but the aorta was not occluded.②Motor function of hindlimb was observed 8,24,72 and 168 hours after reperfusion.A grade of 0-5 was assigned to each animal (grade 0:no voluntary hind limb function;grade 5:normal hop;grades 0-3:paraplegia).③The lumbar segment of the spinal cord(L3 to L5)was used for

  15. Exercise Preconditioning Decreases the Ratio of bax/bcl-2 mRNA Expression in Midbrain of Mouse Model with Parkinson's Disease%运动预适应下调帕金森小鼠中脑bax/bcl-2 mRNA表达比值

    Institute of Scientific and Technical Information of China (English)

    薛宏斌; 张勇; 刘洪涛; 马强

    2009-01-01

    目的:探讨运动预适应是否下调帕金森小鼠中脑细胞bax/bcl-2 mRNA表达比值.方法:32只雄性小鼠(8~9周龄)首先随机分为安静组、运动组.运动组连续5周,每天1次中等强度(12米/分,20分钟)跑台训练.然后以上两组再各自随机分成两组,于训练结束后第2天分别注射生理盐水或中等剂量MPTP(30mg/kg×2次).只有表现典型行为变化的MPTP小鼠被认为是成功帕金森模型小鼠,进入最终分组,分为安静+生理盐水组(Se+Sa)、运动+生理盐水组(E+Sa)、安 +MPTP组(Se+M)、运 +MPTP组(E+M)4组,每组8只.训练结束后第11天处死动物,检测小鼠中脑bax、bcl-2 mRNA表达,计算bax/bcl-2 mRNA表达比值.结果:E+M组小鼠中脑bax mRNA表达较Se+M组显著降低(P<0.05),E+M组bcl-2 mRNA表达较Se+M组显著增加(P<0.05),E+M组bax/bcl-2比值显著小于Se+M组(P<0.05).结论:运动预适应改变帕金森小鼠中脑黑质细胞凋亡信号分子bcl-2、bax mRNA表达,降低bax/bcl-2 mRNA表达比值.

  16. Ginkgo biloba leaf extract effects on inducible nitric oxide synthase, Bcl-2, and Bax expression in rat models of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Jiejun Jiao; Bin Du

    2008-01-01

    BACKGROUND: Ginkgo biloba leaf extract exhibits neuroprotective effects in spinal cord injury. However,the mechanisms of action remain unclear.OBJECTIVE: To investigate inducible nitric oxide synthase (iNOS) and Bcl-2/Bax expression in the injured spinal cord, and to explore the neuroprotective mechanisms of ginkgo biloba leaf extract in rats with spinal cord injury.DESIGN, TIME AND SETTING: The randomized, controlled, cell molecular biology experiment was performed at Soochow University, China from March 2007 to March 2008.MATERIALS: A total of 120 healthy, adult Sprague Dawley rats were selected for this study. Rat models of moderate acute thoracic (T9) spinal cord injury were established using the modified Allen method.Shuxuening injection was obtained from Zhenbaodao Pharmaceutical Co., Ltd., China. Methylprednisolone was purchased from North China Pharmaceutical Co., Ltd.METHODS: All rats were equally and randomly divided into four groups. Only the spinal cord was exposed in the sham operation group rats. In the trauma group, rats were not treated with drugs following spinal cord injury. Rats in the hormone group were intraperitoneally injected with 30 mg/kg methylprcdnisolone following spinal cord injury. Rats in the ginkgo biloba leaf extract group were intraperitoneally infused with a 1.0 mL/kg Shuxuening injection per day.MAIN OUTCOME MEASURES: At l hour, as well as 1, 3, 5, 7, and 14 days after spinal cord injury,iNOS- and Bcl-2/Bax-positive cells were quantified with immunohistochemistry. Pathological changes were detected using hematoxylin-eosin staining under an optical microscope.RESULTS: Spinal cord injury in the ginkgo biloba leaf extract and hormone groups was milder compared with the trauma group. Demyelination was significantly ameliorated and the necrotic cavity was obviously reduced in the injured spinal cord of rats in the ginkgo biloba leaf extract and hormone groups at each time point, iNOS expression was increased in the injured spinal cord

  17. Effects of exercises on mitochondrial permeability transition pore,and bcl-2 and bax mRNA expression in rat skeletal muscle%骨骼肌细胞线粒体通透性转换孔及bcl-2和bax mRNA表达与运动

    Institute of Scientific and Technical Information of China (English)

    王冬梅; 漆正堂; 丁树哲

    2011-01-01

    BACKGROUND:Exercises influence the apoptosis of skeletal muscle cells and mitochondrial pathway is one of important pathways mediating cellular apoptosis.OBJECTIVE:To investigate the effects of exercises on mitochondrial permeability transition pore, and bcl-2 and bax mRNA expression in rat skeletal muscle .METHODS:Twenty-four Sprague-Dawley male rats were randomly divided into three groups: the control group, 6-week swimming training group (six swimming trainings per week) and one -off exhaustive swimming group (one -off exhaustive swimming exercise).The opening state of mitochondrial permeability transition pore in skeletal muscle was examined with ultraviolet spectrophotometer,and the mRNA expression of bcl-2 and bax in rat skeletal muscle was determined by reverse transcription-polymerase chain reaction.RESULTS AND CONCLUSION:6-week swimming training resulted in significant increase of bcl-2 mRNA expression and significant decrease of bax mRNA expression , as well as significant increase of bcl-2lbax mRNA (P < 0.01) but the opening state of mitochondrial permeability transition pore was not altered obviously, compared with the control group. The opening state of mitochondrial permeability transition pore was significantly increased (P < 0.01), bcl-2 mRNA expression was significantly decreased, bax mRNA expression was significantly increased, bcl-2/bax mRNA expression was significantly decreased in the one-off exhaustive swimming group than in the control group (P < 0.01). These findings suggest that exercise training can regulate skeletal muscle cell apoptosis by altering the opening stage of mitochondrial permeability transition pore and regulating bcl-2/bax mRNA expression in rat skeletal muscle.%背景:运动影响骨骼肌细胞的凋亡,而线粒体途径是介导细胞凋亡的一个重要途径.目的:研究运动对大鼠骨骼肌线粒体通透性转换孔、凋亡调控基因bcl-2 和bax 表达的影响.方法:将24 只成

  18. Garlic ((Allium sativum)) Fresh Juice Induces Apoptosis in Human Oral Squamous Cell Carcinoma: The Involvement of Caspase-3, Bax and Bcl-2.

    Science.gov (United States)

    Farhadi, Farrokh; Jahanpour, Salar; Hazem, Kameliya; Aghbali, Amirala; Baradran, Behzad; Vahid Pakdel, Seyyed Mahdi

    2015-01-01

    Background and aims. There is no report on the apoptotic impact of Allium sativum L.(Garlic) on the oral squamous cell carcinoma (KB); hence, this study was designed to survey the apoptotic effects of garlic fresh juice (GFJ) on the KB cells. Materials and methods. MTTassay (MicrocultureTetrazolium Assay) was carried out to evaluate the cytotoxicity of GFJ on KB cells. Furthermore, TUNEL(Terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling)and DNA fragmentation tests were performed to determine if GFJ is able to induce apoptosis in KB cells. Also a standard kit was used to assess caspase-3 activity in KB cells. Also western blotting was employed to evaluate the effect of GFJ on Bax:Bcl-2 ratio. Results. Significant cytotoxic effects were observed for the minimum used concentration (1μg/mL) as calculated to be 77.97±2.3% for 24 h and 818±3.1% for 36h of incubation (P < 0.001). Furthermore, TUNEL and DNA fragmentation tests corroborated the apoptosis inducing activity of GFJ. Consistently, after treating KB cells with GFJ(1μg/mL), caspase-3 activity and Bax:Bcl-2 ratio were raised by 7.3±0.6 and (P <0.001) folds, respectively. Conclusion. The results of this study advanced that GFJ induces apoptosis in the KB cells through increasing caspase-3 activity and Bax:Bcl2 ratio which could be attributed to its organo-sulfurcomponents. PMID:26889365

  19. Dexamethasone protected human glioblastoma U87MG cells from temozolomide induced apoptosis by maintaining Bax:Bcl-2 ratio and preventing proteolytic activities

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    Patel Sunil J

    2004-12-01

    Full Text Available Abstract Background Glioblastoma is the deadliest and most prevalent brain tumor. Dexamethasone (DXM is a commonly used steroid for treating glioblastoma patients for alleviation of vasogenic edema and pain prior to treatment with chemotherapeutic drugs. Temozolomide (TMZ, an alkylating agent, has recently been introduced in clinical trials for treating glioblastoma. Here, we evaluated the modulatory effect of DXM on TMZ induced apoptosis in human glioblastoma U87MG cells. Results Freshly grown cells were treated with different doses of DXM or TMZ for 6 h followed by incubation in a drug-free medium for 48 h. Wright staining and ApopTag assay showed no apoptosis in cells treated with 40 μM DXM but considerable amounts of apoptosis in cells treated with 100 μM TMZ. Apoptosis in TMZ treated cells was associated with an increase in intracellular free [Ca2+], as determined by fura-2 assay. Western blot analyses showed alternations in the levels of Bax (pro-apoptotic and Bcl-2 (anti-apoptotic proteins resulting in increased Bax:Bcl-2 ratio in TMZ treated cells. Western blot analyses also detected overexpression of calpain and caspase-3, which cleaved 270 kD α-spectrin at specific sites for generation of 145 and 120 kD spectrin break down products (SBDPs, respectively. However, 1-h pretreatment of cells with 40 μM DXM dramatically decreased TMZ induced apoptosis, decreasing Bax:Bcl-2 ratio and SBDPs. Conclusion Our results revealed an antagonistic effect of DXM on TMZ induced apoptosis in human glioblastoma U87MG cells, implying that treatment of glioblastoma patients with DXM prior to chemotherapy with TMZ might result in an undesirable clinical outcome.

  20. Suppression of the Arboviruses Dengue and Chikungunya Using a Dual-Acting Group-I Intron Coupled with Conditional Expression of the Bax C-Terminal Domain.

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    James R Carter

    Full Text Available In portions of South Asia, vectors and patients co-infected with dengue (DENV and chikungunya (CHIKV are on the rise, with the potential for this occurrence in other regions of the world, for example the United States. Therefore, we engineered an antiviral approach that suppresses the replication of both arboviruses in mosquito cells using a single antiviral group I intron. We devised unique configurations of internal, external, and guide sequences that permit homologous recognition and splicing with conserved target sequences in the genomes of both viruses using a single trans-splicing Group I intron, and examined their effectiveness to suppress infections of DENV and CHIKV in mosquito cells when coupled with a proapoptotic 3' exon, ΔN Bax. RT-PCR demonstrated the utility of these introns in trans-splicing the ΔN Bax sequence downstream of either the DENV or CHIKV target site in transformed Aedes albopictus C6/36 cells, independent of the order in which the virus specific targeting sequences were inserted into the construct. This trans-splicing reaction forms DENV or CHIKV ΔN Bax RNA fusions that led to apoptotic cell death as evidenced by annexin V staining, caspase, and DNA fragmentation assays. TCID50-IFA analyses demonstrate effective suppression of DENV and CHIKV infections by our anti-arbovirus group I intron approach. This represents the first report of a dual-acting Group I intron, and demonstrates that we can target DENV and CHIKV RNAs in a sequence specific manner with a single, uniquely configured CHIKV/DENV dual targeting group I intron, leading to replication suppression of both arboviruses, and thus providing a promising single antiviral for the transgenic suppression of multiple arboviruses.

  1. Differential regulation of spontaneous and immune complex-induced neutrophil apoptosis by proinflammatory cytokines. Role of oxidants, Bax and caspase-3.

    Science.gov (United States)

    Ottonello, Luciano; Frumento, Guido; Arduino, Nicoletta; Bertolotto, Maria; Dapino, Patrizia; Mancini, Marina; Dallegri, Franco

    2002-07-01

    Neutrophil apoptosis represents a crucial step in the mechanisms governing the resolution of neutrophilic inflammation. Several soluble mediators of inflammation modulate neutrophil survival, retarding their apoptosis, whereas neutrophil activation by immune complexes (IC) results in the acceleration of apoptosis. To investigate neutrophil fate at the site of inflammation, we studied the effects of interleukin (IL)-2, IL-6, IL-8, IL-15, GM-CSF, and fMLP on spontaneous and IC-induced neutrophil apoptosis and the mechanisms regulating the survival of these cells. Spontaneous apoptosis was inhibited by GM-CSF, IL-6, and IL-15, but only GM-CSF overturned IC-induced apoptosis. No role of oxidants on the modulation of IC-dependent apoptosis was found. Indeed, fMLP or GM-CSF augmented the IC-dependent oxidative response, whereas the other compounds were ineffective. CGD neutrophils showed low levels of spontaneous apoptosis, but when exposed to IC, underwent a sharp increment of the apoptotic rate in a GM-CSF-inhibitable manner. Conversely, the expression of the proapoptotic protein Bax in 18-h aged neutrophils was down-regulated by GM-CSF, IL-6, and IL-15. Furthermore, IC induced a nearly threefold Bax up-regulation, which was completely reversed only by GM-CSF. Accordingly, the spontaneous activity of caspase-3 was inhibited by GM-CSF, IL-6, and IL-15. Furthermore, IC induced a sharp increment of enzymatic activity, and only GM-CSF inhibited the IC-dependent acceleration. Our results show that apoptosis of resting and IC-activated neutrophils is regulated differently, GM-CSF being the most potent neutrophil antiapoptotic factor. The results also unveil the existence of an oxidant-independent, Bax- and caspase-3-dependent, intracellular pathway regulating neutrophil apoptosis.

  2. Bone Marrow Stromal Cells Promote Neuronal Restoration in Rats with Traumatic Brain Injury: Involvement of GDNF Regulating BAD and BAX Signaling

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    Qin Shen

    2016-02-01

    Full Text Available Background/Aims: To investigate the effects of bone marrow stromal cells (BMSCs and underlying mechanisms in traumatic brain injury (TBI. Methods: Cultured BMSCs from green fluorescent protein-transgenic mice were isolated and confirmed. Cultured BMSCs were immediately transplanted into the regions surrounding the injured-brain site to test their function in rat models of TBI. Neurological function was evaluated by a modified neurological severity score on the day before, and on days 7 and 14 after transplantation. After 2 weeks of BMSC transplantation, the brain tissue was harvested and analyzed by microarray assay. And the coronal brain sections were determined by immunohistochemistry with mouse anti-growth-associated protein-43 kDa (anti-GAP-43 and anti-synaptophysin to test the effects of transplanted cells on the axonal regeneration in the host brain. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL assay and Western blot were used to detect the apoptosis and expression of BAX and BAD. Results: Microarray analysis showed that BMSCs expressed growth factors such as glial cell-line derived neurotrophic factor (GDNF. The cells migrated around the injury sites in rats with TBI. BMSC grafts resulted in an increased number of GAP-43-immunopositive fibers and synaptophysin-positive varicosity, with suppressed apoptosis. Furthermore, BMSC transplantation significantly downregulated the expression of BAX and BAD signaling. Moreover, cultured BMSC transplantation significantly improved rat neurological function and survival. Conclusion: Transplanted BMSCs could survive and improve neuronal behavior in rats with TBI. Mechanisms of neuroprotection and regeneration were involved, which could be associated with the GDNF regulating the apoptosis signals through BAX and BAD.

  3. Bax, Bcl2, and p53 differentially regulate neomycin- and gentamicin-induced hair cell death in the zebrafish lateral line.

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    Coffin, Allison B; Rubel, Edwin W; Raible, David W

    2013-10-01

    Sensorineural hearing loss is a normal consequence of aging and results from a variety of extrinsic challenges such as excessive noise exposure and certain therapeutic drugs, including the aminoglycoside antibiotics. The proximal cause of hearing loss is often death of inner ear hair cells. The signaling pathways necessary for hair cell death are not fully understood and may be specific for each type of insult. In the lateral line, the closely related aminoglycoside antibiotics neomycin and gentamicin appear to kill hair cells by activating a partially overlapping suite of cell death pathways. The lateral line is a system of hair cell-containing sense organs found on the head and body of aquatic vertebrates. In the present study, we use a combination of pharmacologic and genetic manipulations to assess the contributions of p53, Bax, and Bcl2 in the death of zebrafish lateral line hair cells. Bax inhibition significantly protects hair cells from neomycin but not from gentamicin toxicity. Conversely, transgenic overexpression of Bcl2 attenuates hair cell death due to gentamicin but not neomycin, suggesting a complex interplay of pro-death and pro-survival proteins in drug-treated hair cells. p53 inhibition protects hair cells from damage due to either aminoglycoside, with more robust protection seen against gentamicin. Further experiments evaluating p53 suggest that inhibition of mitochondrial-specific p53 activity confers significant hair cell protection from either aminoglycoside. These results suggest a role for mitochondrial p53 activity in promoting hair cell death due to aminoglycosides, likely upstream of Bax and Bcl2.

  4. Punicalagin attenuated cerebral ischemia-reperfusion insult via inhibition of proinflammatory cytokines, up-regulation of Bcl-2, down-regulation of Bax, and caspase-3.

    Science.gov (United States)

    Yaidikar, Lavanya; Thakur, Santhrani

    2015-04-01

    Punicalagin (PG) is a hydrolysable tannin compound found in Punica granatum L. The purpose of the present work is to explore the neuroprotective mechanism of PG against ischemia-reperfusion (I/R) injury in rat model of middle cerebral artery occlusion (MCAO). Rats were randomly divided into sham, MCAO, and PG-treated groups. PG (15 and 30 mg/kg), the vehicle was administered orally for 7 days prior to MCAO. Rats were anesthetised with ketamine (100 mg/kg/im), xylazine (10 mg/kg/im) and subjected to 2 h occlusion and 22 h reperfusion. The effects of PG on behavioral deficit and infarct volume, the levels of glutamate and calcium as well as the levels of inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) were evaluated. Moreover, the expressions of caspase-3, Bcl-2, and Bax were detected by Western blotting. As compared with MCAO group, PG-treated rats showed dose-dependent reduction in infarct volume and substantial improvement in behavioral deficit. The levels of glutamate, calcium, TNF-α, IL-1β, and IL-6 were restored significantly. The Western blotting results revealed that the expression of Bcl-2 was up-regulated and that of caspase-3, Bax were down-regulated when exposed to PG. From our results, it can be concluded that PG showed an ameliorative effect against cerebral I/R injury in rats through its anti-inflammatory, antioxidant actions besides it inhibits excitotoxicity. It also suppresses apoptosis through regulating, Bcl-2, caspase-3, and Bax protein expressions, perhaps another mechanism by which PG employs its neuroprotective action. PMID:25555468

  5. Multiple doses of erythropoietin impair liver regeneration by increasing TNF-alpha, the Bax to Bcl-xL ratio and apoptotic cell death.

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    Katja Klemm

    Full Text Available BACKGROUND: Liver resection and the use of small-for-size grafts are restricted by the necessity to provide a sufficient amount of functional liver mass. Only few promising strategies to maximize liver regeneration are available. Apart from its erythropoiesis-stimulating effect, erythropoietin (EPO has meanwhile been recognized as mitogenic, tissue-protective, and anti-apoptotic pleiotropic cytokine. Thus, EPO may support regeneration of hepatic tissue. METHODOLOGY: Rats undergoing 68% hepatectomy received daily either high dose (5000 IU/kg bw i.v. or low dose (500 IU/kg bw i.v. recombinant human EPO or equal amounts of physiologic saline. Parameters of liver regeneration and hepatocellular apoptosis were assessed at 24 h, 48 h and 5 d after resection. In addition, red blood cell count, hematocrit and serum EPO levels as well as plasma concentrations of TNF-alpha and IL-6 were evaluated. Further, hepatic Bcl-x(L and Bax protein expression were analyzed by Western blot. PRINCIPAL FINDINGS: Administration of EPO significantly reduced the expression of PCNA at 24 h followed by a significant decrease in restitution of liver mass at day 5 after partial hepatectomy. EPO increased TNF-alpha levels and shifted the Bcl-x(L to Bax ratio towards the pro-apoptotic Bax resulting in significantly increased hepatocellular apoptosis. CONCLUSIONS: Multiple doses of EPO after partial hepatectomy increase hepatocellular apoptosis and impair liver regeneration in rats. Thus, careful consideration should be made in pre- and post-operative recombinant human EPO administration in the setting of liver resection and transplantation.

  6. Involvement of NF-κB and Bcl2/Bax signaling pathways in the apoptosis of MCF7 cells induced by a xanthone compound Pyranocycloartobiloxanthone A.

    Science.gov (United States)

    Mohan, Syam; Abdelwahab, Siddig Ibrahim; Kamalidehghan, Behnam; Syam, Suvitha; May, Koh Sue; Harmal, Nabil Saad Mohammed; Shafifiyaz, Noor; Hadi, A Hamid A; Hashim, Najihah Mohd; Rahmani, Mawardi; Taha, Manal Mohamed Elhassan; Cheah, Shiau-Chuen; Zajmi, Asdren

    2012-08-15

    The plant Artocarpus obtusus is a tropical plant that belongs to the family Moraceae. In the present study a xanthone compound Pyranocycloartobiloxanthone A (PA) was isolated from this plant and the apoptosis mechanism was investigated. PA induced cytotoxicity was observed using MTT assay. High content screening (HCS) was used to observe the nuclear condensation, cell permeability, mitochondrial membrane potential (MMP) and cytochrome c release. Reactive oxygen species formation was investigated on treated cells by using fluorescent analysis. Human apoptosis proteome profiler assays were performed to investigate the mechanism of cell death. In addition mRNA levels of Bax and Bcl2 were also checked using RT-PCR. Caspase 3/7, 8 and 9 were measured for their induction while treatment. The involvement of NF-κB was analyzed using HCS assay. The results showed that PA possesses the characteristics of selectively inducing cell death of tumor cells as no inhibition was observed in non-tumorigenic cells even at 30 μg/ml. Treatment of MCF7 cells with PA induced apoptosis with cell death-transducing signals, that regulate the MMP by down-regulation of Bcl2 and up-regulation of Bax, triggering the cytochrome c release from mitochondria to cytosol. The release of cytochrome c triggered the activation of caspases-9, then activates downstream executioner caspase-3/7 and consequently cleaved specific substrates leading to apoptotic changes. This form of apoptosis was found closely associated with the extrinsic pathway caspase (caspase-8) and inhibition of translocation of NF-κB from cytoplasm to nucleus. The results demonstrated that PA induced apoptosis of MCF7 cells through NF-κB and Bcl2/Bax signaling pathways with the involvement of caspases.

  7. Structural and energetical studies of the adsorption of para and meta-isomers of xylene on pre-hydrated zeolite BaX. Characterization by neutron diffraction and temperature programmed desorption; Etude structurale et energetique de l'adsorption des isomeres para- et meta- du xylene dans la zeolithe BaX prehydratee. Caracterisation par diffraction des neutrons et thermodesorption programmee

    Energy Technology Data Exchange (ETDEWEB)

    Pichon, Ch.

    1999-10-19

    The separation of p-xylene from C{sub 8} aromatics is performed industrially by selective adsorption on zeolitic materials. FAU-type zeolites are currently used for this separation and especially the partially hydrated BaX. The aim of this work is to characterize from a structural (by low temperature neutron powder diffraction) and an energetical (by temperature programmed desorption) point of view, the adsorption of para- and meta- isomers of xylene, for different fillings, as pure substances as well as mixtures, on pre-hydrated zeolite BaX. The influence of the water pre-adsorption on xylene adsorption selectivity is carefully discussed. The crystalline structure of the zeolite BaX (framework and compensation of charge cations) and of the adsorbed phase (water, p- and m-xylene molecules) are completely characterized by neutron diffraction. The location and the distribution of water and xylene molecules on their adsorption sites is especially followed as a function of the filling of the zeolite and of the composition of the adsorbed phase. Microscopic measurements were correlated to the energetical analysis (at a macroscopic level) in order to obtain a consistent description of adsorption phenomenon and to propose a possible origin for adsorption selectivity.

  8. Asiaticoside: attenuation of neurotoxicity induced by MPTP in a rat model of Parkinsonism via maintaining redox balance and up-regulating the ratio of Bcl-2/Bax.

    Science.gov (United States)

    Xu, Chang-Liang; Wang, Qi-Zhi; Sun, Ling-Mei; Li, Xiu-Min; Deng, Ji-Min; Li, Lu-Fan; Zhang, Jin; Xu, Rong; Ma, Shi-Ping

    2012-01-01

    In this study, we investigated the neuroprotective effects of asiaticoside, a triterpenoid saponin isolated from the Chinese medicinal herb Centella asiatica, in the rats model of Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Rats were first injected with MPTP. One day after surgery, asiaticoside was administered and the behavioral tests were assessed. On 14th day, the rats were sacrificed, substantia nigra (SN) and striatum were dissected, and then dopamine (DA) and its metabolites in striatum and malonyldialdehyde (MDA) contents, reduced glutathione (GSH) level and gene expression level in SN were estimated. Treatment with asiaticoside was found to protect dopaminergic neuron by antagonizing MPTP induced neurotoxicity and to improve locomotor dysfunction. Asiaticoside significantly attenuated the MPTP-induced reduction of dopamine in the striatum. The content of MDA was significantly decreased while the GSH level was significantly increased in asiaticoside-treated groups. In addition, asiaticoside increased the Bcl-2/Bax ratio. These results indicated that asiaticoside was effective in reversing MPTP induced Parkinsonism via its neuroprotective effects including antioxidant activity, maintaining the metabolic balance of DA, and increasing ratio of Bcl-2/Bax.

  9. Matrine inhibits diethylnitrosamine-induced HCC proliferation in rats through inducing apoptosis via p53, Bax-dependent caspase-3 activation pathway and down-regulating MLCK overexpression.

    Science.gov (United States)

    Zhang, Xiaolin; Yu, Hao

    2016-01-01

    The proliferation of hepatocellular carcinoma (HCC) cells is one of the leading causes of liver cancer mortality in humans. The inhibiting effects of matrine on HCC cell proliferation have been studied, but the mechanism of that inhibition has not been fully elucidated. Since, apoptosis plays an important role in HCC cell proliferation. We examined the apoptosis-inducing effect of matrine on tumor cells. Western blot analysis of p53, Bax, cleaved caspase-3 and myosin light chain kinase (MLCK) revealed that matrine induced tumor cell apoptosis by controlling anoikis. It activated p53, Bax-dependent caspase-3 and blocked the ECM-integrin mediated cell survival pathway through down-regulating MLCK over-expression in the liver of rats with diethyl nitrosamine (DENA)-induced HCC. Our results suggest that matrine can inhibit the proliferation of HCC cells through inducing tumor cell apoptosis via activation of the p53 pathway and inhibition of MLCK overexpression. Matrine may thus be used as a potentially promising reagent to inhibit HCC cell proliferation and MLCK may be a novel target for the treatment of HCC. PMID:27642320

  10. Levofloxacin increases the effect of serum deprivation on anoikis of rat nucleus pulposus cells via Bax/Bcl-2/caspase-3 pathway.

    Science.gov (United States)

    Yang, Si-Dong; Bai, Zhi-Long; Zhang, Feng; Ma, Lei; Yang, Da-Long; Ding, Wen-Yuan

    2014-12-01

    Levofloxacin, a fluoroquinolone, is a widely-used and effective antibiotic. However, various adverse side effects are associated with levofloxacin. The purpose of this study was to further explore the effects of levofloxacin on rat nucleus pulposus cells (NPCs). Inverted phase-contrast microscopy, flow cytometry and caspase-3 activity assays were used and revealed that serum deprivation induced apoptosis, which was markedly increased by levofloxacin in a dose-dependent manner. Simultaneously, levofloxacin decreased cell binding to type II collagen (COL2). Thus, levofloxacin-induced apoptosis exhibits characteristics of anoikis, the process by which cell death is triggered by separation from the extracellular matrix, which contains COL2. Furthermore, real-time quantitative RT-PCR was used to further confirm that levofloxacin downregulates COL2 expression in a dose-dependent manner. At last, western blot was used to find that levofloxacin increased the ratio of Bax/Bcl-2 and active caspase-3 in a dose-dependent manner. Levofloxacin therefore increases the effects of serum deprivation on anoikis by downregulating COL2 in rat NPCs in vitro via Bax/Bcl-2/caspase-3 pathway. This research provides a novel insight into the mechanisms of levofloxacin-induced toxicity and may potentially lead to a better understanding of the clinical effects of levofloxacin, especially in terms of intervertebral disc degeneration. PMID:25224805

  11. Inotodiol inhabits proliferation and induces apoptosis through modulating expression of cyclinE, p27, bcl-2, and bax in human cervical cancer HeLa cells.

    Science.gov (United States)

    Zhao, Li-Wei; Zhong, Xiu-Hong; Yang, Shu-Yan; Zhang, Yi-Zhong; Yang, Ning-Jiang

    2014-01-01

    Inonotus obliquus is a medicinal mushroom that has been used as an effective agent to treat various diseases such as diabetes, tuberculosis and cancer. Inotodiol, an included triterpenoid shows significant anti-tumor effect. However, the mechanisms have not been well documented. In this study, we aimed to explore the effect of inotodiol on proliferation and apoptosis in human cervical cancer HeLa cells and investigated the underlying molecular mechanisms. HeLa cells were treated with different concentrations of inotodiol. The MTT assay was used to evaluate cell proliferating ability, flow cytometry (FCM) was employed for cell cycle analysis and cell apoptosis, while expression of cyclinE, p27, bcl-2 and bax was detected by immunocytochemistry. Proliferation of HeLa cells was inhibited by inotodiolin a dose-dependent manner at 24h (r=0.9999, pInonotus obliquus inhibited the proliferation of HeLa cells and induced apoptosis in vitro. The mechanisms may be related to promoting apoptosis through increasing the expression of bax and cutting bcl-2 and affecting the cell cycle by down-regulation the expression of cyclin E and up-regulation of p27. The results further indicate the potential value of inotodiol for treatment of human cervical cancer. PMID:24815470

  12. Matrine inhibits diethylnitrosamine-induced HCC proliferation in rats through inducing apoptosis via p53, Bax-dependent caspase-3 activation pathway and down-regulating MLCK overexpression.

    Science.gov (United States)

    Zhang, Xiaolin; Yu, Hao

    2016-01-01

    The proliferation of hepatocellular carcinoma (HCC) cells is one of the leading causes of liver cancer mortality in humans. The inhibiting effects of matrine on HCC cell proliferation have been studied, but the mechanism of that inhibition has not been fully elucidated. Since, apoptosis plays an important role in HCC cell proliferation. We examined the apoptosis-inducing effect of matrine on tumor cells. Western blot analysis of p53, Bax, cleaved caspase-3 and myosin light chain kinase (MLCK) revealed that matrine induced tumor cell apoptosis by controlling anoikis. It activated p53, Bax-dependent caspase-3 and blocked the ECM-integrin mediated cell survival pathway through down-regulating MLCK over-expression in the liver of rats with diethyl nitrosamine (DENA)-induced HCC. Our results suggest that matrine can inhibit the proliferation of HCC cells through inducing tumor cell apoptosis via activation of the p53 pathway and inhibition of MLCK overexpression. Matrine may thus be used as a potentially promising reagent to inhibit HCC cell proliferation and MLCK may be a novel target for the treatment of HCC.

  13. Hsp105 family proteins suppress staurosporine-induced apoptosis by inhibiting the translocation of Bax to mitochondria in HeLa cells

    International Nuclear Information System (INIS)

    Hsp105 (Hsp105α and Hsp105β), major heat shock proteins in mammalian cells, belong to a subgroup of the HSP70 family, HSP105/110. Previously, we have shown that Hsp105α has completely different effects on stress-induced apoptosis depending on cell type. However, the molecular mechanisms by which Hsp105α regulates stress-induced apoptosis are not fully understood. Here, we established HeLa cells that overexpress either Hsp105α or Hsp105β by removing doxycycline and examined how Hsp105 modifies staurosporine (STS)-induced apoptosis in HeLa cells. Apoptotic features such as the externalization of phosphatidylserine on the plasma membrane and nuclear morphological changes were induced by the treatment with STS, and the STS-induced apoptosis was suppressed by overexpression of Hsp105α or Hsp105β. In addition, we found that overexpression of Hsp105α or Hsp105β suppressed the activation of caspase-3 and caspase-9 by preventing the release of cytochrome c from mitochondria. Furthermore, the translocation of Bax to mitochondria, which results in the release of cytochrome c from the mitochondria, was also suppressed by the overexpression of Hsp105α or Hsp105β. Thus, it is suggested that Hsp105 suppresses the stress-induced apoptosis at its initial step, the translocation of Bax to mitochondria in HeLa cells

  14. Matrine inhibits diethylnitrosamine-induced HCC proliferation in rats through inducing apoptosis via p53, Bax-dependent caspase-3 activation pathway and down-regulating MLCK overexpression

    Science.gov (United States)

    Zhang, Xiaolin; Yu, Hao

    2016-01-01

    The proliferation of hepatocellular carcinoma (HCC) cells is one of the leading causes of liver cancer mortality in humans. The inhibiting effects of matrine on HCC cell proliferation have been studied, but the mechanism of that inhibition has not been fully elucidated. Since, apoptosis plays an important role in HCC cell proliferation. We examined the apoptosis-inducing effect of matrine on tumor cells. Western blot analysis of p53, Bax, cleaved caspase-3 and myosin light chain kinase (MLCK) revealed that matrine induced tumor cell apoptosis by controlling anoikis. It activated p53, Bax-dependent caspase-3 and blocked the ECM-integrin mediated cell survival pathway through down-regulating MLCK over-expression in the liver of rats with diethyl nitrosamine (DENA)-induced HCC. Our results suggest that matrine can inhibit the proliferation of HCC cells through inducing tumor cell apoptosis via activation of the p53 pathway and inhibition of MLCK overexpression. Matrine may thus be used as a potentially promising reagent to inhibit HCC cell proliferation and MLCK may be a novel target for the treatment of HCC. PMID:27642320

  15. Insulin-like growth factor-1 protects against prion peptide-induced cell death in neuronal cells via inhibition of Bax translocation.

    Science.gov (United States)

    Park, Yang-Gyu; Jeong, Jae-Kyo; Moon, Myung-Hee; Lee, Ju-Hee; Lee, You-Jin; Seol, Jae-Won; Kim, Shang-Jin; Kang, Seog-Jin; Park, Sang-Youel

    2012-11-01

    Insulin-like growth factor-1 (IGF-1) is one of the most important components of bovine colostrum. It exhibits antiapoptotic and antioxidative activities. Prion diseases are neurodegenerative disorders caused by cell death through mitochondrial dysfunction and increasing generation of reactive oxygen species (ROS). This study examined the protective effect of IGF-1 on residues 106-126 of the cellular prion protein [PrP (106-126)]-mediated mitochondrial neurotoxicity and oxidative stress. In SH-SY5Y human neuronal cells, treatment with PrP (106-126) decreased the cell viability and IGF-1 pretreatment markedly blocked the PrP (106-126)-induced neuronal cell death. IGF-1 inhibited PrP (106-126)-induced intracellular ROS generation and mitochondrial oxidative stress. In addition, IGF-1 blocked the translocation of the Bax protein to the mitochondria induced by PrP (106-126). These results demonstrate that IGF-1 protects neuronal cells against PrP (106-126)-mediated neurotoxicity through an antioxidative effect and blockage of mitochondrial Bax translocation. The results also suggest that regulation of IGF-1 secretion may have a therapeutic potential in the management of mitochondrial dysfunction and oxidative stress-induced neurodegeneration. PMID:22895829

  16. 苦参碱对 HaCaT 细胞 Bcl -2/Bax 和Fas/FasL 的调控%Regulation of Bcl-2/Bax and Fas/FasL by matrine in HaCaT cells

    Institute of Scientific and Technical Information of China (English)

    牟宽厚; 周艳; 韩丹; 穆欣

    2014-01-01

    目的:明确苦参碱对 HaCaT 细胞 Bcl-2/ Bax 和 Fas/ FasL 表达的影响。方法:体外培养HaCaT 细胞,选择第二代细胞对数生长期 HaCaT 细胞作为研究对象,将细胞随机分为4组:苦参碱2 mg/ mL、10 mg/ mL 和50 mg/ mL 3组及对照组(加入相同体积的0.9%盐水),孵育48 h 后,MTT 法测定各浓度下细胞增殖,RT-PCR 检测 Bcl-2/ Bax 和 Fas/ FasL 的表达。结果:与对照组相比,当苦参碱浓度为2 mg/ mL 时,HaCaT 细胞增殖活性无明显变化;Bcl -2、Bax、Fas、FasL 表达也无明显变化( P>0.05)。当苦参碱浓度为10 mg/ mL 时 HaCaT 细胞增殖活性较对照组明显下降(P0.05)。结论:苦参碱能够调控上皮细胞致炎因子的表达,抑制细胞的增殖。%To determine the effect of matrine on Bcl-2/ Bax and Fas/ FasL in keratinocytes in vitro. Methods: Second generation cultured HaCaT cells (logarithmic phase cells) were selected and divided into 4 groups:3 matrine groups (2 mg/ mL, 10 mg/ mL and 50 mg/ mL were used in each group) and the control group (0.9% Natrii Chloride). After 48-hour culture, the proliferation of HaCaT were detected by MTT and the levels of Bcl-2/ Bax and Fas/ FasL were measured by RT-PCR. Results: The viability of HaCaT cells was similar in 2 mg/ mL matrine group and control group (P>0.05). In 10 mg/ mL matrine group the proliferation of the cells was significantly decreased (P<0.001) and the Bcl-2 expression was remarkably reduced (P<0.001), while the expression of Bax, Fas and FasL was significantly increased (P<0.01 and P<0.05, respectively). When the concentration of matrine was increased to 50 mL, the viability and the expression of Bcl-2, Bax, Fas and FasL was similar to the results when 10 mL matrine was used. Conclusion: Matrine can inhibit HaCaT cells proliferation (at 10 mg/ mL or more) and may adjust expression of Bcl-2/ Bax and Fas/FasL in HaCaT cells.

  17. A- and B-site doping effect on physicochemical properties of Sr2‑xBaxMMoO6 (M = Mg, Mn, Fe) double perovskites — candidate anode materials for SOFCs

    Science.gov (United States)

    Zheng, Kun; Świerczek, Konrad

    2016-06-01

    In this work, we evaluate the physicochemical properties of Sr2‑xBaxMMoO6 (M = Mg, Mn, Fe) double perovskites as alternative anode materials for solid oxide fuel cells, for which the effect of substitution of strontium by barium in a full range of compositions is studied. The crystal structure, microstructure, characterization of transport properties (electrical conductivity, Seebeck coefficient) and oxygen content as a function of temperature, as well as chemical stability in oxidizing and reducing conditions are discussed. Fe- and Mo-containing Sr2‑xBaxFeMoO6 oxides show very high total conductivities with values of 100-1000 Sṡcm‑1, while Sr2‑xBaxMgMoO6 present good redox stability.

  18. Expression of protein encoded by apoptosis-associated gene p53, bcl-2, and bax in adaptive response of thymocyte apoptosis in mice induced by low dose radiation with X-rays

    International Nuclear Information System (INIS)

    Objective: To explore the regulative mechanism of apoptosis-associated gene proteins on the adaptive response of thymocyte apoptosis in mice induced by low dose radiation with X-rays. Methods: Kunming male mice were irradiated with the inductive doses (D1: 25, 50, 75, 100 and 200 mGy; dose rate: 12.5 mGy ·min-1) and the challenging dose (D2: 1.5 Gy; dose rate: 287 mGy·min-1). The time interval between D1 and D2 was 6 h. The expressive levels of thymocyte apoptosis-associated gene proteins were measured with flow cytometry. Results: As compared with the sham-irradiation, the positive percentage of thymocyte Bcl-2 protein expression decreased significantly in D2 group (P<0.05), Bax increased significantly (P<0.05), and Bcl-2/Bax decreased significantly (P<0.001); p 53 increased significantly (P<0.001). As compared with D2 group, the positive percentage of thymocyte Bcl-2 protein expression increased in varying degree in D1+ D2 group of 25-75 mGy D1, Bax decreased in varying degree, and Bcl-2/Bax increased significantly (P<0.01); p53 decreased significantly (P<0.001 or P<0.05). Conclusion: The apoptotic thymocytes in the adaptive response of thymocyte apoptosis in mice induced by irradiation with 25-75 mGy decrease significantly due to the increase of apoptosis-associated gene Bcl-2 protein expression and Bcl-2/Bax, the decrease of Bax and p53 protein expressions. (authors)

  19. Effects of acupoint versus non-acupoint electroacupuncture on cerebral cortical neuronal Bcl-2,Bax and caspase-3 expression in a rat model of focal cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    Jun Wang; Junming Fan; Yongshu Dong; Xia Huang; Hongxia Zhang

    2008-01-01

    BACKGROUND: Several studies have demonstrated that electroacupuncture by acupoint selection can inhibit cerebral cortical neuronal apoptosis following cerebral ischemia/reperfusion.OBJECTIVE: To validate the effects of electroacupuncture by acupoint selection on the expression level of cortical neuronal anti-apoptotic Bcl-2 protein and the apoptotic executive protein, caspase-3, in rat models of focal cerebral ischemia/reperfusion.DESIGN, TIME AND SETTING: This randomized grouping, neural cell and molecular biology animal experiment was performed at the Laboratory of Pharmacology of Traditional Chinese Medicine and the Laboratory Animal Center of Henan Institute of Traditional Chinese Medicine between November 2006 and May 2007.MATERIALS: Atotal of 40 healthy male adult Sprague-Dawley rats were randomly and evenly divided into four groups: sham-operated, model, electroacupuncture and non-acupoint control. G6895 electro-acupuncture instruments were purchased from Shanghai Huayi Instrument Factory, China. Caspase-3, Bcl-2 and Bax kits were provided by Wuhan Boster Bioengineering Co., Ltd., China.METHODS: Middle cerebral artery occlusion was induced in the model, electroacupuncture and non-acupoint groups. In the electroacupuncture group, the acupoints Jianyu (LI15), Waiguan (SJ5), Biguan (ST31), and Zusanli (ST36) were given electroacupuncture. In the non-acupoint control group, at each time point (immediately after ischemia and after reperfusion, or 2 hours after reperfusion), electroacupuncture was performed at the midpoints of Tianquan (PC2)-Quze (PC 3) line, Quze (PC 3)-Ximen (PC4) line, Zuwuli (LRlO)-Yinbao (LRg) line, and Xiguan (LR7)-Zhongdu (LR6) line. Electroacupuncture parameters were set with a continuous wave with a frequency of 10 Hz, wave width 0.6 ms, voltage 1.5-3.0 V, and a duration of 10 minutes. The sham-operated and model groups received only animal fixation without electroacupuncture procedure.MAIN OUTCOME MEASURES: Five rats were selected from

  20. Preparation of BaxSr1-xTiO3 Functional Ceramic Film by Liquid Self-Assembly Technology%液相自组装制备BaxSr1-xTiO3功能陶瓷薄膜

    Institute of Scientific and Technical Information of China (English)

    谈国强; 程蕾; 苗鸿雁; 王艳

    2011-01-01

    以Sr(NO3)2,Ba(NO3)2,(NH4)2TiF6和H3BO3作为原料,采用自组装单分子膜(self-assembled monolayers,SAMs)技术以及利用紫外光修饰技术对十八烷基三氯硅烷(C18H37SiCl3,OTS)单分子膜进行官能团改性,在氧化铟锡(indium tin oxide,ITO)玻璃基板上成功制备了BaxSr1-xTiO3功能陶瓷薄膜.通过动态/静态接触角仪测量了SAMs功能化的ITO玻璃基板表面与水的接触角,探讨功能化ITO玻璃基板在紫外光照射前后的润湿情况.通过X射线衍射、能量色散光谱和扫描电子显微镜等测试方法分析了制备的BaxSr1-xTiO3功能陶瓷薄膜的物相组成、微区结构和形貌.结果表明:改性的SAMs功能化ITO玻璃基板在50℃的前驱溶液中沉积18h后,在600℃煅烧晶化2h,可以成功制备出纯相BaxSr1-xTiO3功能陶瓷薄膜,薄膜的颗粒均一,形貌均匀.%Using strontium nitrate, barium nitrate, ammonium hexafluorotitanate and boric acid as raw materials, the functional groups of octadecyltrichlorosilane (C18H37SiCl3, OTS) monolayer were modified via self-assembled monolayers (SAMs) technology and ultraviolet modification technique, and the BaxSr1-xTiO3 functional ceramic film on the indium tin oxide (ITO) glass substrate was prepared successfully. The contact angle between the surface of the SAM functionalized ITO glass substrate and water was measured by dynamic/static contact angle instrument in order to study the wetting conditions of the substrates before and after ultraviolet light irradiation. The phase composition, microstructure and morphology of the prepared BaxSr1-xTiO3 functional ceramic thin films were analyzed by X-ray diffraction, energy dispersive spectroscopy and scanning electron microscopy. The results indicate that pure phase BaxSr1-xTiO3 functional ceramic film can be prepared on the SAMs functionalized ITO glass substrate successfully after depositing on the surface of ITO glass substrate in the precursor at 50 ℃ for 18h, and then crystallized

  1. Dielectric dispersion of BaxSr1-xTiO3 thin film with parallel-plate and coplanar interdigital electrodes

    Science.gov (United States)

    Zhang, Xiao-Yu; Song, Qing; Xu, Feng; Sheng, Su; Wang, Peng; Ong, C. K.

    2009-03-01

    Ferroelectric BaxSr1-xTiO3 (BST) thin films with x = 0.25 and 0.5 were grown by pulsed laser deposition on single crystal LaAlO3 and Pt/Ti/SiO2/Si substrates, respectively. Capacitors were then fabricated from the BST thin films based on coplanar interdigital electrodes (CIEs) and parallel-plate electrodes (PPEs). The dielectric properties of the BST film with CIE and PPE were investigated and compared over a wide frequency range from 100 Hz to 10 GHz. The dielectric dispersion in PPE configuration, caused by the interfacial polarization in film/electrode interfaces, exhibited a strong dependence on frequency. However, the permittivity ɛCIE in CIE configuration shows a gentle variation with the frequency indicating interfacial polarization substantially suppressed. The influence upon the dielectric properties of the columnar BST grains due to the use of different forms of electrodes was discussed.

  2. Both p53-PUMA/NOXA-Bax-mitochondrion and p53-p21cip1 pathways are involved in the CDglyTK-mediated tumor cell suppression

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Zhendong, E-mail: zdyu@hotmail.com [Department of Clinical laboratory, Peking University Shenzhen Hospital, Guangdong (China); Wang, Hao [Department of pathology, The Chinese University of Hong Kong, Hong Kong (China); Zhang, Libin; Tang, Aifa; Zhai, Qinna; Wen, Jianxiang; Yao, Li [Department of Clinical laboratory, Peking University Shenzhen Hospital, Guangdong (China); Li, Pengfei, E-mail: lipengfei@cuhk.edu.hk [Department of pathology, The Chinese University of Hong Kong, Hong Kong (China)

    2009-09-04

    CDglyTK fusion suicide gene has been well characterized to effectively kill tumor cells. However, the exact mechanism and downstream target genes are not fully understood. In our study, we found that CDglyTK/prodrug treatment works more efficiently in p53 wild-type (HONE1) cells than in p53 mutant (CNE1) cells. We then used adenovirus-mediated gene delivery system to either knockdown or overexpress p53 and its target genes in these cells. Consistent results showed that both p53-PUMA/NOXA/Bcl2-Bax and p53-p21 pathways contribute to the CDglyTK induced tumor cell suppression. Our work for the first time addressed the role of p53 related genes in the CDglyTK/prodrug system.

  3. Influence of Tanshinone IIa on heat shock protein 70, Bcl-2 and Bax expression in rats with spinal ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Li Zhang; Weidong Gan; Guoyao An

    2012-01-01

    Tanshinone IIa is an effective monomer component of Danshen, which is a traditional Chinese medicine for activating blood circulation to dissipate blood stasis. Tanshinone IIa can effectively improve brain tissue ischemia/hypoxia injury. The present study established a rat model of spinal cord ischemia/reperfusion injury and intraperitoneally injected Tanshinone IIa, 0.5 hour prior to model establishment. Results showed that Tanshinone IIa promoted heat shock protein 70 and Bcl-2 protein expression, but inhibited Bax protein expression in the injured spinal cord after ischemia/reperfusion injury. Furthermore, Nissl staining indicated a reduction in nerve cell apoptosis and fewer pathological lesions in the presence of Tanshinone IIa, compared with positive control Danshen injection.

  4. Both p53-PUMA/NOXA-Bax-mitochondrion and p53-p21cip1 pathways are involved in the CDglyTK-mediated tumor cell suppression

    International Nuclear Information System (INIS)

    CDglyTK fusion suicide gene has been well characterized to effectively kill tumor cells. However, the exact mechanism and downstream target genes are not fully understood. In our study, we found that CDglyTK/prodrug treatment works more efficiently in p53 wild-type (HONE1) cells than in p53 mutant (CNE1) cells. We then used adenovirus-mediated gene delivery system to either knockdown or overexpress p53 and its target genes in these cells. Consistent results showed that both p53-PUMA/NOXA/Bcl2-Bax and p53-p21 pathways contribute to the CDglyTK induced tumor cell suppression. Our work for the first time addressed the role of p53 related genes in the CDglyTK/prodrug system.

  5. Dielectric dispersion of BaxSr1-xTiO3 thin film with parallel-plate and coplanar interdigital electrodes

    International Nuclear Information System (INIS)

    Ferroelectric BaxSr1-xTiO3 (BST) thin films with x = 0.25 and 0.5 were grown by pulsed laser deposition on single crystal LaAlO3 and Pt/Ti/SiO2/Si substrates, respectively. Capacitors were then fabricated from the BST thin films based on coplanar interdigital electrodes (CIEs) and parallel-plate electrodes (PPEs). The dielectric properties of the BST film with CIE and PPE were investigated and compared over a wide frequency range from 100 Hz to 10 GHz. The dielectric dispersion in PPE configuration, caused by the interfacial polarization in film/electrode interfaces, exhibited a strong dependence on frequency. However, the permittivity εCIE in CIE configuration shows a gentle variation with the frequency indicating interfacial polarization substantially suppressed. The influence upon the dielectric properties of the columnar BST grains due to the use of different forms of electrodes was discussed.

  6. Characteristics of silicon-based BaxSr1-xTiO3 thin films prepared by a sol-gel method

    International Nuclear Information System (INIS)

    Silicon-based BaxSr1-xTiO3 (BST) thin films have been prepared by a sol-gel method with rapid thermal annealing (RTA) processes. Phase structure of the films has been investigated by x-ray diffraction. Atomic force microscopy studies reveal a dense and smooth surface of the sol-gel prepared films. Microstructure and electrical properties of the BST films can be affected by the substrate and the annealing process. RTA method is found to be very efficient to improve the electrical properties of the films. Dielectric constant and dielectric loss of the BST films at 100 kHz are 230 and 0.02, respectively. Leakage current density of the BST capacitors is 1.6x10-7A cm-2 at 3 V. (author)

  7. Diffuse phase transition and high-temperature dielectric relaxation study on (Bi0.5Na0.5)1-xBaxTiO3 ceramics

    Science.gov (United States)

    Chen, Feng; Liu, Qiu-Xiang; Tang, Xin-Gui; Jiang, Yan-Ping; Yue, Jing-Long; Li, Jin-Kai

    2016-09-01

    Lead free (Bi0.5Na0.5)1-xBaxTiO3 (x=0.6, 0.7, 0.8, 0.9) ferroelectric ceramics were synthesized by the traditional solid state reaction method. Sintering was carried out at 1200 °C for 2 h in air atmosphere. The structural, microstructure and Ferroelectric of ceramics were investigated. In dielectric studies, a diffuse phase transition was exhibited and a dielectric relaxation behavious was observed at high temperature range. Impedance analysis characterized grain and grain boundaries resistivities of the ceramics and calculated activation energy and the activation energy for conduction. Polaron theory indicates that the relaxation of the samples at high temperatures was associated with the hopping ions caused by oxygen vacancies.

  8. AC Conductivity and Dielectric Relaxation Behavior of Sol-gel BaxSr1-xTiO3 Thin Films

    Institute of Scientific and Technical Information of China (English)

    Ala'eddin A. Saif; P. Poopalan

    2011-01-01

    BaxSr1-xTiO3 sol-gel thin films with x--0.5, 0.7 and 0.8 have been fabricated as AI/BST/Pt capacitor. The AC conductivity and dielectric properties over a frequency rang of 10 Hz and I MHz have been studied in order to explore the ion dynamics and relaxation mechanisms in the films. The frequency dependent conductivity plots show three regions of conduction processes. Dielectric results show that ε' at low frequencies increases as Sr content decreases, whereas at high frequencies, it shows opposite variation, which is attributed to the dipole dynamics. The electric modulus plots reveal the relaxation peaks which are not observed in the ε" plots and the contribution of the grains, grain boundaries and electrode to the relaxation mechanisms.

  9. Magnetic and thermoelectric properties of the ternary pseudo-hollandite BaxCr5Se8 (0.5 < x < 0.55) solid solution.

    Science.gov (United States)

    Lefèvre, Robin; Berthebaud, David; Bux, Sabah; Hébert, Sylvie; Gascoin, Franck

    2016-07-26

    The structure of Ba0.5Cr5Se8 has been recently resolved, and its thermoelectric and magnetic properties have been studied. A ZT of 0.12 was found at around 800 K. Here, we report a study on the pseudo-hollandite BaxCr5Se8 solid-solution with 0.5 ≤ x ≤ 0.55 and its thermoelectric and magnetic properties. There is no significant impact either on the cell parameters depending on the cation content or on the magnetic properties. However, thermoelectric properties are radically changed depending on x content. While the low thermal conductivity, around 0.8 W m(-1) K(-1), remains similar for all samples, a respective increase and decrease of the resistivity and the Seebeck coefficient are observed with increasing Ba content. The maximum Seebeck coefficient is found with Ba0.5Cr5Se8 at around 635 K with 315 μV K(-1), and the Seebeck coefficient then decreases and is correlated with an activation of minority charge carriers confirmed by Hall measurements. A similar but steeper behavior is observed for the Ba0.55Cr5Se8 temperature dependence plot at around 573 K. Finally, the best thermoelectric performances are found using the lowest content of Ba, unlike when x tends to 0.55, ZT approaches a tenth of the initial best value. BaxCr5Se8 compounds are antiferromagnetic with TN = 58 K. A large peak in thermal conductivity is observed around the antiferromagnetic transition for all stoichiometry.

  10. The ethanol extract of Scutellaria baicalensis and the active compounds induce cell cycle arrest and apoptosis including upregulation of p53 and Bax in human lung cancer cells

    International Nuclear Information System (INIS)

    Despite a lack of scientific authentication, Scutellaria baicalensis is clinically used in Chinese medicine as a traditional adjuvant to chemotherapy of lung cancer. In this study, cytotoxicity assays demonstrated that crude ethanolic extracts of S. baicalensis were selectively toxic to human lung cancer cell lines A549, SK-LU-1 and SK-MES-1 compared with normal human lung fibroblasts. The active compounds baicalin, baicalein and wogonin did not exhibit such selectivity. Following exposure to the crude extracts, cellular protein expression in the cancer cell lines was assessed using 2D gel electrophoresis coupled with MALDI-TOF-MS/Protein Fingerprinting. The altered protein expression indicated that cell growth arrest and apoptosis were potential mechanisms of cytotoxicity. These observations were supported by PI staining cell cycle analysis using flow cytometry and Annexin-V apoptotic analysis by fluorescence microscopy of cancer cells treated with the crude extract and pure active compounds. Moreover, specific immunoblotting identification showed the decreased expression of cyclin A results in the S phase arrest of A549 whereas the G0/G1 phase arrest in SK-MES-1 cells results from the decreased expression of cyclin D1. Following treatment, increased expression in the cancer cells of key proteins related to the enhancement of apoptosis was observed for p53 and Bax. These results provide further insight into the molecular mechanisms underlying the clinical use of this herb as an adjuvant to lung cancer therapy. - Research highlights: → Scutellaria baicalensis is a clinical adjuvant to lung cancer chemotherapy in China. → Scutellaria ethanol extracts selectively toxic to A549, SK-LU-1 and SK-MES-1. → Baicalin, baicalein and wogonin were toxic to all lung cancer cell lines. → Proteomics identified increased p53 and BAX in response to Scutellaria extracts.

  11. Adsorption of xylene para- and meta- isomers in NaX and BaX zeolites. Study of properties-structure relations; Adsorption des isomeres para- et meta- du xylene dans les zeolithes NaX et BaX. Etude des relations proprietes-structure

    Energy Technology Data Exchange (ETDEWEB)

    Descours, A.

    1997-02-14

    The separation of para-xylene from C8 aromatics is performed industrially bu adsorption process on zeolitic molecular sieves. The sorption properties of these zeolites are strongly linked to their structure, and their comprehension require an accurate knowledge of the interactions between sorbate molecules and zeolitic structure. The aim of this work is to characterise from a structural point of view the adsorption of para- and meta-xylenes in BaX and NaX zeolites. The former is selective for para-xylene, and the latter has not selective properties for para- and meta-isomers of xylene. For each zeolite, the adsorption of pure para-xylene and meta-xylene or a mixture of the two isomers, is investigated as a function of coverage. Powder neutron diffraction is used to determine the crystalline structure of these zeolites and the different crystallographic adsorption sites of the molecules. The influence of coverage on sorbate-sorbent and sorbate-sorbate interactions is investigated. Infrared spectroscopy allows to determine the chemical environment of the sorbate molecules at low coverage or when the coverage increases, and is particularly effective for the study of the binary mixture of xylenes. This study is performed by sorbing a mixture of xylene isomers, or by sorbing these isomers successively. Infrared studies and crystallographic analysis are compared in order to get a consistent description of adsorption mechanism of xylene isomers for both zeolites as a function of coverage. The role of coverage, of cation type, an the presence of the two xylene isomers is the super-cages is essential. For both zeolites, the increase of coverage actually leads to steric hindrances between sorbed molecules and molecular rearrangements. These reorganizations are connected to the cationic distribution of NaX and BaX zeolites. The sorbed molecules are connected to the cationic distribution of NaX and BaX zeolites. The sorbed molecules are particularly confined in BaX zeolite

  12. 细胞凋亡相关基因Bcl-2及Bax在骨肉瘤中的表达与自下而上质量的关系%Expression of apoptosis related gene Bcl 2 and Bax in osteosarcoma and their relationship with the prognosis

    Institute of Scientific and Technical Information of China (English)

    黄鲁豫; 刘建; 王臻; 吕荣

    2002-01-01

    Objective Apoptosis related gene Bcl 2 and Bax in osteosarcoma patients with different clinical appearance were being studied to analyze the prognosis of the patients. Method The cases were divided into two different groups according to the results of the follow up.33 cases in high risk group and 18 cases in low risk group. Expression of Bcl 2 and Bax were immunohistochemically stained by ABC method. Result Positive expression rate of Bcl 2 was 61% in high risk group (20/23) and 33% in low risk group (1/8). Positive expression of Bax was 22% in high risk group (6/27) and 67% in low risk group(12/18).Conclusion Expression of Bcl 2 and Bax was related to the prognosis of osteosarcoma. Positively expressed Bcl 2 in osteosarcoma cells may indicate bad prognosis. If Bax is highly expressed in osteosarcoma cells, this may indicated a good prognosis.

  13. Study of Ganoderma lucidum spores on pentylenetetrazol activation of hippocampal neurons bax expression%灵芝孢子粉对戊四氮活化海马神经细胞bax表达的研究

    Institute of Scientific and Technical Information of China (English)

    张金波; 王淑秋; 张淑红; 金岳雷; 朱金玲; 刘爽

    2012-01-01

    目的 本实验研究灵芝孢子粉对戊四氮活化大鼠海马神经细胞bax表达变化的影响,进一步探讨灵芝孢子粉的作用机制和癫痫与海马神经细胞凋亡调控基因之间的关系.方法 通过制备癫痫模型和RT-PCR检测正常对照组、癫痫模型组和灵芝孢子粉用药组bax的表达.结果 癫痫模型组和灵芝孢子粉用药组bax的表达较正常对照组(0.17±0.04)均升高;其中癫痫模型组(0.66±0.09)bax的表达水平与对照组(0.17±0.04)比较明显升高(P<0.01),灵芝孢子粉用药组(0.47±0.1)bax的表达水平与癫痫模型组比较明显降低(P<0.01),差异有统计学意义.结论 本研究结果证实,在PTZ点燃癫痫后,模型组和治疗组促凋亡基因bax表达较正常对照组显著升高,表明bax基因在细胞凋亡的调控过程中起到促进作用,而给予灵芝孢子粉治疗后,bax的表达与模型组比较显著降低,提示灵芝孢子粉有效成份能充分作用于脑组织,可以调控bax的表达,借以发挥抗凋亡的神经保护作用.%Objective; This study is Ganoderma lucidum spores on pentylenetetrazol activation of rat hippocampal neurons bax expression changes to further explore the relationship between the action mechanism of the Ganoderma lucidum spores and epilepsy with apoptosis regulatory genes of hippocampal neural. Methods; Through the preparation of the epileptic model and RT — PCR to detect of bax expression in the normal control group, epilepsy model group and Ganoderma spore powder medication group. Results;/ Bax expression in epilepsy model group and Ganoderma lucidum spores medication group were higher than in the normal control group (0. 17 ± 0. 04) ; including bax expression level in epilepsy model group (0. 66 ± 0. 09) was significantly higher than in the control group (0. 17 ± 0.04) (P<0. 01) , bax expression level in Ganoderma spore powder medication group (0.47 ± 0. 1 ) were significantly lower than in epilepsy model group

  14. 雌激素对大鼠胸腺细胞凋亡及Bcl-2、Bax表达的影响%Effects of estrogen on apoptosis and expression of Bcl-2 and Bax in rat thymus

    Institute of Scientific and Technical Information of China (English)

    李雅娜; 孙研; 崔春红; 殷彦君

    2011-01-01

    目的:探讨苯甲酸雌二醇对大鼠胸腺Bcl-2和Bax表达及细胞凋亡的影响及其机制.方法:雌性大鼠行卵巢切除术,给予苯甲酸雌二醇后,观察胸腺指数的变化,Hochest33342荧光染色及透射电镜标本观察胸腺细胞凋亡情况,免疫组织化学检测胸腺组织中Bcl-2和Bax的表达情况,原位杂交技术检测Bcl-2、Bax m RNA的表达情况.结果:双侧卵巢切除组大鼠胸腺指数较假手术组增加,双侧卵巢切除+雌激素组大鼠胸腺指数较双侧卵巢切除组减小;假手术组和双侧卵巢切除组大鼠胸腺组织中以正常胸腺细胞为主,偶见凋亡细胞或凋亡小体,双侧卵巢切除+雌激素组可见较多凋亡细胞和凋亡小体;双侧卵巢切除+雌激素组大鼠胸腺组织中Bcl-2表达较双侧卵巢切除组和假手术组增高明显降低,而Bax表达呈现相反趋势;Bcl-2 mRNA、Bax mRNA的表达与Bcl-2、Bax的表达呈一致性.结论:雌激素可以降低大鼠胸腺指数,抑制胸腺组织中Bcl-2的表达,促进Bax的表达,从而诱导大鼠胸腺细胞凋亡,促进雌性大鼠胸腺退化.%Objective-. To explore the effects of estrogen on the apoptosis and the expression of Bcl-2 and Bax in rat thymus. Methods-. The rats performed with ovariectomy were injected with estradiol benzoate. Thymus was obtained 7 days after the injection. Thymic indexes were measured. Apoptosis of the thymus was detected after Hochest 33342 staining and examined under an electron microscope. The expression of Bcl-2 and Bax in the thymus was detected with a immunohistochemical method. The expression of Bcl-2 mRNA and Bax mRNA in the thymus was detected by in situ hybridization. The test was taken in statistical treatment. Results: The thymus quality index in ovariectomy group was higher than that in the model control group. The thymus quality index of rats injected with estradiol benzoate was reduced respectively. Apoptotic cells and apoptotic bodies were found in the

  15. Ginkgo biloba extract mitigates liver fibrosis and apoptosis by regulating p38 MAPK, NF-κB/IκBα, and Bcl-2/Bax signaling

    Directory of Open Access Journals (Sweden)

    Wang YY

    2015-12-01

    Full Text Available Yuanyuan Wang, Rong Wang, Yujie Wang, Ruqin Peng, Yan Wu, Yongfang Yuan Department of Pharmacy, Shanghai 9th People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China Background: Liver fibrosis is the consequence of diverse liver injuries and can eventually develop into liver cirrhosis. Ginkgo biloba extract (GBE is an extract from dried ginkgo leaves that has many pharmacological effects because of its various ingredients and has been shown to be hepatoprotective. Purpose and methods: Aimed to investigate the underlying protective mechanisms of GBE on carbon tetrachloride (CCl4-induced liver fibrosis in rats. Male Sprague Dawley rats were randomly divided into four groups: control group (C, model group (M, low-dose group (L, and high-dose group (H. Liver fibrosis was induced by CCl4 groups M, L, and H: group C was administered saline. In addition, GBE at different doses was used to treat groups L and H. Results: The results of hematoxylin and eosin staining, Masson’s trichrome staining, a liver function index, and a liver fibrosis index showed that GBE application noticeably mitigated fibrosis and improved the function of the liver. The western blotting and immunohistochemistry analyses indicated that GBE reduced liver fibrosis not only by inhibiting p38 MAPK and NF-κBp65 via inhibition of IκBα degradation but also by inhibiting hepatocyte apoptosis via downregulation of Bax, upregulation of Bcl-2, and subsequent inhibition of caspase-3 activation. Inflammation-associated factors and hepatic stellate cell (HSC-activation markers further demonstrated that GBE could effectively inhibit HSC activation and inflammation as a result of its regulation of p38 MAPK and nuclear factor-kappa B/IκBα signaling. Conclusion: Our findings indicated a novel role for GBE in the treatment of liver fibrosis. The potential mechanisms may be associated with the following signaling pathways: 1 the p38 MAPK

  16. Expression of P53, P21/WAF/CIP, BCL-2, BAX, BCL-X, and BAK in radiation-induced apoptosis in testicular germ cell tumor lines

    International Nuclear Information System (INIS)

    Purpose: Testicular germ cell tumors (TGCTs) represent one of the few tumor types that are curable by antineoplastic therapy, probably due to the high sensitivity of this neoplasm to induction of apoptosis by chemotherapeutic agents and/or ionizing radiation. Here, we tested cell susceptibility to radiation-induced apoptosis in a panel of TGCT cell lines and attempted to correlate this with the known potentially relevant molecular determinants (p53 gene status and Bcl-2 family proteins) of apoptosis. Methods and Materials: Induction of apoptosis by γ-radiation was morphologically recognized in NT2, NCCIT, S2, and 2102 EP using Hoechst/PI staining and additionally confirmed by Western blot analysis of PARP cleavage. The p53 gene status was estimated by sequence analysis. Expression of p21/WAF/CIP was determined by Northern blot analysis and immunoblotting was used to monitor p53, Bax, Bcl-2, Bcl-x, and Bak protein levels. In vitro colony formation was studied to establish clonogenic survival curves. Results: NT2 and NCCIT appeared to be susceptible for radiation-induced apoptosis, contrasting 2102 EP and S2 which were highly resistant. Sequence analysis showed that NT2, S2, and 2102 EP are homozygous for wild-type p53 (wtp53), whereas NCCIT contains mutant p53 (mtp53). NT2 and 2102 EP cells showed radiation-induced p53 upregulation, while NCCIT (mtp53) and S2 (no p53 protein) cells did not. Consistently, γ-radiation-induced DNA damage resulted in a p53-dependent transactivation of the p21/WAF/CIP gene in NT2 and 2102 EP, but not in mtp53-containing NCCIT cells and p53 nonexpressing S2 cells. Constitutive expression of Bax, Bcl-2, Bcl-x, and Bak was not affected by radiation and showed no correlation with cell susceptibility to radiation-induced apoptosis. A discrepancy was found between apoptosis and reproductive death. Conclusions: The present study revealed that: i) the presence of wtp53 may not be absolutely required for the hypersensitivity for radiation

  17. 血糖波动对2型糖尿病大鼠认知功能及海马Bax/Bcl-2的影响%The Effect of Glucose Fluctuate on the Cognitive Function and the Bax/Bcl-2 in Hippocampal of Rats with Type 2 Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    徐志伟; 寿旗扬; 李守业; 蔡月琴; 刘琼; 徐文聃; 洪春兰; 王辉

    2013-01-01

    [目的]探讨血糖波动对糖尿病大鼠认知功能和海马Bax/Bcl-2的影响.[方法]取45只雄性大鼠禁食不禁水16h,用链脲佐菌素30 mg·kg-1加高脂饲料诱导2型糖尿病大鼠模型,挑选出糖尿病大鼠30只,分成糖尿病模型组(Diabetes Model,M)、持续高血糖糖尿病组(High Glucose Diabetes Sustain Model,MS)、血糖波动糖尿病组(Glucose Fluctuate Diabetes Model,MF),另取10只正常大鼠做正常对照组(Normal,N).血糖波动糖尿病组错时腹腔注射葡萄糖0.38 g·kg-1和皮下注射胰岛素1U制备糖尿病血糖波动模型.血糖波动6周后,进行水迷宫定位航行实验和空间探索实验,同时检测海马组织中Bax、Bcl-2的表达.[结果]M组、MS组、MF组比N组逃避潜伏期明显增长(P<0.05),空间探索实验结果显示60s内穿越平台所在位置的次数明显下降,在平台所在象限内的游泳距离明显减少(P<0.05).MF组和M组、MS组相比.逃避潜伏期进一步增长(P<0.05),空间探索实验结果显示60s内穿越平台所在位置次数也明显下降,在平台所在象限游泳距离也减少(P<0.05).MF组、M纽、MS组Bcl-2的表达较N组显著下降,Bax显著升高(P<0.05).MF组Bcl-2的表达较M组、MS组进一步下降,Bax进一步升高(P<0 05).[结论]血糖波动能加重损伤糖尿病大鼠的学习记忆功能,并促进海马组织的凋亡相关蛋白Bax/Bcl-2的表达,诱导海马神经元的凋亡.%[Objective] To explore the effection of glucose fluctuation on the cognitive function and the Bax/Bcl-2 in hippocampal of rats with type 2 diabetes mellitus. [Methods] The SD rats were randomly divided into four groups: normal group(N); diabetes model group(M);high glucose sustain diabetes model group(MS); glucose fluctuate diabetes model group(MF). The diabetic rats model was developed by injection with streptozotocin(STZ) 30 mg·kg-1, regularly staggered insulin 1U and glucose 0.38 mg·kg-1 administration was used to set up blood

  18. Anti-apoptotic mechanism of Bacoside rich extract against reactive nitrogen species induced activation of iNOS/Bax/caspase 3 mediated apoptosis in L132 cell line.

    Science.gov (United States)

    Anand, T; Pandareesh, M D; Bhat, Pratiksha V; Venkataramana, M

    2014-10-01

    Nitric oxide is a highly reactive free radical gas that reacts with a wide range of bio-molecules to produce reactive nitrogen species and exerts nitrative stress. Bacopa monniera is a traditional folk and ayurvedic medicine known to alleviate a variety of disorders. Aim of the present study is to evaluate the protective propensity of Bacopa monniera extract (BME) through its oxido-nitrosative and anti-apoptotic mechanism to attenuate sodium nitroprusside (SNP)-induced apoptosis in a human embryonic lung epithelial cell line (L132). Our results elucidate that pre-treatment of L132 cells with BME ameliorates the mitochondrial and plasma membrane damage induced by SNP as evidenced by MTT and LDH leakage assays. BME pre-treatment inhibited NO generation by down-regulating inducible nitric oxide synthase expression. BME exhibited potent antioxidant activity by up-regulating the antioxidant enzymes. SNP-induced damage to cellular, nuclear and mitochondrial integrity was also restored by BME, which was confirmed by ROS estimation, comet assay and mitochondrial membrane potential assays respectively. BME pre-treatment efficiently attenuated the SNP-induced apoptotic biomarkers such as Bax, cytochrome-c and caspase-3, which orchestrate the proteolytic damage of the cell. By considering all these findings, we report that BME protects L132 cells against SNP-induced toxicity via its free radical scavenging and anti-apoptotic mechanism.

  19. Enhancement of Photon Absorption on BaxSr1-xTiO3 Thin-Film Semiconductor Using Photonic Crystal

    Directory of Open Access Journals (Sweden)

    Abd. Wahidin Nuayi

    2014-01-01

    Full Text Available Enhancement of photon absorption on barium strontium titanate (BaxSr1-xTiO3 thin-film semiconductor for mole fraction x=0.25, 0.35, 0.45, and 0.55 using one-dimensional photonic crystal with defect was investigated experimentally. The thin film was grown on transparent conductive oxide (TCO substrate using chemical solution deposition method and annealed at 500°C for 15 hours with increasing rate of 1.6°C/min. From optical characterization in visible spectrum it was found that the average absorption percentages are 92.04%, 83.55%, 91.16%, and 80.12%, respectively. The BST thin film with embedded photonic crystal exhibited a relatively significant enhancement on photon absorption, with increasing value of 3.96%, 7.07%, 3.04%, and 13.33% for the respective mole fraction and demonstrating absorbance characteristic with flat feature. In addition, we also discuss the thin-film properties of attenuation constant and electrical conductivity.

  20. Study on the in-plane electrical resistivity and thermoelectric power in single crystals of La2-xBaxCuO4

    Institute of Scientific and Technical Information of China (English)

    李鹏程; 杨宏顺; 李志权; 柴一晟; 曹烈兆

    2002-01-01

    The in-plane electrical resistivity and thermoelectric power have been measured on single crystals ofLa2-xBaxCuO4 at around x=0.125. The room temperature resistivity and thermopower have their maximum val-ues at x=0.125, indicating that the carrier concentration is the minimum and the carriers are most strongly localized atx=0.125. The observed semiconductor-like behaviour can be well described by the weak-localized quasi-two-dimensionalstate. The steep rise in electric resistivity of the sample at x=0.125 below 70K is attributed to the formation of staticstripe-order of holes and spins, which are pinned by the low-temperature tetragonal (LTT) structure, as discovered inLa1.4sNd0.4Sr0.12CuO4.The temperature dependence of electric resistivity below 70K is still well described by theformula p ∝ lnT. A definite change in the slope of thermopower is observed at the low-temperature orthorhombic-LTTstructural phase transition temperature. The origin of the 1/8 anomaly is discussed in the text.

  1. Bcl-2、Bax及M30在Bowen病中的表达%Expression of Bcl-2、 Bax and M30 in Bowen's disease

    Institute of Scientific and Technical Information of China (English)

    张敏; 张谊之; 王琳; 李俸媛

    2002-01-01

    为了研究细胞凋亡与Bowen病发病的关系,我们采用免疫组化方法检测了28例Bowen病皮损中Bcl-2、Bax及M30的表达.结果发现M30及Bax染色阳性分别见于4例和8例表皮角质形成细胞,Bcl-2在10例表皮角质形成细胞和12例真皮淋巴细胞呈阳性表达;Bcl-2表达阳性率高于Bax,但无统计学差异(χ2=2.1053,P>0.05);M30与Bax表达显著正相关(r=0.6455,P0.05).提示Bowen病发病可能与表皮角质形成细胞凋亡降低有关.

  2. Phenomenological theory of phase transitions in epitaxial BaxSr1-xTiO3 thin films on (111)-oriented cubic substrates

    Science.gov (United States)

    Shirokov, V. B.; Shakhovoy, R. A.; Razumnaya, A. G.; Yuzyuk, Yu. I.

    2015-07-01

    A phenomenological thermodynamic theory of BaxSr1-xTiO3 (BST-x) thin films epitaxially grown on (111)-oriented cubic substrates is developed using the Landau-Devonshire approach. The group-theoretical analysis of the low-symmetry phases was performed taking into account two order parameters: the polarization related to ionic shifts in polar zone-center F1u mode and the out-of-phase rotation of TiO6 octahedra corresponding to the R25 zone-boundary mode in the parent cubic phase P m 3 ¯ m . The eight-order thermodynamic potential for BST-x solid solutions was developed and analyzed. We constructed the "concentration-misfit strain" phase diagram for BST-x thin films at room temperature and found that polar rhombohedral R3m phase with the polarization normal to the substrate is stable for x > 0.72 and negative misfit strains, while ferroelectric monoclinic C2 and Cm phases with in-plane polarization are stable for much smaller x and positive or slightly negative misfit strains. We constructed the "temperature-misfit strain" phase diagrams for several concentrations (x = 1, 0.8, 0.6, 0.4, and 0.2). Systematic changes of the phase transition lines between the paraelectric and ferroelectric phases are discussed. The phase diagrams are useful for practical applications in thin-film engineering.

  3. Moessbauer study of the relationship between magnetic properties and Jahn-Teller distortion in La1-xBax(Mn,Fe)O3 perovskites

    International Nuclear Information System (INIS)

    The local structural distortion and its effect on the magnetic and magnetotransport properties of the Fe-doped La1-xBaxMnO3 (0.00≤x≤0.35) compounds were investigated by means of X-ray diffraction, Moessbauer spectroscopy, and magnetization measurements. The Moessbauer spectra show clear evidence of the local structural distortion of the Mn(Fe)O6 octahedron on the basis of non-zero nuclear quadrupole interactions for high-spin Fe3+ ions. It was found that the local structural distortion decreases significantly with the introduction of a few per cent of Ba, reaches a minimum around x=0.13, and then increases slightly on further increasing the Ba concentration. The Ba-concentration dependence of the Jahn-Teller coupling strength estimated from the Moessbauer results was found to be consistent with the magnetic properties. Consequently, the connection between this local structural distortion and the colossal magnetoresistive behavior of this family of materials can be well explained. (copyright 2005 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  4. Layered Bi4BaxV2-xO11-(3x/2)-δ perovskite oxide as solid electrolyte for intermediate temperature solid oxide fuel cells

    International Nuclear Information System (INIS)

    A continuous series of Bi4BaxV2-xO11-(3x/2)-δ solid solutions are prepared by conventional solid state reactions. The polymorphism and electrical properties of these samples are studied by FT-IR spectroscopy, X-ray diffraction, differential thermal analysis (DTA) and AC impedance. The solid solutions with composition 0.07≤x≤0.13 are isostructural with the monoclinic phase α-Bi4V2O11. However, orthorhombic β-phase is observed for x=0.17 and tetragonal γ-phase is stabilized for x≤0.30. X-ray and DTA results reveal the occurrence of α↔γ transition for x≤0.13, β↔γ transition for x=0.17 and γ'→γ transition for x≥0.20. AC impedance plots at 280 deg. C for all compositions show greater contribution of grain to ionic conductivity than grain boundary. The highest ionic conductivity, σ300oC=4.456x10-5 S cm-1 is observed for x=0.17. The ionic conductivity of the substituted compounds is higher than the parent α-Bi4V2O11, due to the increased oxygen ion vacancies generated as a result of barium doping.

  5. Protective Effect of Aliskiren in Experimental Ischemic Stroke: Up-Regulated p-PI3K, p-AKT, Bcl-2 Expression, Attenuated Bax Expression.

    Science.gov (United States)

    Miao, Jiangyong; Wang, Lina; Zhang, Xiangjian; Zhu, Chunhua; Cui, Lili; Ji, Hui; Liu, Ying; Wang, Xiaolu

    2016-09-01

    Aliskiren (ALK), a pharmacological renin inhibitor, is an effective antihypertensive drug and has potent anti-apoptotic activity, but it is currently unknown whether ALK is able to attenuate brain damage caused by acute cerebral ischemia independent of its blood pressure-lowering effects. This study aimed to investigate the role of ALK and its potential mechanism in cerebral ischemia. C57/BL6 mice were subjected to transient middle cerebral artery occlusion (tMCAO) and treated for 5 days with Vehicle or ALK (10 or 25 mg/kg per day via intragastric administration), whereas Sham-operated animals served as controls. Treatment with ALK significantly improved neurological deficits, infarct volume, brain water content and Nissl bodies after stroke (P < 0.05), which did not affect systemic blood pressure. Furthermore, the protection of ALK was also related to decreased levels of apoptosis in mice by enhanced activation of phosphatidylinositol 3-kinase (PI3K)/AKT pathway, increased level of Bcl-2 and reduced Bax expression (P < 0.05). In addition, ALK's effects were reversed by PI3K inhibitors LY294002 (P < 0.05). Our data indicated that ALK protected the brain from reperfusion injuries without affecting blood pressure, and this effect may be through PI3K/AKT signaling pathway. PMID:27180190

  6. Resistance Fluctuation Spectroscopy of Charge Stripes and Intertwined Orders in the Phase Diagram of La2-xBaxCuO4

    Science.gov (United States)

    Weis, Adam; Fizari, Mounir; Hamilton, David; Wells, Azton; Lane, Justin; Chung, So Ra; Sellappan, Pathikumar; Kriven, Waltraud; van Harlingen, Dale

    The unusual phase diagram of La2-xBaxCuO4 (LBCO) near x=1/8 doping suggests a complex intertwined relationship between high-temperature superconductivity, charge stripes, spin order, and phase coherence. The charge stripe state's short-range conductance anisotropy may be observable as fluctuations in resistance. In thin film LBCO devices grown by pulsed laser deposition, our time-resolved resistance measurements have revealed an onset of resistance noise at dopings and critical temperatures consistent with charge stripes. The phase diagram of LBCO is explored by comparing the noise onset signature of charge order to measurements of superconductivity, the Hall effect, and other phenomena. I will briefly discuss the relevance of our results in LBCO thin films and crystals to a proposed ''pair-density-wave'' state near x=1/8. This research was supported by the DOE-BES under Grant DE-SC0012368, through the Frederick Seitz Materials Research Laboratory at the University of Illinois at Urbana-Champaign. SRC was sponsored by NSF-REU 13-59126.

  7. Lycopene modulates cholinergic dysfunction, Bcl-2/Bax balance, and antioxidant enzymes gene transcripts in monosodium glutamate (E621) induced neurotoxicity in a rat model.

    Science.gov (United States)

    Sadek, Kadry; Abouzed, Tarek; Nasr, Sherif

    2016-04-01

    The effect of monosodium glutamate (MSG) on brain tissue and the relative ability of lycopene to avert these neurotoxic effects were investigated. Thirty-two male Wistar rats were distributed into 4 groups: group I, untreated (placebo); group II, injected with MSG (5 mg·kg(-1)) s.c.; group III, gastrogavaged with lycopene (10 mg·kg(-1)) p.o.; and group IV received MSG with lycopene with the same mentioned doses for 30 days. The results showed that MSG induced elevation in lipid peroxidation marker and perturbation in the antioxidant homeostasis and increased the levels of brain and serum cholinesterase (ChE), total creatine phosphokinase (CPK), creatine phosphokinase isoenzymes BB (CPK-BB), and lactate dehydrogenase (LDH). Glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities and gene expression were increased and glutathione content was reduced in the MSG-challenged rats, and these effects were ameliorated by lycopene. Furthermore, MSG induced apoptosis in brain tissues reflected in upregulation of pro-apoptotic Bax while lycopene upregulated the anti-apoptotic Bcl-2. Our results indicate that lycopene appears to be highly effective in relieving the toxic effects of MSG by inhibiting lipid peroxidation and inducing modifications in the activity of cholinesterase and antioxidant pathways. Interestingly, lycopene protects brain tissue by inhibiting apoptosis signaling induced by MSG. PMID:26900785

  8. Effect of Buspirone, Fluoxetine and 8-OH-DPAT on Striatal Expression of Bax, Caspase-3 and Bcl-2 Proteins in 6-Hydroxydopamine-Induced Hemi-Parkinsonian Rats

    OpenAIRE

    Hamdollah Sharifi; Alireza Nayebi; Safar Farajnia; Rasool Haddadi

    2015-01-01

    Purpose: The exact pathogenesis of sporadic parkinson’s disease (PD) is still unclear. Numerous evidences suggest involvement of apoptosis in the death of dopaminergic neurons. In this study we investigated the effect of sub-chronic administration of buspirone, fluoxetine and 8-hydroxy-2-[di-n-propylamino]tetralin (8-OH-DPAT) in 6-hydroxydopamine (6-OHDA)-lesioned rats and assayed striatal concentrations of apoptotic (Bax, Caspase3) and anti-apoptotic (Bcl-2) proteins. M...

  9. Der Einfluss der Anästhetika Sevofluran und Propofol auf die Regulation der apoptoseassoziierten Proteine Bax, Bcl-2, Mdm-2 und p53 nach inkompletter zerebraler Hemisphärenischämie bei der Ratte

    OpenAIRE

    Bachl, Monika Maria

    2005-01-01

    Der Einfluss der Anästhetika Sevofluran und Propofol auf apoptoseassoziierte Proteine während zerebraler Ischämie ist bisher nicht erforscht. In der vorliegenden Studie wurden die Effekte dieser Narkotika auf die Regulation der Apoptosefaktoren Bax, Bcl-2, Mdm-2 und p53 bei 36 narkotisierten Sprague-Dawley-Ratten untersucht, bei denen eine inkomplette zerebrale Hemisphärenischämie mit anschließender Reperfusion induziert wurde. Die Apoptosefaktoren wurden mittels Immunfluoreszenz- und Western...

  10. P53,Bax,Bcl-2蛋白表达及细胞凋亡在急性放射性皮肤溃疡发生发展过程中的作用探讨%The role of P53, Bax, Bcl-2 expression and cell apoptosis in the formation and development of acute radiation-induced skin ulcers

    Institute of Scientific and Technical Information of China (English)

    谷庆阳; 曹卫红; 王德文; 高亚兵; 杨志祥; 赵坡

    2001-01-01

    目的:研究细胞凋亡及一些凋亡相关基因(p53,bcl-2,bax)的表达在急性放射性皮肤溃疡发生发展过程中的作用.方法:采用Wistar大鼠以60Co γ射线进行局部照射,建立急性放射性皮肤溃疡动物模型,观察病变40 d,然后采用免疫组化方法检测皮肤溃疡组织中P53,Bcl-2,Bax蛋白表达,并采用原位末端标记法(TUNEL)检测细胞凋亡.结果:照后14 d照射野内开始出现皮肤溃疡,之后逐渐扩大、融合、加深;照后11~40 d,P53蛋白表达明显增强,主要定位于血管内皮细胞和小血管平滑肌中;照后14~21 d为Bax蛋白表达高峰,之后逐渐减弱,主要定位于血管内皮细胞、部分成纤维细胞及新生表皮细胞中;Bcl-2则在照后1~11 d呈弱或中度阳性,定位于表皮、毛囊上皮及血管内皮中,之后为阴性或可疑阳性;照后11~35 d,上述细胞特别是血管内皮细胞凋亡率较正常伤口愈合早期增高.结论:辐射诱导的P53,Bax,Bcl-2表达的变化及细胞凋亡率特别是血管内皮细胞凋亡率的增高与放射性皮肤溃疡发生、发展及难愈合(不能形成有效肉芽组织)的分子机制相关.%Objective:To study the expression of P53, Bax, Bcl-2 proteins and the role of cell apoptosis in the formation and development of acute radiation-induced skin ulcers.Methods:A rat model which was locally irradiated with 60 Co γ-rays was used, and the pathological changes were observed for 40 days. Immunohistochemistry and TUNEL assay were performed which enabled the detection of P53, Bax, Bcl-2 and cell apoptosis during the formation and development of radiation skin ulcers.Results: Skin ulcers were found on day 14 after irradiation, and enlarged and deepened gradually during the observation period. P53 was over expressed during days 11 to 40 after irradiation and was localized in vascular endotheliocytes and smooth muscle cells. Bax was moderately positive during days 14 to 21 and weakly positive during days

  11. Impact of resveratrol on the expression of apoptosis related gene survivin and bax in human cancer cells%白藜芦醇对食管癌细胞凋亡相关基因survivin和bax表达的影响

    Institute of Scientific and Technical Information of China (English)

    Yongjun Li; Xiaohui Sun; Rui Zhang

    2009-01-01

    Objective: We explored the mechanism of apoptosis in human esophageal cancer Eca109 cells by resveratrol.Methods: The suppressive ratio of resveratrol on Ecal09 cells proliferation was evaluated by MTT colorimetric assay and morphology was observed by transmission electron microscope. The expression of survivin and bax was analyzed by RT-PCR and Flow Cytometry (FCM). Results: Resveratrel inhibited the growth of Ecal09 cells in a dose-and time-dependent man-ner, and the suppressive ratio arrived at 76.42%. Morphological apoptosis could be observed after treated with resveratrol.The bulk of some drug-treated cells turned small and the nuclear chromatin became condensed and marginated. The results determined by RT-PCR and FCM showed that resveratrol could down-regulate surviving, while up-regulate bax. Conclusion:Resveratrol could induce the apoptosis of human esophageal cancer Eca109 cells, and its possible molecular mechanisms might be related to modulation the expression of survivin and bax.

  12. Cisplatin-induced apoptosis in non-small-cell lung cancer cells is dependent on Bax- and Bak-induction pathway and synergistically activated by BH3-mimetic ABT-263 in p53 wild-type and mutant cells.

    Science.gov (United States)

    Matsumoto, Masaru; Nakajima, Wataru; Seike, Masahiro; Gemma, Akihiko; Tanaka, Nobuyuki

    2016-04-29

    Cisplatin is a highly effective anticancer drug for treatment of various tumors including non-small-cell lung cancer (NSCLC), and is especially useful in cases nonresponsive to molecular-targeted drugs. Accumulating evidence has shown that cisplatin activates the p53-dependent apoptotic pathway, but it also induces apoptosis in p53-mutated cancer cells. Here we demonstrated that DNA-damage inducible proapoptotic BH3 (Bcl-2 homology region 3)-only Bcl-2 family members, Noxa, Puma, Bim and Bid, are not involved in cisplatin-induced apoptosis in human NSCLC cell lines. In contrast, the expression of proapoptotic multidomain Bcl-2-family members, Bak and Bax, was induced by cisplatin in p53-dependent and -independent manners, respectively. Moreover, in wild-type p53-expressing cells, cisplatin mainly used the Bak-dependent apoptotic pathway, but this apoptotic pathway shifted to the Bax-dependent pathway by loss-of-function of p53. Furthermore, both Bak- and Bax-induced apoptosis was enhanced by the antiapoptotic Bcl-2 family member, Bcl-XL knockdown, but not by Mcl-1 knockdown. From this result, we tested the effect of ABT-263 (Navitoclax), the specific inhibitor of Bcl-2 and Bcl-XL, but not Mcl-1, and found that ABT-263 synergistically enhanced cisplatin-induced apoptosis in NSCLC cells in the presence or absence of p53. These results indicate a novel regulatory system in cisplatin-induced NSCLC cell apoptosis, and a candidate efficient combination chemotherapy method against lung cancers.

  13. Microsatellite instability and frameshift mutations in BAX and transforming growth factor-beta RII genes are very uncommon in acute lymphoblastic leukemia in vivo but not in cell lines.

    Science.gov (United States)

    Molenaar, J J; Gérard, B; Chambon-Pautas, C; Cavé, H; Duval, M; Vilmer, E; Grandchamp, B

    1998-07-01

    Mutations in the DNA mismatch repair (MMR) system lead to an instability of simple repetitive DNA sequences involved in several cancer types. This instability is reflected in a high mutation rate of microsatellites, and recent studies in colon cancer indicate that defects in MMR result in frequent frameshift mutations in mononucleotide repeats located in the coding regions of BAX and transforming growth factor-beta (TGF-beta) receptor genes. Circumstantial evidence suggests that the MMR defect may be involved in some lymphoid malignancies, although several allelotype analyses have concluded on the low level of microsatellite instability in acute lymphoblastic leukemias. To further evaluate the implication of MMR defects in leukemogenesis, we have studied a series of 98 children with acute lymphoblastic leukemia and 14 leukemic cell lines using several indicators of MMR defects. Microsatellite markers were compared between blast and normal DNA from the same patients and mutations were sought in mononucleotide repeat sequences of BAX and TGF-beta receptor II (TGF-beta RII). The absence of microsatellite instability (MI) and the absence of mutations in the genes examined from patient's leukemic cells contrasted with the observation that half of the cell lines displayed a high degree of MI and that three of seven of these mutator cell lines harbored mutations in BAX and/or TGF-beta RII. From these results we conclude that MMR defects are very uncommon in freshly isolated blasts but are likely to be selected for during the establishment of cell lines.

  14. Deregulated expression of A1, Bcl-2, Bcl-xL, and Mcl-1 antiapoptotic proteins and Bid, Bad, and Bax proapoptotic genes in polycythemia vera patients

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    Elainy Patricia Lino Gasparotto

    2011-12-01

    Full Text Available Apoptosis deregulation might have a role in the pathophysiology of polycythemia vera (PV. This study evaluated Bcl-2 molecule expression in CD34+ cells and leukocytes in 12 PV patients. Gene expression was investigated by real time PCR using SybrGreen Quantitect kit and protein expression was evaluated by western-blotting. JAK2 V617F mutation was detected according to Baxter et al (2005. CD34+ cells from PV patients presented higher levels of A1 and Mcl-1 expression (median: 22.6 and 5.2, respectively in comparison with controls (0.9 and 0.5, p=0.004 and p=0.020; while Bcl-2 and Bcl-xL expression decreased in PV patients (0.18 and 1.19 compared with controls (1.39 and 2.01, p=0.006 and p=0.020. CD34+ cells in PV patients showed an elevated Bid expression (14.4 in comparison with healthy subjects (1.0; p=0.002. Patients' leukocytes showed an A1 augmentation (7.41, p=0.001 and a reduced expression of Bax (0.19; p=0.040 and Bad (0.2; p=0.030. There was no correlation between JAK2 V617F allele burden and molecular expression. PV patients showed alterations in Bcl-2 members' expression, which may interfere with control of apoptotic machinery and contribute to disease pathogenesis.A desregulação da apoptose parece participar da fisiopatologia da policitemia vera (PV. Este estudo avaliou a expressão das moléculas da família Bcl-2 em células hematopoéticas CD34 + e leucócitos de 12 pacientes com PV. Foram realizados: a quantificação da expressão gênica por PCR em tempo real utilizando kit Sybrgreen Quantitect, avaliação da expressão de proteínas por western-blot e detecção da mutação JAK2 V617F segundo Baxter et al. (2005. Células CD34 + dos pacientes com PV apresentaram maior expressão de A1 e Mcl-1 (mediana: 22,6 e 5,2, respectivamente em comparação com controles (0,9 e 0,5, p = 0,004 e p = 0,020 e expressão de Bcl-2 e Bcl-xL diminuída nestes pacientes (0,18 e 1,19 em relação aos controles (1,39 e 2,01, p = 0,006 e p = 0

  15. THE EXPRESSIONS OF HIF-1α AND Bax AND THEIR CORRELATION IN SUDDEN CARDIAC DEATH%心脏性猝死心肌组织HIF-1α和Bax表达及其相关性

    Institute of Scientific and Technical Information of China (English)

    刘德衍; 袁磊; 杨彦华; 纪萍; 于建宪; 张七一; 林梅

    2011-01-01

    目的 探讨缺氧诱导因子1 alpha(HIF-1α)和Bax蛋白在心脏性猝死(SCD)者心肌组织中的表达与相关性,并为法医学鉴定SCD提供客观依据.方法 应用免疫组织化学方法,检测25例SCD者心肌组织中HIF-1α和Bax蛋白的表达,并以25例非SCD者心肌组织作为对照.结果 SCD者心肌组织HIF-1α与Bax的表达明显高于对照组(uc=6.083、5.573,P<0.01).在SCD心肌组织中,HIF-1α表达与Bax表达呈正相关(r=0.736,P<0.01).结论 HIF-1α与Bax表达的增高与SCD的发生有一定的相关性,HIF-1α与Bax可望作为诊断SCD较为客观的病理形态学指标.%Objective To investigate the expressions of hypoxia-inducible factor-1 alpha (HIF-1α) and Bcl-2 associated X protein (Bax) and their correlation in myocardium of sudden cardiac death (SCD) and provide an objective evidence for forensic identification.Methods The expressions of HIF-la and Bax in myocardium of 25 SCD were detected using immunohistochemical technique, and 25 of non-sudden cardiac death served as controls.Results The expressions of HIF-1α and Bax in myocardium of the SCD were significantly higher than that of the control (Uc = 6.083,5.573;P<0.01), and the expressions were positively correlated (r=0.736,P<0.01) Conclusion The elevation of the expressions of HIF-1α and Bax is associated with SCD to a certain extent.The HIF-1α and Bax will hopefully become a relatively objective pathomorphologic index in the diagnosis of SCD.

  16. MicroRNA-650 was a prognostic factor in human lung adenocarcinoma and confers the docetaxel chemoresistance of lung adenocarcinoma cells via regulating Bcl-2/Bax expression.

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    Jia-Yuan Huang

    Full Text Available Increasing evidence shows that dysregulation of microRNAs (miRNAs is involved in malignant transformation. We investigated the clinical significance of miR-650 and its involvement in chemoresistance to docetaxel. Our results showed that the relative expression level of miR-650 was significantly higher in LAD tissues than in corresponding nontumor tissues and high level of miR-650 expression was found to be significantly associated with high incidence of lymph node metastasis, advanced clinical stage and poor prognosis of LAD patients. Univariate and multivariate analyses indicated that high miR-650 expression was an independent prognostic factor for survival. Also, we found that the level of miR-650 in LAD tissues was correlated with the response of patients to docetaxel-based chemotherapy. Silencing of miR-650 could increase the in vitro sensitivity of docetaxel-resistant LAD cells to docetaxel, while upregulation of miR-650 decreased the sensitivity of parental LAD cells to docetaxel both in vitro and in vivo. Additionally, silencing of miR-650 could enhance the caspase-3-dependent apoptosis, which might be correlated with the decreased ratio of Bcl-2/Bax. Further researches suggested that inhibitor of growth 4 (ING4 was a direct target of miR-650. Downregulated or upregulated ING4 expression could partially rescue the effects of miR-650 inhibitor or mimics in docetaxel-resistant or parental LAD cells. Furthermore, we found that ING4 was upregulated in docetaxel-responding LAD tissues, and its expression was inversely correlated with miR-650. Thus, miR-650 is a novel prognostic marker in LAD and its expression is a potential indicator of chemosensitivity to docetaxel-based chemotherapy regimen.

  17. Yeast Bax inhibitor, Bxi1p, is an ER-localized protein that links the unfolded protein response and programmed cell death in Saccharomyces cerevisiae.

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    James Cebulski

    Full Text Available Bax inhibitor-1 (BI-1 is an anti-apoptotic gene whose expression is upregulated in a wide range of human cancers. Studies in both mammalian and plant cells suggest that the BI-1 protein resides in the endoplasmic reticulum and is involved in the unfolded protein response (UPR that is triggered by ER stress. It is thought to act via a mechanism involving altered calcium dynamics. In this paper, we provide evidence that the Saccharomyces cerevisiae protein encoded by the open reading frame, YNL305C, is a bona fide homolog for BI-1. First, we confirm that yeast cells from two different strain backgrounds lacking YNL305C, which we have renamed BXI1, are more sensitive to heat-shock induced cell death than wildtype controls even though they have indistinguishable growth rates at 30°C. They are also more susceptible both to ethanol-induced and to glucose-induced programmed cell death. Significantly, we show that Bxi1p-GFP colocalizes with the ER localized protein Sec63p-RFP. We have also discovered that Δbxi1 cells are not only more sensitive to drugs that induce ER stress, but also have a decreased unfolded protein response as measured with a UPRE-lacZ reporter. Finally, we have discovered that deleting BXI1 diminishes the calcium signaling response in response to the accumulation of unfolded proteins in the ER as measured by a calcineurin-dependent CDRE-lacZ reporter. In toto, our data suggests that the Bxi1p, like its metazoan homologs, is an ER-localized protein that links the unfolded protein response and programmed cell death.

  18. Silver Nanoparticles Biosynthesized Using Achillea biebersteinii Flower Extract: Apoptosis Induction in MCF-7 Cells via Caspase Activation and Regulation of Bax and Bcl-2 Gene Expression

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    Javad Baharara

    2015-02-01

    Full Text Available Silver nanoparticles (Ag-NPs, the most popular nanoparticles, possess unique properties. Achillea biebersteinii is a plant of the Asteraceae family rich in active antitumor components. The aim of this research was the characterization and investigation of the cytotoxic properties of Ag-NPs synthesized using A. biebersteinii flower extract, on a human breast cancer cell line. The Ag-NPs were synthesized after approximately 180 min of reaction at 40 °C, then they were characterized by UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR, transmission electron microscopy (TEM and dynamic light scattering (DLS. The anti-apoptosis effect of Ag-NPs on the MCF-7 cell line was investigated by MTT assay, DAPI and acridine orange staining and caspase activity. The transcriptional expression of bax, bcl-2, caspase-3, -8 and -9 were also evaluated by RT-PCR. The TEM images revealed that the Ag-NPs morphology had a different shape. The DLS indicated that the average hydrodynamic diameter of the biosynthesized Ag-NPs was around 12 nm. By UV-visible spectroscopy the strongest absorbance peak was observed at 460 nm. The FTIR results also showed interaction between the plant extract and Ag-NPs due to the similarity in the peak patterns. The EDS results showed that Ag-NPs display an absorption peak at 3 keV, indicating the presence of the element silver. The Ag-NPs caused a dose-dependent decrease in cell viability, fragmentation in nucleic acid, inhibited the proliferation and induction of apoptosis on MCF-7 by suppressing specific cell cycle genes, and simulation programmed cell dead genes. Further investigation is required to establish the potential of this novel and promising approach in cancer therapy.

  19. The influence of sleep deprivation on expression of apoptosis regulatory proteins p53, bcl-2 and bax following rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide

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    Juliana Noguti

    2013-01-01

    Full Text Available Background: The aim of this study was to evaluate whether paradoxical sleep deprivation could affects the mechanisms and pathways essentials for cancer cells in tongue cancer induced by 4-nitroquinole 1-oxide in Wistar rats. Materials and Methods: For this purpose, the animals were distributed into 4 groups of 5 animals each treated with 50 ppm 4 nitroquinoline 1 oxide (4 NQO solution through their drinking water for 4 and 12 weeks. The animals were submitted to paradoxical sleep deprivation (PSD for 72 h using the modified multiple platform method, which consisted of placing 5 mice in a cage (41 × 34 × 16 cm containing 10 circular platforms (3.5 cm in diameter with water 1 cm below the upper surface. The investigations were conducted using immunohistochemistry of p53, Bax and Bcl-2 proteins related to apoptosis and its pathways. Statistical analysis was performed by Kruskal-Wallis non-parametric test followed by the Dunn′s test using SPSS software pack (version 1.0. P value < 0.05 was considered for statistic significance. Results: Although no histopathological abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure in all groups, in 12 weeks were observed pre-neoplasic lesions. Data analysis revealed statistically significant differences ( P < 0.05 in 4 weeks group for p53 and for bcl-2 and for all immunomarkers after 12 weeks of 4NQO administration. Conclusion: Our results reveal that sleep deprivation exerted alterations in proteins associated with proliferation and apoptosis in carcinogenesis.

  20. Tubeimoside-1 induces glioma apoptosis through regulation of Bax/Bcl-2 and the ROS/Cytochrome C/Caspase-3 pathway

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    Jia G

    2015-01-01

    Full Text Available Geng Jia,1,* Qiang Wang,2,* Rong Wang,2,* Danni Deng,2 Lian Xue,2 Naiyuan Shao,1 Yi Zhang,1 Xiwei Xia,1 Feng Zhi,2 Yilin Yang1,2 1Department of Neurosurgery, Third Affiliated Hospital of Soochow University, Jiangsu, People’s Republic of China; 2Modern Medical Research Center, Third Affiliated Hospital of Soochow University, Jiangsu, People’s Republic of China * These authors contributed equally to this workBackground: Tubeimoside-1 (TBMS1 is a natural compound isolated from tubeimoside, which has been widely used as a traditional Chinese herbal medicine. The purpose of the present study is to investigate the anti-tumor effect and the underling mechanism of TBMS1 on glioma cancer cells.Methods: The MTT assay was performed to evaluate the effect of TBMS1 on glioma cell proliferation. The fluorescent microscopy and flow cytometry analysis were performed to evaluate the effect of TBMS1 on glioma cell apoptosis. The Western blot analysis was used to evaluate the protein change.Results: TBMS1 inhibited glioma cancer cell proliferation in a dose- and time-dependent manner. Fluorescent microscopy and flow cytometry analysis demonstrated that TBMS1 induced glioma cell apoptosis in a concentration-dependent manner. Western blotting showed that TBMS1 induced apoptosis by increasing the expression of Bax and downregulating the level of Bcl-2. Furthermore, we found that TBMS1 induced apoptosis by increasing the concentration of reactive oxygen species through the release of Cytochrome C and activation of Caspase-3.Conclusion: These findings indicate that TBMS1 may be developed as a possible therapeutic agent for the management of glioma. Keywords: Tubeimoside-1, glioma, proliferation, apoptosis

  1. bax和p53基因共转染对人舌癌细胞增 殖和凋亡的影晌%Effect on Proliferation and Apoptosis of Human Lingual Carc inoma Cells Cotransfected by bax and p53 Genes

    Institute of Scientific and Technical Information of China (English)

    马英红; 杨绍华; 陈俊杰; 高家让; 彭文珍; 王若菡

    2001-01-01

    Objective To investigate th e effects on prolife ration andapoptosis of human cancerous cells cotransfected by bax apoptosis-in ducing gene and p53 tumor suppressor gene. Methods The chi meric gene pSV-CIP-bax -CAT was constructed in which bax gene was flanked upstream by a 217bp fragment (+822~+1093) of the first intron and a 317bp promoter fragment of human a 1(Ⅰ) colla gen gene . Human lingual carcinoma cell line Tca 8113 (LCC) in culture was respe ctively transfected with pSV-CIP-bax-CAT, and cotransfected with pSV-p53-CA T and pSV-CIP-bax-CAT by using the transfection reagent DOSPER. Res ults Immuno- slot blot and ELISA demonstrated that the expression of bax and p53 genes incr eased remarkably in the transfected and cotransfected LCC, compared with the con trols(LCC transfected with pSV-CIP-CAT and LCC).MTT colorimetric assay,TUNE L fluorecence microscopy and flow cytometry showed that foreign bax or p53 gene inhibited the LCC growth and induced apoptosis(23.9% and 26.1% of inhibitory ra te by bax gene and p53 plus bax genes respectively). Conclusion The ectopic expression of the bax gene in the LCC promoted by the cis-act ing elements of human a1(Ⅰ)collagen gene has obviously synergistic effect on th e proliferation and apoptosis of the LCC cotransfected with p53 gene plus bax gene for 48 hours.%目的 探讨诱导凋亡的bax基因和p53抑癌基因共转染对人癌细胞增殖和凋亡的作用。方法 构建pSV-CIP-bax-CAT嵌合基因。在其bax基因上游含人a1(Ⅰ)型胶原基因的第一内含子217bp片段(+822~+1093)和317bp启动子片段。经阳离子转染试剂DOSPER介导,分别用pSV-CIP-bax-CAT转染、pSV-CIP-bax-CAT和pSV-p53-CAT共转染培养的人舌癌Tca8113细胞系(LCC)。结果 免疫狭缝印迹和ELISA检测证实,转染组和共转染组比对照的bax和p53基因表达量明显增加。MTT显色分析、TUNEL荧光显微镜和流式细胞仪监测结果显示,bax基因或p53基因均具抑

  2. Expression of Smac and Bax in chronic periodontal tissues and their roles in apoptosis%慢性牙周炎龈组织中Smac和Bax的表达及其对细胞凋亡的作用

    Institute of Scientific and Technical Information of China (English)

    冯利; 董跟喜; 孙晓玮

    2012-01-01

    AIM: To investigate the expression of Smac and Bax in gingival tissues of chronic periodontitispatients. METHODS; Gingival tissues from 27 periodontitis patients and 27 periodontally healthy subjects were obtained from extracted teeth. Light microscope and transmission electron microscope were used to observe the morphology and structure of apoptotic cells in gingival tissues. Mitochondria] transmembrane potential ( △ψm) was measured by flow cytometry. The expression of Smac and Bax was detected with immunohistochemistry in gingival tissues. RESULTS; Under light microscope, apoptotic cells could be observed. Morphological and structural changes could beseen in mitochondria under transmission electron microscope. △ψm was significantly lower in chronic periodontal tissues as compared with healthy gingiva (P <0.05). Smac and Bax expression was significantly stronger in gingival epithelial and connective tissues of chronic periodontitis patients (P < 0. 05). Smac expression was positively related to Bax expression (P<0.05) in chronic periodontal tissues. CONCLUSION: Apoptotic cells exist in gingival tissue of chronic periodontitis patients. Smac expression is positively related to Bax expression. Both Smac and Bax expression are significantly enhanced, indicating that they might play important roles in the destruction of periodontal tissues.%目的:通过检测Smac和Bax蛋白在慢性牙周炎龈组织中的表达,旨在探讨二者的相关性及其在细胞凋亡中与牙周炎发生、发展的关系.方法:慢性牙周炎测试组27人,健康对照组27人,利用光镜和透射电镜观察凋亡细胞形态结构,流式细胞仪测定线粒体膜电位.免疫组化检测Smac、Bax在龈组织不同区域的表达.结果:光镜观察慢性牙周炎龈组织中存在有凋亡细胞;电镜观察凋亡细胞中线粒体形态结构改变;慢性牙周炎龈组织线粒体膜电位降低,与健康组比较,两组间有显著性差异(P<0.05);慢性牙周

  3. Study on the Relationship between the Gene Expression of Bax and Apoptosis in Tongue Mycoderma Epithelium of Common Tongue Coating%bax mRNA和蛋白产物与常见舌苔舌上皮细胞凋亡关系的研究靠

    Institute of Scientific and Technical Information of China (English)

    李明; 吴正治; 何朝; 张永锋; 陈嫚茵

    2003-01-01

    目的:检测常见舌苔舌上皮细胞凋亡情况及凋亡相关基因bax mRNA和蛋白产物,探讨舌苔厚度变化与舌上皮细胞凋亡、bax基因表达的关系.方法:运用TUNEL(末端脱氧核苷酸转移酶介导的脱氧尿嘧啶核苷三磷酸缺口末端标记)技术、原位杂交、免疫组化和图像分析技术.结果:与正常薄苔比较,剥苔bax基因过度表达伴随细胞凋亡增多,而厚苔bax基因低表达伴随细胞凋亡减少.bax基因表达水平变化趋势与细胞凋亡水平变化趋势一致.结论:bax基因表达水平的变化可能是影响舌苔上皮细胞凋亡并导致舌苔厚度变化的重要原因.

  4. Histological structure and expression of Bax protein in Pavo cristatus kidney%白孔雀肾脏的组织结构及Bax蛋白在肾脏中的表达

    Institute of Scientific and Technical Information of China (English)

    俞诗源; 王小勇; 吴勍

    2012-01-01

    To study Pavo cristatus kidney histological structure and the expression of relevant active substances, histological structure is obvserved by light microscopy and expression of Bax protein is examined by immunohistochemical methods. The results indicate that Pavo cristatus kidney consists of many nephrons, collecting ducts and small amounts of areolar tissue. The glomerular capillary is simpler, renal tubules arrange closely and the quantity is more. The proximal tubule consists of monolayer cuboidal epithelium cells, with brush border and deeper color. Bax protein immune response positive material is mainly distributed in proximal tubule epithelium. Bax protein may be involved in the cell apoptosis of Pavo cristatus kidney and plays an important regulation role in the development of bird kidney.%为了搞清白孔雀(Pavo cristatus)肾脏的结构特征和相关活性物质的表达问题,利用生物显微技术观察了白孔雀肾脏的组织结构,用免疫组织化学方法检测了Bax蛋白在肾组织中的表达.结果显示白孔雀肾脏主要由许多肾单位、集合管和少量结缔组织组成.白孔雀肾小球毛细血管网较简单,肾小管之间排列紧密,数量较多,近端小管由单层立方上皮细胞组成,细胞顶端有刷状缘,细胞着色较深;Bax蛋白免疫反应阳性物质主要分布在近端小管上皮细胞;Bax蛋白可能与白孔雀肾脏细胞的凋亡有关.

  5. 激活素A、Bax和XIAP在特发性胎儿生长受限患者的表达及意义%The Expression and Significance of Activin A, Bax and XIAP in Idiopathic Fetal Growth Restriction

    Institute of Scientific and Technical Information of China (English)

    崔世红; 张婷; 刘萍萍; 程国梅; 贾国占; 管秀娟; 韩笑

    2012-01-01

    Objective:To investigate the expression and significance of Activin A in maternal and cord serum idiopathic fetal growth restriction (IFGR), B-cell lymphoma associated x protein (Bax), and X-linked inhibitor of apoptosis protein (XIAP) in placenta of idiopathic fetal growth restriction (IFGR). Methods:From July 2010 to May 2011, 30 pregnant women with IFGR underwent cesarean section in our hospital were selected as experimental group, and 30 normal term pregnant women underwent cesarean section due to social factors were matched as control group. Activin A in maternal and umbilical cord serum were analyzed by enzyme-linked immunosorbent assay (ELISA), while Bax and XIAP in placenta were detected by immunohis-tochemical method. Results:The level of Activin A both in maternal and cord serum of the experimental group (102. 659 ±16.467, 57.752 ±13.498) ng/ml ,were significantly higher than those in control group (75. 927 ±10. 519,29. 870 ±5. 992) ng/ml(P<0.05). The expression of Bax in placental syncytiotropho-blast in experimental group (146. 513 ± 10. 611) was significantly increased as compared to the control group (113. 672 ±9. 631) (P <0. 05). The expression of XIAP in placental syncytiotrophoblast in experimental group (114. 562 ±5.167) was significantly decreased as compared to the control group (144. 430 ± 7. 311) (P <0. 05). The level of Activin A in maternal and cord serum was positively correlated with the expression of Bax in placenta in experimental group (p<0. 05), whilst it showed negative correlation with the expression of XIAP in placenta in experimental group (P<0. 05). Moreover, the expression of XIAP in syn-cytiotrophoblast was found negetively correlated with Bax (P<0. 05). Conclusions:The increased Activin A in maternal and cord serum, as well as the increased expression of Bax and decreased expression of XIAP in placenta, may play important roles in the pathogenisis of IFGR. The increased Activin A may lead to excessive apoptosis of

  6. Changes of NF-κB, Bax and Caspase 3 in Apoptosis lnduced by Ligustrazine Combined with Cis-dichlorodiamine Platinum in Human Gastric Carcinoma SGC-7901 Cell Lines

    Institute of Scientific and Technical Information of China (English)

    Tao HUANG; Liyan Ll; Xiaona GUO; Zhigang GUO; Yalin Zhang

    2015-01-01

    Objective] This study aimed to investigate the mechanism of apoptosis in-duced by ligustrazine (TMP) and cis-dichlorodiamine platinum (DDP) in SGC-7901 cel lines in vitro. [Methods] SGC-7901 cel lines were treated with ligustrazine and DDP alone or combined for 48 h for Western blot analysis, respectively. Western blot analysis was used to determine the expression of proteins involved in apoptosis including NF-κB p65, bax and caspase-3. [Results] The viability of SGC-7901 cel s was inhibited after treated with ligustrazine and/or combined with DDP. The expres-sion of NF-κB P65 protein decreased after treated with drugs, in which the protein decreased significantly in 1.2 mg/ml of TMP combined with 2 μg/ml of DDP group. Meanwhile, we investigated the protein expression of bax and caspase-3. The re-sults showed that the expression of the two proteins increased fol owing with the in-creasing concentration of TMP. [Conclusion] Al the results indicated that ligustrazine combined with DDP could induce the apoptosis of SGC-7901 cel lines, and NF-κB maybe the possible way to induce the cel apoptosis.

  7. Synthetic Bichalcone TSWU-BR23 Induces Apoptosis of Human Colon Cancer HT-29 Cells by p53-Mediated Mitochondrial Oligomerization of BAX/BAK and Lipid Raft Localization of CD95/FADD.

    Science.gov (United States)

    Lin, Meng-Liang; Chen, Shih-Shun; Wu, Tian-Shung

    2015-10-01

    A synthetic bichalcone analog, (E)-1-(3-((4-(4-acetylphenyl)piperazin-1-yl)methyl)-4-hydroxy-5-methoxyphenyl)-3-(pyridin-3-yl)prop-2-en-1-one (TSWU-BR23), has been shown to induce apoptosis in human colon cancer HT-29 cells involving the induction of CD95 and FAS-associated protein death domain (FADD), but its precise mechanism of action has not been fully elucidated. Using cell-surface biotinylation and sucrose density-gradient-based membrane flotation techniques, we showed that the disruption of TSWU-BR23-induced lipid raft localization of CD95/FADD by cholesterol-depleting agent (methyl-β-cyclodextrin) was reversed by cholesterol replenishment. Blockade of p53 expression by short-hairpin RNA (shRNA) suppressed oligomeric Bcl-2-associated x protein (BAX)/Bcl-2 antagonist killer 1 (BAK)-mediated mitochondrial apoptosis but did not inhibit lipid raft localization of CD95/FADD and pro-caspase-8 cleavage induced by TSWU-BR23. Co-expression of p53 shRNA and dominant-negative mutant of FADD completely inhibited TSWU-BR32-induced mitochondrial apoptotic cell death. Collectively, these data demonstrate that TSWU-BR23 leads to HT-29 cell apoptosis by inducing p53-mediated mitochondrial oligomerization of BAX/BAK and the localization of CD95/FADD with lipid rafts at the cell surface.

  8. Microstructure and microwave dielectric properties of Ba6-3xSm8+2xTi18Os4ceramics with various BaxSr1-xTiO3 additions

    Institute of Scientific and Technical Information of China (English)

    ZHOU Lingling; ZHOU Hongqing; SHAO Hui; ZHU Haikui

    2012-01-01

    The Ba6-3xSm8+2xTi18O54 (x=2/3) microwave dielectric ceramics were prepared by traditional solid sate reaction technique.The experiment was based on the Ba6-3xSm8+2xTi18O54 (BST) microwave dielectric ceramics doped with a certain amount of Bi2O3,then the effects of BaxSr1-xTiO3 additives on the structure and microwave dielectric properties of Ba6-3xSm8+2xTi18O54 ceramics were investigated using X-ray diffraction and scanning electron microscopy.In this study,the small amount substitution of Sr for Ba was effective for the microwave dielectric properties of BST,especially the τf could be tuned to near zero.The result showed that the BST possessed excellent dielectric properties when the addition of Bi2O3 and BaxSr1-xTiO3 was 1 wt.% respectively:εr=79.6,Qf=10789 GHz,τf=-1.5 ppm/℃.

  9. Synergistic Effect of Subtoxic-dose Cisplatin and TRAIL to Mediate Apoptosis by Down-regulating Decoy Receptor 2 and Up-regulating Caspase-8, Caspase-9 and Bax Expression on NCI-H460 and A549 Cells

    Directory of Open Access Journals (Sweden)

    Xiaoyan Zhang

    2013-05-01

    Full Text Available Objective(s: Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL can selectively induce apoptosis in tumor cells, more than half of tumors including non-small cell lung cancer (NSCLC exhibit TRAIL-resistance. The purpose of this study was to determine whether subtoxic-dose cisplatin and TRAIL could synergistically enhance apoptosis on NSCLC cells and investigate its underlying mechanisms. Materials and Methods:NCI-H460 and A549 cells were treated with TRAIL alone, cisplatin alone or combination treatment in this study. The cytotoxicity was evaluated according to Sulforhodamine B assay, and apoptosis was examined using Hoechst 33342 staining and flow cytometry. The mRNA and protein levels of TRAIL receptors and apoptotic proteins including caspase-8, caspase-9, Bcl-2 and Bax were determined by RT-PCR and Western blotting, respectively. Results:Our results showed that NCI-H460 cells were sensitive to TRAIL, whereas A549 cells were resistant. However, subtoxic-dose cisplatin could enhance the both cells to TRAIL-mediated cell proliferation inhibition and apoptosis. The underlying mechanisms might be associated with the down-regulation of DcR2 and up-regulation of Caspase-8, Caspase-9 and Bax. Conclusion:Subtoxic-dose cisplatin could enhance both TRAIL- sensitive and TRAIL- resistant NSCLC cells to TRAIL-mediated apoptosis. These findings motivated further studies to evaluate such a combinatory therapeutic strategy against NSCLC in the animal models.

  10. Darbepoetin alpha, a long-acting erythropoeitin derivate, does not alter LPS evoked myocardial depression and gene expression of Bax, Bcl-Xs, Bcl-XL, Bcl-2, and TNF-alpha.

    Science.gov (United States)

    Brendt, Peter; Frey, Ulrich; Adamzik, Michael; Schäfer, Simon T; Peters, Jürgen

    2009-01-01

    Darbepoetin alpha (DA), a long-acting erythropoietin derivative stimulating erythropoiesis, can, by antiapoptotic effects, mitigate myocardial I/R injury. We tested the hypothesis that DA treatment improves left ventricular function (LV) in LPS evoked cardiomyopathy and alters gene expression of apoptosis-regulating proteins (Bcl-XL, Bcl-2, Bax, and Bcl-Xs) and TNF-alpha. In a prospective, controlled, randomized study in Lewis rats (n = 56; 8 groups), myocardial depression was evoked by LPS administration (serotype O127:B8; 10 mg/kg, i.p.). Darbepoetin alpha or vehicle was injected either 24 h before (pretreatment) or 2 h after LPS injection (treatment). Hearts were isolated 8 h after LPS injection, perfused (Krebs-Henseleit solution) in a Langendorff apparatus, and LV developed pressure and its derivatives were measured. For gene expression analysis, real-time polymerase chain reaction of LV specimen was performed. LPS decreased LV developed pressure (-64.6 +/- 7.9 mmHg) and its derivates by more than 60% in comparison to vehicle (P Xs, Bax, and TNF-alpha, but this was not altered by DA pretreatment. Furthermore, there was no effect on Bcl-Xl and Bcl-2 expression by DA alone. Whereas proapoptotic genes of the myocardium are up-regulated in LPS-induced cardiomyopathy, neither DA pretreatment nor treatment has significant effects on LV function or gene expression. This may suggest cardiac resistance to darbepoetin in LPS-mediated sepsis.

  11. Dioscorealide B from the traditional Thai medicine Hua-Khao-Yen induces apoptosis in MCF-7 human breast cancer cells via modulation of Bax, Bak and Bcl-2 protein expression.

    Science.gov (United States)

    Saekoo, Jiraporn; Graidist, Potchanapond; Leeanansaksiri, Wilairat; Dechsukum, Chavaboon; Itharat, Arunporn

    2010-12-01

    Dioscorealide B is a pharmacologically active compound from the rhizome of the Thai medicinal plant Dioscorea membranacea. Here, we demonstrated that in vitro treatment of dioscorealide B resulted in a cytotoxic effect on MCF-7 human breast cancer cells (IC50 = 2.82 microM). To determine whether this compound induces apoptosis in MCF-7, the Annexin V assay was performed. The data showed that the number of apoptotic cells were increased 7-12 folds over that of the control cells after treatment with various concentrations of dioscorealide B (3, 6 and 12 microM) for 24 hours. Dioscorealide B-induced apoptosis was associated with modulation of the multidomain Bcl-2 family members Bax, Bak and Bcl-2. After treatment with 3 microM dioscorealide B, acceleration of the level of proapoptotic proteins Bax and Bak were observed at 6 hours and 12 hours, respectively, while the decrease in the expression of antiapoptotic protein Bcl-2 was observed 3 hours after the treatment. These effects of dioscorealide B might result in the activation of caspase-8, -9 and -7, which lead to apoptosis in MCF-7 cells. Taken together, the results of this study provide evidence that dioscorealide B possesses an antitumor property against human breast cancer cells and thus provide the molecular basis for the further development of dioscorealide B as a novel chemotherapeutic agent for breast cancer treatment. PMID:21299121

  12. Protective Effects of Scutellarin on Type II Diabetes Mellitus-Induced Testicular Damages Related to Reactive Oxygen Species/Bcl-2/Bax and Reactive Oxygen Species/Microcirculation/Staving Pathway in Diabetic Rat

    Directory of Open Access Journals (Sweden)

    Lingli Long

    2015-01-01

    Full Text Available The goal of our study is to evaluate the effect of Scutellarin on type II diabetes-induced testicular disorder and show the mechanism of Scutellarin’s action. We used streptozotocin and high-fat diet to establish type II diabetic rat model. TUNEL and haematoxylin and eosin staining were used to evaluate the testicular apoptotic cells and morphologic changes. Immunohistochemical staining was used to measure the expression level of vascular endothelial growth factor and blood vessel density in testes. Oxidative stress in testes and epididymis was tested by fluorescence spectrophotometer and ELISA. The expression of Bcl-2/Bax and blood flow rate in testicular vessels were measured by western blot and Doppler. Our results for the first time showed that hyperglycemia induced apoptotic cells and morphologic impairments in testes of rats, while administration of Scutellarin can significantly inhibit these damages. This effect of Scutellarin is controlled by two apoptotic triggers: ROS/Bcl-2/Bax and ROS/microcirculation/starving pathway.

  13. 化癥散积颗粒对小鼠原位肝癌Bcl-2/Bax表达的影响%The effects of Huazhengsanjikeli on Bcl-2/Bax expression in mouse of primary Hepatic carcinoma

    Institute of Scientific and Technical Information of China (English)

    金学洙; 李超英; 周磊; 邢美茜; 刘铁军

    2012-01-01

    目的 通过建立小鼠原位肝癌模型,给予化癥散积颗粒灌胃,探讨其对小鼠原位肝癌Bcl-2/Bax表达的影响.方法 将H22瘤株直接注射到肝脏的方法建立小鼠原位肝癌模型;分组:模型组、阳性对照组、化癥散积颗粒高、中、低剂量组;采用TUNEL染色法检测凋亡细胞;RT-PCR和Western-Blot分别检测肿瘤组织Bcl-2和Bax mRNA和蛋白表达差异.结果 阳性对照组(又称斑蝥组)和中、高剂量组中药可以诱导肝癌细胞发生凋亡;可以显著增加肿瘤组织中Bax(P<0.05),同时Bcl-2表达与对照组相比明显降低(P<0.05),低剂量组Bcl-2和Bax表达与对照组相比无明显差异(P>0.05).结论 斑蝥组和中、高剂量组中药诱导肝癌细胞发生凋亡可能是通过抑制Bcl-2基因表达,同时增加Bax表达,从而引发一系列凋亡级联反应.%Objective To study the antitumor mechanism of Granules scattered plot of disease through the insitu-liver cancer model,in order to offer some evidence for clinical Chinese crude drug treatment. Methods Use H22 cells inject liver to build liver caner modcr; Detect apoptosis cells in tumor by TUNKL; Detect the expression difference of Bel-2/Bax by RT-PCR and Western-blot;Results The number of apoptosis cells were significantly increased in Cantharidin,medium and high dose Granules scattered plot of disease groups than in control and low dose groups; The mRNA and protein expression of Bax can be significantly up-rcgulation(P0. 05). Conclusion Cantharidin,medium and high dose Granules scattered plot of disease can induce H22 liver cancr cells to apoptosis; Granules? Scattered plot of disease can be induce liver cancer cells to apoptosis through inhibited the expression of Bcl-2 and up-regulated the expression of Bax at the same time.

  14. Expression of APE1, Bcl-2 and Bax in retinoblastoma and their clinical significance%APE1、Bcl-2及 Bax在视网膜母细胞瘤中的表达及临床意义

    Institute of Scientific and Technical Information of China (English)

    李静; 李德全

    2015-01-01

    目的:分析APE1、Bcl-2及Bax在视网膜母细胞瘤( Rb)中的表达及临床意义。方法选取2011年9月至2013年11月经病理学检查确诊为Rb患者32例及正常视网膜组织16例作为研究对象,免疫组织化学及Western blot分析APE1、Bcl-2及Bax在Rb中及正常视网膜中的表达,比较其在分化及未分化型Rb中的表达。结果 APE1、Bax及Bcl-2在Rb中呈现出高表达,阳性率分别为90.63%、65.63%及68.75%,与正常组比差异均具有统计学意义(χ2=30.13,χ2=12.31,χ2=16.91, P <0.01),与Western blot结果一致;分化组与未分化组中APE1、Bax存在差异显著(χ2=4.99,χ2=7.85, P <0.05),Bcl-2无统计学差异(χ2=0.73, P >0.01)。结论 Rb的发生发展涉及多个基因及生物学过程,分析APE1、bcl-2及bax在Rb中的表达,对Rb的诊断与治疗有重要的参考价值。%Objective To analyze the expression of APE1, Bcl-2 and Bax in retinoblastoma (Rb) and to evaluate their clinical significance.Methods A total of 32 retinoblastoma patients were enrolled for this study from September 2011 to November 2013.Sixteen normal retinal tissues were collected as control.Immunohistochemistry and Western blot were used to evaluate the expression of APE1, Bcl-2 and Bax in retinoblastoma tumor tissues and normal retina.Their expres-sions in differentiated and undifferentiated Rb were also compared.Results APE1, Bax and Bcl-2 were highly expressed in retinoblastoma with positive rates being 90.63%, 65.63% and 68.75%, respectively, and were significantly higher than in normal retina tissues (χ2 =30.13 for APE1,χ2 =12.31 for Bax, andχ2 =16.91 for Bcl-2;P 0.01).Conclusion The development of Rb involves multiple genes and biological processes.Analysis of the expression of APE1, Bcl-2 and Bax in Rb has important clinical value for the diagnosis and treat-ment of Rb.

  15. 奥曲肽对人肝星状细胞凋亡及Bcl-2/Bax表达的影响%Effects of octreotide on the apoptosis of human HSCs and expression of Bcl-2/Bax in HSCs

    Institute of Scientific and Technical Information of China (English)

    李春艳; 贾丽萍; 石蕾; 周贤

    2015-01-01

    Objective To investigate the effects of octreotide on the apoptosis of human hepatic stellate cells (HSCs) and expression of Bcl-2/Bax in HSCs,and to reveal the mechanism underlying octreotide against hepatic fibrosis. Methods HSCs lines (HSC-LX2) were incubated with different concentrations of octreotide for 24 and 48 hours. Cell apoptosis was evaluated by Fitc-tunel fluorescence staining. Bcl-2 and Bax protein exoression in HSC-LX2 was detected by immunocytochemistry. Meanwhile, Bcl-2 protein of HSC-LX2 were detected by Western blot assay. Results Octreotide could promote the apoptosis of HSC-LX2, and the apoptosis rate was significantly increased with the concentration of octreotide(P < 0.05). The HSC-LX2 were incubated with the same concentration of octreotide for 24 and 48 hours, the cell apoptosis rate of 48-hour octreotide treatment was significantly higher than that of 24-hour octreotide treatment (P < 0.05). The immunocytochemistry result indicated that octreotide could significantly decrease Bcl-2 expression and increase Bax expression in HSC-LX2 (P<0.05); Western blot assay showed that octreotide could also significantly inhibit Bcl-2 expression in HSC-LX2 (P<0.05). Conclusions Octreotide could induce the apoptosis of HSCs in a dose-and time-dependent manner, the mechanism of octreotide inducing HSCs apoptosis might be associated with down-regulation of Bcl-2 and upregulation of Bax in HSC.%目的:观察奥曲肽对活化人肝星状细胞凋亡和凋亡相关蛋白Bcl-2/Bax 表达的影响,探讨奥曲肽抗肝纤维化可能的作用机制。方法:不同浓度的奥曲肽作用于传代的人肝星状细胞株(HSC-LX2)24 h、48 h后,应用FITC-TUNEL检测各组细胞凋亡,应用免疫细胞化学法检测HSC-LX2中Bcl-2、Bax蛋白表达,应用Western-blot法检测HSC-LX2中Bcl-2蛋白表达。结果:奥曲肽可促进HSC-LX2细胞调亡,细胞凋亡率随奥曲肽浓度增加而增高(P <0.05);与24 h比较,相

  16. Expression and significance of Bcl-2 gene and Bax gene in lung cancer%凋亡相关基因bcl-2和bax在肺癌中的表达及意义

    Institute of Scientific and Technical Information of China (English)

    郭雷; 王福昌; 杨五计

    2001-01-01

    To study the relationship between expression of bcl-2 and baxgene and lung cancer.The bcl-2 and bax gene expression in 51 lung cancer tissues and tissues near cancer were deteeted by immunohistochemical SP method.The positive degree of bcl-2 gene expression in lung cancer was higher than that in tissues near cancer.The positive degree of bax gene expression in lung cancer was lower than that in tissues near cancer.Both differences were very significant(P<0.01).There was no correlations between the immunoreactivity of bcl-2 and bax gene and histology,gender,smoking history,clinical subtypes,stage and lymphatic metastasis(P>0.05).It suggests that bcl-2 and bax gene may play an important role in tumorgenesis and tumor development.The detection and determination of bcl-2 and bax gene in preinvasive lesions may contribute to the early diagnosis of lung cancer.Some drugs can down-regulate bcl-2 expression and speed apoptosis so as to improve the sensitivity to chemical therapy and radiation.%为探讨B细胞淋巴瘤/白血病-2(bcl-2)基因及其同源类似物bax基因的表达与肺癌发生的关系,应用免疫组化SP法检测了51例肺癌患者的肺癌标本及其癌旁组织中bcl-2、bax的表达。结果显示,bcl-2在肺癌中染色比在癌旁组织中深,bax在肺癌中染色比在癌旁组织中浅,两者之间均有极显著差异(P<0.01);bcl-2、bax表达与肺癌的组织分型、患者的性别、吸烟史、临床分型、分期及淋巴结转移无关(P>0.05)。提示:①bcl-2、bax在肺癌发生中具有重要作用。②在癌前病变组织中检测并比较bcl-2和bax的表达,有利于肺癌的早期诊断。③可通过药物使bcl-2表达降低,促进凋亡,提高患者对放、化疗的敏感性。

  17. Bcl-2 and Bax expression in mice with collagen-induced arthritis following heterogenic umbilical cord blood stem cell transplantation%异种脐血干细胞移植胶原性关节炎小鼠Bcl-2和Bax 的表达

    Institute of Scientific and Technical Information of China (English)

    牛广华; 高玉洁; 孙旭; 都静; 明彩荣; 高明利

    2012-01-01

    BACKGROUND: The occurrenceand development of rheumatoid arthritis were strongly associated with unbalance proliferation and apoptosis of synovial cells and lymphocytes. Some synovial cell apoptosis was abnormal. OBJECTIVE: To observe effects of heterogenic double umbilical cord blood stem cell transplantation on Bcl-2 and Bax expression in mice with type Ⅱcollagen-induced arthritis. METHODS: C57BL/6(H-2b) mice were induced with Freund's complete adjuvant and type Ⅱcollagen to establish mouse models of type Ⅱcollagen-induced arthritis.At 2days after secondary immunity incubation, mice were injected with saline via tail vein in the model and normal control groups. Umbilical cord blood hemopoietic stem cells were injected into mouse tail vein in the UBSCs transplantation groups (single dose:2×106/50 g; double dose: 1×106/50 g each, totally 2×106/50 g). Mice were intragastrically administrated methotrexate in the methotrexate positive control group, 0.017 5 g/kg once, once every 5 days, totally six times. RESULTS AND CONCLUSION: Joint tissue below knee and elbow was obtained at42 days following transplantation. Histopathology displayed that smooth and glossy articular surface, no inflammatory cell infiltration in the synovial layer and normal chondrocytes in the normal control group. Hyperplasia, a lot of inflammatory cell infiltration and damaged cartilage surface were visible in the model group. Slight hyperplasia and a little inflammatory cell infiltration were detectable in the methotrexate positive controlgroup and single UBSCs transplantation group. Double UBSCs transplantation group exhibited smooth and glossy articular cartilage surface, no damage, a little inflammatory cell infiltration. Immunohistochemistry demonstrated that Bcl-2 and Bax expression was lower in the double UBSCs transplantation group compared with single UBSCs transplantation group (P 0.05). Results suggest that double umbilical cord blood stem cells can induce synovial cell

  18. Caractérisation structurale de l'adsorption des isomères para- et meta- du xylène dans la zéolithe de type faujasite BaX Structural Characterization of Para- and Meta- Xylene in Bax Zeolite

    Directory of Open Access Journals (Sweden)

    Mellot C.

    2006-11-01

    Full Text Available La séparation du para-xylène des isomères aromatiques en C8 est réalisée industriellement grâce à l'adsorption sur tamis moléculaire zéolithique. Une amélioration des propriétés de séparation des tamis, et en particulier de leur sélectivité, nécessite, entre autres, une bonne connaissance des interactions entre les molécules d'adsorbat et la structure zéolithique. Pour ce faire, nous avons fait appel à deux techniques de caractérisation physico-chimique : la diffraction des neutrons et la spectroscopie infrarouge. Nous avons étudié une zéolithe BaX de type faujasite sur laquelle nous avons adsorbé, à l'état de corps purs, les isomères para- et méta- du xylène. Cette zéolithe est connue industriellement pour ses propriétés sélectives performantes pour le paraxylène. Les analyses ont été réalisées en considérant tout d'abord un faible taux de remplissage, voisin d'une molécule par supercage de zéolithe, et ensuite à saturation où la zéolithe contient sensiblement trois molécules par supercage. La diffraction des neutrons permet, à basse température, de localiser les molécules dans la zéolithe et de préciser leur interaction avec le cation Ba²+. La spectroscopie infrarouge permet une étude des caractéristiques vibrationnelles de l'adsorbat en fonction du taux de recouvrement. Une synthèse des résultats obtenus à l'aide de ces deux méthodes d'investigation nous a permis de dégager un modèle de remplissage des supercages pour les deux isomères considérés. Ainsi, des différences significatives sont mises en évidence. En ce qui concerne le para-xylène, pour un taux de remplissage inférieur à deux molécules par supercage, les molécules de para-xylène viennent se positionner au voisinage des cations en site SII de la supercage. La troisième molécule de para-xylène introduite dans la zéolithe n'est pas en interaction avec un cation Ba²+ et sera localisée dans un nouveau site F

  19. 溴隐亭对大鼠催乳素瘤细胞表达bcl-2、Bax的影响%Effect of bromocriptine on expression of Bax and bcl-2 in rat prolactinoma

    Institute of Scientific and Technical Information of China (English)

    杨雪梅; 徐春; 梁立武; 程海梅

    2012-01-01

    目的 研究溴隐亭对大鼠催乳素(prolactinoma,PRL)瘤表达bcl-2、Bax的影响.方法 (1)用皮下植入17β-雌二醇的方法制备大鼠催乳素瘤模型,同时设立10只大鼠为对照组;(2)将成功诱发出催乳素瘤的大鼠随机分2组,分别给予自来水(安慰剂组)、溴隐亭(溴隐亭组)灌胃,对照组也给予安慰剂灌胃,用药4周后处死动物,垂体称重,测定PRL、Bax、bcl-2的表达水平.结果 (1)17β-雌二醇组大鼠血清PRL水平[(4236.9±416.9) vs (121.2±12.8) ng/ml]和垂体重量[(62.0±5.1) vs (13.8±1.2) mg]均明显高于对照组(P<0.01),证实17β-雌二醇组成功诱发出大鼠泌乳素瘤.(2)溴隐亭组血清PRL水平和垂体重量低于安慰剂组(P<0.01),bcl-2表达水平较安慰剂组明显下降[(1.8±0.5) vs (4.0±0.6),P<0.01],Bax表达水平明显增高[(4.5±0.6) vs ( 1.0±0.3),P<0.01].结论 抑制bcl-2的表达,刺激Bax的表达,从而促进催乳素瘤细胞的凋亡可能是溴隐亭抗催乳素瘤的重要机制之一.%Objective To study the effect of bromocriptine on expression of Bax and bcl -2 in rat prolactinoma. Methods Firstly, to develop prolactinoma rats model. Adult Wistar rats were divided into two groups at random. The rats in control group were subscutaneously implanted with a blank implant . Rats in 17 p - estradiol group were implanted with 17 p - estradiol - containing implants. Secondly, Rats in 17p - estradiol group were divided into two groups at random, i. e. placebo group and bromocriptine group. Water was given to rats in placebo group. Bromocriptine was orally adminstered to rats in bromocriptine group. After 4 weeks of treatment, all the animals were sacrificed. Each pituitary gland was weighed. Serum prolactin(PRL) levels were measured by RIA. Expression level of Bax and bcl -2 in pituitary tissue were measured by Western blotting. Results (1) The weights of pituitary gland and PRL levels in 17p - estradiol group were significantly higher than those

  20. The Influence of Matrine on Apoptosis and Expression of Bax and Bci-2 in Colorectal Cancer Cells%苦参碱对大肠癌细胞凋亡及Bax、Bcl-2表达的影响

    Institute of Scientific and Technical Information of China (English)

    王雷; 刘明

    2012-01-01

    [Purpose] To investigate the effect of Matrine on proliferation inhibition, apoptotic and Bax and Bcl-2 expression in human colorectal cancer cell line Lovo. [Methods] Lovo cells cultured in vitro were interfered with 0.05-1.6mg/ml different concentration of Matrine. The proliferation inhibition effect on Lovo cells was observed by MTT method. Apoptosis induction effect on Lovo cells was detected by DNA ladder, flow cytometer and TUNEL staining. The expression of Bcl-2 and Bax proteins correlated with apoptosis were detected by Western Blot assay. [Results] After being exposed to Matrine (0.05-1.6mg/ml) for 24 and 48h, the proliferation of Lovo cells was inhibited in a dose-time dependent manner. DNA ladder, Annexin V-PI method and TUNEL staining showed Matrine was obviously increased along with Matrine concentration increased. The expression of pro-apoptotic protein Bax was increased, while anti-apoptotic protein Bcl-2 was decreased as Matrine doses increased. [Conclusion] Matrine can inhibit proliferation and induction of apoptosis in colorectal cancer cells. Increased expression of Bax and decreased expression of Bcl-2 might involve in Matrine-induced apoptosis.%[目的]探讨苦参碱对人大肠癌Lovo细胞增殖抑制和凋亡诱导作用及其对Bax、Bcl-2表达的影响.[方法] 0.05~l.6mg/ml不同浓度苦参碱作用Lovo细胞,采用MTT法检测苦参碱对大肠癌Lovo细胞增殖抑制作用,DNA ladder、AnnexinV -PI法及TUNEL染色检测细胞凋亡,Western Blot法检测凋亡相关蛋白Bax、Bcl-2表达的变化.[结果]0.05~1.6mg/ml苦参碱处理Lovo细胞24h或48h后,细胞增殖均明显受抑制;DNA ladder、Annexin V-PI法及TUNEL染色检测结果显示苦参碱呈时间、剂量依赖性诱导细胞凋亡;促凋亡蛋白Bax随着苦参碱剂量增加表达增加,抗凋亡蛋白Bcl-2随着苦参碱剂量增加表达减少.[结论]苦参碱具有抑制大肠癌细胞增殖,诱导其凋亡的作用.苦参碱诱导大肠癌细胞凋

  1. Relationship between ferroelectric properties and local structure of Pb1-xBaxZr0.40Ti0.60O3 ceramic materials studied by X-ray absorption and Raman spectroscopies

    Science.gov (United States)

    Mesquita, Alexandre; Michalowicz, Alain; Moscovici, Jacques; Pizani, Paulo Sergio; Mastelaro, Valmor Roberto

    2016-08-01

    This paper reports on the structural characterization of Pb1-xBaxZr0.40Ti0.60O3 (PBZT) ferroelectric ceramic compositions prepared by the conventional solid state reaction method. X-ray absorption spectroscopy (XAS) and Raman spectroscopy were used in the probing of the local structure of PBZT samples that exhibit a normal or relaxor ferroelectric behavior. They showed a considerable local disorder around Zr and Pb atoms in the samples of tetragonal or cubic long-range order symmetry. The intensity of the E(TO3) mode in the Raman spectra of PBZT relaxor samples remains constant at temperatures lower than Tm, which has proven the stabilization of the correlation process between nanodomains.

  2. Downregulation of uPAR and cathepsin B induces apoptosis via regulation of Bcl-2 and Bax and inhibition of the PI3K/Akt pathway in gliomas.

    Directory of Open Access Journals (Sweden)

    Ramarao Malla

    Full Text Available BACKGROUND: Glioma is the most commonly diagnosed primary brain tumor and is characterized by invasive and infiltrative behavior. uPAR and cathepsin B are known to be overexpressed in high-grade gliomas and are strongly correlated with invasive cancer phenotypes. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we observed that simultaneous downregulation of uPAR and cathepsin B induces upregulation of some pro-apoptotic genes and suppression of anti-apoptotic genes in human glioma cells. uPAR and cathepsin B (pCU-downregulated cells exhibited decreases in the Bcl-2/Bax ratio and initiated the collapse of mitochondrial membrane potential. We also observed that the broad caspase inhibitor, Z-Asp-2, 6-dichlorobenzoylmethylketone rescued pCU-induced apoptosis in U251 cells but not in 5310 cells. Immunoblot analysis of caspase-9 immunoprecipitates for Apaf-1 showed that uPAR and cathepsin B knockdown activated apoptosome complex formation in U251 cells. Downregulation of uPAR and cathepsin B also retarded nuclear translocation and interfered with DNA binding activity of CREB in both U251 and 5310 cells. Further western blotting analysis demonstrated that downregulation of uPAR and cathepsin B significantly decreased expression of the signaling molecules p-PDGFR-β, p-PI3K and p-Akt. An increase in the number of TUNEL-positive cells, increased Bax expression, and decreased Bcl-2 expression in nude mice brain tumor sections and brain tissue lysates confirm our in vitro results. CONCLUSIONS/SIGNIFICANCE: In conclusion, RNAi-mediated downregulation of uPAR and cathepsin B initiates caspase-dependent mitochondrial apoptosis in U251 cells and caspase-independent mitochondrial apoptosis in 5310 cells. Thus, targeting uPAR and cathepsin B-mediated signaling using siRNA may serve as a novel therapeutic strategy for the treatment of gliomas.

  3. Significance and expression of Bax, Survivin and p53 in gastric carcinoma and precancerous lesions using tissue microarray%利用组织芯片技术研究胃癌及其癌前病变中Bax、p53、Survivin表达的关系及意义

    Institute of Scientific and Technical Information of China (English)

    Yuping Xiao; Zhi Lin; Lili Mao; Dongying Wu; Yujia Gao; Hongwei Sun; Yan Xin

    2007-01-01

    Objective: To explore the relationship between expressions of apoptosis-related protein Bax, Survivin and p53 and the molecular mechanisms of carcinogenesis and progression of gastric carcinoma. Methods: Tissue microarray and immunohistochemistry were used in this study. Results: The positive rate of Bax protein in gastric cancer (17.7%, 17/96) was significantly lower than those in adjacent normal mucosa (51%), intestinal metaplasia (69.2%) and dysplasia (75%), P < 0.01.The positive rate of Survivin expression in gastric cancer (80.6%, 89/98) was significantly higher than that in adjacent normal mucosa (3.9%), P < 0.01. The positive rates of Survivin expression in tumors with different organ metastases (in lymph node metastasis 86.2%, liver 100% and ovarian 100%) were statistically higher than in tumors without metastasis (64.3%), P <0.05. Bax expression was correlated with Survivin but not with mp53 that was closely related to Survivin expression (P < 0.05)in gastric cancer. Conclusion: The abnormal expressions of Bax, Survivin and mp53 were correlated with the tumorigenesis and progression of gastric carcinoma. P53 and Survivin genes may share the similar mechanism in regulating cell apoptosis,and because of the mutation, p53 gene may lower its down-regulation to Survivin expression.

  4. CEPO调控新生大鼠缺氧缺血性脑损伤Bcl-2、Bax基因表达的研究%Effect of CEPO on the expression of Bcl-2 and Bax genes in hypoxic ischemic brains of neonatal

    Institute of Scientific and Technical Information of China (English)

    付中秋; 姚笠; 田执梁; 张玉晶; 邵庆亮; 张海涛; 赵霞霞

    2014-01-01

    Objective To investigated the association between the expressions of Bcl-2 and Bax genes in neonatal rats upon cerebral hypoxic-ischemia and the effects of Carbamylated Erythropoietin (CEPO.) administration on both genes.Methods An animal model of neonatal hypoxic-ischemia brain damage was established.The changes of Bcl-2 and Bax mRNAs in brain tissues were detected in rats after HI or CEPO administration by RT-PCR.Results The levels of Bcl-2 and Bax mRNAs were increased upon HIBD compared with sham-operated group at 2 h,12 h,24 h,48 h,72 h time points post treatment (P < 0.05).On the contrary,only the level of Bcl-2 mRNA was increased (P < 0.05) while the level of Bax mRNA was decreased (P < 0.05) in CEPOintervention group.Conclusion The levels of Bcl-2 and Bax mRNAs in HIBD of neonatal rats were altered.CEPO may exert some neuroprotective effects on the brain tissues via interventing the expression of Bcl-2 and Bax.%目的 观察新生大鼠缺氧缺血性脑损伤(HIBD)脑组织Bcl-2、Bax基因表达变化及氨基甲酰化促红细胞生成素(CEPO)干预对其表达的影响,探讨CEPO发挥脑保护作用的可能机制.方法 将新生7日龄SD大鼠建立HIBD模型,利用RT-PCR检测缺氧缺血和CEPO干预后2h、12h、24 h、48 h、72 h凋亡基因Bcl-2、Bax的mRNA表达的改变.结果 与假手术组相比,缺氧缺组在2h、12h、24 h、48 h、72 h脑组织中Bcl-2、Bax的表达均增加(P<0.05),与缺氧缺血组相比,CEPO干预组在不同时间点Bcl-2表达增加(P<0.05),Bax表达下降(P<0.05).结论 在新生大鼠HIBD中Bcl-2、Bax mRNA的表达发生改变,调控二者的表达水平可能是CEPO发挥脑保护的作用机制之一.

  5. Effect of acrylonitrile on the expression of Bcl-2 and Bax in spermatogenic cell of mice%丙烯腈对小鼠生精细胞Bcl-2、Bax蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    裴凌云; 马国燕; 金娜; 陈亚; 冯玉娟; 党瑜慧; 薛红丽; 李芝兰

    2012-01-01

    Objective To explore the effect of acrylonitrile exposure on the expression of Bcl-2 and Bax in mice spermatogenic cells. Methods Based on body weight, 250 SPF Kunming adult male mice were randomly divided into five groups; negative control group (normal saline 0. 01ml/g), three AN exposure groups (intraperitoneal injection of 1.25, 2. 50 or 5. 00 mg/kg of AN daily for 5 days, respectively) and positive control group (intraperitoneal injection of cyclophosphamide 40mg/kg) . Mice were killed in the 7th, 14th, 21st, 28th and 35th day after the first exposure by cervical dislocation. Immunohistochemical method ( SABC ) was used to detect the expression of Bcl-2 and Bax protein in spermatogenic cells. Results The average optical density values of Bcl-2 at five time points of the AN 2. 50 mg/kg group and the 21th day point of the AN 1. 25 mg/kg group were significantly lower than the negative control group ( P < 0. 05 ) . Except the 21st day point of the AN 1. 25 mg/kg group, the mean optical density values of Bax in all time points of AN exposure groups were significantly higher than the negative control group (P < 0. 05 ). The decreased expression of Bcl-2 protein was most distinct in AN 2. 50mg/kg group and the positive control group at all time points. The expression of Bax protein was significantly increased in all groups at the 14th day point. Conclusion The expression of Bel-2 protein could be weakened in spermatogenic cells induced by AN, especially in the AN 2. 50 mg/kg8roup; while the expression of Bax was enhanced, and the amplitude of change in the 14th day point was more obvious.%目的 探讨丙烯腈(AN)暴露对小鼠睾丸生精细胞Bcl-2、Bax蛋白表达水平的影响.方法 将250只成年健康SPF级昆明种雄性小鼠,按体重随机分为阴性对照组、3个AN染毒组和阳性对照组,阴性对照组用生理盐水,各染毒组分别以1.25、2.50、5.00mg/kg AN腹腔注射(注射剂量为0.01 ml/g BW),每天1次,连续5天,阳性

  6. Expression of bcl-2, bax in renal proximal tubular epithelial cells of rats with arsenic poisoning%bcl-2、bax在砷中毒大鼠肾近端小管表达

    Institute of Scientific and Technical Information of China (English)

    李远慧; 金婷婷

    2011-01-01

    Objective To investigate the influence of arsenic poisoning on the expressions of bcl-2, bax apoptosis control gene in renal proximal tubular epithelial cells in rtas.Methods Forty normal SD rats were divided into high and low dose of arsenic poisoning group and control group.The body weights of the rats were 120-150g.There were 15 rats in high and low dose exposure groups,and 10 rats in the control group.The rats in high and low groups were treated with As2O3 through drinking water at the doses of 10 and 0.4 mg/kg·d.The control group was given distilled water.Four months after the treatment,the kidney tissue of the rats was collected.Two step immunohistochemistry method, cell number count, and image analyses were used in the study.Results The bcl-2 immunoractive cells decreased and the average gray value gradually increased in arsenic poisoning groups(P < 0.05).The bax immunoractive cells of renal proximal tubular epithelial were increased and the average gray value decreased ( P < 0.05 ) in arsenic poisoning groups compared to those of the control group.Conclusion The expression of bcl-2, bax apoptosis control gene are involved in the process of apoptosis of renal proximal tubular epithelial cells in arsenic poisoning rats.%目的 探讨砷中毒对大鼠肾近端小管上皮细胞凋亡调控基因bcl-2、bax影响.方法 清洁级SD大鼠40只,体重为120~150g,高、低剂量染砷组各15只,对照组10只.高、低剂量染砷组分别给予三氧化二砷(AS2O3)10、0.4 mg/kg水溶液自由饮用,对照组饮用蒸馏水.分笼喂养4个月,取肾脏标本,采用免疫组织化学二步法、细胞计数和图像分析方法测定bcl-2、bax表达.结果 高、低剂量染砷组肾近端小管上皮bcl-2阳性细胞计数分别为(1.85±1.22)与(5.47±1.62)个,明显低于对照组(8.03±2.42)个,平均灰度值逐渐增高,差异具有统计学意义(P<0.05);高、低剂量染砷组肾近端小管上皮bax阳性细胞数分别为(14.88±3.02)与(6

  7. 特发性胎儿生长受限患者胎盘组织中XIAP和Bax的意义%Significances of XIAP and Bax in placental tissue of patients with idiopathic fetal growth restriction

    Institute of Scientific and Technical Information of China (English)

    崔世红; 张婷; 管秀娟; 程国梅; 贾国占; 刘萍萍; 杨健丽

    2012-01-01

    Objective; To explore the expressions and significances of XIAP and Bax in placental tissue of patients with idiopathic fetal growth restriction (IFGR) . Methods: Thirty pregnant women with IFGR who gave birth to their babies in the hospital via cesarean section from July 2010 to April 2011 were selected as experimental group, while thirty full - term pregnant women who gave birth to their babies in the hospital via cesarean section because of social factor during the same period were selected as control group. Immunohistochemical method was used to detect the expression levels of XIAP and Bax in placental tissue. Results: The expression level of XIAP in placental syn-cyliolrophoblast cells of experimental group was ( 114. 562 ± 5. 167) , which was significantly lower than that of control group (144. 430 ± 7. 311) (P 0. 05) . Conclusion: Down - regulation of XIAP and up - regulation of Bax in placental tissue can promote excessive apoptosis of placental syncytiotrophoblast cells, which may be one of the important pathogenesis of IFGR.%目的:探讨特发性胎儿生长受限(IFGR)胎盘组织中XIAP、Bax的表达及意义.方法:选取我院2010年7月~2011年4月剖宫产分娩的IFGR孕妇30例作为实验组,同期因社会因素剖宫产分娩的正常足月孕妇30例作为对照组.用免疫组化法检测胎盘组织XIAP、Bax的表达水平.结果:①XIAP在胎盘合体滋养细胞中的表达,实验组(114.562±5.167)低于对照组(144.430 +7.311),差异有统计学意义(P<0.05).②Bax在胎盘合体滋养细胞中的表达,实验组(146.513±10.611)高于对照组(113.673±9.631),差异有统计学意义(P<0.05);③实验组胎盘组织中XIAP与Bax的表达呈负相关(r=-0.761,P<0.05);对照组胎盘组织中XIAP与Bax的表达无相关性(r=0.034,P>0.05).结论:胎盘组织中XIAP表达降低、Bax表达增加促使了胎盘滋养细胞的过度凋亡,可能是IFGR发病机制中的重要环节之一.

  8. Effect of Sargassum fusiforme Polysaccharide on the Ethology and Expressions of Bcl-2 and Bax in Brain Tissue for Alzheimer's Disease Rat model%羊栖菜多糖对老年痴呆模型大鼠Bcl-2和Bax基因表达的分析

    Institute of Scientific and Technical Information of China (English)

    汤从容; 曹高忠; 叶晓兰

    2012-01-01

    Objective:To study effect of Sargassum fusiforme Polysaccharide( SFPS) on ethology and expressions of Bcl - 2 and Bax in brain tissue of AD rats. Methods:The D - galactose AD rat model was applied,and blank group,model group, Piracetam control group and herbal group were designed. Index change of ethology , expressions of Bcl -2 and Bax in brain tissue were tested. Results: AD model may decrease cognitive ability,the ratio of Bcl -2/Bax in the hippocampus came down(P <0.05 ). Compared to the model group,Sargassum fusiforme Polysaccharide with 0. 8 ,1. 6g/kg can alleviate cognitive ability significantly,and the action had a does —dependent increase,the ratio of Bcl -2/Bax increased(P< 0.05). Conclusion; Sargassum fusiforme Polysaccharide can up - regulate expression of protein Bax and down -regulate expression of Bcl - 2 in brain tissu. It inhibits apoptosis through regulating the expressions of Bcl - 2 and Bax protein in hippocampal , which might be one of mechanisms of Sargassum fusiforme Polysaccharide to prevent and treat AD disease.%目的:探讨羊栖菜多糖提取物(SFPS)对阿尔茨海默病(AD)大鼠模型行为的干预作用及脑皮质Bcl-2和Bax基因表达的影响.方法:制作D-半乳糖阿尔茨海默病大鼠模型,设计正常对照组、模型组、吡拉西坦片、羊栖菜多糖提取物不同剂量组,观察大鼠行为学及脑皮质Bcl -2和Bax基因表达指标的改变.结果:与正常对照组相比,模型组学习记忆能力显著下降(P<0.05),其Bcl - 2/Bax值下降;与模型组相比,0.8g/kg、1.6g/kg羊栖菜多糖提取物治疗组均能较好的改善学习记忆能力,且具有一定剂量依赖性,其Bcl - 2/Bax值增加.结论:SFPS能调节海马组织Bcl -2和Bax的表达,显著提高Bcl - 2/Bax值,抑制海马神经元的凋亡,改善AD大鼠学习记忆能力.

  9. A-site compositional effects in Ga-doped hollandite materials of the form BaxCsyGa2x+yTi8−2x−yO16: implications for Cs immobilization in crystalline ceramic waste forms

    Science.gov (United States)

    Xu, Yun; Wen, Yi; Grote, Rob; Amoroso, Jake; Shuller Nickles, Lindsay; Brinkman, Kyle S.

    2016-01-01

    The hollandite structure is a promising crystalline host for Cs immobilization. A series of Ga-doped hollandite BaxCsyGa2x+yTi8−2x−yO16 (x = 0, 0.667, 1.04, 1.33; y = 1.33, 0.667, 0.24, 0) was synthesized through a solid oxide reaction method resulting in a tetragonal hollandite structure (space group I4/m). The lattice parameter associated with the tunnel dimension was found to increases as Cs substitution in the tunnel increased. A direct investigation of cation mobility in tunnels using electrochemical impedance spectroscopy was conducted to evaluate the ability of the hollandite structure to immobilize cations over a wide compositional range. Hollandite with the largest tunnel size and highest aspect ratio grain morphology resulting in rod-like microstructural features exhibited the highest ionic conductivity. The results indicate that grain size and optimized Cs stoichiometry control cation motion and by extension, the propensity for Cs release from hollandite. PMID:27273791

  10. A-site compositional effects in Ga-doped hollandite materials of the form BaxCsyGa2x+yTi8‑2x‑yO16: implications for Cs immobilization in crystalline ceramic waste forms

    Science.gov (United States)

    Xu, Yun; Wen, Yi; Grote, Rob; Amoroso, Jake; Shuller Nickles, Lindsay; Brinkman, Kyle S.

    2016-06-01

    The hollandite structure is a promising crystalline host for Cs immobilization. A series of Ga-doped hollandite BaxCsyGa2x+yTi8‑2x‑yO16 (x = 0, 0.667, 1.04, 1.33; y = 1.33, 0.667, 0.24, 0) was synthesized through a solid oxide reaction method resulting in a tetragonal hollandite structure (space group I4/m). The lattice parameter associated with the tunnel dimension was found to increases as Cs substitution in the tunnel increased. A direct investigation of cation mobility in tunnels using electrochemical impedance spectroscopy was conducted to evaluate the ability of the hollandite structure to immobilize cations over a wide compositional range. Hollandite with the largest tunnel size and highest aspect ratio grain morphology resulting in rod-like microstructural features exhibited the highest ionic conductivity. The results indicate that grain size and optimized Cs stoichiometry control cation motion and by extension, the propensity for Cs release from hollandite.

  11. A-site compositional effects in Ga-doped hollandite materials of the form BaxCsyGa2x+yTi8-2x-yO16: implications for Cs immobilization in crystalline ceramic waste forms.

    Science.gov (United States)

    Xu, Yun; Wen, Yi; Grote, Rob; Amoroso, Jake; Shuller Nickles, Lindsay; Brinkman, Kyle S

    2016-01-01

    The hollandite structure is a promising crystalline host for Cs immobilization. A series of Ga-doped hollandite BaxCsyGa2x+yTi8-2x-yO16 (x = 0, 0.667, 1.04, 1.33; y = 1.33, 0.667, 0.24, 0) was synthesized through a solid oxide reaction method resulting in a tetragonal hollandite structure (space group I4/m). The lattice parameter associated with the tunnel dimension was found to increases as Cs substitution in the tunnel increased. A direct investigation of cation mobility in tunnels using electrochemical impedance spectroscopy was conducted to evaluate the ability of the hollandite structure to immobilize cations over a wide compositional range. Hollandite with the largest tunnel size and highest aspect ratio grain morphology resulting in rod-like microstructural features exhibited the highest ionic conductivity. The results indicate that grain size and optimized Cs stoichiometry control cation motion and by extension, the propensity for Cs release from hollandite. PMID:27273791

  12. Triphala Extract Suppresses Proliferation and Induces Apoptosis in Human Colon Cancer Stem Cells via Suppressing c-Myc/Cyclin D1 and Elevation of Bax/Bcl-2 Ratio

    Directory of Open Access Journals (Sweden)

    Ramakrishna Vadde

    2015-01-01

    Full Text Available Colon cancer is the second leading cause of cancer related deaths in the USA. Cancer stem cells (CSCs have the ability to drive continued expansion of the population of malignant cells. Therefore, strategies that target CSCs could be effective against colon cancer and in reducing the risk of relapse and metastasis. In this study, we evaluated the antiproliferative and proapoptotic effects of triphala, a widely used formulation in Indian traditional medicine, on HCT116 colon cancer cells and human colon cancer stem cells (HCCSCs. The total phenolic content, antioxidant activity, and phytochemical composition (LC-MS-MS of methanol extract of triphala (MET were also measured. We observed that MET contains a variety of phenolics including naringin, quercetin, homoorientin, and isorhamnetin. MET suppressed proliferation independent of p53 status in HCT116 and in HCCSCs. MET also induced p53-independent apoptosis in HCCSCs as indicated by elevated levels of cleaved PARP. Western blotting data suggested that MET suppressed protein levels of c-Myc and cyclin D1, key proteins involved in proliferation, and induced apoptosis through elevation of Bax/Bcl-2 ratio. Furthermore, MET inhibited HCCSCs colony formation, a measure of CSCs self-renewal ability. Anticancer effects of triphala observed in our study warrant future studies to determine its efficacy in vivo.

  13. Preparation of nanostructured La0.7Ca0.3-xBaxMnO3 ceramics by a combined sol-gel and spark plasma sintering route and resulting magnetocaloric properties

    Science.gov (United States)

    Ayadi, F.; Regaieg, Y.; Cheikhrouhou-Koubaa, W.; Koubaa, M.; Cheikhrouhou, A.; Lecoq, H.; Nowak, S.; Ammar, S.; Sicard, L.

    2015-05-01

    This work proposes an original, easy to achieve and inexpensive route to synthesize manganite ceramics for magnetic refrigeration, combining sol-gel chemistry to Spark Plasma Sintering (SPS). The target La0.7Ca0.3-xBaxMnO3 (x=0, 0.1, 0.2) compounds are obtained as single phases which crystallize in the orthorhombic structure (Pnma space group). SPS allows a quick sintering at a relatively low temperature (700 °C in this work) compared to the conventional solid state method (≥1100 °C), leading to densified ultrafine grained pellets (85% of compactness). Magnetic studies show that Ba substitution does not affect significantly the relative cooling power (RCP) of these manganites, while it increases their Curie temperature (TC) by several tens of degrees. Typically, RCP values ranging between 267 and 270 J/kg (for a magnetic field change of 5 T) and TC between 205 and 245 K were measured when x was increased from 0 to 0.2, respectively. These results combined to the fact that the synthesis route is economically advantageous makes the obtained ceramics interesting as active refrigerants for magnetic refrigeration technology below room temperature.

  14. Effect of Heroin Dependence on Expression of Bcl-2 and Bax in Submandibular Gland of Rats%海洛因依赖对大鼠颌下腺Bcl-2和Bax表达的影响

    Institute of Scientific and Technical Information of China (English)

    胡赟; 梁文妹; 洪艳; 韩晶; 夏白娟; 李一欣

    2013-01-01

    目的:观察海洛因依赖对大鼠颌下腺Bcl-2、Bax阳性细胞表达及分布的影响.方法:正常SD大鼠,随机分为正常对照组和海洛因依赖组,皮下注射海洛因建立海洛因依赖大鼠模型,分别于第10、17、24、31、38天取颌下腺组织,用免疫组织化学Envision法并结合图像分析方法,观察Bcl-和Bax表达.结果:(1) Bcl-2阳性细胞数量在海洛因依赖第10天明显下降(P<0.05),此后开始增加,至第24天时达最高峰(P<0.05),而在第38天时低于正常水平(P<0.05);平均灰度值在依赖第10天明显上升(P<0.05),后开始下降,第24天时达最低值(P<0.05),至第31 ~38天时接近正常水平(P>0.05);(2)Bax阳性细胞数量在依赖第10天明显降低(P<0.05),第17天时又增加达峰值(P<0.05);之后即开始下降,第31-38天时接近正常水平(P>0.05);其平均灰度值在依赖第10天显著上升(P<0.05),而在第17天时达最低值(P<0.05),后随依赖时间延长,与正常水平无显著性差异(P>0.05).结论:海洛因对颌下腺Bcl-2、Bax的表达有明显影响,且与依赖时间长短有关.%Objective:To observe the effect of heroin dependence on Bcl-2 and Bax positive cells in the submandibular gland of rats.Methods:Normal SD rats were divided into normal control group (NGC) and heroin dependence group (HDG).The heroin dependent model of rats was established by subcutaneous injection of heroin,and submandibular glands were excised on the following 10th,17th,24th,31st and 38th days respectively.Immunohistochemical Envision method and image analysis were used in the study.Results:1.The number of Bcl-2 positive cells descended obviously on the 10th d (P < 0.05),then,increased and peaked on the 24th d (P < 0.05).However,it was lower than that of NCG on the 38th d (P < 0.05) ; the mean grey value increased obviously on the 10th d (P < 0.05),but decreased and to the lowest on the 24th d (P <0.05).Between the 31st d and the 38th d

  15. Persea declinata (Bl. Kosterm Bark Crude Extract Induces Apoptosis in MCF-7 Cells via G0/G1 Cell Cycle Arrest, Bcl-2/Bax/Bcl-xl Signaling Pathways, and ROS Generation

    Directory of Open Access Journals (Sweden)

    Putri Narrima

    2014-01-01

    Full Text Available Persea declinata (Bl. Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill, which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl. Kosterm bark methanolic crude extract (PDM. PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48 h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.

  16. Persea declinata (Bl.) Kosterm Bark Crude Extract Induces Apoptosis in MCF-7 Cells via G0/G1 Cell Cycle Arrest, Bcl-2/Bax/Bcl-xl Signaling Pathways, and ROS Generation.

    Science.gov (United States)

    Narrima, Putri; Paydar, Mohammadjavad; Looi, Chung Yeng; Wong, Yi Li; Taha, Hairin; Wong, Won Fen; Ali Mohd, Mustafa; Hadi, A Hamid A

    2014-01-01

    Persea declinata (Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48 h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development. PMID:24808916

  17. 甘草黄酮对大强度耐力运动大鼠肾脏组织Ca2+、Mg2+-ATPase及Bax,Bc1-2蛋白表达的影响%Effect of High-Intensity Endurance Exercise on Ca2+,Mg2+-ATPase and Bax, Bcl-2 Protein Expression With Glycyrrhiza Flavonoids in rat Nephridial Tissue

    Institute of Scientific and Technical Information of China (English)

    王东旭; 陈艳艳

    2013-01-01

    Objective To explore Glycyrrhiza Elavonoids on the rat nephridial tissue of Ca2+, Mg2+-ATPase and Bax, Bcl-2 protein expression with high-intensity endurance exercise. Methods The twenty-four healthy male rats were randomly divided into quiet groups, high-intensity exercise group and exercise plus Glycyrrhiza Elavonoids group, After 6 weeks of treadmill training, Using the box of reagent and immunity histochemistry examined the changing of Ca2+, Mg2+-ATPase and Bax, Bcl-2 protein expression on each groups . Results Compared with the quiet groups, the activity of Ca2+, Mg2+-ATPase both had significant droped (P<0.01), and the groups of plus drog had very difference increased than high-intendity exerxise groups (P<0.01); High-intensity endurance exercise group and exercise dosing rats AI apoptosis index increased in varying degrees;high-intensity exercise group (MOD) were very significant difference(P<0.01), exercise plus drug group Bac protein expression (MOD)were very significant difference (P<0.01); Exercise plus drug group Bcl-2 protein expression(MOD) with the high-intersity exercise group had significant difference(P<0.01), High-intensity exercise group and exercise plus drug group Bax/Bcl-2 ratio of distribution is significantly difference degrees of difference(P<0.05,P<0.01).%目的:探讨甘草黄酮对大强度耐力运动大鼠肾脏组织Ca2+、Mg2+-ATPase及Bax、Bcl-2表达的影响。方法:选取SD雄性健康大鼠24只,随机分为安静组、大强度运动组和运动加药组;采用跑台训练6周后取材,应用试剂盒和免疫组织化学法测检测各组大鼠肾脏组织Ca2+、Mg2+-TPase活性及Bax和Bcl-2表达的变化。结果:与安静对照组相比,大强度运动组和运动加药组肾脏组织Ca2+、Mg2+-TPase活性均呈非常显著性下降(P<0.01);其中运动加药组Ca2+、Mg2+-TPase活性均较大强度运动组具有非常显著差异性提高(P<0.01);大强度耐力运动组和运动加

  18. THE EFFECT OF EXERCISE PRECONDITION INDUCED MIR-21 AND BAX GENE EXPRESSIONS ON RATS' CARDIAC MYOCYTE AFTER EXHAUSTIVE EXERCISES%运动预适应对力竭运动后心肌mir-21和bax基因表达的研究

    Institute of Scientific and Technical Information of China (English)

    黄雅雯

    2011-01-01

    [目的]探讨运动预适应(excerise preconditioning,EP)对大鼠一次性力竭运动后心肌mir-21和bax基因表达的影响.[方法]健康雄性SD大鼠36只,随机分为对照组(C组)、一次性力竭运动组(E组)、运动预适应+一次性力竭运动组(EP组).力竭运动后即刻和24 h取各组心肌采用real-time PCR检测各心肌内mir-21和bax基因表达情况.[结果]EP可以显著抑制一次性力竭运动后心肌内mir-21基因的下调表达(P<0.05)和bax基因的上调表达(P<0.05).[结论]EP可以通过抑制mir-21基因下调从而抑制bax基因的上调来发挥保护作用.%[ Objective] To explore the effect of exercise preconditioning induced mir-21 and bax gene expressions on rats' cardiac myocyte after exhaustive exercises. [Methods] 36 healthy male SD rats were randomly divided into control group (C group) , exhaustive exercises (E group) , exercise preconditioning+ exhaustive exercises (EP group) .Used real-time PCR to detect expressions of mir-21 and bax after exhaustive exercises and 24h. [Results] The results of real-time PCR suggested that in EP group, down-regulation of mir-21 and up-regulation of bax cardiac myocyte were obviously inhibited by exhaustive exercises. [Conclusion] EP could inhibit the down-regulation of bax gene through inhibiting up-regulation of mir-21 gene.

  19. 海洛因成瘾模型建立及中脑腹侧被盖区Bax的表达%Effect of heroin on Bax expression in the brain ventral tegmental area and establishment of a rat model of heroin addiction

    Institute of Scientific and Technical Information of China (English)

    俞发荣; 连秀珍; 谢明仁; 张红梅; 李立新; 张琛; 李世平

    2012-01-01

    Objective To study the effects of heroin on Bax expression in the midbrain ventral tegmental area (VTA) of rat. Methods Heroin was intramuscularly injected into rats and a rat model of addiction was generated . Bax expression in the midbrain ventral tegmental area (VTA) was detected by i m muno hist o chemistry. Results The rats had significant withdrawal symptoms after continuous injection of heroin for 7 days. The expression of Bax-positive cells in cere-bellar cortex of rat was significantly increased than that in the control group ( P < 0. 01 ). Conclusion Heroin has effect of inducing Bax gene expression and damage to brain cells .%目的 探索海洛因对中脑腹侧被盖区细胞Bax表达的影响.方法 肌肉注射海洛因,建立成瘾大鼠模型,用免疫组化方法检测中脑腹侧被盖区细胞Bax的表达.结果 连续给大鼠注射海洛因7d后,大鼠出现明显的戒断症状;中脑腹侧被盖区细胞Bax表达阳性细胞比对照组明显增多,与对照组相比差异有显著性 (P<0.01).结论 海洛因具有诱导Bax基因表达、损伤脑组织细胞的作用.

  20. Apoptosis of Hepatoma Cell Line HepG2 Induced by the Combination of Radiotherapy and Thermotherapy and Its Relationship with Bcl-2/Bax Protein Expressions%放疗联合热疗诱导肝癌HepG2细胞凋亡及其与Bcl-2和Bax蛋白表达关系的研究

    Institute of Scientific and Technical Information of China (English)

    张力; 龚明玉; 李毅学; 张立广; 王兴艳

    2011-01-01

    Objective To explore the apoptosis of hepatoma cell line HepG2 induced by the combination of radiotherapy and thermotherapy and its relationship with Bcl - 2/Bax protein expressions. Methods In vitro cultured HepG2 cells were randomly divided into four groups: control group ( not treated ), radiotherapy group, thermotherapy group, and combination group. The apoptosis of HepG2 cells were detected by flow cytometry. The expressions of the apoptosis-related proteins of Bcl-2 and Bax were detected by immunohistochemical methods. Results The apoptosis rates of HepG2 cells were significantly different among these four groups ( P < 0. 05 ). The apoptosis rates were significantly higher in radiotherapy group, thermotherapy group, and combination group than in control group ( P <0. 05 ). It was also significantly higher in combination group than in radiotherapy group and thermotherapy group ( P < 0. 05 ). The expressions of Bcl-2 and Bax and the Bax/Bcl-2 ratio were also significantly different among these four groups ( P <0. 05 ). The expression of Bcl -2 protein were significantly decreased and the expression of Bax protein significantly increased in radiotherapy group, thermotherapy group, and combination group than in control group ( both P < 0. 05 ), and the Bax/Bcl - 2 ratio was also significantly increased ( P < 0. 05 ). The expression of Bcl - 2 protein were significantly decreased and the expression of Bax protein significantly increased in combination group than in radiotherapy group and thermotherapy group ( both P < 0. 05 ), and the Bax/Bcl - 2 ratio was also significantly increased ( P < 0. 05 ). Conclusion The combination of radiotherapy and thermotherapy can more effectively induce the apoptosis of HepG2, and it may be achieved by inhibiting the expression of Bcl - 2 protein and promoting the expression of Bax protein.%目的 探讨放疗联合热疗诱导人肝癌HepG2细胞凋亡及其与Bcl-2和Bax蛋白表达的关系.方法

  1. 低频电磁场对大鼠生精细胞凋亡基因表达影响%Effect of extremely low frequency electromagnetic fields on Bax and Bcl-2 expression in spermatogenic cells of rats

    Institute of Scientific and Technical Information of China (English)

    孙晓芳; 段斐; 寇素茹; 刘晋芝; 马幼敏

    2009-01-01

    目的 探讨极低频电磁场对大鼠生精细胞凋亡相关基因Bax和Bcl-2表达的影响.方法 Wistar大鼠60只随机分为低剂量(0.1 mT)、高剂量(12.8 mT)电磁场暴露组及对照组,每组20只,分别有10只持续暴露2和12周;用苏木苏-伊红(H-E)染色及免疫组织化学法观察睾丸形态学和细胞凋亡相关基因Bax、Bcl-2表达的变化,用图像分析系统进行测定.结果 低、高剂量电磁场暴露组暴露2周Bax灰度值分别为(25.58±4.98),(39.17±4.33);Bcl-2灰度值分别为(68.12±3.64),(39.62±4.35);暴露12周Bax灰度值分别为(40.12±2.45),(62.32±5.90);Bcl-2灰度值分别为(55.78±2.43)(23.84±3.62).结论 随着电磁场暴露频率的升高和时间的延长,大鼠生精细胞Bax的表达明显上调,Bcl-2的表达逐渐下调.%Objective To study the effect of extremely low frequency electromagnetic fields on Boa and Bcl-2 expres-sion in the spermatogertic cells of rats. Methods Sixty adult female Wistar rats were divided into 0. 1 naT, 12. 8 rat and control group. After electromagnetic radiation for 2 and 12 weeks, HE staining and immunohistochemical methods were used to detected Bax and Bcl-2 expression with image analysis. Results After electromagnetic exposure for 2 week,the gray scale values of Bax were 25.58±4. 98 and 39. 17±4. 33 for low and high intensity groups and that of Bcl-2 were 68. 12± 3. 64 and 39. 62±4.35. The gray scale values of Boa were 40.12±2.45 and 62.32±5.90 for low and high intensity groups for 12 weeks exposure and that of Bcl-2 were 55.7±2.43 and 23.84±3.62. Conclusion With the increase of exposure in-tensity and time, the Box and Bcl-2 exprseeion in spermatogenie cells in rats were gradually decreased.

  2. 深Ⅱ度烧伤愈合后Bcl-xl、Bax蛋白表达与增生性瘢痕的相关性%The relationship of hypertrophic scar with the expression of Bcl-xl and Bax proteins in deep Ⅱ burns coalesce skin

    Institute of Scientific and Technical Information of China (English)

    李泰然; 王振宇; 孟庆延; 骆宁

    2012-01-01

    目的 探讨Bcl-xl和Bax蛋白在深Ⅱ度烧伤愈合后不同时期增生性瘢痕中的表达特点.方法 人深Ⅱ度烧伤愈合后不同时期的增生性瘢痕皮肤40例,正常皮肤组织10例.分为增生期组、减退早期组、减退晚期组、成熟期组,正常对照组.免疫组织化学染色,检测Bcl-xl和Bax蛋白的表达.结果 深Ⅱ度烧伤创面愈合后,Bcl-xl和Bax蛋白主要表达于表皮基底细胞和真皮层成纤维细胞,增生期和减退早期Bcl-xl和Bax蛋白产物光密度值明显高于正常皮肤(P<0.01),减退晚期和成熟期随瘢痕成熟而逐渐递减接近正常皮肤.结论 Bcl-xl和Bax蛋白表达与深Ⅱ度烧伤创面愈合后增生性瘢痕的发生和瘢痕成熟相关.%Objective To study the expression and histological distribution of apoptosis-related gene Bel-xl and Bax in hypertrophic scars (HS) in deep Ⅱ burns coalesce skin. Method Ten specimens of normal skin (NS), 40 skin specimens of hypertrophic scars (HS) in deep II bums coalesce skin were divided into four groups: hypertrophic phase group (1-6 months after burned), early hypotrophic group (7-12 months after burned), later hypotrophic group (13-18 months after burned) and full recovered stage group (longer than 18 months). Immunochemistry was used to detect the expressions of Bcl-xl and Bax protein. Results The Bcl-xl and Bax positive product was found mainly in the fibroblast cytoplasm and nucleus of the basal layer in normal skin and deep II burns coalesce skin. The average optical density values of Bcl-xl and Bax protein product were significantly higher in the hypertrophic phase group and early hypotrophic group than in control group (P< 0.01), but decreased gradually to normal skin in later hypotrophic group and full recovered stage group. Conclusion The expressions of Bcl-xl and Bax proteins are related to the occurrence of hvpertrophic scars and wound healing in deep II burns coalesce skin.

  3. Electric-field-controlled interface strain coupling and non-volatile resistance switching of La1-xBaxMnO3 thin films epitaxially grown on relaxor-based ferroelectric single crystals

    Science.gov (United States)

    Zheng, Ming; Zhu, Qiu-Xiang; Li, Xue-Yan; Yang, Ming-Min; Wang, Yu; Li, Xiao-Min; Shi, Xun; Luo, Hao-Su; Zheng, Ren-Kui

    2014-09-01

    We have fabricated magnetoelectric heterostructures by growing ferromagnetic La1-xBaxMnO3 (x = 0.2, 0.4) thin films on (001)-, (110)-, and (111)-oriented 0.31Pb(In1/2Nb1/2)O3-0.35Pb(Mg1/3Nb1/2)O3-0.34PbTiO3 (PINT) ferroelectric single-crystal substrates. Upon poling along the [001], [110], or [111] crystal direction, the electric-field-induced non-180° domain switching gives rise to a decrease in the resistance and an enhancement of the metal-to-insulator transition temperature TC of the films. By taking advantage of the 180° ferroelectric domain switching, we identify that such changes in the resistance and TC are caused by domain switching-induced strain but not domain switching-induced accumulation or depletion of charge carriers at the interface. Further, we found that the domain switching-induced strain effects can be efficiently controlled by a magnetic field, mediated by the electronic phase separation. Moreover, we determined the evolution of the strength of the electronic phase separation against temperature and magnetic field by recording the strain-tunability of the resistance [(ΔR/R)strain] under magnetic fields. Additionally, opposing effects of domain switching-induced strain on ferromagnetism above and below 197 K for the La0.8Ba0.2MnO3 film and 150 K for the La0.6Ba0.4MnO3 film, respectively, were observed and explained by the magnetoelastic effect through adjusting the magnetic anisotropy. Finally, using the reversible ferroelastic domain switching of the PINT, we realized non-volatile resistance switching of the films at room temperature, implying potential applications of the magnetoelectric heterostructure in non-volatile memory devices.

  4. Identification of human ferritin, heavy polypeptide 1 (FTH1) and yeast RGI1 (YER067W) as pro-survival sequences that counteract the effects of Bax and copper in Saccharomyces cerevisiae.

    Science.gov (United States)

    Eid, Rawan; Boucher, Eric; Gharib, Nada; Khoury, Chamel; Arab, Nagla T T; Murray, Alistair; Young, Paul G; Mandato, Craig A; Greenwood, Michael T

    2016-03-01

    Ferritin is a sub-family of iron binding proteins that form multi-subunit nanotype iron storage structures and prevent oxidative stress induced apoptosis. Here we describe the identification and characterization of human ferritin, heavy polypeptide 1 (FTH1) as a suppressor of the pro-apoptotic murine Bax sequence in yeast. In addition we demonstrate that FTH1 is a general pro-survival sequence since it also prevents the cell death inducing effects of copper when heterologously expressed in yeast. Although ferritins are phylogenetically widely distributed and are present in most species of Bacteria, Archaea and Eukarya, ferritin is conspicuously absent in most fungal species including Saccharomyces cerevisiae. An in silico analysis of the yeast proteome lead to the identification of the 161 residue RGI1 (YER067W) encoded protein as a candidate for being a yeast ferritin. In addition to sharing 20% sequence identity with the 183 residue FTH1, RGI1 also has similar pro-survival properties as ferritin when overexpressed in yeast. Analysis of recombinant protein by SDS-PAGE and by electron microscopy revealed the expected formation of higher-order structures for FTH1 that was not observed with Rgi1p. Further analysis revealed that cells overexpressing RGI1 do not show increased resistance to iron toxicity and do not have enhanced capacity to store iron. In contrast, cells lacking RGI1 were found to be hypersensitive to the toxic effects of iron. Overall, our results suggest that Rgi1p is a novel pro-survival protein whose function is not related to ferritin but nevertheless it may have a role in regulating yeast sensitivity to iron stress.

  5. All-trans retinoic acid inhibits KIT activity and induces apoptosis in gastrointestinal stromal tumor GIST-T1 cell line by affecting on the expression of survivin and Bax protein

    Directory of Open Access Journals (Sweden)

    Taguchi Takahiro

    2010-12-01

    Full Text Available Abstract Background Imatinib, a selective tyrosine kinase inhibitor, has been used as a standard first-line therapy for irresectable and metastasized gastrointestinal stromal tumor (GIST patients. Unfortunately, most patients responding to imatinib will eventually exhibit imatinib-resistance, the cause of which is not fully understood. The serious clinical problem of imatinib-resistance demands alternative therapeutic strategy. This study was conducted to investigate the effect of all-trans retinoic acid (ATRA on GIST cell lines. Methods Cell proliferation was determined by trypan blue dye exclusion test. Western blot analysis was performed to test the expression of activated KIT, its downstream proteins, and apoptosis associated proteins. The cytotoxic interactions of imatinib with ATRA were evaluated using the isobologram of Steel and Peckham. Results and conclusion In this work, for the first time we have demonstrated that ATRA affected on cell proliferation of GIST-T1 and GIST-882 cell line through inhibition of cell growth in a dose dependent manner and induced apoptosis. High dose of ATRA induced morphologic change in GIST-T1 cells, rounded-up cells, and activated the caspase-3 protein. In further examination, we found that the ATRA-induced apoptosis in GIST-T1 cells was accompanied by the down-regulated expression of survivin and up-regulated expression of Bax protein. Moreover, ATRA suppressed the activity of KIT protein in GIST-T1 cells and its downstream signal, AKT activity, but not MAPK activity. We also have demonstrated that combination of ATRA with imatinib showed additive effect by isobologram, suggesting that the combination of ATRA and imatinib may be a novel potential therapeutic option for GIST treatment. Furthermore, the scracht assay result suggested that ATRA was a potential reagent to prevent the invasion or metastasis of GIST cells.

  6. The correlation research on the expression of Bcl-2,Bax and eNOS in the ICR mice testicles%Bcl-2和Bax在ICR小鼠睾丸中的表达及与eNOS的关联性研究

    Institute of Scientific and Technical Information of China (English)

    左俐俊; 任亚萍; 赵玮; 宋婉玲

    2016-01-01

    目的 探讨B淋巴细胞瘤/白血病-2 ( Bcl-2 )和Bcl-2相关X蛋白( Bax)在雄性ICR小鼠睾丸中的表达及与内皮型一氧化氮合酶( eNOS)的联系和意义. 方法 30只(分别为4、8、12周龄,各10只)健康雄性ICR小鼠,分为性成熟前(4周龄组)、性成熟(8周龄组)、性成熟后(12周龄组),取左侧睾丸经石蜡切片,免疫组化法检测小鼠睾丸中 eNOS、Bcl-2和Bax蛋白的表达分布情况;取右侧睾丸,Western blot法检测eNOS、Bcl-2 和 Bax的表达情况. 结果 Bcl-2 在睾丸间质细胞高表达,Bax在生精上皮有表达;8周龄小鼠睾丸间质细胞Bcl-2表达明显高于4、12周龄组,且8周龄组小鼠Bax表达明显低于4、12周龄组小鼠( P<0. 05 );4周龄组小鼠睾丸eNOS蛋白表达明显高于8、12 周龄组( P <0. 01 ).结论 Bcl-2、Bax与eNOS在睾丸间质细胞的表达并没有直接的相关性,提示NO或许未直接参与睾丸间质细胞的凋亡活动.%Objective To explore the expression and significance of the B-cell lymphoma/leukemia-2(Bcl-2),Bcl-2 associated X protein ( Bax ) in ICR mice testicles, and the correlation with endothelial nitric oxide synthase (eNOS). Methods 30 (4 weeks,8 weeks and 12 weeks respectively,each 10) healthy male ICR mice were divid-ed into three groups randomly:young period,adolescent period and the period of sexual maturity. Paraffin section of the left testis was made, the expressions of the Bcl-2,Bax and eNOS in the testis of male mice were observed with immunohistochemical method. Then Western blot was carried out to screen the protein of Bcl-2,Bax and eNOS in the right side of the mice testicles. Results The Bcl-2 highly appeared in leydig cells,while Bax in rawhide cell. The expression of Bcl-2 in the 8-week-old mice leydig cells was significantly higher than that in 4 or 12-week-old groups. The protein levels of Bax in the 8-week-old mice was lower than that in 4 or 12-week-old group ( P <0. 05). Besides,the expression of eNOS in 4-week

  7. The effects of the Reinforcing Kidney and Activating Blood Recipe Affecting the Value of bcl-2, bax and caspase-3 in the Tissue of Corpus Cavernosum Smooth Muscle of DMED- Rats%补肾活血合剂对糖尿病阳痿大鼠阴茎平滑肌组织中Bcl-2 Bax和Caspase-3表达的影响

    Institute of Scientific and Technical Information of China (English)

    张国豪; 方再军; 黄青松

    2011-01-01

    目的:观察补肾活血合剂对糖尿病阳痿(DMED)大鼠阴茎平滑肌组织中Bcl-2、Bax、Caspase-3表达的影响.方法:将实验小鼠用2%链脲佐菌素液(STZ)接60mg/kg,腹腔注射建立糖尿病模型,然后在每只糖尿病模型大鼠颈项处注射阿朴吗啡(APOsigma公司)80μg/kg,录相记录阴茎勃起次数.筛选DMED模型,将造成DMED模型随机分为正常组、模型组、中药高、低剂量组、达美康组、达美康+安雄组.除正常组外,其余各组连续给药12周,然后处死测定阴茎平滑肌组织中Bcl-2,Bax,Caspase-3的表达情况.结果:补肾活血合剂对Bc1-2,Bax,Caspase-3有改善作用.结论:补肾活血合剂对糖尿病阳痿大鼠阴茎平滑肌组织中Bcl-2,Bax,Caspase-3有调控效果.%Objective: Observing the effects of reinforcing kidney and activating blood recipe affecting the value of bcl - 2, bax and caspase - 3 in the tissue of corpus cavernosum Smooth muscle of DMED - rats. Methods: An animal model of diabetes was induced by a single intravenous dose of streptozotocin (STZ, 60mg/kg body weight) in Wistar rats. Recording the numbers of penile erection of each rat by camera after subcutaneous inject of apomorphine (80mg/kg).Screening the model of STZ - rats with erectile dysfunction and grouping into 6 groups: control group, model group, Chinese Medicine group, low- dosage group, Diamicron group, Diamicron combined Testosterone Undecanoate group. After administrating 12 weeks, observed the value of bcl -2, bax and caspase-3 in the tissue of corpus cavernosum smooth muscle of DMED - rats. Results: The reinforcing kidney and activating blood recipe can improve the vulue of bcl - 2,bax and caspase -3. Conclusion: The reinforcing kidney and activating blood recipe has regulatory function for bcl -2,bax and caspase - 3 in the tissue of corpus cavernosum smooth muscle of DMED - rats.

  8. Sundew plant, a potential source of anti-inflammatory agents, selectively induces G2/M arrest and apoptosis in MCF-7 cells through upregulation of p53 and Bax/Bcl-2 ratio.

    Science.gov (United States)

    Ghate, N B; Das, A; Chaudhuri, D; Panja, S; Mandal, N

    2016-01-01

    The worldwide cancer incidences are remarkable despite the advancement in cancer drug discovery field, highlighting the need for new therapies focusing on cancer cell and its microenvironment, including inflammation. Several species of Drosera (family: Droseraceae) are used in various traditional as well as homeopathic systems of medicine. Drosera burmannii Vahl. is also enlisted in French Pharmacopoeia in 1965 for the treatment of inflammatory diseases, including chronic bronchitis, asthma and whooping cough. The present study is designed to substantiate the potential of D. burmannii in in vitro anticancer activity and its relation with anti-inflammatory property. In vitro anticancer study revealed that DBME is inhibiting the proliferation of MCF-7 cells without affecting the viability of other malignant and non-malignant cells. DBME induced G2/M phase arrest and apoptosis in MCF-7 cells by suppressing the expression of cyclin A1, cyclin B1 and Cdk-1 and increasing the expression of p53, Bax/Bcl-2 ratio leading to activation of caspases and PARP degradation. Presence of caspase-8 (Z-IETD-fmk) and caspase-9 (Z-LEHD-fmk) inhibitors alone did prevent the apoptosis partially while apoptosis prevention was significantly observed when used in combination, suggesting vital role of caspases in DBME-induced apoptosis in MCF-7 cells. DBME also downregulated LPS-induced increased expression of iNOS, COX-2 and TNF-α along with suppression on intracellular ROS production that confirms the potential of DBME as anti-inflammatory extract. GCMS analysis revealed the presence of four major compounds hexadecanoic acid, tetradecanoic acid, hexadecen-1-ol, trans-9 and 1-tetradecanol along with some other fatty acid derivatives and carotenoids (Beta-doradecin) in DBME. These findings confirmed the anti-inflammatory activity of DBME, which is already listed in French Pharmacopeia in 1965. Here we have additionally reported the anti-breast cancer activity of DBME and its relation to the

  9. The expression of Bax, Bcl-2 and NF-κB in the early stage of liver regeneration%Bax、Bcl-2和NF-κB在肝再生早期中的表达

    Institute of Scientific and Technical Information of China (English)

    杜赵康; 杨开明

    2014-01-01

    目的 研究在大鼠大部肝切除(partial hepatectomy,PH)术后细胞凋亡调节基因(Bcl-2 associated X protein Bax)、Bcl-2(B-cell lymphoma-2)及NF-κB(nuclear factor-kappa B)三者的分布和表达,探讨三者在肝再生早期中的调节机制及其相互调控作用.方法 采用SD大鼠35只分7组,每组5只构建大鼠肝脏再生模型,并在显微镜下观察肝大部切除后早期(0.5、1、4、6、8、12、24 h)肝组织的形态学变化,采用免疫组织化学SABC法检测Bax、Bcl-2、NF-κB在正常肝组织中的表达,并研究在肝再生早期中的分布及表达变化.结果 Bax、Bcl-2、NF-κB在正常肝组织未见表达,但在PH后30 min,Bax、Bcl-2及NF-κB即在肝细胞和胆管上皮细胞和肝血窦内皮内开始出现表达,PH后6h表达达到高峰,之后其表达逐渐下降,而Bcl-2的表达一直保持在较高水平.NF-κB于PH后6h表达出现高峰后其表达逐渐下调,24h时NF-κB表达上调,出现另一表达高峰.结论 肝大部切除后再生早期,存在着凋亡和抑制凋亡的分子调控机制,NF-κB的表达可能与激活Bcl-2、抑制肝细胞的凋亡从而促进肝细胞再生有关.

  10. Sundew plant, a potential source of anti-inflammatory agents, selectively induces G2/M arrest and apoptosis in MCF-7 cells through upregulation of p53 and Bax/Bcl-2 ratio

    Science.gov (United States)

    Ghate, NB; Das, A; Chaudhuri, D; Panja, S; Mandal, N

    2016-01-01

    The worldwide cancer incidences are remarkable despite the advancement in cancer drug discovery field, highlighting the need for new therapies focusing on cancer cell and its microenvironment, including inflammation. Several species of Drosera (family: Droseraceae) are used in various traditional as well as homeopathic systems of medicine. Drosera burmannii Vahl. is also enlisted in French Pharmacopoeia in 1965 for the treatment of inflammatory diseases, including chronic bronchitis, asthma and whooping cough. The present study is designed to substantiate the potential of D. burmannii in in vitro anticancer activity and its relation with anti-inflammatory property. In vitro anticancer study revealed that DBME is inhibiting the proliferation of MCF-7 cells without affecting the viability of other malignant and non-malignant cells. DBME induced G2/M phase arrest and apoptosis in MCF-7 cells by suppressing the expression of cyclin A1, cyclin B1 and Cdk-1 and increasing the expression of p53, Bax/Bcl-2 ratio leading to activation of caspases and PARP degradation. Presence of caspase-8 (Z-IETD-fmk) and caspase-9 (Z-LEHD-fmk) inhibitors alone did prevent the apoptosis partially while apoptosis prevention was significantly observed when used in combination, suggesting vital role of caspases in DBME-induced apoptosis in MCF-7 cells. DBME also downregulated LPS-induced increased expression of iNOS, COX-2 and TNF-α along with suppression on intracellular ROS production that confirms the potential of DBME as anti-inflammatory extract. GCMS analysis revealed the presence of four major compounds hexadecanoic acid, tetradecanoic acid, hexadecen-1-ol, trans-9 and 1-tetradecanol along with some other fatty acid derivatives and carotenoids (Beta-doradecin) in DBME. These findings confirmed the anti-inflammatory activity of DBME, which is already listed in French Pharmacopeia in 1965. Here we have additionally reported the anti-breast cancer activity of DBME and its relation to the

  11. Bax、Bcl-2在局部晚期宫颈癌中的表达及意义%Studies on the Expression and Clinical Significance of Bax and Bcl-2 before neoadjuvant chemotherapy in Local y advanced cervical cancer

    Institute of Scientific and Technical Information of China (English)

    夏红; 易建华; 杨丽; 褚桂芬

    2014-01-01

    Objective To investigate the expression and clinical significance of Bax and Bcl-2 before neo-adjuvant chemotherapy (NACT) in local y advanced cervical cancer (LACC) . Methods 47 patients with stage ⅠB2-ⅡB of LACC treated with neoadjuvant chemotherapy(NACT) between January 2010 and December 2013 in our hospital were retrospectively analyzed. The expressions of Bax and Bcl-2 were determined by means of immunohistochemistry before NACT. Results: The total effective rate of NACT was 72.3%, including CR 14.9%. The Bax and Bcl-2 expression was 55.3% and 36.2% before NACT. In patients who react and react poorly to NACT, the expression of Bax was 64.7% and 38.5% (p0.05). The staining intensity for Bax was related to histopathological grade and lymphatic metastasis (p0.05). The staining intensity for Bcl-2 was not related to the above clinical and pathological factor (P>0.05). Conclusions The NACT of paclitaxel and cisplatin was effective to LACC. The expression of Bax could be related with biological behavior of the tumor and considered as the index to predict efficacy in NACT.%目的:探讨Bax、Bcl-2蛋白在局部晚期宫颈癌(LACC)中的表达及其临床意义。方法应用免疫组化检测47例LACC 组织中化疗前Bax、Bcl-2蛋白的表达情况。结果①47例LACC中,NACT有效率为72.3%,CR 为14.9%。②化疗前,Bax及Bcl-2蛋白阳性表达率分别为:55.3%、36.2%。临床有效及无效病例中,B a x阳性表达率分别为64.7%、38.5%,差异有统计学意义(P0.05)。③肿瘤低分化患者中B a x阳性表达率明显低于高中分化患者,有淋巴结转移者明显低于无淋巴结转移者(P0.05)。Bcl-2表达在各临床病理参数方面均无明显差异(P>0.05)。结论紫杉醇+顺铂静脉化疗对LACC有效,Bax蛋白异常表达与宫颈癌的生物学行为有关,可作为预测和判定NACT疗效的指标。

  12. Investigation of benazepril protection on diabetic myocardium by downregulating the expression of TGF-β1 and Bax%贝那普利下调TGF-β1及Bax表达对糖尿病大鼠心肌的保护作用

    Institute of Scientific and Technical Information of China (English)

    符丽娟; 杨育红; 包翠芬; 刘婉珠

    2011-01-01

    Objective To investigate the effect of benazepril (BZ) on the expression of TGF-β1 and Bax on diabetic myocardium and myocardial hypertrophy. Methods Diabetic animal models were induced by injecting streptozotocin. Model rats were divided into diabetes and BZ groups, control group was also established. BZ was given to treatment group at dose of 10 mg/kg each day by gavage. At 8 weeks, heart mass indexes (HMI) and left ventricular myocardium mass indexes (LVMI) were measured. The expressions of TGF-β1 and Bax in cardiomyocyte were detected and myocardium was studied by electronic microscope. Results Compared with control group, HMI and LVMI were significantly increased in diabetes group ( P < 0. 05 ). The expression of TGF-β1 and Bax were strengthened in diabetic myocardium. Electron microscopic morphometry of heart samples revealed typical diabetic alterations consisting in a focal loss, disorganization of myofihril, mitochondria swelling, collagen proliferation in extracellular matrix. After treatment with BZ for 8 weeks, HMI and LVMI were decreased ( P < 0. 01 ). The expression of TGF-β1 and Bax were weakened and myocardial ultrastructure was better than that of diabetes group. Conclusions TGF-β1 can induce myocardial apoptosis by stimulating the expression of Bax and promote diabetic cardiac hypertrophy, BZ can improve the cardiac function partly due to its effects of downregulating the expression of TGF-β1 and Bax.%目的 探讨贝那普利(BZ)对糖尿病(DM)大鼠心肌转化生长因子β1(TGF-β1)和Bax的表达及心肌肥厚指标的影响.方法 SD大鼠腹腔注射链脲佐菌素(STZ)制备DM模型.实验分为正常对照组(CON)、DM组和BZ治疗组(BZ).治疗组每日灌胃给予贝那普利(10 mg·kg-1·d-1).8 w后测定心脏质量指数(HMI)、左心室质量指数(LVMI),并取左心室心肌免疫组化法检测TGF-β1和 Bax在心肌组织中的表达,透射电镜观察心肌组织超微结构变化.结果 与CON组相比,DM组大

  13. C57/BL6小鼠海马发育和老化过程中Bcl-2及Bax的表达%Expression of Bcl-2 and Bax protein in the development and aging of C57/BL6 mouse hippocampus

    Institute of Scientific and Technical Information of China (English)

    李潮; 张敬坤; 张莉

    2011-01-01

    目的 观察C57/BL6小鼠海马发育老化过程中Bcl-2、Bax蛋白的表达变化.方法 取不同胚龄(embryonic day,E)、生后(postnatal day,P)日龄或月龄的小鼠海马,应用免疫组化及图像分析技术检测Bcl 2和Bax蛋白的表达.结果 E16 d~P7 d,海马CA区锥体细胞层和齿状回颗粒细胞层Bcl 2和Bax阳性细胞均逐渐增多,平均吸光度( average optical,AO)值逐渐增大;P14 d~P21 d阳性细胞逐渐减少,CA区AO值逐渐减小,齿状回AO值先增大后减小;P28 d后趋于稳定.CA区Bcl 2/Bax比值E16 d~E20 d增大,P1 d减小,P3 d~P5 d增大,P7 d~P21 d减小;以后趋于稳定.齿状回Bcl 2/Bax比值只在P1 d降低.结论 Bcl-2和Bax蛋白可能与小鼠海马发育和老化过程中的形态学变化密切相关.%Objective To observe the changes of expression of Bcl-2 and Bax protein in the development and aging of C57/BL6 mouse hippocampus. Methods Immunohistochemical and image analysis methods were used to detect the expression of Bcl-2 and Bax protein in the mouse hippocampus of different age. Results From embyronic (E) 16 day (d) to postnatal day (P) 7 d, Bcl-2 and Bax immunoreactive cells increased in the pyramidal layer and granular layer, and the average optical (AO) increased too. From P14 d to P21 d, immunoreactive cells decreased, and their AO decreased gradually in the CA area; AO increased first but then decreased in dentate gyrus. On P28 d, the immunoreactive cells and their AO were unchanged. Moreover, the ratio of Bcl-2/Bax rose on E16 d to E20 d, diminished on P1 d, increased on P3 d to P5 d, and decreased on P7 d to P21 d. Then the ratio of Bcl-2/ Bax remained unchanged after P28 d. Conclusion Bcl-2 and Bax protein may be correlated with the morphological changes in the development and aging of mouse hippocampus.

  14. Comparative study of Bax, Bcl-2 protein expression in villi structure during normal pregnancy and missed abortion%正常早孕与稽留流产绒毛组织结构中Bax和Bcl-2蛋白表达的对比研究

    Institute of Scientific and Technical Information of China (English)

    杨兴爽

    2014-01-01

    Objective To study apoptosis regulating proteins Bcl-2 and Bax in normal pregnancy and missed abortion villi structure and its significance, and explore the reasons for missed abortion. Methods Choose our hospital patients missed abortion and early pregnancy abortion patients, 60 cases in total, divided into group A and group B. Immediately after abortion, embryonic villi specimens sent to pathology. Light microscopy were applied in each group villi morphological changes in the structure, while applying immunohistochemical methods and computer image analysis system to detect Bax, Bcl-2 expression in each group villi and cell apoptosis. Results Missed abortion group trophoblast cell apoptosis index was (33.32±0.79)%, was significantly higher in group B(18.90±0.63)%, difference was statistically significant (P<0.01). Bax and Bcl-2 in the two groups syncytiotrophoblast cells show positive rate. In missed abortion group, Bax positive rate increased, Bcl-2 positive rate of decline, Bcl-2/Bax ratio increased, differences were statistically significant (P<0.01). Conclusion The increasing positive expression rate of Bax and the decreasing positive expression rate of Bcl-2 in decidua villi can lead to villous syncytiotrophoblast cells increased significantly,and further lead to missed abortion.%目的:研究凋亡调控蛋白Bcl-2和Bax在正常早孕与稽留流产绒毛组织结构中的表达及其意义,探讨稽留流产原因。方法选择本院就诊的稽留流产患者和早孕人工流产患者各60例,分为A组、B组。流产后立即留取胚胎绒毛组织送病理。分别应用光镜观察各组绒毛组织细胞形态结构的改变;同时应用免疫组织化学方法和计算机图文分析系统检测Bax、Bcl-2在各组绒毛的表达及细胞凋亡情况。结果稽留流产组绒毛滋养细胞中凋亡指数为(33.32±0.79)%,明显高于对照组B组的(18.90±0.63)%,差异有统计学意义(P<0.01)。Bax和Bcl-2在两组合体滋养

  15. Expression of Cell Apoptosis Protein-Bax in Locally Advanced Cervical Carcinoma after Neoadjuvant Chemotherapy as an Indicator of the Efficiency of the Therapy%局部晚期宫颈癌新辅助化疗后Bax蛋白作为治疗有效性的指标

    Institute of Scientific and Technical Information of China (English)

    游艳琴; 宋磊

    2006-01-01

    探讨Bax蛋白与宫颈癌新辅助化疗疗效之间的关系,用免疫组化方法检测23例局部晚期宫颈癌组织新辅助化疗前后Bax蛋白的表达.结果化疗后2例为临床完全缓解,17例为临床部分缓解,4例患者对新辅助化疗无反应,总有效率为82.61%.NACT前有反应者和无反应者宫颈癌组织的Bax表达无统计学差异(P>0.05).对化疗有反应者NACT后Bax WS值有显著性差异(P<0.05);无反应者NACT后Bax WS值无统计学差异(P>0.05).不同病理类型和临床分期患者NACT前后Bax变化值无显著性差异(P>0.05);不同病理分级患者NACT前后Bax变化值有统计学差异(P<0.05).说明Bax与化疗疗效有显著相关性.NACT前后Bax变化值与临床分期和病理类型无关,而与病理分级有显著相关性.Bax有可能作为判断化疗疗效的指标.

  16. Effects of Zuogui Pill and Yougui Pill on Expression of Apoptosis Protein Fas and Bax of Brain Tissue in Rat with Experimental Autoimmune Encephalomyelitis%左归丸和右归丸对自身免疫性脑脊髓炎大鼠脑组织中凋亡蛋白Fas、 Bax表达的影响

    Institute of Scientific and Technical Information of China (English)

    寇爽; 王义周; 李明; 齐放; 郑琦; 赵晖; 王蕾

    2011-01-01

    Objective:To observe the effects of Zuogui Pill and Yougui Pill on the expression of apoptosis protein Fas and Bax of brain tissue in rat with experimental autoimmune encephalomyelitis ( EAE ) .Methods: The Lewis rat were immunized with myelin basic protein ( MBP ) 68-86 to be made EAE model. The animals were measured the body weight, temperature, volume of food and drink as well as graded daily for clinical disability. The rats were observed the incidence, incubation period, mortality rate and the change of disease course. Brain and spinal cord of the rats were harvested and the pathological changes were studied after dying by HE staining. The expression of Fas and Bax in brain and spinal cord of rats were detected by the method by immunohistochemisty. Results: Zuogui Pill and Yougui Pill can relieve the infiltrated inflammatory cells around focal zone, and inhibited the expression of Fas and Bax, similarly the hormone. Conclusion: Zuogui Pill and Yougui Pill have the effects on prevent and treatment the rats with EAE, the mechanism may be related with regulating expression of apoptosis protein Fas and Bax.%目的:观察左、右归丸对实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE )大鼠脑组织中凋亡蛋白Fas、Bax表达的影响.方法:用髓鞘碱性蛋白(myelin basic proteir68-86,MBP68-86)免疫Lewis 大鼠建立EAE模型.观察各组大鼠体重体温变化,饮食和饮水变化,神经功能评分,发病率、死亡率、潜伏期及病程变化.取脑和脊髓,HE染色后进行病理观察;用免疫组化法检测大鼠脑组织中Fas、Bax的表达情况.结果:左归丸组和右归丸组明显减轻病灶区域的炎性细胞浸润,对Fas、Bax的表达均有一定的抑制作用,与激素组类似.结论:左、右归丸均有防治小鼠EAE的作用,其作用机制可能与调节细胞凋亡蛋白Fas、Bax的表达有关.

  17. Inhibitory effect and affect on Bcl-2 and Bax protein expression of renal cancer prescription No.1 in mice with renal cancer%解氏肾癌一号方对小鼠肾癌的抑制作用及对Bcl-2和Bax蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    朱成功; 崔佳; 赵莹莹; 解建国

    2015-01-01

    Objective To investigate inhibitory effect and affect on Bcl-2 and Bax protein expression of renal cancer prescription No.1 in mice with renal cancer. Methods The animal models of renal cancer were established and divided into saline control group,Chinese medicine control group,interleukin-2 group and renal cancer prescription NO.1 group. Inhibitory rate of tumor in four groups was calculated and the apoptosis-related protein Bcl-2 and Bax index were de-tected by immuno- histochemistry. Results The inhibitory rate of tumor in renal cancer prescription NO.1 group was higher than that in saline control group and interleukin-2 group respectively,and the weight of mice was increased.The expression of Bcl-2 in renal cancer prescription NO.1 group was lower,but expression of Bax in renal cancer prescrip-tion NO.1 group was higher. Conclusion Renal cancer prescription NO.1 can inhibit the expression of Bcl-2,raise the expression of Bax,and suppress tumor growth,improve the quality of life in mice.%目的:探讨解氏肾癌一号方对小鼠肾癌的抑制作用及对Bcl-2和Bax蛋白表达的影响。方法建立肾癌小鼠动物模型,分为生理盐水对照组、中药对照组、白介素-2组、解氏肾癌一号方组,计算各组抑瘤率以及采用免疫组化法检测凋亡相关蛋白Bcl-2和Bax的表达。结果解氏肾癌一号方组抑瘤率高于生理盐水对照组及白介素-2组,小鼠体重增加。解氏肾癌一号方组小鼠肿瘤组织Bcl-2表达下调,Bax表达上调。结论解氏肾癌一号方可以下调Bcl-2的表达,上调Bax的表达,从而抑制肿瘤生长,改善小鼠的生存质量。

  18. PEP-1-SOD1对离体缺血再灌注损伤大鼠心肌Bax、Bcl-2蛋白表达的影响%Effects of PEP-1-SOD1 on Expression of Bax,Bcl-2 of Myocardium in Rats Induced with Ischemia-Reperfusion Injury ex vivo

    Institute of Scientific and Technical Information of China (English)

    柯尊平; 王家宁; 王磊; 唐俊明; 杨建业; 黄永章; 张宏考

    2011-01-01

    Objective To investigate the effects of PEP-1 mediated human Cu,Zn superoxide dismutase on the myocardium apoptosis induced by ischemia-reperfusion injury(IRI) in rats ex vivo.Methods The MIRI rats model were prepared with Langendorff perfusion system ex vivo.The model rats were randomly divided into control group ,SOD1 pretreated group,PEP1-SOD1 pretreated with 25,50,100 μmol/L groups.The myocardium apoptosis and expression of Bax, Bcl-2 were determined with TUNEL method and immunofluorescencein method after reperfusion.Results Compared with control and SOD1 groups,the apoptosis indexes(AI) were significantly decreased,the expression of Bcl-2 were upregulated,the expression of Bax were downregulated in all PEP-1-SOD1 groups( all P < 0.01 ).Conclusion The fusion protein PEP-1-SOD1 could inhibit the apoptosis of myocardium in MIRI rats,which may be related to its upregulation of Bax expression and downregulation of Bcl-2 expression.%目的:研究细胞穿透肽PEP-1介导人铜锌-超氧化物歧化酶(cu,Zn-SOD,SOD1)对大鼠离体心肌缺血再灌注损伤(MIRI)细胞凋亡的影响.方法:采用Langendorff灌流系统对离体大鼠心脏进行停灌-复灌建立心肌缺血再灌注损伤模型.大鼠随机分为对照组、SODI蛋白预处理组,25、50、100μmol/L PEP-1-SOD1蛋白预处理组.复灌结束后,TUNEL法检测心肌细胞凋亡,免疫荧光法检测心肌组织Bax、Bel-2蛋白表达.结果:与对照组及SOD1组相比,各PEP-1-SOD1组心肌细胞凋亡指数(AI)显著下降,Bcl-2蛋白表达升高,Bax蛋白表达显著减少(P<0.01).结论:PEP-1-SOD1融合蛋白可抑制离体心脏缺血再灌注损伤大鼠心肌细胞凋亡,其机制可能与上调Bax表达及下调Bcl-2表达有关.

  19. 黄芪多糖对力竭运动大鼠心肌细胞凋亡及BcL-2、Bax蛋白表达的影响%Effects of acute exercise to exhaustion on BcL-2,Bax gene of rat, sheart after supplyment of astragalus polysaccharide

    Institute of Scientific and Technical Information of China (English)

    马兰军; 田振军

    2012-01-01

    为了探讨黄芪多糖(APS)对力竭运动大鼠机体的保护作用,通过建立大强度力竭运动大鼠模型,选取成年健康雄性SD大鼠24只,随机分为安静对照组,运动组和运动加药组,运动组和运动加药组按照训练模型进行为期6周的耐力训练,最后1次训练进行1次力竭运动,随后取心肌组织并进行样本处理.检测大鼠心肌MDA含量,用缺口末端标记法(TUNEL法)及免疫组织化学法检大鼠心肌细胞凋亡指数(AI)及BcL-2、Bax蛋白表达的变化.结果表明:运动组MDA含量、AI和BcL-2、Bax蛋白表达水平均明显高于安静对照组(P<0.05);与运动组比较,运动加药组MDA含量,AI与Bax蛋白表达水平均下降,而BcL-2蛋白表达水平显著增高(P<0.05).黄芪多糖可有效抑制力竭运动大鼠心肌细胞凋亡,此作用可能与其减轻氧化应激、上调BcL-2和下调Bax蛋白表达水平有关.%To study the supplementary astragalus polysaccharide (APS) to exhaustion movement rats myocardial cell apoptosis, observe the influence of myocardial cell apop-tosis BcL-2, the regulation of gene Bax changes, explore astragalus polysaccharide (APS) to exhaustion movement rats airframe of protection. By establishing high intensity exhaustion movement model of rats, the selection of adult health male SD rats 24 only randomly divided into quiet in the exercise group and control group, sports dosing group, the exercise group and exercise dosing groups according to training model six-week endurance training, last training once exhaustion movement, exhaustion after motion myocardial organize and sample processing. Detection rats myocardial MDA content, using gap end labeling (TUNEL law) and the method of immunohis to chemistry methods were used by rats myocardial cell apoptosis I,ndex (AI) and BcL-2, Bax protein expression changes. In the exercise group MDA content, AI and BcL-2, Bax protein expression levels were significantly higher in quiet in control group (P

  20. Effect of single prolonged stress on behavior and expression of Bcl-2 and Bax in the rat hippocampus%单一连续应激对大鼠行为学和海马Bcl-2、Bax表达的影响

    Institute of Scientific and Technical Information of China (English)

    徐爱军; 耿菲; 王海涛

    2012-01-01

    Objective To observe the behavior change and the expression of Bcl-2 and Bax in the hippocampus of rats after treated with single-prolonged stress. Method Wistar rats were divided randomly into control group and stress group,and the stress rats were treated with single-prolonged stress. The behavior changes of rats were observed with open-field test, reject grip test and Morries water mace test. Hydrocortisone level in rats blood serum was determined with chemi-luminescence. Immunohistochemistry was used to detect the expressions of Bax and Bal-2 in the hippocampal neurons. . Results Morris water mace test showed that escape latency of control group was 5. 632s ± 1. 065s and stress group was 20. 762s ±3.236s(t = 8.934,P<0.01). Hydrocortisone level of control group was 1.25μg/dl ±0. 12μg/dl and model was 0. 58μg/dl ±0.09μg/dl(t =8.075 ,P <0.01). The ratio of Bcl-2/Bax in control group was 0.904 ±0.109, while the stress group was 1.440 ±0.091(t = 5.458,P <0. 01). Conclusion The neuronal apoptosis in hippocampus may play a role in posttraumatic stress disorder. The increasing of Bcl-2 and Bax protein and the change of Bcl-2/Bax ratio may be the mechanism during single-prolonged stress.%目的 检测单一连续应激(single prolonged stress,SPS)对大鼠行为学和海马神经细胞Bax、Bcl-2表达的影响.方法 将Wistar大鼠分为对照组和应激组.应激组给予SPS应激,采用旷场实验、拒俘反应实验、Morries水迷宫实验等观察大鼠情感行为改变,采用化学发光法测定血清皮质醇浓度,应用免疫组织化学方法检测海马神经元Bcl-2、Bax的表达.结果 对照组水迷宫实验逃避潜伏期为5.632s±1.065s,应激组为20.762s±3.236s(t=9.932,P<0.01);对照组血清皮质醇浓度为1.25 μg/dl ±0.12μg/dl,应激组为0.58μg/dl±0.09μg/dl(t=7.340,P<0.01).应激组海马Bcl-2、Bax表达升高,Bcl-2/Bax上调.结论 SPS应激能使大鼠表现出创伤后应激障碍行

  1. 30例自然流产患者绒毛滋养细胞凋亡及调控蛋白Bcl-2、Bax的表达研究%Study on apoptosis and expression of modulin Bcl-2, Bax in villus syncytiotrophoblast cells in 30 patients with spontaneous abortion

    Institute of Scientific and Technical Information of China (English)

    郭冬瑾; 林秀玲; 樊柳宜

    2012-01-01

    目的 通过观察绒毛合体滋养细胞凋亡以及凋亡调控蛋白Bcl-2和Bax在自然流产患者中的表达,探讨细胞凋亡在自然流产的发病机制.方法 采用原位末端标记法(TUNEL)和免疫组织化学法对30例自然流产患者绒毛合体滋养细胞中调亡指数及凋亡调控蛋白Bcl-2和Bax阳性表达率进行检测,并以30例人工终止早孕的健康妇女做对照(对照组),所有数据采用SPSS16.0进行统计学分析.结果 自然流产组绒毛滋养细胞中凋亡指数为(32.45±5.87)%,明显高于对照组的(19.38±4.16)%,差异有统计学意义(P<0.01).Bax和Bcl-2在两组合体滋养细胞中的阳性率比较显示,自然流产组中Bax阳性率增高,Bcl-2阳性率下降,Bcl-2/Bax比值升高,差异均有统计学意义(P<0.01).结论 绒毛合体滋养细胞凋亡明显增加、Bax阳性率增高和Bcl-2阳性率下降在自然流产中产生重要作用.%Objective To observe the apoptosis and expression of modulin Bcl-2, Bax in villus syncytiotrophoblast cells in patients with spontaneous abortion, and to investigate the pathogenesis of apoptosis in spontaneous abortion. Methods TdT-mediated dUTP nick end labeling (TUNEL) and immunohistochemistry were respectively used in 30 patients with spontaneous abortion (the study group) and 30 individuals with artificial abortion (the control group). The apoptosis index, the positive expression rates of Bax and Bcl-2 in villus syncytiotrophoblast cells were detected. All the data were analyzed by SPSS 16.0. Results The apoptosis index of syncytiotrophoblast cells in the study group was (32.45±5.87)%, significantly higher than (19.38±4.16)% in the control group (P<0.01). The positive expression rate of Bax in the study group was significantly higher than in the control group, while that of Bcl-2 was significantly lower and Bcl-2/Bax ratio was significantly higher (P<0.01). Conclusion Intensive apoptosis, the increasing positive expression rate of Bax, and

  2. 灯盏花注射液抗新生鼠缺氧缺血性脑损伤的作用及对Bcl-2、Bax蛋白表达的影响%The anti-injury effect of Breviscapine injection on the hypoxic ischemic brain damage of neonatal rats and the expression of Bcl-2 and Bax

    Institute of Scientific and Technical Information of China (English)

    张明艳; 范淑娟; 李利平; 武变瑛; 王宇

    2011-01-01

    目的:观察灯盏花注射液对新生大鼠缺氧缺血脑损伤(HIBD)的保护作用及对Bcl-2、Bax蛋白表达的影响.方法:采用新生7日龄SD大鼠缺氧缺血性脑损伤模型,设立假手术组、缺氧缺血脑损伤模型组、灯盏花注射液治疗大、中、小剂量组、无菌注射用水对照组.采用硫堇染色、免疫组织化学染色的方法测定各组大鼠海马CA1区神经元密度、组织学分级及凋亡相关基因Bcl-2、Bax蛋白表达情况,并计数各时间点Bcl-2、Bax免疫阳性细胞数目及测定积分光密度值.结果:假手术组,大鼠海马CA1区无锥体细胞缺失,未见明显免疫阳性细胞.与假手术组比较,缺氧缺血脑损伤模型组、无菌注射用水对照组Bcl-2、Bax蛋白表达均于3 d时达到高峰(与其余各时间点比较差别有显著意义P<0.05),神经元密度明显降低,组织学分级显著增高,积分光密度值增加.灯盏花治疗组,与无菌注射用水对照组比较,Bcl-2蛋白表达进一步增加,积分光密度值增加;而Bax蛋白表达则减少,积分光密度值降低;神经元密度显著高于对照组,组织学分级明显降低.结论:灯盏花注射液可能是通过上调Bcl-2表达,抑制Bax表达,减轻缺氧缺血引起的神经元凋亡及迟发性神经元死亡.%Objective: To observe the protective effect of Breviscapine injection on the hypoxic ischemic brain damage of neonatal rats, and the expression of Bcl-2 and Bax. Methods: In this experiment 7-day-old newborn rat with hypoxic-ischemic brain damage model was used and divided into four groups: sham group, model group, control with sterile water for injection group and Breviscapine injection group. Breviscapine injection group was divided into large, medium, and small doses. Used thionin staining and immunohistochemical staining to assay the neuronal density, histological grade, and the expresssion of Bcl-2 and Bax protein in the CA1 hippocampus of each group , the number of

  3. Effect of nitric oxide with different doses on Bcl-2/Bax in spinal dorsal horn in rats induced by formalin%不同剂量的一氧化氮对福尔马林炎性痛大鼠脊髓背角Bcl-2/Bax表达的影响

    Institute of Scientific and Technical Information of China (English)

    未小明; 李宽; 祁文秀

    2011-01-01

    Objective: To investigate the effects of multiple application of different doses of nitric oxide (NO) on Bcl-2/ Bax in spinal dorsal horn induced by formalin. Methods: A succession of 4 d intrathecal injection of NO precursor L-arginine (L-Arg)10 μg/d (low L-Arg group) or 250 μg/d (high L-Arg group) or NOS inhibitor Nω-nitro-L-arginine methylester (L-NAME) 2700 μg/d (L-NAME group) in rats, and normal saline (NS group) was applied as a control, and administration once a day. Then rats were subcutaneously injected formalin (2%, 100 μL) into the right hindpaw, four hours later after formalin injection, Bcl-2 or Bax protein expression were detected with immunocytochemistry and Western Blot. Results: The immunocytochemistry showed the distributions of Bcl-2 and Bax were in both sides of the dorsal horn,especially in superficial laminae, and the expressions of bcl-2 and bax in the ipsilateral side of formalin injection were significantly increased than that in contralateral side of formalin injection in all four groups; the ratio of Bcl-2/Bax with Western-Blot was increased in low L-Arg group compared with normal saline group and was all decreased in high L-Arg group or L-NAME group compared with normal saline group. bcl-2 and bax are two major genes in the regulation of apoptosis, bcl-2 inhibits apoptosis and bax promotes apoptosis. Conclusion: Therefore, in inflammatory pain model, low doses of NO can promote the antiapoptotic gene expression, while high doses of NO and insufficient of NO both can promote pro-apoptotic gene expression, which affect the incidence of inflammatory pain.%目的:探讨多次应用不同剂量的一氧化氮(NO)对福尔马林炎性痛中脊髓背角神经元Bcl-2、Bax表达的影响.方法:连续4 d给大鼠各进行鞘内注射不同剂量的一氧化氮前体左旋精氨酸(L-arginine,L-Arg)10μg/d(低L-Arg组)、250 μg/d(高L-Arg组)或一氧化氮合酶(nitric oxide synthase,NOS)抑制剂Nω-硝基-L

  4. FK506对大鼠面神经损伤后面运动神经元凋亡及bcl-2,bax表达的影响%Effects of FK506 on the Apoptosis and bcl-2, bax Expression of Rat Facial Motor Neurons after Facial Nerve Injury

    Institute of Scientific and Technical Information of China (English)

    惠莲; 刘凤啸; 袁婧; 姜学钧; 任重

    2013-01-01

    目的 研究FK506对大鼠面神经损伤后运动神经元凋亡及bcl-2和bax表达的影响.方法 将40只Wistar大鼠随机分为实验组和对照组,制作大鼠单侧面神经总干切断模型,实验组每日腹腔注射FK506注射液,对照组给予相同剂量的盐水,在术后各时间点,通过Nissl染色观测面神经核神经元的形态学变化;TUNEL检测细胞凋亡;免疫组化检测bcl-2和bax表达的变化.结果 面神经损伤后,FK506组与盐水组相比较,FK506组运动神经元凋亡明显减少,bcl-2表达增加,bax表达降低.结论 FK506有助于增加面神经损伤后运动神经元bcl-2的表达、降低bax表达,抑制细胞凋亡,为药物在神经损伤疾病的临床应用提供了实验依据.%Objective To investigate effects of FKS06 on the apoptosis and the expression of bcl-2 and bax of rat facial motor neurons after facial nerve injury.Methods A total of 40 Wistar rats were randomly divided into experimental and control group.Facial nerve injury model was established by transecting facial nerves at its stylomastoid foramen,and then the experimental group and the control group were treated with FK506(FK506-treated group) and normal saline(saline control group)by intraperitoneal injection,respectively.The morphology of facial neurons were observed under light microscope at different time points after injury;the apoptotic cells of injured facial motor neurons were detected by TUNEL staining;the expression of bcl-2 and bax were evaluated by immunohistochemistry method.Results After facial nerve transection,the apoptotic cells were significantly decreased in FK506-treated group compared with saline control group (P < 0.05).The expression level of bcl-2 in FKS06-treated group were higher than that in saline control group,and the expression level of bax in FK506-treated group were lower than the control group.Conclusion FK506 could increase the expression of bcl-2,and decrease the expression of bax,and inhibit the

  5. 光动力学调控miR143激活Bcl-2/Bax的信号路径对人宫颈癌的治疗机制%Regulation Effect of Photodynamic Therapy on Bcl-2/Bax Signal Path Activated by miR143 in Human Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    兰艳丽; 刘韵

    2016-01-01

    Objective To investigate the regulation effect of photodynamic therapy on Bcl-2/Bax signal path activated by miR143 in human cervical cancer ,and lay foundation for cervical cancer treated with photodynamic therapy along with miR 143. Methods Human HeLa cells received miR 143 interference ( miR143 group ) , photodynamic irradiation treatment ( PDT group ) and miR143 interference combined with photodynamic irradiation (PDT +miR143 group).The rate of inhibition,apoptosis and invasion were detected by CCK8,flow cytometry and Transwell model ,respectively.Meanwhile the expression levels of miR143, Bcl-2 and Bax before and after different treatments were detected by fluorescence quantitative PCR .Results The inhibition rates and apoptosis rates among the 3 groups were significantly different (P0.05).Conclusion In cervical cancer,photodynamic therapy upregulated the Bcl-2/Bax signal path activated by miR 143,and lay foundation for cervical cancer treated with photodynamic therapy along with miR 143.%目的 探讨在宫颈癌中光动力学调控对miR143激活Bcl-2/Bax的信号路径的影响,为光动力学联合miR143应用于宫颈癌的治疗机制奠定基础.方法 人宫颈癌HeLa细胞分别进行miR143干扰处理(miR143组)、光动力照射处理(PDT组)及miR143干扰联合光动力照射处理(PDT+miR143组),采用CCK8法、流式细胞术及Transwell小室侵袭模型对各组处理后HeLa细胞的抑制率、凋亡率及侵袭能力进行分析,同时采用荧光定量PCR检测不同处理前后各组细胞的miR143、Bcl-2和Bax的mRNA表达水平.结果 3组之间的细胞抑制率、凋亡率差异有统计学意义(P<0.05),PDT+miR143组细胞抑制率和凋亡率分别高于PDT组和miR143组,差异具有统计学意义(P<0.05),而PDT+miR143组穿膜细胞数显著高于miR143组和PDT组(P<0.05).处理后,3组miR143和Bcl-2 mRNA表达水平较处理前均显著升高(P<0.0001),且处理后PDT+miR143组miR143和Bcl-2 mRNA表达

  6. Effects of Radix notoginseng extracts drug-containing serum on expressions of bcl-2, Bax and p21WAF1 proteins in MNNG transformed GES-1 cells%三七提取物含药血清对MNNG转化后GES-1细胞凋亡相关基因蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    李军祥; 王志斌; 朱陵群; 牛福玲; 崔巍

    2008-01-01

    Objective: To investigate the effects of Radix notoginseng extracts drug-containing serum on the expressions of apoptosis-regulating proteins including Bax, bcl-2 and p21WAF1 in precancerous gastric cells. Methods: The N-methyI-N'-nitro-N-nitroso-guanidine (MNNG) transformed eternalized human gastric mucosa epithelium GES-I cell line (MC cell) was used in vitro as a model of gastric precancerous lesion. The medicated canine serum was prepared by feeding to the adult Beagle dog with Radix notoginseng extracts and obtaining the serum after 2-hour medication. MC cells were cultured with medicated canine serum (medicated serum group) or non-medicated canine serum (normal control group) for 72 hours. Expressions of Bax, bcl-2 and p21WAF1 proteins were detected by immunocytochemical assay and the average optical density of the cells was determined by an image analysis system. Results. Compared with those of the normal control group, Bax and p21WAF1 expressions in medicated serum group were significantly enhanced (P<0.01), while the expression of bcl-2 was significantly reduced (P 001). Conclusion. Radix notoginseng extracts may inhibit the proliferation and promote the apoptosis of precancerous gastric cells through altering expressions of the bcl-2, Bax and p21WAF1 genes.%目的:研究三七提取物犬药物血清作用于胃癌前细胞后,其凋亡相关基因蛋白表达的变化.方法:采用被N-甲基-N-硝基-N-亚硝基胍(N-methyl-N-nitroso-guanidine,MNNG)转化后的永生化人胃黏膜上皮细胞系GES-1细胞(简称MC细胞)作为胃癌前病变细胞的体外研究模型,用三七提取物一次性灌胃彼格犬,取给药后2 h的血清作为实验药物血清.以免疫组织化学法检测药物血清对MC细胞作用72 h后bcl-2、Bax和p21WAF13种凋亡相关基因蛋白表达情况,并与正常培养的MC细胞相比较.结果:药物血清作用后的MC细胞中Bax和p21WAF1的表达较正常培养的MC细胞升高(P<0.01);Bc1-2表达较

  7. 辛伐他汀诱导人胃癌SGC7901细胞凋亡及其对Bax和Bcl-2表达的影响%Effect of Simvastatin on apoptosis and expressions of Bax and Bcl-2 gene in human gastric cancer cell line SGC7901

    Institute of Scientific and Technical Information of China (English)

    朱梦霞; 王芳; 谢娟; 熊文昊; 杨璐; 黄靓

    2015-01-01

    目的 研究辛伐他汀对人胃低分化腺癌细胞株SGC7901凋亡的影响及其可能的分子机制.方法 体外培养人胃癌SGC7901细胞至对数生长期, 再分别用不同浓度的辛伐他汀处理SGC7901细胞,48h后采用流式细胞术检测细胞凋亡;RT-PCR法和Western Blot法观察Bax和Bcl-2的表达.结果 辛伐他汀能诱导SGC7901细胞凋亡,且呈浓度依赖性.流式细胞术检测显示10、20、40μmol/L辛伐他汀组细胞凋亡率分别为(20.37±3.60)%、(35.17±3.91)%、(58.39±4.06)%,与对照组(4.78±1.51)%相比,凋亡率显著增强(P<0.05).不同浓度的辛伐他汀作用后能显著增强SGC7901细胞Bax mRNA和蛋白的表达,降低Bcl-2 mRNA和蛋白的表达(P<0.05). 结论 辛伐他汀呈浓度依赖性地诱导胃癌SGC7901细胞凋亡,其机制可能与上调Bax、下调Bcl-2表达有关.%Objective To investigate the effects of Simvastatin on apoptosis in human gastric lower-differentiation ade-nocarcinoma cell line SGC7901 and to explore its potential molecular mechanisms. Methods Gastric SGC7901 cells were cultured in vitro, cells of exponential phase of growth were used to experiment. Then using different concentrations of Simvas-tatin role in SGC7901, 48 hours later, flow cytometry method was used to detect the cell apoptosis, the expressions of Bax and Bcl-2 were tested by RT-PCR and Western-Blot assay. Results Simvastatin could promote the apoptosis of gastric cell line SGC7901 in a dose-dependent manner. Flow cytometry method showed that,Simvastatin (10μmol/L, 20μmol/L, 40μmol/L) role in SGC7901 for 48 hours, the apoptosis rates of the three groups were (20.37±3.60)%,(35.17±3.91)%,(58.39±4.06)%, the apoptosis rate of the control group was (4.78±1.51)%, the experimental groups were significantly higher than the control group (P<0.05). Different concentrations of Simvastatin could promote the expression of mRNA and protein of Bax, reduce the expres-sion of mRNA and protein of Bcl-2 in SGC7901

  8. Expression level of bcl-2 and bax in endometrial hyperplasia glandular epithelia with mifepristone treatment%Bcl-2、Bax在米非司酮治疗前后子宫内膜单纯性增生组织中的表达

    Institute of Scientific and Technical Information of China (English)

    高燕; 章明放; 付稳; 季福水

    2011-01-01

    Objective: To explore the adjust mechanism of simple hyperplasia (SH) endometrium treated by mifepristone. Methods: Immunohistochemical SP method was used to measure the expression of bcl-2 and bax in 10 normal endometrium (5 cases proliferative endometrium and secretory endometrium respectively), 43 SH and 43 endometrium after treatment with mifepristone. Results: The expression of bcl-2 in proliferative endometrium (PE) was higher than that in secretory endometrium (SE)(P<0.05), and that in SH was higher than that in PE (P<0.05). Compared with SH, the expression of bcl-2 decreased after treatment with mifepristone (P<0.05). The expression of bax in SE was higher than that in PE (P<0.05), and that in SH was lower than in PE (P<0.05). Compared with SH, the expression of bax increased after treatment with mifepristone (P<0.05). Conclusion: Mifepristone induced bax levels, while suppressing bcl-2 levels. The ability of mifepristone probably promote cellular apoptosis, which was one of the reasons to reduce endometrial hyperplasia.%目的:探讨米非司酮对子宫内膜单纯性增生的调节机制.方法:正常子宫内膜组织10例(增生期和分泌期各5例),单纯性增生子宫内膜43例,同一患者口服3个月米非司酮(10 mg/d)治疗后的子宫内膜标本43例.采用链酶菌素-生物素(S-P)免疫组化染色方法测定bcl-2、bax的表达量采用SPSS11.5统计学软件包进行数据处理,以P<0.05为有显著性差异.结果:增生期子宫内膜bcl-2阳性信号明显高于分泌期(P<0.05),单纯性增生bcl-2表达明显高于正常增生期子宫内膜(P<0.05).与单纯性增生相比,米非司酮治疗后,子宫内膜bcl-2明显下降(P<0.05).分泌期bax表达明显高于增生期(P<0.05),单纯性增生bax表达明显低于正常增生期子宫内膜(P<0.05).与单纯性增生相比,米非司酮治疗后,子宫内膜bax明显增高(P<0.05).结论:RU486增加了子宫内膜bax的表达,减少了bcl-2的表达,可能是其

  9. Effects of Jiedu Quyu Ziyin Recipe on the apoptosis and expressions of bcl-2 and bax mRNA of peripheralblood lymphocyte in MRL/lpr mice%解毒祛瘀滋阴药对MRL/lpr小鼠外周血淋巴细胞凋亡及线粒体跨膜电位的影响

    Institute of Scientific and Technical Information of China (English)

    曹灵勇; 谢志军; 王新昌; 温成平; 范永升

    2010-01-01

    Objective To explore the effects of Jiedu Quyu Ziyin Recipe (JQZR) on the apoptosis and expressions of bcl-2 and bax mRNA of peripheral-blood lymphocyte in MRL/lpr mice. Methods 80 MRL/lpr mice were randomly divided into model group,TCM group, Western medicine group and TCM and Western medicine group,20 mice in each group, meanwhile,20 Kunming mice were selected as normal group, then intragastrically administered normal sodium, JQZR apozem, prednisone suspension and JQZR apozem and prednisone suspension, 0. 5ml every time,once daily for 12 weeks respectively. At the end of the 12th week, peripheral-blood lymphocytes of every mice purified by gradient centrifugation were cultivated for 48 hours ,then the apoptosis was detected by flow cytometry. Furthermore,the expressions of bcl-2 and bax mRNA of peripheral-blood lymphocyte were detected by RT-PCR. Results At Oh or 48h,the apoptosis ratios of PBLC in normal group, TCM group,Western medicine group and TCM and Western medicine group are higher than model group and the differences are significant(P 0. 05) ,even if which are significant between TCM group and TCM and Western medicine group or between model group and TCM and Western medicine group( P 0.05),但中药组和模型组与中西药组比较,差异有显著性(P0.05);西药组与中西药组之间差异无显著性(P>0.05).结论 解毒祛瘀滋阴药能增加MRL/lpr小鼠的PBLC凋亡率并下调其线粒体跨膜电位水平.

  10. 犬弓首线虫感染小鼠脑组织细胞凋亡及凋亡基因bcl-2、bax的表达%Apoptosis in cerebral histiocytes and the expression of apoptosis-related genes Bcl-2 and bax in mice infected with Toxocara canis

    Institute of Scientific and Technical Information of China (English)

    郑胜生; 李建华; 沈继龙; 汪学龙

    2006-01-01

    目的研究犬弓首线虫(Toxocara canis)感染小鼠脑组织细胞凋亡及凋亡基因bcl-2、bax mRNA表达情况,探讨幼虫移行症对脑组织细胞影响可能机理.方法取狗小肠内犬弓首线虫成虫进行解剖,取子宫段的虫卵培养至感染期,感染小鼠后不同时间段取脑组织采用流式细胞仪检测小鼠脑组织细胞凋亡;应用原位杂交技术检测bcl-2、bax mRNA表达情况.结果 1.犬弓首线虫子宫段虫卵经培养有98%达感染期.2.病理切片HE染色均见感染小鼠脑组织有犬弓首线虫幼虫.3.流式细胞仪检测小鼠脑组织细胞凋亡10 d、15 d、20 d、25 d对照组与实验组比较,具统计学意义差别(P0.05).结论 1.犬弓首线虫感染小鼠早期,脑组织细胞有不同程度细胞凋亡出现.2.其细胞凋亡与凋亡基因bcl-2、bax无明显关系.

  11. 新生鼠坏死性小肠结肠炎肠上皮细胞Bax表达与细胞凋亡的初步研究%Expression of Bax and apoptosis in enterocytes of neonatal rats with necrotizing enterocolitis

    Institute of Scientific and Technical Information of China (English)

    张勇; 蒋迎佳; 廖志; 叶飘; 郝静梅; 余绍兰; 胡语航

    2014-01-01

    目的 探讨新生鼠坏死性小肠结肠炎(necrotizing enterocolitis,NEC)时肠上皮细胞Bax表达与凋亡相关性.方法 出生当日48只清洁级SD新生鼠采用奇、偶数方法随机分为对照组和NEC模型组,每组24只.对照组由母鼠喂养.模型组与母鼠分开,通过代乳品人工喂养+缺氧-复氧-冷刺激建立新生鼠NEC动物模型.分别于实验开始后24h、48 h、72 h留取大鼠回盲部近段回肠组织行免疫组织化学法检查肠上皮细胞Bax表达,原位末端标记法检测肠上皮细胞凋亡率.结果 与对照组[(666.55±15.77)IOD; (4.73±0.04)%]相比,NEC模型组新生鼠肠上皮细胞Bax表达和细胞凋亡率在实验开始后24 h开始升高[(1 005.06±11.96) IOD; (15.04 ±0.24)%](P<0.01),72 h后达到高峰[(3 340.66±68.72) IOD; (35.65±0.61)%](P<0.01).NEC模型组新生鼠肠上皮细胞凋亡率与肠上皮细胞Bax表达量呈正相关(r=0.94,P<0.01).结论 新生鼠NEC肠上皮细胞凋亡与Bax表达有明确相关性.新生鼠NEC肠上皮细胞可能通过高表达Bax导致肠上皮细胞凋亡.%Objective To investigate the correlation of Bax and apoptosis in enterocytes of neonatal rats with necrotizing enterocolitis (NEC).Methods Forty-eight neonatal rats (1 day) were randomly divided into control group (n =24) and NEC model group (n =24) by use of odd and even.The rats in control group were maternal breast-fed.The rats in NEC model group were separated from their mothers.To be given formula feeding,cold exposure after hypoxic-reoxygenation treatment.The intestinal tissue located at the boundary of ileum and caecum of two groups were gained on the 24 h,48 h and 72 h with which that all rats were sacrificed by cutting neck.Section of intestinal tissue were stained with immunohistochemistry to detect the expression of Bax and were stained with TdT mediated dUTP nick end labeling(TUNEL) to evaluate the apoptosis in each group.Results The integrate optical density (IOD) value of

  12. Detect of P53,bax and caspase 3 genes expression after optic nerve injury in rats with SYBR green I fluorescence quantitative PCR%SYBR Green I荧光定量PCR检测大鼠外伤性视神经损伤后P53、bax和caspase 3基因表达

    Institute of Scientific and Technical Information of China (English)

    吕瀛娟; 赵秀兰; 杨洁; 于金国; 颜华

    2009-01-01

    目的 应用SYBR Green Ⅰ荧光定量PCR法检测外伤性视神经损伤后P53、bax和caspase 3基因mRNA表达的变化.方法 应用液压颅脑损伤仪建立大鼠外伤性视神经损伤动物模型,伤后1、3、5、7、9、14、28d处死,以Trizol法提取新鲜视网膜组织的总RNA,以Oligo (dt) 18 为引物逆转录合成cDNA 并进行扩增,以T/A克隆法将纯化的目的 片断与T/A克隆载体(pTZ57R/T)连接成重组质粒并转化入E.coli DH5α.采用碱裂解法提取重组质粒,经蓝白斑筛选、酶切、测序鉴定后,根据标准品建立标准曲线,由软件自动计算出待测样本中靶基因mRNA的含量,并以靶基因和内参GAPDH mRNA含量的比值作为评价靶基因表达水平的指标.结果 由pTZ57R/T与目的 基因所构建的标准曲线的线性关系良好、灵敏度高、特异性强、准确可靠.P53和bax均在视神经损伤后3d mRNA表达明显增加,5d时达到高峰,7d后开始下降;伤后5d caspase 3 mRNA表达明显增加,9d时达到高峰,14d后开始下降.三者表达水平与对照组相比,差异均有统计学意义(P<0.05).结论 促凋亡基因P53、bax和caspase 3在视神经损伤后视网膜神经节细胞(RGCs)的凋亡发生中起到重要作用.%Objective Previous study showed that the histopathological basis of visual function damage caused by optical nerve injury is apoptosis of retinal ganglion cells(RGCs). This procedure is regulated by P53, bax and caspase 3 genes. Present study aimed to observe the expression of bax, P53 and caspase 3 mRNA in RGCs after traumatic optic nerve damage in the rats by SYBR green I fluorescence quantitative PCR method. Methods The animal model of optic nerve injury was established in the right eyes of 56 adult Wistar rats by a fluid percussion brain injury device (FPI) . Animal were killed on days 1, 3, 5, 7, 9, 14, 28 days separately after injury. Other 16 Wistar rats were divided into normal control group and sham operation group. The total RNA

  13. 中度低温体外循环后大鼠海马bcl-2和bax的表达与神经元凋亡%Hippocampal bcl-2 and bax expressions and neuronal apoptosis after moderate hypothermic cardiopulmonary extracorporeal circulation in rats

    Institute of Scientific and Technical Information of China (English)

    张挺杰

    2005-01-01

    BACKGROUND: Hippocampus injury is wildly believed to involve in neurocognitive dysfunction; the establishment of a rat model of cardiopulmonary bypass(CPB) allows us to investigate the mechanism of CPB-related hippocampus injury.OBJECTIVE: To investigate the effects of moderate hypothermic CPB with a hemodilution on hippocampal bcl-2 and bax gene expression and neuronal apoptosis in rats.DESIGN: A randomized group division study based on the experimental animals.SETTING: Department of anesthesiology in a university hospital.MATERIALS: Thirty Sprague-Dawley (SD) rats were randomly divided into two groups, CPB group and sham-CPB group with 15 rats in each group.METHODS: Total 15 rats of CPB group were subjected to 60-minute moderate hypothermic nonpulsatile CPB using a peristaltic pump and a membrane oxygenator. The CPB circuit was primed with approximately 20 mL 1:1crystaloid-colloid liquid, while another 15 rats of sham-CPB group underwent identical anesthetic and surgical procedures(including cannulation) except CPB itself. At 1 hour post-CPB, six rats in each group were decapitated, and hippocampi were removed, homogenized, and processed for apoptotic gene ( bcl-2 and bax) mRNAs detection. Reverse transcriptase polymerase chain reaction(RT-PCR) is used to detect expression of mRNA by comparing the PCR product of bcl-2 or bax to those of β-actin housekeeping gene. Immunohistochemistry is used to detect bcl-2 and bax protein expressions and terminal deoxynucleiotidyl transferase-mediated dUTP-biotion nick end labeling(TUNEL) staining method was used to detect neuronal apoptosis at 6 hours post-CPB ( n = 6 in each group) . The protein expression was quantitated as percentage of the positively stained area in the total stained. In addition, hippocampal neuronal ultrastructures were studied by electron microscopy at 6 hours post-CPB( n = 3 in each group).ronal apoptosis and ultrastructure changes between the two groups.RESULTS: At 1 hour post-CPB, the expressions of

  14. Effect of Shenfu parenteral injection on the expressions of Bcl-2, Bax and c-Fos proteins in ischemia reperfusion myocardium of rats%参附注射液影响大鼠缺血再灌注心肌Bcl-2,Bax与c-Fos蛋白的表达

    Institute of Scientific and Technical Information of China (English)

    陈玉培; 牟崇明; 季道如; 但伶; 龚文婷; 王莉莎

    2006-01-01

    -2/Bax比率显著升高(P<0.01).结论:参附注射液对缺血再灌注心肌保护效应可能与其促进Bcl-2蛋白高表达、抑制Bax与c-Fos蛋白表达、增加Bcl-2/Bax比率,从而抑制心肌细胞凋亡有关.%BACKGROUND: It has been confirmed that Shenfu parenteral injection can ameliorate and treat various shocks, heart failure, myocardial ischemia and supraventricular/ventricular arrhythmia, and it also has a good protective effect on myocardial ischemia/reperfusion injury in rats.OBJECTIVE: To observe the effects of Shenfu parenteral injection on the protein expressions of myocardial apoptosis-related genes of Bcl-2, Bax and c-Fos in rats with acute ischemia/reperfusion injury.DESIGN: A complete randomized grouping design, controlled experiment.SETTING: Department of Anesthesiology, the Second Affiliated Hospital,Chongqing University of Medical Sciences.MATERIALS: The experiments were carried out in the Staff Room of Anesthesiology, the Second Affiliated Hospital, Chongqing University of Medical Sciences from April to December in 2004. Thirty-five healthy adult Wistar rats were provided by the experimental animaI center of Daping Hospital, Third Military Medical University of Chinese PLA. Shenfu parenteral injection was the TCM formula of Shenfu Tang, which is for recuperating depleted yang and rescuing the patient from collapse, and its main components are ginsenoside and aconitum alkaloid. It was the product of Yaan Sanjiu Pharmaceutical Co., Ltd., 10 mL/piece, the batch number was 030110.METHODS: In vivo models of myocardial ischemia/reperfusion injury were used. The 35 rats were divided into 5 groups according to the number of random number table, with 7 rats in each group: ① Sham-operated group: The rats were treated with only insertion of thread without ligation, followed by intravenous injection of saline (8 mL/kg), and then observed for 120 minutes. ② Shenfu parenteral injection 30-minute group: The rats were treated with intravenous

  15. Effect of myocardial reperfusion on cardiocyte apoptosis and expression of bcl-2, bax and caspase-3 in rats with depression%心肌再灌注对抑郁大鼠心肌细胞凋亡以及bcl-2、bax和caspase-3表达的影响

    Institute of Scientific and Technical Information of China (English)

    刘淑珍; 尤鑫; 熊小栓; 刘兴德

    2012-01-01

    目的:探讨心肌缺血再灌注(I/R)对抑郁大鼠心肌细胞凋亡及凋亡基因bcl-2、bax和caspase-3的影响.方法:Wistar大鼠32只,随机分为4组,每组各8只.A组:非抑郁大鼠假手术组;B组:抑郁大鼠假手术组;C组:非抑郁大鼠心肌I/R组;D组:抑郁大鼠心肌I/R组.采用慢性轻度不可预知性应激结合孤养制备抑郁模型,用敞箱实验和液体消耗实验观察大鼠行为改变;运用结扎左冠状动脉前降支的方法复制心肌I/R模型.运用TUNEL法检测心肌凋亡细胞;运用免疫组化法和逆转录-聚合酶链反应(RT- PCR)方法检测bcl-2、bax和caspase-3的表达.结果:(1)与A、B组比较,C、D组心肌细胞凋亡数量显著增加(P<0.01),A、B两组间比较无显著差异;与C组比较,D组心肌细胞凋亡数量显著增加(P<0.05).(2)与A、B组比较,C、D组Bcl-2、Bax和caspase-3蛋白和mRNA表达显著增加(P<0.01),A、B两组间比较无显著差异;与C组比较,D组Bcl-2蛋白和mRNA表达显著减少(P<0.05),而Bax和caspase-3蛋白和mRNA表达显著增加(P<0.05).结论:心肌缺血再灌注可加重抑郁大鼠缺血心肌细胞凋亡,其机制可能与上调bax和caspase-3基因表达、下调bcl-2基因表达有关.%AIM:To explore ihe effecl of ischemia/reperfusion (I/R) on cardiac myocyle apoplosis and ihe expression of bcl -2, bax and caspase - 3 in ihe rals wilh depression. METHODS; Thirty - Lwo Wislar rals were randomly divided inlo 4 groups,including group A; sham operation group; group B; ihe rals wilh depression undergoing sham opera-lion; group C; ihe rals wilh myocardial I/R operalion; group D; ihe rals wilh depression undergoing myocardial I/R opera-lion. The ral model of depression was produced by chronic mild unpredictable slress and separalion. The behaviors of ihe rals were delecled by open field lesl and fluid consumption lesl. The myocardial I/R model was made by ligaling ihe lefl an-lerior descending branch of coronary artery in ihe rals. The

  16. 头针电刺激对急性脑梗死大鼠 Bax与 Bcl-2蛋白的影响%Effect of Scalp Acupuncture and Electrical Stimulation on Protein Bax and Bcl-2 in Rats with Acute Cerebral Infarction

    Institute of Scientific and Technical Information of China (English)

    李晓宁; 綦雪巍; 王振宇

    2016-01-01

    Objective:To observe the changes of protein Bax and Bcl -2 after treating acute cerebral infarction of rats with scalp acupuncture and electrical stimulation , and to discuss the mechanism on how these treatments affect cerebral infarction .Methods:Divide healthy female wistar rats into a treatment group , a model control group and a sham operation group randomly .Then divide every group into seven -days group and fourteen -days group by their treatment starting time after infarction ,with fifteen rats every time point .Make focal cerebral infarction models by suture method , then from the first day after making models , intervene the treatment group with scalp acupuncture , choose BaiHui and DaZhui acupoints , stimulate the acupoints with 100 Hz electrical wave , once per day , 30 minutes every time .For other two groups of rats , just fix them on the table with no in-tervention .After seven days and fourteen days , when the treatment was over , cut off their heads and take out the brains .Examine the infarction brain tissues with Western blot technology and determine the expressions of protein Bax and Bcl -2.Results:The expression of protein Bax was descended gradually , but the expression of Bcl-2 was ascended in the treatment group;in the model control group , the expressions of two proteins were descended .Compared with the model control group , the expressions of protein Bax in the treatment group on the seventh day and fourteenth day were descended ,and the expression of Bcl -2 was ascended .The difference had a statistical significance (P<0.05).Conclusion:Scalp acupuncture with electrical stimulation can effec-tively protect the infarction brain tissues .It can descend the expression of protein Bax , ascend the expression of Bcl-2 at the same time , maximize the difference between the expression of the two proteins , inhibit apoptosis in the ischemic regions .This might be the mechanism on how scalp acupuncture with electrical stimulation im-prove the

  17. 氯胺酮对兔膝骨性关节炎软骨细胞Bcl-2及Bax表达的影响%Influence of Ketamine (KET,Ketamine) of intra-articular injection of rabbit chondrocytes and Bax expression

    Institute of Scientific and Technical Information of China (English)

    王雯; 王林; 陆巍

    2015-01-01

    Objective To explore the different concentrations of after the Bcl‐2 ,and the influence of Bax expres‐sion .Method The rest of rabbits with left knee immobilized in extension position to establish osteoarthritis models , then ,divided the models into model group ,ketamine60 group ,ketamine100 group and ketamine200 group in ran‐dom .They were received 0 .4 ml physiologic saline ,KET of 60μmol/L ,KET of 100μmol/L ,KET of 200μmol/L intra‐articular respectively ,two times a week for 4 weeks ,and sacrificed one week after last injection .To return af‐ter knee joint cartilage specimens corresponding processing ,using immunohistochemical method to observe the Bcl‐2 in the articular cartilage and the expression of bax .Result Compared with model group ,the injection of ketamine and promote cartilage cells apoptosis gene Bcl‐2 and Bax genes are changed (P<0 .05) .ketamine200 group of antiapop‐totic effect is the most significant (P<0 .05) .Conclusion Ketamine can suppress the cartilage cell apoptosis induced by osteoarthritis .%目的:观察不同浓度氯胺酮(Ketamine ,KET )家兔关节腔内注射后软骨细胞Bcl‐2及Bax表达的影响。方法通过管型石膏伸直位制动法造模成功后,随机分为模型组、氯胺酮60组、氯胺酮100组、氯胺酮200组,其中模型组、氯胺酮60组、氯胺酮100组、氯胺酮200组分别给予0.4 mL的生理盐水、KET(60μmol/L)、KET(100μmol/L)、KET(200μmol/L)关节腔内注射,每周2次,共进行4周,最后一次注射后1周处死动物。留取膝关节软骨标本作相应处理后,利用免疫组化法观察关节软骨中Bcl‐2及Bax的表达情况。结果与模型组比较,注射氯胺酮的软骨细胞促凋亡基因Bcl‐2及Bax均改变(P<0.05),其中氯胺酮200组的抗凋亡效果最为显著(P<0.05)。结论氯胺酮可以抑制骨关节炎诱导的软骨细胞凋亡。

  18. Influence of Zedoray Turmeric Oil on Expression of Bcl- 2/Bax in Human Breast Cancer MCF-7 Cells%莪术油对人乳腺癌MCF-7细胞凋亡及Bcl-2、Bax表达的影响

    Institute of Scientific and Technical Information of China (English)

    杨丽华; 姜杰

    2010-01-01

    目的:观察中药提取物莪术油(zedoray turmeric oil)对人乳腺癌(human breast cancer)细胞系MCF-7的凋亡诱导作用.方法:用不同浓度的莪术油对体外培养的MCF-7细胞进行干预.分别采用MTT、细胞免疫组织化学染色、流式细胞仪检测等方法,观察其对MCF-7细胞增殖的抑制和凋亡诱导作用,并对凋亡相关Bcl-2与Bax蛋白的表达变化进行定性检测.结果:经不同浓度的莪术油处理后的MCF-7细胞,其生长受到明显的抑制,细胞凋亡指数随药物浓度增加而明显增加;莪术油作用后,细胞中Bax蛋白表达明显高于对照组.结论:一定浓度的莪术油能抑制MCF-7细胞增殖,促进其凋亡;其机制可能与调控Bcl-2、Bax 表达有关.

  19. 吲哚美辛对COPD大鼠TNF-α与Bcl-2和Bax表达的影响%The Influence of Indomethacin on the Expression of TNF-α and Bcl-2 and Bax in Chronic Obstructive Pulmonary Disease Rat Model

    Institute of Scientific and Technical Information of China (English)

    周兰英; 孙圣华; 高健; 宋薇; 杨小仙; 唐文祥

    2012-01-01

    目的:探讨吲哚美辛对慢性阻塞性肺疾病(COPD)模型大鼠趾长伸肌TNF-α及Bcl-2和Bax表达的影响.方法:100只健康Wistar大鼠随机分为模型组和对照组(A组).模型组采用熏香烟和气管内滴注猪胰蛋白酶(PEE)法建立COPD模型大鼠,以低于A组大鼠平均体重的90%判断发生营养不良的标准,将模型组大鼠分为COPD营养正常组(B组)和COPD营养不良组,COPD营养不良组随机化原则分为COPD营养不良生理盐水组(C组)、吲哚美辛1组(D组)、吲哚美辛2组(E组)、吲哚美辛3组(F组).A、B、C三组灌注等量生理盐水,D、E、F组给予不同剂量吲哚美辛(IND)灌胃干预.TUNEL法测定趾长伸肌细胞凋亡率,免疫组织化学法测定Bcl-2、Bax蛋白表达,双抗体夹心法测定血清及趾长伸肌肿瘤坏死因子α(TNF-α)浓度.结果:吲哚美辛干预后,E组趾长伸肌细胞凋亡率、Bcl-2、Bax的蛋白表达、趾长伸肌匀浆和吲哚美辛干预后血清TNF-α浓度低于C、D、F组,但高于A、B组,P<0.05;E组趾长伸肌Bcl-2蛋白表达高于C、D、F组,低于A、B组,P<0.05,结论:Bcl-2、Bax及TNF-α参与COPD模型大鼠趾长伸肌细胞凋亡,适当剂量的吲哚美辛可改善COPD营养不良模型骨大鼠趾长伸肌的凋亡.%Objective: To investigate the effect of indomethacin on the expression of Bcl-2 , TNF-a and Bax in extensor digito-rum longus in the COPD rafs models. Methods: 100 healthy Wistar rats were randomly divided into model group and control group (group A). The model group rat was performed with intratracheal instillation of porcine pancreatic elastase (PEE) and exposed to cigarette smoke to establish COPD models. Malnutrition was defined if the body weight of the rats in the model group was lower than 90% of the mean body weight of the control group. All model rats were divided into non-malnutntion COPD group (group B) and malnutrition COPD group, and the malnutrition COPD group rats were randomly divided

  20. Dipeptidyl peptidase-4 inhibitor impacts the expression of Bcl-2 and Bax throughγamino acid bwtyric acid in pancreas islets%二肽基肽酶4抑制剂通过胰岛γ氨基丁酸影响Bcl-2及Bax蛋白的表达

    Institute of Scientific and Technical Information of China (English)

    董莹; 李强; 陈静芳; 王萍; 张巾超

    2016-01-01

    目的:研究二肽基肽酶4(dipeptidyl peptidase-4, DPP-4)抑制剂对胰岛β细胞Bcl-2及Bax蛋白表达的调节作用是否通过增加胰腺组织中γ氨基丁酸(γamino acid butyric acid, GABA)含量这个途径实现。方法清洁级SD大鼠50只,随机选取10只为正常对照组。余40只采用高脂喂养联合链脲佐菌素( STZ)的方法诱导成糖尿病模型。随机分为3组:糖尿病对照组、DPP-4抑制剂组、拮抗剂组( DPP-4抑制剂+GABA受体拮抗剂)。药物干预6周后检测血糖、血清胰岛素、胰升糖素的水平及胰岛β细胞中GABA、Bcl-2及Bax蛋白的表达情况。结果(1) DPP-4抑制剂组与糖尿病对照组相比,血清胰岛素水平升高(P<0.05),血糖水平降低(P<0.05),血清胰升糖素水平降低(P<0.05)。(2)拮抗剂组与DPP-4抑制剂组相比,大鼠血清胰岛素水平降低(P<0.05),血糖水平升高(P<0.05),血清胰升糖素水平升高(P<0.05)。(3) DPP-4抑制剂组与糖尿病对照组相比,大鼠胰岛β细胞GABA表达升高(P<0.05),Bax蛋白表达降低(P<0.05),Bcl-2蛋白的表达升高(P<0.05)。(4)拮抗剂组与糖尿病对照组相比,大鼠胰岛β细胞GABA表达升高(P<0.05),与DPP-4抑制剂组相比,大鼠胰岛β细胞Bax蛋白表达升高(P<0.05),Bcl-2蛋白的表达降低(P<0.05)。结论 DPP-4抑制剂能够通过增加胰岛GABA表达来促进胰岛素分泌,减少胰升糖素分泌,增加胰岛β细胞抗凋亡蛋白Bcl-2的表达,降低胰岛β细胞促凋亡蛋白Bax的表达,抑制2型糖尿病大鼠胰岛β细胞的凋亡。%Objective To explore the effects of dipeptidyl peptidase ( DPP-4 ) inhibitor on proteins expression of Bcl-2 and Bax of islet β-cells through increasing the expression of islet γ amino acid butyric acid ( GABA) . Methods A total of 50 rats of clean grade were studied. Among them, ten rats were randomly selected as normal controls, the remaining forty rats were fed with high-fat diet and then intraperitoneal injection with

  1. 去甲斑蝥素对人肝癌SMMC-7721细胞凋亡相关因子半胱天冬酶3、bax和细胞色素 C 表达的影响%Influence of norcantharidin on expression of apoptosis related factors caspase-3,bax and cytochrome C in human liver cancer SMMC-7721 cells

    Institute of Scientific and Technical Information of China (English)

    张梅

    2015-01-01

    目的:了解去甲斑蝥素对人肝癌SMMC‐7721细胞增殖的影响,通过分子生物学手段探讨其诱导肿瘤细胞凋亡的作用机制。方法:以1、5、25、125mg/L去甲斑蝥素作为药物组,不加药物的细胞作为对照组。通过MTT比色法检测去甲斑蝥素对SMMC‐7721细胞生长的抑制率;采用AnnexinV‐FITC/PI双染色法测定肿瘤细胞的凋亡率;通过免疫印迹法测定caspase‐3、bax和细胞色素C的表达水平。结果:相同浓度的去甲斑蝥素作用时间越长,细胞生长抑制率越高;作用相同时间的去甲斑蝥素浓度越高,细胞生长抑制率越高。药物组细胞均有不同程度的早期凋亡和晚期凋亡。随着去甲斑蝥素浓度的提高,总凋亡率相应升高;药物组的总凋亡率均高于对照组(t=10.758、16.931、33.955、22.358,P均<0.05)。随着去甲斑蝥素的浓度提高,caspase‐3、bax和细胞色素C的表达量均升高;浓度为25、125mg/L的去甲斑蝥素处理细胞后,caspase‐3、bax和细胞色素C的蛋白表达量均高于对照组(t=4.246、2.521、5.842、6.654、7.137、4.825,P均<0.05)。结论:去甲斑蝥素通过诱导细胞凋亡抑制SMMC‐7721细胞生长,其作用机制在于上调凋亡相关因子caspase‐3、bax和细胞色素C的表达。%Objects :To learn the influence of norcantharidin on proliferation of human liver cancer SMMC‐7721 cells ;To adopt the method of molecular biology to explore its mechanism of action of inducing tumor cell apoptosis . Methods :Drug groups included 1 ,5 ,25 ,125 mg/L of norcantharidin ,and the control group included no drug .The rates of Inhibition of norcantharidin on the growth of SMMC‐7721 cells were tested by M TT assay ;The apoptosis rates of tumor cells was determined by Annexin V‐FITC/PI double staining ;The expression levels of Caspase‐3 ,Bax and cyto‐chrome C were detected by Western blot

  2. 细胞凋亡及bax基因表达与舌苔变化关系的研究%A Study on the Relationship Between the Gene Expression of Bax and Cell Apoptosis in Tongue Mycoderma Epithelium of Common Tongue Coating

    Institute of Scientific and Technical Information of China (English)

    李新华; 吴正治; 李明; 张永锋; 陈嫚茵

    2006-01-01

    目的:检测常见舌苔舌上皮细胞凋亡情况及凋亡相关基因bax mRNA和蛋白产物,探讨舌苔厚度变化与舌上皮细胞凋亡、bax基因表达的关系.方法:运用TUNEL(末端脱氧核苷酸转移酶介导的脱氧尿嘧啶核苷三磷酸缺口末端标记)技术、原位杂交、免疫组化和图像分析技术.结果:与正常薄苔比较,剥苔bax基因过度表达伴随细胞凋亡增多,而厚苔bax基因低表达伴随细胞凋亡减少.bax基因表达水平变化趋势与细胞凋亡水平变化趋势一致.结论:bax基因表达水平的变化可能是影响舌苔上皮细胞凋亡并导致舌苔厚度变化的重要原因.

  3. 细胞凋亡调控蛋白bcl-2和bax在涎腺肿瘤中的表达及意义%Expression and significance of apoptosis regulatory protein bcl-2 and bax in tumor of salivary gland

    Institute of Scientific and Technical Information of China (English)

    齐红; 袁红民; 安文生; 杨荔琳

    2002-01-01

    目的:探讨bcl-2和bax基因蛋白在涎腺肿瘤(Salivary tumer,ST)中表达及意义.方法:SABC法观察87例ST及12例正常涎腺组织(Natural salivary tissue,NST)中bcl-2及bax表达.结果:bcl-2及bax蛋白在ST中表达明显高于NST;bcl-2在涎腺恶性肿瘤(Salivary malignacy,SM)中表达明显高于良性肿瘤;SM中bcl-2表达与其恶性程度及临床分期显著相关;bax蛋白表达与SM临床病理指标均无相关性.结论:bcl-2蛋白表达有助于SM恶性程度判断;可作为判断SM生物特性、临床分期的重要指标;bax/bcl-2比率变化参与了ST发生及发展过程.

  4. Effects of Roubin-manipulation on apoptosis of chondrocytes and expression of Bcl-2, Bax and Fas in rabbit knee joint%揉髌手法对兔膝关节软骨细胞凋亡及Bcl-2、Bax和Fas表达的影响

    Institute of Scientific and Technical Information of China (English)

    戴七一; 覃杰; 袁经阳; 吴兆沛; 王雄; 阮萍; 崔伟; 黎强; 覃学流; 林光琪; 刘靖; 容向宾; 韩杰

    2011-01-01

    BACKGROUND: Modern studies have demonstrated that excess we cellular apoptosis accelerates the degeneration ofrarety reported.OBJECTIVE: To observe the effects of flouAm-manipulation on apoptosis of chondrocytes and expression of Bck2.Bax and Fa;in rabbitknee joint.Hyaluronate groups. Rabbits in the latter three groups were established into high intraosseous pressure experiment model of rightRESULTS AND COHC LUSIOH: At the end of the 8n week, cartilaginous tissue of medial tibial plateau of rabbit right knee joint obvious, and chondrocyte apoptosis rate was significantly increased (P < 0.01). And Bcl-2. Bax and Fas expression in the tibialtissue degeneration was slight, chondrocyte apoptosis rate and BaxandFas expression were significantly decreased (p<0.01) but Bcl-2 expression in the tibial cartilaginous tissue was significantly increased (F < 0.01) in the manipulation and sodium%背景:现代研究证实细胞的过度凋亡加速软骨组织的退变,而手法的力学刺激对关节软骨影响的分子层面研究至今少有报道.目的:观察揉髌手法对兔膝关节软骨细胞凋亡及Bcl-2、Bax、Fas 表达的作用.方法:50 只新西兰兔随机等分为正常组、假手术组、模型组、手法组和针剂组,后3 组建立右下肢骨内高压型膝关节骨性关节炎模型.造模1 周后,手法组使用揉髌手法隔天治疗1 次,每次10 min,共治疗5 周共17 次;针剂组关节内注射玻璃酸钠液0.6 mL,每周1 次,共5 次.结果与结论:造模后8 周末取兔右膝关节内侧胫骨平台软骨组织,苏木精-伊红染色提示模型组软骨组织退变明显,软骨细胞凋亡率明显增加(P < 0.01),胫骨平台软骨组织中Bcl-2、Bax、Fas 表达率明显升高(P < 0.01),而手法组和针剂组软骨组织退变轻微,软骨细胞凋亡率及Bax、Fas 表达率较模型组降低(P < 0.01),但胫骨平台软骨组织中Bcl-2 表达升高(P < 0.01).说明揉髌手法与关节内注射玻璃酸钠一样可以明显降

  5. Effect of Shengqing Jiangtang Decoction on Expression of Bcl-2,Bax,Akt in Beta Cells with Oxidative Damage%升清降糖合剂对氧化损伤胰岛β细胞Bcl -2、Bax、Akt表达的影响

    Institute of Scientific and Technical Information of China (English)

    倪小芬; 胡臻; 郑超; 徐晓峰

    2011-01-01

    It is a study on protective mechanism of Shengqing Jiangtang decoction (SQ) on pancreatic beta - cells with oxidative damage. We made the oxidative damage of beta - cells by H2O2 and interfered with SQ, we assayed the cell apotosis rate, the expression levels of Bel - 2, Bax and phosphorylated Akt (pAkt) by flow cytometry, fluroimmuno -assay and Western Blot method, respectively. We found the apotosis rate of model group (35. 18 ±2.41)% had statistical defference compared with protection group (19. 56 ± 1.08) % , P < 0. 01. Bel - 2 expression increased and Bax expression decreased in protection group, which had a difference compared with model group(P <0.05) , respectively. We found pAkt protein expressed in both RINm5F and primary rat pancreatic islets. In each object, expression of pAkt declined in model group, which had a statistical difference compared with negative group; pAkt increased in protection group, which had a statistical difference compared with model group, respectively.%目的:研究升清降糖合剂(SQ)对氧化损伤胰岛β细胞凋亡的保护作用,探讨其对凋亡蛋白Bcl -2和Bax、Akt蛋白表达的影响.方法:H2O2诱导胰岛细胞氧化损伤模型,流式细胞术测定胰岛细胞凋亡率,以荧光免疫法检测细胞凋亡蛋白Bcl -2和Bax的表达,免疫印迹测定细胞Akt磷酸化表达.结果:模型组细胞凋亡率增高,达(35.18±2.41)%,与正常组比较有差异(P<0.01),与SQ保护组比较有差异(P<0.01).模型组细胞内Bax荧光表达较正常组增加(P<0.05);SQ保护组Bcl -2荧光表达上升,Bax荧光表达下降,与模型组比较,均有统计学差异(P<0.05).对于胰岛细胞瘤株RINm5F,模型组磷酸化Akt蛋白表达减少,与正常组比较有统计学差异(P<0.05),与保护组比较有统计学差异(P<0.01);对于原代胰岛,模型组磷酸化Akt蛋白减少,与正常组比较有统计学差异(P<0.05),与保护组比较有统计学差异(P<0.05).结论:升清降糖合

  6. Influence of oxidative stress on apoptosis and expression of bax and bcl-2 of enterocytes in burn rats with delayed resuscitation on the plateau%高原地区烧伤后延迟复苏氧化应激对大鼠肠上皮细胞凋亡及bax和bcl-2基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    周文军; 张诚; 刘毅; 刘萍; 马明; 张世范

    2009-01-01

    Objective To explore influence of oxidative stress reaction on apoptosis rate and expres-sion of apoptosis-related genes bax and bcl-2 of enterocytes in severely burned rats with delayed resuscitation on the plateau. Methods One hundred and twenty rats subjected to 30% TBSA full-thickness scald on the back were derided into plateau experimental group (PE, altitude 3840 m) and Lanzhou experimental group (LE, altitude 1517 m). Then LE and PE groups were subdivided into Lanzhou immediate fluid resus-citation group (LIFR, with immediate intraperitoneal injection of isotonic saline after scald, 40 mL/kg), Lanzhou delayed fluid resuscitation group [LDFR, with intraperitoneal injection of isotonic saline at 6 post scald hour (PSH), 40 mL/kg], and plateau immediate fluid resuscitation group (PIFR, with immediate in-traperitoneal injection of isotonic saline after scald, 40 mL/kg), plateau delayed fluid resuscitation group (PDFR, with intraperitoneal injection of isotonic saline at 6 PSH, 40 mL/kg). Another 12 rats were divided into Lanzhou sham scald group (LS) and plateau sham scald group (PS), with 6 rats in each group. Rats in LS and PS groups were sham scalded in a water bath for 15 s without fluid infusion. Rats were sacrificed at 6, 12, 24, 48, 72 PSH for collection of small intestine samples to determine the contents of malonaldehyde (MDA) and total hydrosulfide (TSH). The apoptosis of enterocytes was determined by TUNEL, and the ex-pression of bax and bcl-2 in epithelial cells were observed by immunohistochemical method. Intestinal sample of LS and PS groups were collected to determine the contents of MDA and TSH. Results After being scal-ded, content of MDA in intestinal tissue of rats in LDFR group and PDFR group was respectively greater than that in LIFR group and PIFR group (P<0.05 or P<0.01). Intestinal tissue content of MDA of rats in LDFR group (9.8±4.0 nmol/mg) and PDFR group (10.2±1.3 nmol/mg) was respectively greater than that in LIFR group (9.5±2

  7. Effects of intermittent hypoxic preconditioning on apoptosis-related Bcl-2 and Bax protein expression in rat liver after partial hepatectomy under ischemia-reperfusion%间断低氧预适应对大鼠肝切除缺血再灌注肝脏凋亡相关蛋白Bcl-2、Bax表达的影响

    Institute of Scientific and Technical Information of China (English)

    王健; 李鹏飞; 韩效帆; 朱世春; 李广; 李俊; 张培建

    2014-01-01

    目的 观察术前间断低氧预适应对大鼠70%肝切术后缺血再灌注损伤肝脏凋亡相关蛋白Bcl-2和Bax表达的影响.方法 健康清洁级SD大鼠54只,用SPSS软件随机分为3组,每组18只:(1)肝切除组(PH组),切除肝脏的左叶和中叶(约占总肝重的70%);(2)缺血再灌注组(IR组),即在肝门阻断下切除肝脏的左叶和中叶,肝门阻断20 min后开放血流,残余肝脏发生了缺血再灌注过程;(3)间断低氧预适应组(IHP组),术前1周将大鼠置于氧气体积分数为10%的低氧环境中,每天1h.1周后在肝门阻断下行肝切除术(同IR组).各组分别于术后12、24、48 h进行取材检测,用全自动生化分析仪检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)含量,采用免疫组化方法检测残余肝组织Bcl-2、Bax表达情况.结果 在术后各时间点,IR组和IHP组血清ALT和AST水平均显著高于PH组,但IHP组明显低于IR组.与IR组相比,IHP组术后各时间点肝脏Bcl-2蛋白表达显著升高,而Bax蛋白表达显著下降.差异均有统计学意义(P<0.05).结论 间断低氧预适应对残余肝脏缺血再灌注损伤具有保护作用,其途径可能是通过促进抗凋亡蛋白Bcl-2表达和抑制促凋亡蛋白Bax表达,来减少肝细胞凋亡.%Objective To observe the effects of intermittent hypoxic preconditioning on the expression of apoptosis-related Bcl-2 and Bax protein after 70% hepatectomy combined with ischemia-reperfusion injury.Methods A total of fifty-four SD rats were randomly divided into three groups (n =18).Partial hepatectomy hroup (PH Group):Rats underwent the left and middle lobectomy of liver(70% hepatectomy).Ischemia reperfusion group (IR group):The left and middle lobes of liver were resected during the occlusion of the hepatoduodenal ligament for 20 minutes.Residual liver underwent the process of ischemia-reperfusion.Intermittent hypoxia preconditioning group (IHP group):rats were exposed to hypoxic environment of 10

  8. Association of Bax Expression and Bcl2/Bax Ratio with Clinical and Molecular Prognostic Markers in Chronic Lymphocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Vucicevic Ksenija

    2016-04-01

    Full Text Available Background: In chronic lymphocytic leukemia (CLL, in vivo apoptotic resistance of malignant B lymphocytes results, in part, from the intrinsic defects of their apoptotic machinery. These include genetic alterations and aberrant expression of many apoptosis regulators, among which the Bcl2 family members play a central role.

  9. ЕКСПРЕСІЯ BCL-2 ТА BAX У ГЛАДКОМ''ЯЗОВИХ ПУХЛИНАХ ТІЛА МАТКИ

    OpenAIRE

    Гончарова, Г.

    2011-01-01

    Некоторые типы лейомиом тела матки сложно отличить от лейомиоcарком, если использовать только рутинные морфологические методы диагностики. Мы исследовали операционный материал 10 пациенток с лейомиомами и 6 пациенток с лейомиосаркомами тела матки и определяли в нем уровень экспрессии bcl-2 и bax в дополнение к стандартной окраске гематоксилин-эозином микропрепаратов опухолевой ткани. Мы определили в большинстве, 8 из 10 лейомиом (80%), позитивную реакцию с bcl-2, в 2 из 10 (20%) была получена...

  10. 8周中等强度低负荷量训练对老龄雌性大鼠骨骼肌Bax和Bcl-2蛋白及SIRT1/SIRT3信号轴基因表达的影响%Effects of 8-week medium intensity low load training on proteins Bax and Bcl-2 and the gene expression of signal axis SIRT1/SIRT3 of skeletal muscle of aged female rats

    Institute of Scientific and Technical Information of China (English)

    李方晖; 肖琳; 覃飞; 刘承宜

    2014-01-01

    In order to observe the effects of 8-week medium intensity low load training on the levels of proteins Bax and Bcl-2 and the gene messenger RNA (mRNA) expression of axis sirtuin 1 (SIRT1)/sirtuin 3 (SIRT3) of gastrocne-mius of aged rats, the authors divided 16 18-month old female SD rats randomly into a control group and an exercise group, each of which contained 8 rats, let the rats in the exercise group do an aerobic exercise on a treadmill for con-secutive 8 weeks, at a speed of 15 km/h (with 60%~75%VO2max), 15 minutes a day, 5 days a week, let the rats in the control group live freely, in 24 hours after rat exercising at the end of week 8, killed the rats, measured gastrocnemius index, measured the levels of proteins Bax and Bcl-2 of gastrocnemius by means of Western blot analysis, measured the mRNA levels of SIRT3, SIRT1, manganese superoxide dismutase (MnSOD), Caspase 3, peroxisome prolifera-tor-activated receptor-γcoactivator-1 (PGC-1α), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF1) by means of RT-PCR, and revealed the following findings:as for the rats in the exercise group, their gastrocnemius mass and gastrocnemius index increased significantly (P<0.05 and P<0.01 respectively), their protein Bax level decreased significantly (P<0.05), their protein Bcl-2 level and Bcl-2/Bax ratio increased significantly (P<0.05);their mRNA levels of SIRT3, SIRT1, PGC-1α, NRF1, TFAM and MnSOD increased significantly (P<0.05), their mRNA level of Caspase-3 decreased significantly (P<0.05). The said findings indicated the followings:medium intensity low load training could delay the changing of muscle cell apoptosis signal of aged rats; the homeostatic mechanism mediated by axis SIRT1/SIRT3 played an important role in medium intensity low load training increasing the mitochondria refreshing rate and antioxidase level of skeletal muscle of aged rats.%观察8周中等强度低负荷量训练对老龄雌性大鼠腓肠肌Bax和Bcl-2

  11. Farnesyltransferase inhibitor tipifarnib inhibits Rheb prenylation and stabilizes Bax in acute myelogenous leukemia cells

    OpenAIRE

    Ding, Husheng; McDonald, Jennifer S.; Yun, Seongseok; Schneider, Paula A.; Peterson, Kevin L.; Flatten, Karen S.; Loegering, David A.; Ann L Oberg; Riska, Shaun M.; Huang, Shengbing; Sinicrope, Frank A.; Adjei, Alex A.; Judith E Karp; Meng, X. Wei; Kaufmann, Scott H.

    2014-01-01

    Although farnesyltransferase inhibitors have shown promising activity in relapsed lymphoma and sporadic activity in acute myelogenous leukemia, their mechanism of cytotoxicity is incompletely understood, making development of predictive biomarkers difficult. In the present study, we examined the action of tipifarnib in human acute myelogenous leukemia cell lines and clinical samples. In contrast to the Ras/MEK/ERK pathway-mediated Bim upregulation that is responsible for tipifarnib-induced ki...

  12. Enhancing Survival of Mouse Oocytes Following Chemotherapy or Aging by Targeting Bax and Rad51

    OpenAIRE

    Kujjo, Loro L.; Tiina Laine; Pereira, Ricardo J. G.; Wataru Kagawa; Hitoshi Kurumizaka; Shigeyuki Yokoyama; Perez, Gloria I.

    2010-01-01

    BACKGROUND: Therapeutic approaches to preserve fertility in females undergoing cancer treatments are currently ineffective. This is partly due to limited knowledge of the molecular mechanisms that injured germ cells elicit to repair damage and survive or to abort repair and activate biochemical pathways leading to death. So far, we know that following spontaneously occurring or drug-induced DNA damage, the efficiency of DNA repair is a critical determinant of the cell's fate. The protein enco...

  13. Upregulation of Bax and Bcl-2 following prenatal cocaine exposure induces apoptosis in fetal rat brain

    OpenAIRE

    Xiao, DaLiao; Zhang, Lubo

    2008-01-01

    Cocaine abuse during pregnancy has been associated with numerous adverse perinatal outcomes. Aims: The present study was to determine whether prenatal cocaine exposure induced apoptosis and the possible role of Bcl-2 family genes in the programming cell death in fetal rat brain. Main methods: Pregnant rats were treated with cocaine subcutaneously (30 & 60 mg/kg/day) from day 15 to 21 of gestation. Then the fetal and maternal brains were isolated. Key findings: Cocaine produced a dose-dependen...

  14. Upregulation of Bax and Bcl-2 following prenatal cocaine exposure induces apoptosis in fetal rat brain

    OpenAIRE

    DaLiao Xiao, Lubo Zhang

    2008-01-01

    Cocaine abuse during pregnancy has been associated with numerous adverse perinatal outcomes. Aims: The present study was to determine whether prenatal cocaine exposure induced apoptosis and the possible role of Bcl-2 family genes in the programming cell death in fetal rat brain. Main methods: Pregnant rats were treated with cocaine subcutaneously (30 & 60 mg/kg/day) from day 15 to 21 of gestation. Then the fetal and maternal brains were isolated. Key findings: Cocaine produced a dose-depe...

  15. Staphylococcus aureus Panton-Valentine leukocidin directly targets mitochondria and induces Bax-independent apoptosis of human neutrophils

    OpenAIRE

    Genestier, Anne-Laure; Michallet, Marie-Cécile; Prévost, Gilles; Bellot, Gregory; Chalabreysse, Lara; Peyrol, Simone; Thivolet, Françoise; Etienne, Jerome; Lina, Gérard; Vallette, François M.; Vandenesch, François; Genestier, Laurent

    2005-01-01

    Panton-Valentine leukocidin (PVL) is a pore-forming toxin secreted by Staphylococcus aureus that has recently been associated with necrotizing pneumonia. In the present study, we report that in vitro, PVL induces polymorphonuclear cell death by necrosis or by apoptosis, depending on the PVL concentration. PVL-induced apoptosis was associated with a rapid disruption of mitochondrial homeostasis and activation of caspase-9 and caspase-3, suggesting that PVL-induced apoptosis is preferentially m...

  16. Defect chemistry and transport properties of BaxCe0.85M0.15O3-d

    OpenAIRE

    Wu, J.; Li, L. P.; Espinosa, W. T. P.; Haile, S. M.

    2004-01-01

    The site-incorporation mechanism of M3+ dopants into A2+B4+O3 perovskites controls the overall defect chemistry and thus their transport properties. For charge-balance reasons, incorporation onto the A2+-site would require the creation of negatively charged point defects (such as cation vacancies), whereas incorporation onto the B4+-site is accompanied by the generation of positively charged defects, typically oxygen vacancies. Oxygen-vacancy content, in turn, is relevant to proton-conducting...

  17. High temperature thermoelectric properties of p-type skutterudites BaxYbyCo4-zFezSb12

    KAUST Repository

    Dong, Y.

    2012-01-01

    Several polycrystalline p-type skutterudites with compositions Ba xYb yCo 4-zFe zSb 12, with varying filler concentrations x and y, and z = 1 to 2, were synthesized by reacting the constituents and subsequent solid state annealing, followed by densification by hot-pressing. Their thermoelectric properties were evaluated from 300 to 820 K. The Yb filling fraction increased with Fe content while the amount of Fe substitution had little influence on the Ba filling fraction. High purity specimens were obtained when the Fe content was low. Bipolar conduction contributed to the thermal conductivity at elevated temperatures. A maximum ZT value of 0.7 was obtained at 750 K for the specimen with the highest Fe content and filling fraction. The potential for thermoelectric applications is also discussed. © 2012 American Institute of Physics.

  18. Probucol Attenuates Cyclophosphamide-induced Oxidative Apoptosis, p53 and Bax Signal Expression in Rat Cardiac Tissues

    OpenAIRE

    Asiri, Yousif A.

    2010-01-01

    Cyclophosphamide (CP) is a widely used drug in cancer chemotherapy and immunosuppression, which could cause toxicity of the normal cells due to its toxic metabolites. Probucol, a cholesterol-lowering drug, acts as potential inhibitor of DNA damage and shows to protect against doxorubicin-induced cardiomyopathy by enhancing the endogenous antioxidant system including glutathione peroxidase, catalase and superoxide dismutase. This study examined the possible protective effects of probucol, a li...

  19. Interaction of Insulin-like Growth Factor-binding Protein-3 and BAX in Mitochondria Promotes Male Germ Cell Apoptosis

    OpenAIRE

    Jia, Yue; Lee, Kuk-Wha; Swerdloff, Ronald; Hwang, David; Cobb, Laura J.; Sinha Hikim, Amiya; Lue, Yan He; Cohen, Pinchas; Wang, Christina

    2009-01-01

    Germ cell apoptosis is crucial for spermatogenesis and can be triggered by various stimuli, including intratesticular hormone deprivation. This study proposes a role for insulin-like growth factor binding protein-3 (IGFBP-3) in male germ cell apoptosis. Groups of adult Sprague-Dawley male rats received one of the following treatments for 5 days: (i) daily intratesticular (IT) injections with saline (control); (ii) a single subcutaneous injection of the gonadotropin-releasing hormone antagonis...

  20. Biphasic onset of splenic apoptosis following hemorrhagic shock : critical implications for Bax, Bcl-2, and Mcl-1 proteins

    OpenAIRE

    Hostmann, Arwed; Jasse, Kerstin; Schulze-Tanzil, Gundula; Robinson, Yohan; Oberholzer, Andreas; Ertel, Wolfgang; Tschoeke, Sven K

    2008-01-01

    INTRODUCTION: The innate immune response to trauma hemorrhage involves inflammatory mediators, thus promoting cellular dysfunction as well as cell death in diverse tissues. These effects ultimately bear the risk of post-traumatic complications such as organ dysfunction, multiple organ failure, or adult respiratory distress syndrome. In this study, a murine model of resuscitated hemorrhagic shock (HS) was used to determine the apoptosis in spleen as a marker of cellular injury and reduced immu...

  1. Hesperetin inhibit adipocyte differentiation and enhance Bax- and p21-mediated adipolysis in human mesenchymal stem cell adipogenesis.

    Science.gov (United States)

    Subash-Babu, Pandurangan; Alshatwi, Ali A

    2015-03-01

    We aimed to explore the antiadipogenic and adipolysis effect of hesperetin in human mesenchymal stem cells (hMSCs)-induced adipogenesis. IC50 value of hesperetin was higher for hMSCs such as 149.2 ± 13.2 μmol for 24 h and 89.4 ± 11.4 μmol in 48 h, whereas in preadipocytes was 87.6 ± 9.5 μmol and 72.4 ± 5.6 μmol in 24 h and 48 h, respectively. Hesperetin treatment (5, 10, and 20 μmol) to adipogenesis-induced hMSCs (Group 1) and preadipocytes (Group 2) resulted in a significantly (p p21 expression in Group 2 compared to untreated preadipocytes. hMSCs cultured in adipogenic medium along with hesperetin significantly inhibited adipocyte differentiation and increased the proapoptotic gene expression levels in preadipocyte. Our result indicates the antiadipogenic and adipolysis effects of hesperetin.

  2. XRF and SIMS/SNMS analyses of BaxSr1-xTiO3 dielectrics.

    Science.gov (United States)

    Breuer, U; Krumpen, W; Fitsilis, F

    2003-04-01

    The development of analytical tools and procedures for process control is a prerequisite for the integration of high permittivity and/or ferroelectric materials in CMOS devices. The thickness and composition of perovskite oxide films were determined by wavelength dispersive X-ray fluorescence analysis (XRF) with special emphasis on the ratio of the group-II elements to the Ti content, and a precision of 0.5% was achieved for a typical film thickness of 20-30 nm. Secondary ion mass spectrometry (SIMS) and sputtered neutrals mass spectrometry (SNMS) was used for depth profiling to determine film homogeneity and elemental interdiffusion at hetero-interfaces. Examples are given for Ba(x)Sr(1-x)TiO(3) and SrTiO(x) thin films which were grown in a prototype MOCVD production tool. No interdiffusion was observed for films grown at 600 degrees C on Pt electrodes in contrast to films grown directly on Si. PMID:12707759

  3. Accelerated apoptosis of lymphocytes by augmented induction of Bax in SSI-1 (STAT-induced STAT inhibitor-1) deficient mice

    OpenAIRE

    Naka, Tetsuji; Matsumoto, Tomoshige; Narazaki, Masashi; Fujimoto, Minoru; Morita, Yoshiaki; Ohsawa, Yoshiyuki; SAITO, HIROSHI; Nagasawa, Takashi; Uchiyama, Yasuo; Kishimoto, Tadamitsu

    1998-01-01

    Growth, differentiation, and programmed cell death (apoptosis) are mainly controlled by cytokines. The Janus kinase–signal transducers and activators of transcription (JAK-STAT) signal pathway is an important component of cytokine signaling. We have previously shown that STAT3 induces a molecule designated as SSI-1, which inhibits STAT3 functions. To clarify the physiological roles of SSI-1 in vivo, we generated, here, mice lacking SSI-1. These SSI-1−/− mice displayed growth retardation and d...

  4. Involvement of VDAC, Bax and ceramides in the efflux of AIF from mitochondria during curcumin-induced apoptosis.

    NARCIS (Netherlands)

    Scharstuhl, A.; Mutsaers, H.A.M.; Pennings, S.W.C.; Russel, F.G.M.; Wagener, F.A.D.T.G.

    2009-01-01

    BACKGROUND: We previously identified curcumin as a potent inducer of fibroblast apoptosis, which could be used to treat hypertrophic scar formation. Here we investigated the underlying mechanism of this process. PRINCIPAL FINDINGS: Curcumin-induced apoptosis could not be blocked by caspase-inhibitor

  5. The broccoli-born isothiocyanate sulforaphane impairs nucleotide excision repair: XPA as one potential target.

    Science.gov (United States)

    Piberger, Ann Liza; Köberle, Beate; Hartwig, Andrea

    2014-03-01

    The isothiocyanate sulforaphane (SFN), the major hydrolysis product of glucosinolates present in broccoli, has frequently been proposed to exert anticarcinogenic properties, mainly due to the induction of the nrf2/Keap1/ARE-signaling pathway. As potential underlying mechanism, a SFN-dependent zinc release from Keap1, the negative regulator of nrf2, has been described. This raises the question whether SFN is able to interfere with other zinc binding structures as well, for example those essential for DNA repair. Within this study, a SFN-induced deliberation of zinc from a synthesized peptide resembling the zinc binding domain of the xeroderma pigmentosum A (XPA) protein was observed starting at 50 μM SFN. Since XPA is absolutely required for nucleotide excision repair, the impact of SFN on the repair of (+)-anti-benzo[a]pyrene 7,8-diol-9,10-epoxide ((+)-anti-BPDE)-induced DNA adducts in HCT 116 cells was investigated. While preincubation with SFN did not affect initial lesion levels, a dose-dependent repair inhibition of (+)-anti-BPDE-induced DNA damage during the first 12 h after lesion induction was observed, starting at 1 μM SFN. In contrast, the later phase of DNA repair was not impaired by SFN. In support of an inactivation of XPA also in cells, SFN increased the (+)-anti-BPDE-induced cytotoxicity XPA dependently in XP12RO cells. Comparison of p53-proficient and p53-deficient cells revealed no difference in SFN-induced DNA repair inhibition, indicating that p53 is no cellular target of SFN. Since DNA repair processes are required to maintain DNA integrity, the presented data suggest a potential impairment of genomic stability by SFN.

  6. Over-expressed Genes Detected by Suppression Subtractive Hybridization in Carcinoma Derived From Transformed 16HBE Cells Induced by BPDE

    Institute of Scientific and Technical Information of China (English)

    SHE-JUAN AN; JIA-KUN CHEN; LI-LI LIU; YAN-FENG ZHAO; XUE-MIN CHEN

    2005-01-01

    Objective To screen the over differentially expressed genes in carcinoma induced by BPDE-transformed 16HBE cells (16HBE-C cells). Methods The suppression subtractive hybridization (SSH) method was performed to profile differentially expressed genes between 16HBE-C cells and 16HBE cells. The cDNA fragments of differentially expressed genes were inserted into TA cloning vector and transformed competent E. coli strain. Positive clones were randomly picked up and identified by the colony PCR method. Dot blot was used to test the same source with the tester. The differentially expressed cDNA fragments were sequenced and compared with known genes and EST database in Genbank. Results Eight known genes were over-expressed in 16HBE-C cells including eukaryotic translation elongation factor 1 alpha 1, HIF-1 responsive RTP801, ribosomal protein L10 (RPL10), ribosomal protein S29 (RPS29), mitochondrion related genes, and laminin receptor 1. Three differentially expressed cDNA fragments could not be matched to the known genes but to the EST database. Conclusion The SSH method can detect differentially expressed genes between 16HBE-C and 16HBE cells. BPDE-induced carcinogenesis may be related to alteration of at least eight known genes and three unknown genes. These expression data provide a clue to further cloning novel genes and studying functions in BPDE-induced carcinoma.

  7. Inhibition of Nuclear Factor-kappa B or Bax Prevents Endoplasmic Reticulum Stress-But Not Nitric Oxide-Mediated Apoptosis in INS-1E Cells

    DEFF Research Database (Denmark)

    Tonnesen, M.F.; Grunnet, L.G.; Friberg, J.;

    2009-01-01

    Accumulating evidence suggests that endoplasmic reticulum ( ER) stress by mechanisms that include ER Ca2+ depletion via NO-dependent down-regulation of sarcoendoplasmic reticulum Ca2+ ATPase 2b (SERCA2b) contributes to beta-cell death in type 1 diabetes. To clarify whether the molecular pathways ...

  8. Recombinant human erythropoietin suppresses endothelial cell apoptosis and reduces the ratio of Bax to Bcl-2 proteins in the aortas of apolipoprotein E-deficient mice

    OpenAIRE

    Warren, Jeffrey S.; Zhao, Ying; Yung, Raymond; Desai, Anjali

    2011-01-01

    Recent clinical trials have raised concern that therapy with recombinant human erythropoietin (EPO) may increase cardiovascular disease risk, event rate, and mortality. Endothelial cell (EC) apoptosis has been implicated in both atherogenesis as well as in the destabilization and rupture of atheromatous plaques.

  9. THE EXPRESSION OF BCL-2, BAX AND CASPASE-3 IN NEURON OF THE SPINAL CORD ANTERIOR HORN AFTER CAUDA EQUINA ACUTE COMPRESSION

    Institute of Scientific and Technical Information of China (English)

    王栋; 王展; 李浩鹏; 贺西京

    2006-01-01

    Cauda equina syndrome(CES)is common inclinic,and acute CES are difficult to recover.So,it s very i mportant to i mprove the treat ment ofCES.The study of nerve was turned fromthe si m-ple nerve shift injury research to the neuron changeafter the axon injury.Peripheral nerve injury cancause their central neuron apoptosis was confir medby experi ment,but rare report was observed withthe motor neuron change after the cauda equina in-jury.The present studies want to set the acute CESani mal model and observe th...

  10. A levedura como modelo para o estudo da regulação de Bax por isoformas da proteína cinase C

    OpenAIRE

    Silva, Rui Filipe Duarte da

    2011-01-01

    Tese de doutoramento em Ciências Programmed cell death (PCD), of which apoptosis is the most common morphological expression, is an orchestrated collapse of the cell resulting from the activation of a widely described cascade of molecular events. Due to the importance of this process in tissue homeostasis and development of multicellular organisms, its deregulation is associated with several disorders, including cancer and neurodegenerative diseases. A crucial event in mamma...

  11. Bax和TGFβRⅡ基因在肺癌组织中的移码突变%Bax and TGFβRⅡ frameshift mutations in lung cancer

    Institute of Scientific and Technical Information of China (English)

    陈国安; 刘天菊; 张伟; 李申德; 杨德昌; 孙燕

    2000-01-01

    目的探讨Bax和TGFβRⅡ基因在肺癌组织中的移码突变及其与微卫星改变的关系.方法用PCR-变性聚丙烯酰胺凝胶电泳-银染法,检测50例肺癌组织Bax和TGFβRⅡ基因移码突变及微卫星改变.结果 Bax基因(G)8移码突变12例,占24%(12/50),主要是碱基丢失.TGFβRⅡ的(A)10未发现移码突变.Bax移码突变与微卫星不稳定和/或杂合性缺失有密切关系(P<0.05).结论肺癌组织中存在Bax基因移码突变且与微卫星改变密切相关,它们在肺癌发病中可能有一定作用.

  12. Effect of PAMd on proteins expression of Bax and Bcl-2 of nerve cells in the brain tissue of ischemia-reperfusion mice

    Institute of Scientific and Technical Information of China (English)

    GUOLianjun; LVQing; QULing

    2004-01-01

    AIM : To study the effects of PAMd ( Phenolic alkaloids from Menispermum dauricum on Brain ischemia and ischemic reperfusion injury in mice. METHODS : Bilateral carotid arteries of mice were ligated and 0. 3ml blood was letted from post-eyeball venous jungle, one hour later the carotid arteries were loosed. After cerebral ischemia-reperfusion, mice

  13. Multiple Doses of Erythropoietin Impair Liver Regeneration by Increasing TNF-α, the Bax to Bcl-xL Ratio and Apoptotic Cell Death

    OpenAIRE

    Katja Klemm; Christian Eipel; Daniel Cantré; Kerstin Abshagen; Menger, Michael D.; Brigitte Vollmar

    2008-01-01

    BACKGROUND: Liver resection and the use of small-for-size grafts are restricted by the necessity to provide a sufficient amount of functional liver mass. Only few promising strategies to maximize liver regeneration are available. Apart from its erythropoiesis-stimulating effect, erythropoietin (EPO) has meanwhile been recognized as mitogenic, tissue-protective, and anti-apoptotic pleiotropic cytokine. Thus, EPO may support regeneration of hepatic tissue. METHODOLOGY: Rats undergoing 68% hepat...

  14. Spin-orbit Coupling Induced Magnetism in the d-density Wave Phase of La2-xBaxCuO4 Superconductors

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Congjun; /Stanford U., Phys. Dept. /Santa Barbara, KITP; Zaanen, Jan; Zhang, Shou-Cheng; /Stanford U., Phys. Dept.

    2010-01-15

    We study the effects of spin-orbit coupling in the d-density wave (DDW) phase. In the low-temperature orthorhombic phase of La{sub 2-x}Ba{sub x}CuO{sub 4}, we find that spin-orbit coupling induces ferromagnetic moments in the DDW phase, which are polarized along the [110] direction with a considerable magnitude. This effect does not exist in the superconducting phase. On the other hand, if the d-density wave order does not exist at zero field, a magnetic field along the [110] direction always induces such a staggered orbital current. We discuss experimental constraints on the DDW states in light of our theoretical predictions.

  15. Effects of human interleukin 10 gene transfer on the expression of Bcl-2 Bax and apoptosis of hepatocyte in rats with acute hemorrhagic necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    GU Jun-chao; WANG Yu; ZHANG Zhong-tao; XUE Jian-guo; LI Jian-she; ZHOU Yan-zhong

    2005-01-01

    @@ Acute necrotising pancreatitis is characterized by inflammatory and necrotic events, which follow the initial intra-acinar injury involving enzyme activation, and disruption of the acinar cytoskeleton.1 At present, apoptosis has become a hot topic in many kinds of disease.

  16. Caspase-3和bax在视网膜母细胞瘤中的表达%Expression of caspase-3 and bax gene protein in retinoblastoma

    Institute of Scientific and Technical Information of China (English)

    孙红; 惠延年; 王立勤; 马吉献

    2003-01-01

    目的: 观察凋亡及凋亡调控基因caspase-3/bax在视网膜母细胞瘤(retinoblastoma, RB)中的表达及与凋亡的相关性. 方法: 收集35例RB标本,对其分别进行caspase-3和bax免疫组织化学染色,观察表达情况及染色强度. 结果: Caspase-3及bax在未分化型(n=15)分别有较好的表达(11/12例),caspase-3及bax在分化型(n=20)中也有较好的表达(17/18例). 正常视网膜组织中无caspase-3及bax的表达. 结论: 凋亡在RB中是存在的,caspase-3及bax在RB的发生发展中起重要作用.

  17. Inhibition of nuclear factor-kappaB or Bax prevents endoplasmic reticulum stress- but not nitric oxide-mediated apoptosis in INS-1E cells

    DEFF Research Database (Denmark)

    Tonnesen, Morten F; Grunnet, Lars G; Friberg, Josefine;

    2009-01-01

    Accumulating evidence suggests that endoplasmic reticulum (ER) stress by mechanisms that include ER Ca(2+) depletion via NO-dependent down-regulation of sarcoendoplasmic reticulum Ca(2+) ATPase 2b (SERCA2b) contributes to beta-cell death in type 1 diabetes. To clarify whether the molecular pathwa...

  18. Effects of Exercise Pre-Conditioning on Hippocampus Expression of Bcl-2 and Bax Protein and Apoptosis Following Ischemia/Reperfusion Injury in Male Rats

    OpenAIRE

    Nabi Shamsaei; Hamid Rajabi; Nahid Aboutaleb; Farnaz Nikbakht; Pezhman Motamedi; Mehdi Khaksari; Sohaila Erfani

    2015-01-01

    Introduction: Cerebral ischemia/reperfusion leads to loss of vulnerable neurons by apoptosis in specific brain regions specially in the hippocampus. There is some evidence indicating that the neuroprotective effects of physical activity on the brain. Therefore,the main purpose of this study was to investigate the effect of exercise pre-conditioning on apoptosis-related proteins expression in hippocampal CA1 neurons after induction of ischemia. Methods: 21 Male rats weighing 260-300g were ...

  19. Resveratrol Reverses Cadmium Chloride-induced Testicular Damage and Subfertility by Downregulating p53 and Bax and Upregulating Gonadotropins and Bcl-2 gene Expression

    OpenAIRE

    Eleawa, Samy M.; ALKHATEEB, Mahmoud A; ALHASHEM, Fahaid H; BIN-JALIAH, Ismaeel; SAKR, Hussein F; ELREFAEY, Hesham M; ELKARIB, Abbas O; ALESSA, Riyad M; HAIDARA, Mohammad A; Shatoor, Abdullah S.; KHALIL, Mohammad A

    2014-01-01

    This study was performed to investigate the protective and therapeutic effects of resveratrol (RES) against CdCl2-induced toxicity in rat testes. Seven experimental groups of adult male rats were formulated as follows: A) controls+NS, B) control+vehicle (saline solution of hydroxypropyl cyclodextrin), C) RES treated, D) CdCl2+NS, E) CdCl2+vehicle, F) RES followed by CdCl2 and M) CdCl2 followed by RES. At the end of the protocol, serum levels of FSH, LH and testosterone were measured in all gr...

  20. BAX-mediated cell death affects early germ cell loss and incidence of testicular teratomas in Dnd1Ter/Ter mice

    OpenAIRE

    Cook, Matthew S; Coveney, Douglas; Batchvarov, Iordan; Nadeau, Joseph H.; Capel, Blanche

    2009-01-01

    A homozygous nonsense mutation (Ter) in murine Dnd1 (Dnd1Ter/Ter) results in a significant early loss of primordial germ cells (PGCs) prior to colonization of the gonad in both sexes and all genetic backgrounds tested. The same mutation also leads to testicular teratomas only on the 129Sv/J background. Male mutants on other genetic backgrounds ultimately lose all PGCs with no incidence of teratoma formation. It is not clear how these PGCs are lost or what factors directly control the strain-s...

  1. Inhibition of constitutively activated Stat3 correlates with altered Bcl-2/Bax expression and induction of apoptosis in mycosis fungoides tumor cells

    DEFF Research Database (Denmark)

    Nielsen, M; Kaestel, C G; Eriksen, K W;

    1999-01-01

    in malignant transformation. In a previous study, we found constitutively tyrosine phosphorylated Stat3 in mycosis fungoides tumor cells. Here, we show that the Jak kinase inhibitor, Ag490, inhibits the constitutive binding of Stat3 to an oligonucleotide representing the Stat-binding sequence from the ICAM...

  2. Nimbolide Sensitizes Human Colon Cancer Cells to TRAIL through Reactive Oxygen Species- and ERK-dependent Up-regulation of Death Receptors, p53, and Bax*

    OpenAIRE

    Gupta, Subash C.; Reuter, Simone; Phromnoi, Kanokkarn; Park, Byoungduck; Hema, Padmanabhan S.; Nair, Mangalam; Aggarwal, Bharat B.

    2010-01-01

    TNF-related apoptosis-inducing ligand (TRAIL) shows promise as a cancer treatment, but acquired tumor resistance to TRAIL is a roadblock. Here we investigated whether nimbolide, a limonoid, could sensitize human colon cancer cells to TRAIL. As indicated by assays that measure esterase activity, sub-G1 fractions, mitochondrial activity, and activation of caspases, nimbolide potentiated the effect of TRAIL. This limonoid also enhanced expression of death receptors (DRs) DR5 and DR4 in cancer ce...

  3. Effect of Jiangru Power on the Expression of Bcl-2 and Bax in Rat Prolactinoma%中药降乳散对大鼠催乳素瘤细胞表达Bcl-2、Bax的影响

    Institute of Scientific and Technical Information of China (English)

    徐春; 邱文娟; 付淑云; 徐立红

    2009-01-01

    体质量,血清催乳素水平均明显低于雌激素组,具有显著差别(P<0.01).Bax在降乳散组的表达量明显高于雌激素组(P<0.01).Bcl-2在降乳散组的表达量明显低于雌激素组(P<0.01).结论 中药降乳散具有促进催乳素瘤细胞凋亡的作用.本实验从分子水平探讨了中药抗催乳素瘤的机制,为中药治疗催乳素瘤提供了理论基础.

  4. Bcl-2、Bax在慢性高眼压大鼠视网膜的表达%The expression of Bcl-2 and Bax in chronic glaucom model rat retina

    Institute of Scientific and Technical Information of China (English)

    强晓鑫; 侯力华; 马雅玲; 付金东; 何利东

    2011-01-01

    目的 探讨Bcl-2、Bax在慢性高眼压大鼠视网膜的表达,以及与慢性高眼压大鼠视网膜损伤的关系.方法 健康成年SD大鼠20只,分为正常组和实验组,每组各10只.实验组烙闭大鼠巩膜上静脉制作慢性高眼压模型,造模2个月后,通过HE染色观察视网膜神经节细胞丢失情况,用免疫组织化学法检测视网膜中Bcl-2、bax的表达.结果 光镜下观察实验组较正常组神经节细胞数量减少(P<0.05).Bcl-2蛋白在正常组及实验组大鼠视网膜上均有阳性表达,位于神经节细胞层及内核层,实验组较正常组Bcl-2表达程度有增高,差异有统计学意义(P<0.05).正常组大鼠视网膜中Bax蛋白在神经节细胞层有弱阳性表达,实验组Bax蛋白表达位于神经节细胞层和内核层,表达程度明显增强,与正常组比较差异有统计学意义(P<0.05).结论 Bcl-2及Bax的表达失衡可能是慢性高眼压视网膜神经节细胞凋亡的原因之一.

  5. Properties and performance of BaxSr1−xCo0.8Fe0.2O3−δ materials for oxygen transport membranes

    NARCIS (Netherlands)

    Vente, Jaap F.; McIntosh, Steven; Haije, Wim G.; Bouwmeester, Henny J.M.

    2006-01-01

    The present paper discusses the oxygen transport properties, oxygen stoichiometry, phase stability, and chemical and mechanical stability of the perovskites $${\\text{Ba}}_{{0.5}} {\\text{Sr}}_{{0.5}} {\\text{Co}}_{{0.8}} {\\text{Fe}}_{{0.2}} {\\text{O}}_{{3 - \\delta }} $$ (BSCF) and $${\\text{SrCo}}_{{0.

  6. Influence of Bax on apoptosis and drug sensitivity of HCC-9204 cells%Bax对HCC-9204细胞系的凋亡及化疗敏感性的影响

    Institute of Scientific and Technical Information of China (English)

    郑建勇; 杨广顺; 王为忠; 李江; 李开宗; 管文贤; 王文亮

    2005-01-01

    目的研究Bax对HCC-9204细胞系凋亡和对阿霉素敏感性的影响.方法采用脂质体转染法将Bax基因转入HCC-9204细胞中.免疫组织化学分析Bax在HCC-9204细胞中的表达,TUNEL及细胞周期分析细胞凋亡, MTT实验判断肿瘤细胞的活力.结果免疫组化结果显示转染Bax基因的HCC-9204/Bax细胞的Bax表达显著增加.TUNEL检测显示,HCC-9204/Bax细胞的凋亡指数在ZnSO4诱导后24、48h明显增加(3.6±5.3 vs 27.2±10.5,t=63.45,P<0.05;4.2±4.1 vs 32.3±8.6,t=93.27;P<0.05),流式细胞仪分析显示,诱导后48h出现显著的"亚二倍体峰".MTT实验显示 Bax基因的过表达能够降低阿霉素处理后的细胞活力,呈时间依赖性.结论 Bax基因不仅可以诱导HCC-9204细胞的凋亡,而且能够增加HCC-9204细胞对阿霉素杀伤作用的敏感性.

  7. Evolution of the crystalline structure in (Bi{sub 0}.5Na{sub 0}.5){sub 1}-xBaxTiO{sub 3} thin films around the Morpho tropic Phase Boundary

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Mezcua, D.; Calzada, M. L.; Bretos, I.; Ricote, J.; Chateigner, D.; Escobar-Galindo, R.; Jimenez, R.; Sirera, R.

    2014-02-01

    (Bi{sub 0}.5Na{sub 0}.5){sub 1}-xBa{sub x}TiO{sub 3} (BNBT), which exhibits compositions for the morphotropic phase boundary (MPB) where exist an intimate coexistence of the rhombohedral and tetragonal structures, is being considered as promising lead-free alternative to the well known Pb(Zr{sub x},Ti{sub 1}-x)O{sub 3} (PZT). In this work, BNBT thin films were fabricated by chemical solution deposition (CSD) with a wide range of compositions (x{approx}{approx}0.050-0.150) onto Pt/TiO{sub 2}/SiO{sub 2}/(100)Si substrates. Structural studies by X-ray diffraction ({lambda}Cu{approx}1.5406 A) using a four-circle goniometer were carried out to determine the crystalline structure of the films. Rietveld analysis of the experimental X-ray patterns showed different volume fractions of the rhombohedral and tetragonal phases as a function of the Ba{sup 2}+ content and the coexistence of both phases, characteristic of a MPB region, for x{approx}­0.055-0.080. Finally, Rutherford backscattering experiments (RBS) were performed to determine the compositional profile of the films. This study revealed a homogenous composition of the BNBT films with abrupt film/substrate interfaces. (Author)

  8. 视网膜母细胞瘤Bcl-2和Bax基因蛋白质表达%Expression of Bcl-2 and Bax gene protein in retinoblastoma

    Institute of Scientific and Technical Information of China (English)

    张小猛; 庞利民; 张晓光

    2000-01-01

    目的:研究凋亡及凋亡调控基因Bcl-2/Bax和视网膜母细胞瘤(Retinoblastoma,RB)的发生、发展及退化的关系.方法:收集36例RB标本,对其分别进行Bcl-2和Bax基因的蛋白质免疫组织化学染色.对其表达情况和染色强度进行观察.结果:①Bcl-2在分化型RB中表达比较好;②Bax在未分化型和分化型中表达都比较好.结论:①分化型和未分化型RB中都有Bcl-2/Bax基因蛋白表达;②随RB恶性度的增加,Bcl-2的表达逐渐减弱;Bax的表达无明显改变.③分化型RB受Bcl-2和Bax基因共同控制;未分化型RB受Bax基因调控,Bcl-2基因发挥很少的作用.

  9. Non-secreted clusterin isoforms are translated in rare amounts from distinct human mRNA variants and do not affect Bax-mediated apoptosis or the NF-κB signaling pathway.

    Directory of Open Access Journals (Sweden)

    Hans Prochnow

    Full Text Available Clusterin, also known as apolipoprotein J, is expressed from a variety of tissues and implicated in pathological disorders such as neurodegenerative diseases, ischemia and cancer. In contrast to secretory clusterin (sCLU, which acts as an extracellular chaperone, the synthesis, subcellular localization and function(s of intracellular CLU isoforms is currently a matter of intense discussion. By investigating human CLU mRNAs we here unravel mechanisms leading to the synthesis of distinct CLU protein isoforms and analyze their subcellular localization and their impact on apoptosis and on NF-κB-activity. Quantitative PCR-analyses revealed the expression of four different stress-inducible CLU mRNA variants in non-cancer and cancer cell lines. In all cell lines variant 1 represents the most abundant mRNA, whereas all other variants collectively account for no more than 0.34% of total CLU mRNA, even under stressed conditions. Overexpression of CLU cDNAs combined with in vitro mutagenesis revealed distinct translational start sites including a so far uncharacterized non-canonical CUG start codon. We show that all exon 2-containing mRNAs encode sCLU and at least three non-glycosylated intracellular isoforms, CLU1‑449, CLU21‑449 and CLU34‑449, which all reside in the cytosol of unstressed and stressed HEK‑293 cells. The latter is the only form expressed from an alternatively spliced mRNA variant lacking exon 2. Functional analysis revealed that none of these cytosolic CLU forms modulate caspase-mediated intrinsic apoptosis or significantly affects TNF-α-induced NF-κB-activity. Therefore our data challenge some of the current ideas regarding the physiological functions of CLU isoforms in pathologies.

  10. Inclusion Complex of Zerumbone with Hydroxypropyl- β -Cyclodextrin Induces Apoptosis in Liver Hepatocellular HepG2 Cells via Caspase 8/BID Cleavage Switch and Modulating Bcl2/Bax Ratio

    OpenAIRE

    Nabilah Muhammad Nadzri; Ahmad Bustamam Abdul; Mohd Aspollah Sukari; Siddig Ibrahim Abdelwahab; Eid, Eltayeb E. M.; Syam Mohan; Behnam Kamalidehghan; Theebaa Anasamy; Kuan Beng Ng; Suvitha Syam; Ismail Adam Arbab; Heshu Sulaiman Rahman; Hapipah Mohd Ali

    2013-01-01

    Zerumbone (ZER) isolated from Zingiber zerumbet was previously encapsulated with hydroxypropyl- β -cyclodextrin (HP β CD) to enhance ZER's solubility in water, thus making it highly tolerable in the human body. The anticancer effects of this new ZER-HP β CD inclusion complex via apoptosis cell death were assessed in this study for the first time in liver hepatocellular cells, HepG2. Apoptosis was ascertained by morphological study, nuclear stain, and sub-G1 cell population accumulation with G...

  11. Inclusion Complex of Zerumbone with Hydroxypropyl-β-Cyclodextrin Induces Apoptosis in Liver Hepatocellular HepG2 Cells via Caspase 8/BID Cleavage Switch and Modulating Bcl2/Bax Ratio

    Directory of Open Access Journals (Sweden)

    Nabilah Muhammad Nadzri

    2013-01-01

    Full Text Available Zerumbone (ZER isolated from Zingiber zerumbet was previously encapsulated with hydroxypropyl-β-cyclodextrin (HPβCD to enhance ZER’s solubility in water, thus making it highly tolerable in the human body. The anticancer effects of this new ZER-HPβCD inclusion complex via apoptosis cell death were assessed in this study for the first time in liver hepatocellular cells, HepG2. Apoptosis was ascertained by morphological study, nuclear stain, and sub-G1 cell population accumulation with G2/M arrest. Further investigations showed the release of cytochrome c and loss of mitochondrial membrane potential, proving mitochondrial dysfunction upon the ZER-HPβCD treatment as well as modulating proapoptotic and anti-apototic Bcl-2 family members. A significant increase in caspase 3/7, caspase 9, and caspase 8 was detected with the depletion of BID cleaved by caspase 8. Collectively, these results prove that a highly soluble inclusion complex of ZER-HPβCD could be a promising anticancer agent for the treatment of hepatocellular carcinoma in humans.

  12. Effect of Cnidium Lactone on Serum Mutant P53 and BCL-2/BAX Expression in Human Prostate Cancer Cells PC-3 Tumor-Bearing BALB/C Nude Mouse Model

    OpenAIRE

    Bi, Dongbin; Yang, Mingshan; Zhao, Xia; Huang, Shiming

    2015-01-01

    Background Cnidium lactone is a natural coumarin compound that can inhibit a variety of cancer cell proliferation and induce cancer cell apoptosis. This experiment investigated the effect of cnidium lactone on molecular marker expression in prostate cancer nude mice to study its effect in inducing apoptosis. Material/Methods We randomly and equally divided 30 male BALB/C nude mice inoculated with human prostate cancer cells PC-3 into a negative control group, a cyclophosphamide group (500 mg/...

  13. Protective Effects of Scutellarin on Type II Diabetes Mellitus-Induced Testicular Damages Related to Reactive Oxygen Species/Bcl-2/Bax and Reactive Oxygen Species/Microcirculation/Staving Pathway in Diabetic Rat

    OpenAIRE

    Long, Lingli; Wang, Jingnan; Lu, Xiaofang; Xu, Yuxia; Zheng, Shuhui; Luo, Canqiao; Li, Yubin

    2015-01-01

    The goal of our study is to evaluate the effect of Scutellarin on type II diabetes-induced testicular disorder and show the mechanism of Scutellarin's action. We used streptozotocin and high-fat diet to establish type II diabetic rat model. TUNEL and haematoxylin and eosin staining were used to evaluate the testicular apoptotic cells and morphologic changes. Immunohistochemical staining was used to measure the expression level of vascular endothelial growth factor and blood vessel density in ...

  14. Protective Effects of Scutellarin on Type II Diabetes Mellitus-Induced Testicular Damages Related to Reactive Oxygen Species/Bcl-2/Bax and Reactive Oxygen Species/Microcirculation/Staving Pathway in Diabetic Rat

    OpenAIRE

    Lingli Long; Jingnan Wang; Xiaofang Lu; Yuxia Xu; Shuhui Zheng; Canqiao Luo; Yubin Li

    2015-01-01

    The goal of our study is to evaluate the effect of Scutellarin on type II diabetes-induced testicular disorder and show the mechanism of Scutellarin’s action. We used streptozotocin and high-fat diet to establish type II diabetic rat model. TUNEL and haematoxylin and eosin staining were used to evaluate the testicular apoptotic cells and morphologic changes. Immunohistochemical staining was used to measure the expression level of vascular endothelial growth factor and blood vessel density in ...

  15. Expression and significance of β-catenin,Bcl-2 and Bax in basal cell carcinoma%β-catenin和Bcl-2、Bax蛋白在皮肤基底细胞癌中的表达和意义

    Institute of Scientific and Technical Information of China (English)

    黄卡特; 吕明芬; 徐云升; 邹炳辉

    2010-01-01

    目的:探讨皮肤基底细胞癌(basal cell carcinoma,BCC)中β-catenin和Bcl-2、Bax蛋白的表达与BCC发生发展的关系.方法:采用免疫组化方法检测BCC组织切片中β-catenin和Bcl -2、Bax蛋白的表达.结果:48例BCC标本中β-catenin蛋白的异常表达率为91.67%,Bcl -2、Bax蛋白的表达率分别为89.58%、62.5%,且Bcl-2与Bax蛋白的表达呈负相关.结论:β-catenin和Bcl-2、Bax蛋白的异常表达在BCC的发生、发展中起重要作用.

  16. Abnormal expression of c-Myc in human bronchial epithelial cells malignantly transformed by anti-BPDE

    Institute of Scientific and Technical Information of China (English)

    Juan FU; Yiguo JIANG; Xuemin CHEN

    2008-01-01

    Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (anti-BPDE) is a metabolite of benzo[a]pyrene (B[a] P) and acts as a potent mutagen in mammalian systems. However, molecular mechanisms related to anti-BPDE-induced carcinogenesis are poorly understood. Here, we investigated the expression of proto-oncogene c-myc in human bronchial epithelial cells (16H BE-T) transformed by exposure to anti-BPDE. The levels ofmRNA and pro-tein of c-M yc were examined in the 16HBE-T and vehicle-treated control cells (16HBE-N) by using different meth-ods respectively, including reverse transcriptase-polymer-ase chain reaction (RT-PCR), quantitative real-time PCR (Q-PCR), western blot and immunocytochemical meth-ods. The level of c-myc mRNA appeared to be signifi-cantly increased in 16HBE-T, as compared with those of the 16H BE-N. Likewise, the expression of c-Myc protein was significantly enhanced as compared with those of the control cells. Moreover, the localization of c-Myc protein shows mainly nuclear staining in 16HBE-T. In conclu-sion, the abnormal expression of c-Myc was present in anti-BPDE malignantly transformed 16HBE cells, which may be involved in the carcinogenesis molecular mech-anism of anti-BPDE.

  17. DNA repair in human bronchial epithelial cells

    International Nuclear Information System (INIS)

    The purpose of this investigation was to compare the response of human cell types (bronchial epithelial cells and fibroblasts and skin fibroblasts) to various DNA damaging agents. Repair of DNA single strand breaks (SSB) induced by 5 krads of X-ray was similar for all cell types; approximately 90% of the DNA SSB were rejoined within one hour. During excision repair of DNA damage from u.v.-radiation, the frequencies of DNA SSB as estimated by the alkaline elution technique, were similar in all cell types. Repair replication as measured by BND cellulose chromatography was also similar in epithelial and fibroblastic cells after u.v.-irradiation. Similar levels of SSB were also observed in epithelial and fibroblastic cells after exposure to chemical carcinogens: 7,12-dimethylbenz[a]anthracene; benzo[a]pyrene diol epoxide (BPDE); or N-methyl-N-nitro-N-nitrosoguanidine. Significant repair replication of BPDE-induced DNA damage was detected in both bronchial epithelial and fibroblastic cells, although the level in fibroblasts was approximately 40% of that in epithelial cells. The pulmonary carcinogen asbestos did not damage DNA. DNA-protein crosslinks induced by formaldehyde were rapidly removed in bronchial cells. Further, epithelial and fibroblastic cells, which were incubated with formaldehyde and the polymerase inhibitor combination of cytosine arabinoside and hydroxyurea, accumulated DNA SSB at approximately equal frequencies. These results should provide a useful background for further investigations of the response of human bronchial cells to various DNA damaging agents

  18. Expression of Apoptosis Related Protein in Skin Lesions of Lichen Planus and Its Implication

    Institute of Scientific and Technical Information of China (English)

    Xu'e CHEN; Yan WU; Jiawen LI; Zhixiang LIU; Qing YUE; Houjun LIU

    2008-01-01

    In order to investigate the role of Caspase-3 and Bax in the pathogenesis of lichen planus, immunohistochemistry was used to detect the expression of Caspase-3 and Bax in skin lesions of the patients with lichen planus and skin tissues of normal subjects. The results showed that positive rate of Caspase-3 and Bax expression in lichen planus were significantly higher than that in normal skins (both P<0.05). Meanwhile, there was a obvious correlation between the increase of Caspase-3 and that of Bax in lichen planus. The expression of Caspase-3 and Bax might play an important role in the development of lichen planus.

  19. DNA repair capacity of cultured human lymphocytes exposed to mutagens measured by the comet assay and array expression analysis.

    Science.gov (United States)

    Bausinger, Julia; Speit, Günter

    2015-11-01

    Repair of mutagen-induced DNA lesions during transportation, storage and cultivation of lymphocytes may have a significant impact on results obtained in human biomonitoring after occupational and environmental exposure of human populations to genotoxic chemicals. Using the comet assay in combination with the repair inhibitor aphidicolin and array gene expression analysis of 92 DNA repair genes, we investigated the repair of DNA lesions induced by methyl methanesulfonate (MMS) and benzo[a]pyrenediolepoxide (BPDE) in phytohaemagglutinin (PHA)-stimulated cultured human lymphocytes in the time segment before replication. The comet assay indicated fast repair of MMS-induced damage during the first hours of cultivation. In contrast, removal of BPDE-induced lesions was slower and significant amounts of damage seem to persist until S-phase. Gene expression analysis revealed that PHA stimulation had a clear effect on gene regulation in lymphocytes already during the first 18h of cultivation. Under the conditions of this study, genotoxic concentrations of MMS did not induce significant changes in gene expression. In contrast, exposure to BPDE led to altered expression of several genes in a time- and concentration-related manner. Of the significantly up-regulated genes, only two genes (XPA and XPC) were directly related to nucleotide excision repair. Our results suggest that PHA stimulation of human lymphocytes influences the expression of DNA repair genes in human lymphocytes. The effect of induced DNA damage on gene expression is comparatively low and depends on the mutagens used. PHA-stimulated lymphocytes repair induced DNA damage before they start to replicate but the repair activity during the first 18h of cultivation is not affected by changes in the expression of DNA repair genes during this period of time.

  20. DNA-protective effects of sumach (Rhus coriaria L.), a common spice: Results of human and animal studies

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Asima; Ferk, Franziska; Simic, Tatjana [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria); Brantner, Adelheid [Institute of Pharmacognosy, University of Graz, Universitaetsplatz 4/I, A-8010 Graz (Austria); Dusinska, Maria [Center for Ecological Economics, Norwegian Institute for Air Research, Instituttveien 18, NO-2027 Kjeller (Norway); Kundi, Michael [Institute of Environmental Health, Center for Public Health, Medical Unviversity of Vienna (Austria); Hoelzl, Christine; Nersesyan, Armen [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria); Knasmueller, Siegfried [Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkegasse 8a, A-1090 Vienna (Austria)], E-mail: siegfried.knasmueller@meduniwien.ac.at

    2009-02-10

    Sumach (Rhus coriaria L.) is widely used as a spice. The aim of this study was the investigation of its DNA-protective effects in humans and animals. Prevention of the formation of strand breaks and oxidized DNA bases as well as the protection against H{sub 2}O{sub 2}- and ({+-})-anti-benzo[a]pyrene-7,8-dihydro-diol-9,10-epoxide (BPDE)-induced DNA-damage were monitored in human lymphocytes in a placebo controlled trial (N = 8/group) with ethanolic extract of sumach (3.0 g/day, 3 days) in single cell gel electrophoresis assays. Furthermore, DNA-protective effects of sumach were monitored in different inner organs of rats under identical conditions. No alteration of DNA-migration was detectable in human lymphocytes under standard conditions, but a decrease of the tail-lengths due to formation of oxidized purines and pyrimidines (52% and 36%) was found with lesion-specific enzymes. Also damage caused by H{sub 2}O{sub 2} and BPDE was significantly reduced by 30% and 69%, respectively. The later effect may be due to induction of glutathione S-transferase (GST). After the intervention, the overall GST (CDNB) activity in plasma was increased by 40%, GST-{alpha} by 52% and GST-{pi} by 26% (ELISA). The antioxidant effects of extract are probably due to scavenging which was observed in in vitro experiments, which also indicated that gallic acid is the active principle of sumach. The animal experiments showed that sumach also causes protection in inner organs. Supplementation of the drinking water (0.02 g/kg per animal) decreased the formation of oxidized DNA bases in colon, liver, lung and lymphocytes; also after {gamma}-irradiation pronounced effects were seen.

  1. Benzo[a]pyrene diol epoxide suppresses retinoic acid receptor-β2 expression by recruiting DNA (cytosine-5--methyltransferase 3A

    Directory of Open Access Journals (Sweden)

    Xu Xiao-Chun

    2010-04-01

    Full Text Available Abstract Tobacco smoke is an important risk factor for various human cancers, including esophageal cancer. How benzo [a]pyrene diol epoxide (BPDE, a carcinogen present in tobacco smoke as well as in environmental pollution, induces esophageal carcinogenesis has yet to be defined. In this study, we investigated the molecular mechanism responsible for BPDE-suppressed expression of retinoic acid receptor-beta2 (RAR-β2 in esophageal cancer cells. We treated esophageal cancer cells with BPDE before performing methylation-specific polymerase chain reaction (MSP to find that BPDE induced methylation of the RAR-β2 gene promoter. We then performed chromatin immunoprecipitation (ChIP assays to find that BPDE recruited genes of the methylation machinery into the RAR-β2 gene promoter. We found that BPDE recruited DNA (cytosine-5--methyltransferase 3 alpha (DNMT3A, but not beta (DNMT3B, in a time-dependent manner to methylate the RAR-β2 gene promoter, which we confirmed by reverse transcription-polymerase chain reaction (RT-PCR analysis of the reduced RAR-β2 expression in these BPDE-treated esophageal cancer cell lines. However, BPDE did not significantly change DNMT3A expression, but it slightly reduced DNMT3B expression. DNA methylase inhibitor 5-aza-2'-deoxycytidine (5-Aza and DNMT3A small hairpin RNA (shRNA vector antagonized the effects of BPDE on RAR-β2 expressions. Transient transfection of the DNMT3A shRNA vector also antagonized BPDE's effects on expression of RAR-β2, c-Jun, phosphorylated extracellular signal-regulated protein kinases 1/2 (ERK1/2, and cyclooxygenase-2 (COX-2, suggesting a possible therapeutic effect. The results of this study form the link between the esophageal cancer risk factor BPDE and the reduced RAR-β2 expression.

  2. Effect of strand-specific excision repair on the spectra of mutations induced by benzo[a]pyrene-diol epoxide and ultraviolet radiation in diploid human cells

    International Nuclear Information System (INIS)

    To study the effect of excision repair on the spectra of mutations induced in diploid human cells by UV and ±-7β, 8α-dihydroxy-9α,10α-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), the author synchronized repair-proficient cells, treated them at the beginning of S phase or in G1 phase several hours prior to the onset of S phase, selected for thioguanine resistant cells, and determined the spectra of mutations in the coding region of the hyproxanthine(guanine)phosphoribosyl-transferase (HPRT) gene in the mutants. As a control, the spectra of mutations similarly induced in repair-deficient xeroderma pigmentosum (XP) cells were compared. There was no difference in the kinds of mutations observed in mutants derived from either cell strain treated with a particular mutagen either in S or in G1. With BPDE, the majority were G.C→T.A transversions; with UV, they were mainly G.C.→A.T transitions. The strand distribution of premutagenic lesions in mutants from repair-proficient cells treated in S or G1 differed significantly. The results strongly support the hypothesis that human cells preferentially repair UV- and BPDE-induced lesions from the transcribed strand of the HPRT gene. To test this, the rate of repair of BPDE adducts from individual strands of the HPRT gene was measured, using the UvrABC exinuclease and Southern hybridizations with strand-specific probes to detect lesions remaining. BPDE lesions were removed from the transcribed strand at a significantly faster rate than from the nontranscribed strand, consistent with my hypothesis. It was found that BPDE adducts were removed faster from either strand of the HPRT gene than from a transcriptionally inactive locus, indicating preferential repair of active genes. The results of these studies provide biochemical and biological evidence of strand-specific DNA repair of BPDE adducts in human cells

  3. Effects of growth and Bcl-2 and Bax expression by arsenic trioxide in human colorectal cancer LoVo cells%三氧化二砷对大肠癌LoVo细胞生长及Bcl-2、Bax表达的影响

    Institute of Scientific and Technical Information of China (English)

    张惠; 陈卫昌

    2012-01-01

    目的 研究三氧化二砷(As2O3)对人大肠癌细胞株LoVo中的生长及三氧化二砷对Bcl-2、Bax表达的影响.方法 采用不同浓度的As2O3处理LoVo细胞,MTT法测定细胞的生长抑制效应;免疫细胞化学法检测人结肠癌细胞LoVo中Bcl-2、Bax的表达.结果 MTT结果示As2O3对大肠癌LoVo细胞的生长有抑制作用,且有时间-剂量依赖性(P<0.05或P<0.01);免疫细胞化学法结果示As2O3可使LoVo细胞中Bcl-2表达下降,Bax表达升高(P<0.01).结论 三氧化二砷对大肠癌细胞生长有抑制作用,且呈时间、剂量依赖性;其机制可能与改变Bcl-2和Bax的表达水平有关.

  4. Ki67和Bax在局部晚期宫颈癌新辅助化疗前后表达的意义%The significance of Ki67 and Bax expressions before and after neoadjuvant chemotherapy in locally advanced cervical carcinoma

    Institute of Scientific and Technical Information of China (English)

    游艳琴; 宋磊

    2006-01-01

    目的:探讨Ki67、Bax与宫颈癌新辅助化疗疗效和预后之间的关系.方法:在新辅助化疗(neoadjuvant chemotherapy,NACT)前后用免疫组化方法检测23例局部晚期宫颈癌组织Ki67和Bax的表达.结果:临床总有效率为82.61%.化疗有反应者NACT前后Ki67、Bax表达有统计学差异(P<0.05);无反应者NACT前后Ki67、Bax表达无统计学差异(P>0.05).不同病理类型和临床分期患者NACT前后Ki67和Bax变化值无显著性差异;不同病理分级患者NACT前后Bax变化值有统计学差异(P<0.05).NACT前Ki67 LI>33%和Ki67 LI<33%患者的平均无瘤生存期分别为48.6个月和19个月(P<0.05).结论:Ki67、Bax与化疗疗效显著相关.Ki67、Bax有可能作为判断化疗疗效和预后的指标.

  5. 苯扎贝特对ox-LDL诱导内皮细胞凋亡基因Bcl-2/Bax的影响%Effects of bezafibrate on apoptosis gene Bcl-2/Bax in cultured endothelial cells induced by ox-LDL

    Institute of Scientific and Technical Information of China (English)

    申晓彧; 薛丽霞; 屈巧芳; 曾秋棠

    2008-01-01

    目的 观察苯扎贝特对氧化型低密度脂蛋白(ox-LDL)诱导人脐静脉内皮细胞凋亡基因Bcl-2/Bax的影响. 方法 体外培养人脐静脉内皮细胞(HUVECs),根据实验要求分为正常对照组、ox-LDL组、低浓度苯扎贝特(50μmol/L)组、中浓度苯扎贝特(100 μmol/L)组、高浓度苯扎贝特(200μmol/L)组.RT-PCR观察各组凋亡基因Bcl-2、Bax及Bd-2/BaxmRNA的变化. 结果 与正常对照组比较,ox-LDL组凋亡基因Bcl-2表达下降(P<0.05),凋亡基因Bax表达增加(P<0.05),Bcl-2/Bax比值下降(P<0.05);不同浓度苯扎贝特组与ox-LDL组比较,Bcl-2表达增加(P<0.05),Bax表达降低(P<0.05),Bcl-2/Bax上调(P<0.05),且呈浓度效应依赖关系. 结论 ox-LDL可引起内皮细胞抗凋亡基因Bcl-2表达下调,凋亡基因Bax表达上调,Bcl-2和Bax比值下降,从而引起内皮细胞凋亡增加;苯扎贝特可通过上调Bcl-2与Bax的比值抑制ox-LDL引起的内皮细胞凋亡,起到抗动脉粥样硬化作用.

  6. 龙葵碱调控Bcl-2与Bax蛋白表达及caspase-3活性诱导HepG2细胞凋亡的研究%Induction of solanine on HepG2 cell apoptosis by regulation of Bcl-2/Bax expression and caspase-3 activity

    Institute of Scientific and Technical Information of China (English)

    高世勇; 徐丽丽; 季宇彬

    2009-01-01

    目的 探讨龙葵碱诱导HepG2细胞凋亡的作用机制.方法 透射电镜观察凋亡细胞形态变化,原位缺口末端榆测法(TUNEL法)检测DNA断裂情况,流式细胞术检测细胞凋亡率,间接免疫荧光法激光共聚焦扫描显微术检测Bcl-2与Bax蛋白表达,比色法检测caspase-3活性的变化.结果 在透射电镜下观察,龙葵碱组细胞出现细胞固缩,染色质致密,核凝聚固缩,染色体断裂形成核碎块,凋亡小体形成等细胞凋亡特征形态.TUNEL法发现龙葵碱高、中、低剂量组HepG2细胞均有绿色荧光,阴性对照组无荧光.流式细胞术分析表明0.4、2、10μmol/L龙葵碱作用HepG2细胞24 h凋亡率分别为4.0%、8.5%、20.1%.同时,龙葵碱升高caspase-3活性,下调Bcl-2蛋白表达,上调Bax蛋白表达.结论 龙葵碱通过降低Bcl-2/Bax的值,激活caspase-3酶活性诱导HepG2细胞凋亡.

  7. 小熊猫小脑皮层的组织结构及RT-97、KGF和Bax蛋白在小脑皮层的表达%Histological Structure and Expression of RT-97, KGF and Bax Proteins in the Cerebellar Cortex of Ailurus fulgens

    Institute of Scientific and Technical Information of China (English)

    高先军; 王昱; 俞诗源; 王悦; 郭婷婷

    2009-01-01

    为了解小熊猫(Ailurus fulgens)小脑皮层的结构特征,观察神经丝蛋白抗体RT-97、角质细胞生长因子(KGF)及Bax蛋白在小脑皮层中的表达,利用组织学方法和免疫组织化学方法观察了小熊猫小脑皮层的显微结构,检测了RT-97、KGF和Bax蛋白的表达.结果表明,小脑皮层从外向内依次可分为分子层、Purkinje细胞层、颗粒层3层.RT-97在小熊猫小脑皮层Purkinje细胞层、颗粒层中神经细胞的轴突、分子层中颗粒细胞的轴突及小脑髓质中有阳性表达;KGF在小脑皮层分子层、Purkinje细胞层和颗粒细胞层及髓质中均有阳性表达;Bax蛋白在小脑皮层分子层、Purkinje细胞层和颗粒细胞层中有阳性表达.RT-97、KGF和Bax蛋白在小脑皮层神经结构的构筑中可能发挥着不同的功能.

  8. Láminas delgadas de (Bi0.5Na0.5)1-xBaxTiO3 en torno a la frontera de fase morfotrópica preparadas por métodos de depósito químico y fotoquímico de disoluciones

    OpenAIRE

    Pérez-Mezcua, Dulce

    2016-01-01

    Tesis presentada para aspirar al grado de Doctor por la Universidad de Navarra. El presente trabajo ha sido realizado en los Departamentos de Química de la Facultad de Ciencias de la Universidad de Navarra y de Materiales para las Tecnologías de la Información del Instituto de Ciencia de Materiales de Madrid (ICMM-CSIC).

  9. EFFECTS OF IVABRADINE ON CARDIOMYOCYTE APOPTOSIS AND EXPRESSIONS OF bcl-2 AND bax IN RABBITS AFTER ACUTE MYOCARDIAL INFARTION%伊伐布雷定对兔急性心梗后心肌细胞凋亡及bcl-2与bax蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    徐少杰; 刘松; 王宝魁; 黄玉晓; 张文忠

    2013-01-01

    目的 探讨伊伐布雷定(Iva)对兔急性心肌梗死(AMI)后心肌细胞凋亡及bcl-2、bax蛋白表达的影响.方法 新西兰大白兔32只,雌雄不拘,随机分成4组,各8只.假手术组(S组)只开胸不结扎动脉,心肌梗死组(M组)结扎左冠状动脉前降支建立AMI模型,阿替洛尔治疗组(A组)建立AMI模型后应用阿替洛尔治疗,Iva治疗组(Ⅰ组)建立AMI模型后应用Iva治疗.A组和Ⅰ组于术后12h开始通过食物给药,持续给药28 d.28 d后取缺血坏死区心肌组织,TUNEL法检测心肌细胞凋亡,免疫组织化学法检测bcl-2、bax蛋白的表达;应用心电图机记录并比较M组、A组和Ⅰ组兔术前及术后28d的心率变化.结果 Ⅰ组和A组的心肌细胞凋亡比例显著低于M组,高于S组,差异有显著性(F =89.36,q=5.59~22.25,P<0.01);Ⅰ组和A组之间比较差异无显著性(P>0.05).与M组相比较,Ⅰ组和A组的bcl-2蛋白水平显著升高(F=22.93,q =7.90、8.95,P<0.01),bax蛋白水平显著降低(F=55.59,q=13.83、16.83,P<0.01),Ⅰ组和A组之间比较差异无显著性(P>0.05).M组、A组和Ⅰ组基础心率差异无显著性;术后28 d,A组和Ⅰ组的心率较M组明显减慢,治疗前后心率变化值比较差异有显著性(F=739.55,q =47.18、47.01,P<0.01),而A组和Ⅰ组相比差异无显著性.结论 应用Iva治疗能有效减少心肌梗死后心肌细胞凋亡的发生,有一定的心肌保护作用.

  10. Correlation of apoptosis genes of p53 ,bcl-2 and bax in tissue of prostate%凋亡相关基因p53、bcl-2、bax在前列腺组织中的相关性

    Institute of Scientific and Technical Information of China (English)

    方志启; 吴刚; 王贺彬; 陈晓宇

    2013-01-01

    目的 探讨细胞凋亡相关基因p53、bcl-2、bax在前列腺组织中的相关性.方法 收集36例前列腺癌(prostate caner,PCa)、20例前列腺增生(benign prostatic hyperplasia,BPH)和11例正常前列腺(normal prostatic,NP),应用免疫组织化学S-P法检测凋亡相关基因p53、bcl-2、bax蛋白的表达.结果 ①PCa和BPH组bcl-2蛋白阳性表达率明显高于NP组(P>0.05),而PCa组与BPH组阳性率差异无显著性.PCa组p53蛋白阳性表达率明显高于BPH组和NP组(P<0.01),而BPH组与NP组阳性率无显著性 差异(P>0.05).②p53与PCa分级有关,随着肿瘤分级增高而呈正相关(P<0.05); bcl-2与PCa分级有关,随着肿瘤分级增高而呈正相关(P<0.01),显示bcl-2、p53蛋白表达随着病理分级的增高而增高.PCa、BPH 和NP中bax阳性表达率差异无显著性.③p53蛋白表达阳性率≤5年生存组明显高于>5年生存组,呈负相关(P<0.05);bcl-2、bax蛋白表达与生存期无关(P>0.05).结论 细胞凋亡相关基因p53、bcl-2、bax蛋白的异常表达与PCa的发生和发展、病理分级和预后有相关性.

  11. Study on expression of p53、 bcl-2、 bax and PCNA in retinoblastoma%视网膜母细胞瘤p53、bcl-2、bax及增殖细胞核抗原的表达意义

    Institute of Scientific and Technical Information of China (English)

    李琳; 雷霍; 杨慧

    2002-01-01

    目的了解视网膜母细胞瘤(retinoblastoma,Rb)p53、bcl-2、bax和增殖细胞核抗原表达与Rb及其分化程度的关系.方法用免疫组化检测21例Rb和6例正常视网膜常规石蜡标本进行p53、bcl-2、bax和PCNA表达.结果bc1-2、bax和PCNA在Rb中的表达较高,与正常视网膜相比有显著性差异,分化性Rb组织bcl-2阳性表达率较高,与未分化型Rb组织相比有显著性差异.p53、bcl-2、bax在Rb中的表达与PCNA的表达有显著相关性.结论 Rb的发生与多个细胞凋亡调控基因异常有关,测定和分析Rb的bcl-2、PCNA、bax和表达,对于Rb的诊断和分化程度有重要意义.

  12. Effects of Dietary Glutamine on Serum Indexes, Morphology and Expression of Bax,Bcl-2 of Intestine of Weaned Piglets%谷氨酰胺对断奶仔猪血清、肌肉指标和肌肉热休克蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    陈静; 王丽; 王彤; 刘显军; 李海东; 程奇

    2016-01-01

    A total of 32 crossbred (Landrace×Yorkshire) pigs were used to determine the effect of glutamine on serum indexes, muscle indexes and expression of heat shock protein (HSP 70) of muscle. The piglets were divided into 2 treatments. The control group was fed with basal diet, while the glutamine group was fed with diet added with 1.2% glutamine (Gln). The pigs fed with diet supplemented with glutamine showed an increase tendency (p﹥0.05) concentrations of total protein, albumin protein, alanine aminotransferase and decrease (p﹥0.05) of protein coefficient compared with the control. Glutamine supplementation increased (p﹤0.05) concentrations of muscle glutathione (GSH) and glutathione s-transferase (GST) compared with the control. Glutamine supplementation decreased (p﹤0.05) concentrations of muscle γ-L-glutamyl transpeptidase (γ-GT) and malondialdehyde (MDA) compared with the control. There were no differences (p﹥0.05) in muscle superoxide dismutase (SOD) between pigs fed with the control diet and pigs fed with the Gln diets. The expression of HSP70 in muscle was greater in piglets supplemented with Gln than in control piglets (p﹤0.05). The results indicate that Gln supplementation could improve the synthesis of protein and muscle antioxidant properties and increase muscle HSP70 expression.%为研究谷氨酰胺对断奶仔猪血清、肌肉生化指标和和肌肉热休克蛋白表达的影响,选用(28±1)d 断奶的长白×大约克夏仔猪32头,随机分为2组,对照组饲喂基础日粮,谷氨酰胺组饲喂添加1.2%谷氨酰胺的基础日粮,试验期28d。试验结束采集仔猪血清和肌肉,测定血清和肌肉生化指标及肌肉中热休克蛋白表达情况。结果表明:仔猪日粮中添加谷氨酰胺有提高仔猪血清总蛋白、白蛋白、球蛋白,并降低了蛋白质系数的趋势(p﹥0.05)。谷氨酰胺显著提高了肌肉谷胱甘肽(p﹤0.05)和谷胱甘肽-S转移酶的含量(p﹤0.05),显著降低了γ-L-谷氨酰转肽酶(p﹤0.05)和丙二醛含量(p﹤0.05),但对肌肉中超氧化物歧化酶活性影响不显著(p﹥0.05)。同时,谷氨酰胺显著提高了肌肉中热休克蛋白70的阳性面积比和浓度。说明断奶仔猪日粮中添加1.2%谷氨酰胺促进了血清蛋白合成,并显著提高了肌肉的抗氧化能力和热休克蛋白的表达。

  13. Quantitative expression analysis and prognostic significance of the BCL2-associated X gene in nasopharyngeal carcinoma: a retrospective cohort study

    International Nuclear Information System (INIS)

    Nasopharyngeal carcinoma (NPC) is a highly metastatic epithelial malignancy showing high prevalence in Southeast Asia and North Africa. The BCL2-associated X (BAX) gene encodes the most important pro-apoptotic member of the BCL2 family. We have recently shown that BCL2 and BCL2L12, two other members of the same apoptosis-related family, possess significant prognostic value in NPC. The objective of the current study was to analyze BAX mRNA expression in nasopharyngeal biopsies of NPC patients, and to assess its prognostic potential in this disease. Total RNA was isolated from 88 malignant and 9 hyperplastic nasopharyngeal biopsies, resected from Tunisian patients. After cDNA synthesis by reverse transcription of polyadenylated RNA, BAX mRNA expression was analyzed using a highly sensitive quantitative real-time polymerase chain reaction (qRT-PCR) method. Lower BAX mRNA levels were detected in NPC biopsies than in hyperplastic nasopharyngeal samples. BAX mRNA expression status was associated with low tumor extent, negative regional lymph node status, and absence of distant metastases. Kaplan-Meier survival analysis demonstrated that patients with BAX mRNA-positive NPC have significantly longer disease-free survival (DFS) and overall survival (OS). In accordance with these findings, Cox regression analysis revealed that BAX mRNA expression can be considered as a favorable prognostic indicator of DFS and OS in NPC, independent of their gender, age, tumor histology, tumor extent, and nodal status. Furthermore, NPC patients without distant metastases are less likely to relapse when their primary tumor is BAX mRNA-positive, compared to metastasis-free patients with a BAX-negative nasopharyngeal malignancy. This is the first study examining the potential clinical utility of BAX as a prognostic tumor biomarker in NPC. We provide evidence that BAX mRNA expression can be considered as an independent favorable prognostic indicator of DFS and OS in NPC

  14. c-fos,bax和p53的反义寡聚核苷酸(ASOs)对溶血磷脂酸所致的培养小鼠大脑皮层神经元凋亡的影响%Effects of antisense oligodeoxynucleotides against c-fos,bax,and p53 mRNAs upon apoptosis induced by lysophosphatidic acid in cultured cortical neurons

    Institute of Scientific and Technical Information of China (English)

    郑肇青; 方羡君; 胥显民; 李建国; 乔健天

    2009-01-01

    性,不同于b淀粉样蛋白片段31-35的致凋亡特性.%three genes are indispensable for the LPA-induced apoptosis,showing a different genomic basis as compared to that for AbP31-35-induced apoptosis.

  15. Effect of dentate gyrus disruption on remembering what happened where

    Directory of Open Access Journals (Sweden)

    Min W Jung

    2015-06-01

    Full Text Available Our previous studies using Bax knockout (Bax-KO mice, in which newly generated granule cells continue to accumulate, disrupting neural circuitry specifically in the dentate gyrus (DG, suggest the involvement of the DG in binding the internally-generated spatial map with sensory information on external landmarks (spatial map-object association in forming a distinct spatial context for each environment. In order to test whether the DG is also involved in binding the internal spatial map with sensory information on external events (spatial map-event association, we tested the behavior of Bax-KO mice in a delayed-non-match-to-place task. Performance of Bax-KO mice was indistinguishable from that of wild-type mice as long as there was no interruption during the delay period (tested up to 5 min, suggesting that on-line maintenance of working memory is intact in Bax-KO mice. However, Bax-KO mice showed profound performance deficits when they were removed from the maze during the delay period (interruption condition with a sufficiently long (65 s delay, suggesting that episodic memory was impaired in Bax-KO mice. Together with previous findings, these results suggest the role of the DG in binding spatial information derived from dead reckoning and nonspatial information, such as external objects and events, in the process of encoding episodic memory.

  16. Lattice instabilities and superconductivity in La2-x(Ba,Sr)xCuO4

    International Nuclear Information System (INIS)

    In this paper, the authors present the result of two experiments on the anomalous physical properties of La2-xBaxCuO4 with x = 0.125. The suppression of a low-temperature tetragonal phase by introduction of Sr in the La2-xBaxCuO4 correlates well with the recovery of 30-K superconductivity. Hydrogenation of La2-xBaxCuO4 revealed that the carrier density, rather than the amount of divalent ions, is an essential parameter which governs the anomaly

  17. Effect of propofol pretreatment on apoptosis in rat brain cortex after focal cerebral ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    Haiyan Xu; Chengwei Zhang; Chunxiao Zhang

    2011-01-01

    The present study aimed to observe cortical expression of Bcl-2 and Bax, cysteine-dependent aspartate directed proteases-3 activity and apoptotic cell death in a rat model of middle cerebral artery occlusion pretreated with propofol. Results showed that, propofol pretreatment significantly reduced oxidative stress levels and attenuated neuronal apoptosis in the cortex of rats. Propofol pretreatment upregulated Bcl-2 expression, and downregulated Bax expression and cysteine-dependent aspartate directed proteases-3 activity. These findings indicate that propofol pretreatment inhibits cell apoptosis during focal cerebral ischemia/reperfusion injury. This neuroprotective effect is most likely achieved through the Bcl-2/Bax/cysteine-dependent aspartate directed proteases-3 pathway.

  18. Disease: H00020 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ing microsatellites, such as transforming growth factor receptor II (TGF-RII) and BAX. Hereditary syndromes ...95-406 (2006) PMID:12621137 (gene) Lynch HT, de la Chapelle A. Hereditary colorectal cancer. N Engl J Med 34

  19. EXPRESSION AND SIGNIFICANCE OF bcl-2 FAMILY IN AMELOBLASTONA

    Institute of Scientific and Technical Information of China (English)

    WANG Jie; MA Jie; ZHONG Ming; LIU Jing-dong

    2006-01-01

    Objective: To study the expression of bcl-2 and bax in human ameloblastoma (AB), and investigate the role of apoptosis in genesis and development of AB and the relation of apoptosis with the clinic biological characteristics of AB. Methods:BCL-2 and BAX proteins were detected in 75 cases of AB (primary AB 31 cases, recurrent AB 37 cases, malignant AB 7cases) by S-P method. Oral normal mucosa (NOM) and Odontogenic kerotosyst (OKC) were used as controls. Bcl-2 and bax mRNA in 20 cases of AB, 12 cases of OKC were detected by in situ hybridization. Results: The positive ratio of BCL-2protein was 88.0% ( 66/75 ) in AB, 74.3% (26/35) in OKC and 44.4% (4/9) in NOM, respectively (P<0.001). BCL-2 protein was expressed in peripheral cells and a few scattered stellate-shape cells in AB. The positive ratio of BAX protein was 74.7%(56/75)in AB, 65.7%(23/35)in OKC and 77.8%(7/9) in NOM, respectively (P<0.001). BAX protein was expressed in peripheral cells and stellate-shape cells with similar intensity. BCL-2 expression increased in recurrent and AB canceration(P<0.01), while for BAX expression, the positive ratio was higher in recurrent AB, but lower than that of malignant AB. A moderate negative correlation between BCL-2 and BAX protein was found (rk=-0.331, P<0.001).Conclusion: AB has much more apoptosis-inhibiting protein than apoptosis- accelarating protein. Apoptosis plays an important role in genesis, development of AB. The fashion and intensity of bcl-2 and bax expression were different in various tissues and in benign or malignant AB.

  20. Apoptosis regulates ipRGC spacing necessary for rods and cones to drive circadian photoentrainment

    OpenAIRE

    Chen, Shih-Kuo; Chew, Kylie S.; McNeill, David S.; Keeley, Patrick W.; Ecker, Jennifer L.; Mao, Buqing Q.; Pahlberg, Johan; Kim, Bright; Lee, Sammy C. S.; Fox, Michael; Guido, William; Wong, Kwoon Y.; Sampath, Alapakkam P.; Reese, Benjamin E.; Kuruvilla, Rejji

    2013-01-01

    The retina consists of ordered arrays of individual types of neurons for processing vision. Here we show that such order is necessary for intrinsically photosensitive retinal ganglion cells (ipRGCs) to function as irradiance detectors. We found that during development, ipRGCs undergo proximity-dependent Bax-mediated apoptosis. Bax mutant mice exhibit disrupted ipRGC spacing and dendritic stratification with an increase in abnormally localized synapses. ipRGCs are the sole conduit for light in...

  1. Different Expressions of HIF-1α, Bcl-2 and Baxin DU145 Prostate Cancer Cells Transplanted in Nude Mouse between X-Ray and Neutron Irradiation

    International Nuclear Information System (INIS)

    To investigate the radiobiologic effects of neutron and X-ray irradiation on DU-145 prostate carcinoma cells by identifying the differences of HIF-1α expression and apoptosis. Nude mice were injected with the human prostate cancer cell line, DU-145, and then irradiated with 2 Gy and 10 Gy X-rays, or 0.6 Gy and 3.3 Gy neutrons, respectively. The mice were sacrificed at 24 hours and 120 hours after irradiation. The expression levels of HIF-1α, Bcl-2 and Bax were compared with immunohistochemical staining and western blotting. The apoptotic indexes were compared with the Terminal deoxynucleotidyl biotin-dUTP nick and labeling (TUNEL) assay. At day 1, HIF-1α and Bcl-2 expression decreased, while Bax expression and the number of TUNEL positive cells increased in neutron irradiated groups for the control and X-ray irradiated groups. The Bcl-2/Bax ratio was significantly lower in the neutron irradiated groups regardless of dose (p=0.001). The same pattern of the differences in the expressions of the HIF-1α, Bcl-2, Bax, Bcl-2/Bax ratio, and apoptotic indexes were indentified at day 5. HIF-1α expression was related with Bcl-2 (p=0.031), Bax (p=0.037) expressions and the apoptotic indexes (p=0.016) at day 5. Neutron irradiation showed a decrease in HIF-1α, Bcl-2 expression, and Bcl-2/Bax ratio, but increased Bax expression regardless of dose. This study suggests that the differences radiobiological responses between photon and neutron irradiation may be related to different HIF-1α expression and subsequent apoptotic protein expressions

  2. Production of translationally cold barium monohalide ions

    OpenAIRE

    DePalatis, M. V.; Chapman, M.S.

    2013-01-01

    We have produced sympathetically cooled barium monohalide ions BaX$^+$ (X = F, Cl, Br) by reacting trapped, laser cooled Ba$^+$ ions with room temperature gas phase neutral halogen-containing molecules. Reaction rates for two of these (SF$_6$ and CH$_3$Cl) have been measured and are in agreement with classical models. BaX$^+$ ions are promising candidates for cooling to the rovibrational ground state, and our method presents a straightforward way to produce these polar molecular ions.

  3. Prognostic Significance of Apoptosis Related Gene Family bcl-2 in Human Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    To study the prognostic effect of bcl-2 oncogene and its gene family members bax, bcl-x expression in breast cancer patients. Methods: expression of bcl-2, bax proteins in 91 human breast cancer tissue sections were studied by immunohistochemical method. Bcl-x1 mRNA expression in frozen tissues from 16 breast cancer patients were detected using Northern blot method. Results: bcl-2 protein positivity was found in 60/91 (65.9%) patients, and bax positivity 59/91 (64.8%). Bcl-2 and bax expression levels were associated with apoptotic index(AI), histological grade, axillary lymph node metastasis, postoperative local recurrence and metastasis. Bcl-2 expression was related to ER positivity. In univariate analysis for disease free survival (DFS), bcl-2 and bax protein levels, and Al were all found to have prognostic value. The result of Cox's model multivariate analysis showed that bcl-2 protein level was an independent prognostic factor. In 16 frozen breast cancer tissues, 8/16(50%) had higher level of bcl-x1 mRNA, which showed correlation with bcl-2 protein expression and axillary lymph node metastasis. Conclusion: The findings indicate that dysregulated expressions of bcl-2, bax and bcl-x1 apoptosis-related genes, suggestive of serious deregulation of apoptotic process, may contribute to the biologic aggressiveness of breast cancer. Bcl-2 protein is an independent indicator of prognosis in breast cancer patients.

  4. Preparation and dielectric properties of BTO-based nano-ceramic doped with rare-earth%稀土掺杂BTO基纳米陶瓷的制备及介电性能

    Institute of Scientific and Technical Information of China (English)

    孙家军; 何开棘; 王开明; 李志

    2012-01-01

    BaxSr1-xTiO3 and BaxSr1-x-yGdyTiO3 nano-powders and ceramics were prepared by the technology of continuous and orderly controlled explosive nucleation nanoparticles powders preparation, and using BaCl2. SrCl2 · 6H2O, TiCl4 as raw material. The microstructure and properties of prepared powders and ceramics were studied. The results show that the nano-powders possess good dispersion, narrow particle size distribution on the average particle size of less than 40 nm. The permittivities of the BaxSr1-xTiO3 ceramics increase with increasing of Sr doping amount. The permittivity of BaxSr1-xTiO3 ceramic sintered at 1 325℃ reaches the maximum of 30 000 F/m. The permittivities of BaxSr1-xTiO3 ceramics decrease with increasing of Gd doping amount. The permittivity of BaxSr1-x-yGdyTiO3 ceramic sintered at 1 325 ℃ reaches the maximum of 25 000 F/m.%采用"连续有序可控爆发式成核"纳米粉体制备技术,以BaCl2、SrCl2·6H2O、TiCl4为原料制备了BaxSr1-xTiO3及BaxSr1-x-yGdyTiO3纳米粉体和陶瓷,研究了所制粉体和陶瓷的微观结构及性能.结果表明:所制纳米粉体分散性好,粒径分布范围窄,平均粒径小于40 nm; BaxSr1-xTiO3介电常数随锶掺杂量的增加有增大的趋势,在1 325℃烧结得到的Ba0.7Sr0.3TiO3陶瓷的介电常数最大,达到30 000 F/m.BaxSr1-x-yGdyTiO3介电常数随Gd掺杂量的增加趋于减小,在1 325℃烧结得到的Ba0.8Sr0.18Gd0.02TiO3的介电常数最大,达到近25 000 F/m.

  5. miR-21-mediated decreased neutrophil apoptosis is a determinant of impaired coronary collateral growth in metabolic syndrome.

    Science.gov (United States)

    Hutcheson, Rebecca; Terry, Russell; Hutcheson, Brenda; Jadhav, Rashmi; Chaplin, Jennifer; Smith, Erika; Barrington, Robert; Proctor, Spencer D; Rocic, Petra

    2015-06-01

    Coronary collateral growth (CCG) is impaired in metabolic syndrome. microRNA-21 (miR-21) is a proproliferative and antiapoptotic miR, which we showed to be elevated in metabolic syndrome. Here we investigate whether impaired CCG in metabolic syndrome involved miR-21-mediated aberrant apoptosis. Normal Sprague-Dawley (SD) and metabolic syndrome [J. C. Russel (JCR)] rats underwent transient, repetitive coronary artery occlusion [repetitive ischemia (RI)]. Antiapoptotic Bcl-2, phospho-Bad, and Bcl-2/Bax dimers were increased on days 6 and 9 RI, and proapoptotic Bax and Bax/Bax dimers and cytochrome-c release concurrently decreased in JCR versus SD rats. Active caspases were decreased in JCR versus SD rats (~50%). Neutrophils increased transiently on day 3 RI in the collateral-dependent zone of SD rats but remained elevated in JCR rats, paralleling miR-21 expression. miR-21 downregulation by anti-miR-21 induced neutrophil apoptosis and decreased Bcl-2 and Bcl-2/Bax dimers (~75%) while increasing Bax/Bax dimers, cytochrome-c release, and caspase activation (~70, 400, and 400%). Anti-miR-21 also improved CCG in JCR rats (~60%). Preventing neutrophil infiltration with blocking antibodies resulted in equivalent CCG recovery, confirming a major role for deregulated neutrophil apoptosis in CCG impairment. Neutrophil and miR-21-dependent CCG inhibition was in significant part mediated by increased oxidative stress. We conclude that neutrophil apoptosis is integral to normal CCG and that inappropriate prolonged miR-21-mediated survival of neutrophils plays a major role in impaired CCG, in part via oxidative stress generation.

  6. Functional Mechanism of Resveratrol in Inhabiting Growth of Cells ls174t and Its Mechanism in Subcutaneously Transplanted Tumor of Nude Mice

    Institute of Scientific and Technical Information of China (English)

    CHEN Jie; DONG Xin-shu; GUO Xing-gang

    2008-01-01

    To explore the functional mechanism of Resveratrol against colon cancer cells Is174t and the growth of colon cancer tissue of tumor-bearing mice,MTT method was used to observe the functions of resveratrol for inhibition against cells ls174t in vitro.Transmission electron microscope was used to observe the cell apoptosis.FCM assay was performed to measure the change of the cell apoptosis rate and of cell cycle,RT-PCR method was used to detect the expressions of bc1-2 and bax mRNA.Western blot method was used to detect the expressions of bc1-2 and bax protein.Cells isi74t were transplanted subcutaneously to nude mice to observe the effect of resveratrol on the growth of subcutaneously transplanted tumor.RT-PCR method was used to detect the expressions of bc1-2 and bax mRNA in the tumor tissue.Western blot method was used to detect the expressions of bc1-2 and bax protein in the tumor tissue.Resveratrol has an effect of inhibiting proliferation of cells ls174t in vitro(P<0.01).It is able to induce the apoptosis of cells Is174t,causing the decrease in the expression of bc1-2 and the increase in the expression of bax.Resveratrol could inhibit the growth of subcutaneously transplanted tumor of nude mice(P<0.05),causing the decrease in the expression of bc1-2 and the increase in the expression of bax.Resveratrol can inhibit the growth of cells 174t and the growth of subcutaneously transplanted tumor.The mechanism is possibly related to the induction of the cell apoptosis and the regulation of bc1-2/bax expression.

  7. Effect of pregabalin on apoptotic regulatory genes in hippocampus of rats with chronic temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    ZHANG Yi-dan

    2012-04-01

    Full Text Available Objective To observe the effect of pregabalin on the expression of Bcl-2 and Bax in hippocampus of chronic epileptic rats induced by pilocarpine, to explore the anti-epileptic pharmacology mechanism of pregabalin, and its anti-apoptotic effect on hippocampal neurons of rats. Methods The model of chronic temporal lobe epileptic rats induced by lithium-pilocarpine was established, then the rats in pregabalin treatment group received intraperitoneal injection of pregabalin (40 mg/kg once daily for three weeks. The expression of Bcl-2 and Bax in hippocampus of all rats was detected by immunohistochemical technique and Western blotting. Results Compared with normal saline group rats, the expression of Bcl-2 and Bax in hippocampus of rats with chronic temporal lobe epilepsy was significantly increased (P = 0.000, for all. Pregabalin can down-regulate the expression of Bax and up-regulate the expression of Bcl-2 in hippocampus of rats compared to model group rats (P = 0.000, for all. Conclusion Pregabalin may have the effects of inhibiting cell apoptosis and protecting neurons through lowing Bax level and increasing Bcl-2 level in hippocampus of chronic temporal lobe epileptic rats.

  8. Mechanisms of acupuncture and moxibustion in regulation of epithelial cell apoptosis in rat ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Huan-Gan Wu; Xiao Gong; Li-Qing Yao; Wei Zhang; Yin Shi; Hui-Rong Liu; Ye-Jing Gong; Li-Bin Zhou; Yi Zhu

    2004-01-01

    AIM: To investigate the effect of acupuncture and moxibustion on epithelial cell apoptosis and expression of Bcl-2, Bax, fas and FasL proteins in rat ulcerative colitis.METHODS: A rat model of ulcerative colitis was estabelished by immunological methods and local stimulation. All rats were randomly divided into model control group (MC),electro-acupuncture group (EA), herbs-partition moxibustion group (HPM). Normal rats were used as normal control group (NC). Epithelial cell apoptosis and expression of Bcl-2, Bax, fas and FasL proteins were detected by TUNEL and immunohistochemiscal method respectively.RESULTS: The number of epithelial cell apoptosis in MC was significantly higher than that in NC, and was markedly decreased after the treatment with herbs-partition moxibustion or electro-acupuncture. The expression of Bcl2, Bax, fas and FasL in colonic epithelial cells in MC was higher than that in NC, and was markedly down- regulated by herbspartition moxibustion or electro-acupuncture treatment.CONCLUSION: The pathogenesis of ulcerative colitis in rats involves abnormality of apoptosis. Acupuncture and moxibustion can regulate the expression of Bcl-2, Bax, fas and FasL proteins and inhibit the apoptosis of epithelial cells of ulcerative colitis in rats by Bcl-2/Bax, fas/FasL pathways.

  9. Studies on the mechanism of apoptasis by radon in lung tissue of mice

    International Nuclear Information System (INIS)

    Objective: To study the mechanism of apoptasis by radon in lung tissue of mice. Methods: Male BALB/c mice were exposed to radon with the cumulative dose of 0.02, 30 or 60 working level month (WLM) respectively, and then were raised for different time (24 h, 30 d or 90 d). Apoptosis was detected by terminal deoxynucleotidy transferase-mediated dUTP-biotin nick end labeling (TUNEL). The expression of p 53 and Bcl-2/Bax protein was observed by immunohistochemistry. Results: As compared with the control group, the apoptotic index in lung tissue increased along with the increasing of expose dose and the raise time. The protein expression of p 53 increased significantlyin the 30 d and 90 d groups. But Bcl-2/Bax expression decreased. Conclusions: The apoptosis by radon in lung tissue of mice had close relationship with p 53 and.Bcl-2/Bax pathway. (authors)

  10. Hypergravity modifies the signal transduction of ionizing radiation through p53

    Energy Technology Data Exchange (ETDEWEB)

    Okaichi, Kumio; Usui, Aya; Okumura, Yutaka [Nagasaki Univ. (Japan). Atomic Disease Inst.; Ohnishi, Takeo [Nara Medical Univ., Kashihara (Japan)

    2002-12-01

    To determine the possible effect of hypergravity to modify the signal transduction of ionizing radiation, we analyzed the accumulation of p53 and the expression of p53-dependent genes, Waf-1 and Bax, using the western blot analysis. Hypergravity (20 x g) induced the accumulation of p53 in the human glioblastoma cell line A172 after 3 h of incubation. Low-dose (0.5 Gy) irradiation to the cells accumulated p53 1.5 h after irradiation, and induced Waf-1 and Bax. Under the condition of hypergravity (20 x g), the peak of p53 accumulation was shifted from 1.5 h to 3 h after irradiation, and the inductions of Waf-1 and Bax were suppressed entirely. These results indicate that hypergravity modifies the signal transduction of ionizing radiation through p53 in the cells. (author)

  11. Effect of Yiqi Bushen prescription on hippocampal neuronal apoptosis in diabetic rats

    Institute of Scientific and Technical Information of China (English)

    Deshan Liu; Weiwei Lin; Wei Gao; Ping Chang; Wei Li

    2011-01-01

    This study investigated the neuroprotective effect of Yiqi Bushen prescription (YQBS, supplementing qi and tonifying kidney) on neuronal cell apoptosis. Following YQBS treatment, the number of surviving hippocampal neurons increased, anti-apoptotic Bcl-2 expression increased and pro-apoptotic Bax expression decreased. In addition, diabetic rats exhibited improved learning and memory. YQBS treatment also increased Bcl-2 mRNA expression and the ratio of Bcl-2/Bax, but decreased levels of hypoxia-inducible factor-1α mRNA and Bax mRNA expression after high-glucose/hypoxia-induced injury. Results demonstrated that YQBS inhibited hippocampal neuronal apoptosis by decreasing hypoxia-inducible factor-1α expression and increasing Bcl-2 expression, thereby improving cognitive impairment in diabetic rats.

  12. Methoxychlor induces atresia by altering Bcl2 factors and inducing caspase activity in mouse ovarian antral follicles in vitro.

    Science.gov (United States)

    Basavarajappa, Mallikarjuna S; Karman, Bethany N; Wang, Wei; Gupta, Rupesh K; Flaws, Jodi A

    2012-12-01

    Methoxychlor (MXC) is an organochlorine pesticide widely used in many countries against various species of insects that attack crops and domestic animals. MXC reduces fertility by increasing atresia (death) of antral follicles in vivo. MXC also induces atresia of antral follicles after 96 h in vitro. The current work tested the hypothesis that MXC induces morphological atresia at early time points (24 and 48 h) by altering pro-apoptotic (Bax, Bok, Casp3, and caspase activity) and anti-apoptotic (Bcl2 and Bcl-xL) factors in the follicles. The results indicate that at 24 h, MXC increased Bcl-xL and Bax mRNA levels and increased the ratio of Bax/Bcl2. At 48-96 h, MXC induced morphological atresia. At 24-96 h, MXC increased caspase activities. These data suggest that MXC may induce atresia by altering Bcl2 factors and inducing caspase activities in antral follicles.

  13. Kanglaite combined Gemcitabine inhibits growth of nude mouse subcutaneous transplantation tumor of human PC-3 pancreatic cancer cell

    Institute of Scientific and Technical Information of China (English)

    WANG Wei; JIN Jian-guang; QIN Zhao-yin

    2005-01-01

    Objective:To study the mechanisms of pancreatic cancer treatment with Kanglaite combined Gemcitabine by investigating the relationship between the apoptosis and the expression of bcl-2, Bax and VEGF in pancreatic cancer cells.Methods:Nude mouse subcutaneous transplantation tumor model of Human PC-3 pancreatic cancer was established; the expressions of bcl-2, Bax and VEGF of transplantation tumor cell were determined; the earlier apoptosis rate of pancreatic cancer cell and the gross tumor volume were determined. Results:Kanglaite combined Gemcitabine remarkably decreased the protein expression of bcl-2,raised the expression of Bax,increased the apoptosis rate of the pancreatic cancer and contract the gross tumor volume. Kanglaite greatly decreased the protein expression of VEGF of the tumor cell. Conclusion:Therapeutic efficacy of Kanglaite combined Gemcitabine is far better than separate use of the two medicines in the pancreatic cancer transplantation tumor treatment.

  14. Molecular Mechanism of Bovine Trabecular Meshwork Cells Apoptosis Induced by Dexamethasone and Protection by Pilocarpine

    Institute of Scientific and Technical Information of China (English)

    Yajuan Gu; Shujun Zeng; Pengxin Qiu; Yuping Wu; Dawei Peng; Guangmei Yan

    2005-01-01

    Purpose: To study the molecular mechanism of trabecular meshwork cells apoptosis induced by dexamethasone and the protection of pilocarpine.Methods: Determining mRNA expression with reverse transcription-polymerase chain reaction (RT-PCR), protein expression with Western blots and the percentage of apoptotic cells with fluorescent microscopy.Results: Dexamethasone up-regulated Fas proteins and affected Bax, caspase-8 and caspase-9 proteins in an action of first decrease then increase. Pre-treatment with pilocarpine decreased the four proteins expression, which were increased by dexamethasone. Pilocarpine self could decrease pro-apoptotic factors Bax, caspase-8 and caspase-9 proteins expression.Conclusion: Fas/FasL pathway participated in apoptotic process induced by dexamethasone in trabecular meshwork cells and the process was probably related with both caspase-8 and caspase-9 pathways. Pilocarpine protected the cells against apoptosis through down-regulating Fas, Bax, caspase-8 and caspase-9 proteins expression.

  15. The Anti-apoptosis Effects of Daidzein in the Brain of D-Galactose Treated Mice

    Directory of Open Access Journals (Sweden)

    Xiang-bin Hu

    2007-07-01

    Full Text Available The purpose of this study was to explore the neuroprotective effects of daidzein on the apoptotic pathway in the hippocampus and cortex of D-galactose treated mice. For this purpose we have examined the expression of bcl-2 mRNA, bax mRNA and caspase-3 in the hippocampus and cortex of D-galactose-treated mice after fed with 10 or 5 mg/kg of daidzein. The results of in situ hybridization experiments indicate that daidzein could help increase the transcriptions of bcl-2 and decrease the transcriptions of bax in those brain regions of D-galactose-treated mice. Furthermore, immunohistochemical studies showed that daidzein could reduce the expression of caspase-3 in both brain regions. These results suggest that daidzein in soybean can inhibit the D-gal induced apoptosis via Bcl-2/Bax apoptotic pathway and be a potential medical candidate for neurodegeneration therapy.

  16. Protective Roles of Sodium Selenite against Aflatoxin B1-Induced Apoptosis of Jejunum in Broilers

    Directory of Open Access Journals (Sweden)

    Xi Peng

    2014-12-01

    Full Text Available The effects of aflatoxin B1 (AFB1 exposure and sodium selenite supplementation on cell apoptosis of jejunum in broilers were studied. A total of 240 one-day-old male AA broilers were randomly assigned four dietary treatments containing 0 mg/kg of AFB1 (control, 0.3 mg/kg AFB1 (AFB1, 0.4 mg/kg supplement Se (+ Se and 0.3 mg/kg AFB1 + 0.4 mg/kg supplement Se (AFB1 + Se, respectively. Compared with the control broilers, the number of apoptotic cells, the expression of Bax and Caspase-3 mRNA were significantly increased, while the expression of Bcl-2 mRNA and the Bcl-2/Bax ratio were significantly decreased in AFB1 broilers. The number of apoptotic cells and the expression of Caspase-3 mRNA in AFB1 + Se broilers were significantly higher than those in the control broilers, but significantly lower than those in AFB1 broilers. There were no significant changes in the expression of Bax mRNA between AFB1 + Se and control broilers; the expression of Bcl-2 mRNA and the Bcl-2/Bax ratio in AFB1 + Se broilers were significantly lower than those in the control broilers, but significantly higher than those in AFB1 broilers. In conclusion, 0.3 mg/kg AFB1 in the diet can increase cell apoptosis, decrease Bcl-2 mRNA expression, and increase of Bax and Caspase-3 mRNA expression in broiler’s jejunum. However, supplementation of dietary sodium selenite at the concentration of 0.4 mg/kg Se may ameliorate AFB1-induced apoptosis by increasing Bcl-2 mRNA expression, and decreasing Bax and Caspase-3 mRNA expression.

  17. Caracterización funcional de la molécula proapoptótica Bak en el retículo endoplasmático

    OpenAIRE

    Klee, Martina

    2008-01-01

    Bak y Bax son miembros proapoptóticos de la familia Bcl-2 que presentan una alta redundancia funcional. Ambos homólogos constituyen un punto de control crítico en la vía mitocondrial de apoptosis y están localizados tanto en la mitocondria como en el retículo endoplasmático (RE). Mientras que ya se ha establecido que Bak y Bax mitocondriales son suficientes para la inducción de apoptosis por proteínas BH3-only, todavía se desconoce en gran medida el papel de los homólogos reticulares, aunque ...

  18. Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats

    Energy Technology Data Exchange (ETDEWEB)

    Kheradmand, Arash, E-mail: arashkheradmand@yahoo.com [Department of Clinical Sciences, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Dezfoulian, Omid [Department of Pathobiology, School of Veterinary Medicine, Lorestan University, Khorram Abad (Iran, Islamic Republic of); Alirezaei, Masoud [Division of Biochemistry, School of Veterinary Medicine, Lorestan University, P.O. Box: 465, Khorram Abad (Iran, Islamic Republic of); Rasoulian, Bahram [Razi Herbal Medicine Research Center, Lorestan University of Medical Sciences, Khorram Abad (Iran, Islamic Republic of)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. Black-Right-Pointing-Pointer Numerous studies have documented the direct action of ghrelin in the modulation of apoptosis in different cell types. Black-Right-Pointing-Pointer Ghrelin may be considered as a modulator of spermatogenesis in normal adult rats. Black-Right-Pointing-Pointer Ghrelin may be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. -- Abstract: Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n = 7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P < 0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact

  19. Apoptosis-related protein expression in rabbits with blast brain injury following early hyperbaric oxygen therapy

    Institute of Scientific and Technical Information of China (English)

    Shaonian Xu; Jiachuan Liu; Yongming Zhang; Chunlin Wang; Jinbiao Wang; Yanyan Yang; Jian Huo; Wenjiang Sun

    2012-01-01

    We treated detonator-explosion-induced craniocerebral injury in rabbits with hyperbaric oxygen 1-24 hours post-injury. Expression of the apoptosis-regulating protein cytochrome c, the pro-apoptotic protein Bax and the apoptosis marker caspase-3 in the tissues surrounding the area of injury was significantly reduced, while that of the anti-apoptotic protein Bcl-2 was significantly increased. Our findings indicate that the curative effects of early hyperbaric oxygen on cortical cell apoptosis is associated with suppression of cytochrome c release from mitochondria. This mechanism underlies the observed reduction in Bax expression and upregulation of Bcl-2 expression.

  20. Paeonol Protects Memory after Ischemic Stroke via Inhibiting β-Secretase and Apoptosis

    Directory of Open Access Journals (Sweden)

    Shan-Yu Su

    2012-01-01

    cells, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL-positive cells decreased in the paeonol-administered group. Western blotting revealed decreased levels of Bax protein in mitochondria and apoptosis-inducing factor (AIF in cytosol following paeonol treatment. In conclusion, we speculate that paeonol protected memory after ischemic stroke via reducing APP, BACE, and apoptosis. Supression the level of Bax and blocking the release of AIF into cytosol might participate in the anti-apoptosis provided by paeonol.

  1. Histone deacetylase inhibitors sensitize lung cancer cells to hyperthermia: involvement of Ku70/SirT-1 in thermo-protection.

    Science.gov (United States)

    Hassan, Mohamed K; Watari, Hidemichi; Salah-Eldin, Alaa-Eldin; Sultan, Ahmed S; Mohamed, Zainab; Fujioka, Yoichiro; Ohba, Yusuke; Sakuragi, Noriaki

    2014-01-01

    This study describes the sensitization mechanism to thermal stress by histone deacetylase inhibitors (HDACIs) in lung cancer cells and shows that Ku70, based on its acetylation status, mediates the protection of lung cancer from hyperthermia (42.5°C, 1-6 hrs). Ku70 regulates apoptosis by sequestering pro-apoptotic Bax. However, its role in thermal stress is not fully understood. The findings showed that, pre-treating lung cancer cells with HDACIs, nicotinamide (NM) or Trichostatin A (TsA) or both significantly enhanced hyperthermia-induced Bax-dependent apoptosis in PC-10 cells. We found that hyperthermia induces SirT-1, Sirtuin, upregulation but not HDAC6 or SirT-3, therefore transfection with dominant negative SirT-1 (Y/H) also eliminated the protection and resulted in more cell death by hyperthermia, in H1299 cells through Bax activation. Hyperthermia alone primed lung cancer cells to apoptosis without prominent death. After hyperthermia Bax was upregulated, Bcl-2 was downregulated, the Bax/Bcl-2 ratio was inversed and Bax/Bcl-2 heterodimer was dissociated. Although hyperthermia did not affect total Ku70 expression level, it stimulated Ku70 deacetylation, which in turn could bind more Bax in the PC-10 cells. These findings suggest an escape mechanism from hyperthermia-induced Bax activation. To verify the role of Ku70 in this protection mechanism, Ku70 was silenced by siRNA. Ku70 silencing significantly sensitized the lung cancer cells to hyperthermia. The Ku70 KD cells underwent cytotoxic G1 arrest and caspase-dependant apoptosis when compared to scrambled transfectants which showed only G2/M cytostatic arrest in the cell lines investigated, suggesting an additional cell cycle-dependent, novel, role of Ku70 in protection from hyperthermia. Taken together, our data show a Ku70-dependent protection mechanism from hyperthermia. Targeting Ku70 and/or its acetylation during hyperthermia may represent a promising therapeutic approach for lung cancer. PMID:24728004

  2. Histone deacetylase inhibitors sensitize lung cancer cells to hyperthermia: involvement of Ku70/SirT-1 in thermo-protection.

    Directory of Open Access Journals (Sweden)

    Mohamed K Hassan

    Full Text Available This study describes the sensitization mechanism to thermal stress by histone deacetylase inhibitors (HDACIs in lung cancer cells and shows that Ku70, based on its acetylation status, mediates the protection of lung cancer from hyperthermia (42.5°C, 1-6 hrs. Ku70 regulates apoptosis by sequestering pro-apoptotic Bax. However, its role in thermal stress is not fully understood. The findings showed that, pre-treating lung cancer cells with HDACIs, nicotinamide (NM or Trichostatin A (TsA or both significantly enhanced hyperthermia-induced Bax-dependent apoptosis in PC-10 cells. We found that hyperthermia induces SirT-1, Sirtuin, upregulation but not HDAC6 or SirT-3, therefore transfection with dominant negative SirT-1 (Y/H also eliminated the protection and resulted in more cell death by hyperthermia, in H1299 cells through Bax activation. Hyperthermia alone primed lung cancer cells to apoptosis without prominent death. After hyperthermia Bax was upregulated, Bcl-2 was downregulated, the Bax/Bcl-2 ratio was inversed and Bax/Bcl-2 heterodimer was dissociated. Although hyperthermia did not affect total Ku70 expression level, it stimulated Ku70 deacetylation, which in turn could bind more Bax in the PC-10 cells. These findings suggest an escape mechanism from hyperthermia-induced Bax activation. To verify the role of Ku70 in this protection mechanism, Ku70 was silenced by siRNA. Ku70 silencing significantly sensitized the lung cancer cells to hyperthermia. The Ku70 KD cells underwent cytotoxic G1 arrest and caspase-dependant apoptosis when compared to scrambled transfectants which showed only G2/M cytostatic arrest in the cell lines investigated, suggesting an additional cell cycle-dependent, novel, role of Ku70 in protection from hyperthermia. Taken together, our data show a Ku70-dependent protection mechanism from hyperthermia. Targeting Ku70 and/or its acetylation during hyperthermia may represent a promising therapeutic approach for lung cancer.

  3. Focal Cerebral Ischemia Induces Alzheimer s Disease-like Pathological Change in Rats

    Institute of Scientific and Technical Information of China (English)

    王海均; 赵洪洋; 叶佑范; 熊南翔; 黄俊红; 姚东晓; 沈寅; 赵心同

    2010-01-01

    The changes in the tau protein phosphorylation and expression of bcl-2,and bax in rat parietal cortex neurons after focal cerebral ischemia-reperfusion(I/R)were explored,and the relationship between the tau protein phosphorylation and the expression of bax or apoptosis was clarified in order to elucidate the relationship between cerebral infarction and Alzheimer's disease.The rat focal cerebral I/R model was induced by occlusion of the right middle cerebral artery using the intraluminal suture method.The le...

  4. Vitamin E-deficiency did not exacerbate partial skin reactions in mice locally irradiated with X-rays

    International Nuclear Information System (INIS)

    We previously showed that free radicals and oxidative stress are involved in radiation-induced skin reactions. Since vitamin E (VE) is a particularly important lipophilic antioxidant, VE-deficient mice were used to examine its effects on radiation-induced skin damage. The VE content of the skin was reduced to one fourth of levels of normal mice. Neither the time of onset nor the extent of the reactions quantified with a scoring system differed between normal and VE-deficient mice after local X-irradiation (50 Gy). Similarly, there was no difference in the levels of the ascorbyl radical between the groups, although they were higher in irradiated skin than non-irradiated skin. X-irradiation increased the amount of Bax protein in the skin of normal mice both in the latent and acute inflammatory stages, time- and dose-dependently. The increase was associated with an increase in cytochrome c in the cytosolic fraction, indicating that apoptosis was also promoted by the irradiation. The increase in Bax protein correlated well with the thickness of the skin. Although a deficiency in VE should lower resistance to free radicals in the mitochondrial membrane and thus enhance radiation-induced Bax expression and apoptosis, it actually attenuated the increase in Bax protein caused by irradiation. (author)

  5. Differential roles of tau class glutathione S-transferases in oxidative stress

    DEFF Research Database (Denmark)

    Kilili, Kimiti G; Atanassova, Neli; Vardanyan, Alla;

    2004-01-01

    The plant glutathione S-transferase BI-GST has been identified as a potent inhibitor of Bax lethality in yeast, a phenotype associated with oxidative stress and disruption of mitochondrial functions. Screening of a tomato two-hybrid library for BI-GST interacting proteins identified five homologous...

  6. Combinatorial chemopreventive effect of butyric acid, nicotinamide and calcium glucarate against the 7,12-dimethylbenz(a)anthracene induced mouse skin tumorigenesis attained by enhancing the induction of intrinsic apoptotic events.

    Science.gov (United States)

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2015-01-25

    We explored the basis of the combinatorial chemopreventive effect of butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) on mouse skin exposed to 7,12-dimethylbenz(a)anthracene (DMBA). We studied the effects of topical application of DMBA in the presence or absence of BA, NA and CAG on the regulators of apoptosis. DMBA treatment suppressed Bax, Bax/Bcl-2 ratio, release of cyt c, Apaf1, caspase-9, -3 mediated apoptosis. Downregulation of p21 and upregulation of Bcl-2, mut p53 were also observed in only DMBA treated mice. Simultaneous application of BA, NA and CAG induced a mitochondria-mediated apoptosis, characterized by a rise in the Bax, Bax/Bcl-2 ratio, release of cyt c, upregulation of Apaf1 with down-stream activation of caspase-9, -3. Furthermore treatment with BA, NA and CAG demonstrated an upregulation of p21 and downregulation of Bcl-2, mut p53. But this effect was enhanced in the presence of all the three compounds together in combination. Chemoprevention by a combination of BA, NA and CAG by inducing the apoptosis, the natural cell death, suggest the importance of the potential combinational strategies capable of preventing skin tumor development.

  7. Medium-intensity acute exhaustive exercise induces neural cell apoptosis in the rat hippocampus

    Institute of Scientific and Technical Information of China (English)

    Shanni Li; Jin Liu; Hengmei Yan

    2013-01-01

    The present study assessed the influence of medium-intensity (treadmill at a speed of 19.3 m/min until exhaustion) and high-intensity (treadmill at a speed of 26.8 m/min until exhaustion) acute exhaustive exercise on rat hippocampal neural cell apoptosis. TUNEL staining showed significantly increased neural cell apoptosis in the hippocampal CA1 region of rats after medium- and high-intensity acute exhaustive exercise, particularly the medium-intensity acute exhaustive exercise, when compared with the control. Immunohistochemistry showed significantly increased expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax in the hippocampal CA1 region of rats after medium- and high-intensity acute exhaustive exercise. Additionally, the ratio of Bax to Bcl-2 increased in both exercise groups. In particular, the medium-intensity acute exhaustive exercise group had significantly higher Bax and Bcl-2 protein expression and a higher Bax/Bcl-2 ratio. These findings indicate that acute exhaustive exercise of different intensities can induce neural cell apoptosis in the hippocampus, and that medium-intensity acute exhaustive exercise results in greater damage when compared with high-intensity exercise.

  8. The Clinical and Medicolegal Analysis of Electrical Shocked Rats: Based on the Serological and Histological Methods

    Science.gov (United States)

    Wang, Qiaofeng; Zhao, Ze; Xie, Yanan; Ding, Suzhen

    2016-01-01

    This research was aimed at discovering the serological and histological changes in cardiac and hepatic tissue after electric shock. The CK-MB, ALT, and AMS indexes were tested with serological methods. Moreover, the Bcl-2, Bax, and Hsp-60 expression levels were carefully measured. An electrical injury model was established by giving rats electric shocks at 110 V with alternating electric current. Blood samples from the rats were analyzed for the biochemical indexes. The degrees of pathological changes in the heart and liver were evaluated using IHC staining for Bcl-2, Bax, and Hsp-60. The levels of CK-MB in the electrical injury group rapidly peaked at 0.5 hours after the electric shock. Additionally, the levels of Bcl-2, Bax, and Hsp-60 in the cardiac and hepatic tissues changed regularly after the electrical injury and exhibited apparent differences from the levels in the control group. CK-MB, ALT, and AMS were altered regularly after electric shock, and these results provide significant information for clinical and medicolegal practice. This research has shed light on the assessment of electrical injury without obvious electrical burns. Furthermore, the findings obtained for Bcl-2/Bax and Hsp-60 can also facilitate pathological diagnosis and the identification of antemortem and postmortem electrical injury. PMID:27648446

  9. Apoptosis of human pancreatic cancer cells induced by Triptolide

    Institute of Scientific and Technical Information of China (English)

    Guo-Xiong Zhou; Xiao-Ling Ding; Jie-Fei Huang; Hong Zhang; Sheng-Bao Wu; Jian-Ping Cheng; Qun Wei

    2008-01-01

    AIM:To investigate apoptosis in human pancreatic cancer ceils induced by Triptolide (TL),and the relationship between this apoptosis and expression of caspase-3' bcl-2 and bax.METHODS:Human pancreatic cancer cell line SW1990 was cultured in DIEM media for this study.MTT assay was used to determine the cell growth inhibitory rate in vitro.Flow cytometry and TUNEL assay were used to detect the apoptosis of human pancreatic cancer cells before and after TL treatment.RT-PCR was used to detect the expression of apoptosis-associated gene caspase-3' bcl-2 and bax.RESULTS:TL inhibited the growth of human pancreatic cancer cells in a dose-and time-dependent manner.TL induced human pancreatic cancer cells to undergo apoptosis with typically apoptotic characteristics.TUNEL assay showed that after the treatment of human pancreatic cancer cells with 40 ng/mL TL for 12 h and 24 h,the apoptotic rates of human pancreatic cancer cells increased significantly.RT-PCR demonstrated that caspase-3 and bax were significantly up-regulated in SW1990 cells treated with TL while bcl-2 mRNA was not.CONCLUSION:TL is able to induce the apoptosis in human pancreatic cancer cells.This apoptosis may be mediated by up-regulating the expression of apoptosisassociated caspase-3 and bax gene.

  10. Dicty_cDB: Contig-U15988-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available Sequence 862 from patent US 7135558. 44 4.1 1 ( DL173691 ) Methods for Identifying the Target of a Compound ...... 44 4.1 1 ( DL173298 ) Methods for Identifying the Target of a Compound ... 44 4.1 1 ( DL131093 ) Bax-res

  11. Disease: H00328 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ial use of the bacteria for bioterrorism has focused interest on it. B. anthracis causes symptoms ranging from cutaneous anthrax... that resolves spontaneously to gastrointestinal and inhalational anthrax...ar bat bai bax] Bacillus cereus [GN:bal] anthrax toxin [KO:K11029 K11030 K08645] pore-forming toxin [KO:K110

  12. Medium-intensity acute exhaustive exercise induces neural cell apoptosis in the rat hippocampus.

    Science.gov (United States)

    Li, Shanni; Liu, Jin; Yan, Hengmei

    2013-01-15

    The present study assessed the influence of medium-intensity (treadmill at a speed of 19.3 m/min until exhaustion) and high-intensity (treadmill at a speed of 26.8 m/min until exhaustion) acute exhaustive exercise on rat hippocampal neural cell apoptosis. TUNEL staining showed significantly increased neural cell apoptosis in the hippocampal CA1 region of rats after medium- and high-intensity acute exhaustive exercise, particularly the medium-intensity acute exhaustive exercise, when compared with the control. Immunohistochemistry showed significantly increased expression of the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax in the hippocampal CA1 region of rats after medium- and high-intensity acute exhaustive exercise. Additionally, the ratio of Bax to Bcl-2 increased in both exercise groups. In particular, the medium-intensity acute exhaustive exercise group had significantly higher Bax and Bcl-2 protein expression and a higher Bax/Bcl-2 ratio. These findings indicate that acute exhaustive exercise of different intensities can induce neural cell apoptosis in the hippocampus, and that medium-intensity acute exhaustive exercise results in greater damage when compared with high-intensity exercise. PMID:25206482

  13. Potential mechanisms involved in resistant phenotype of MCF-7 breast carcinoma cells to ionizing radiation induced apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yanling [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate School of Chinese Academy of Sciences, Beijing 100039 (China); Zhang Hong [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China)], E-mail: zhangh@impcas.ac.cn; Li Ning [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate School of Chinese Academy of Sciences, Beijing 100039 (China); Wang Xiaohu [Department of Radiotherapy, Gansu Tumor Hospital, Lanzhou 730050 (China); Hao Jifang [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Zhao Weiping [Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Key Laboratory of Heavy Ion Radiation Medicine of Gansu Province, Lanzhou 730000 (China); Graduate School of Chinese Academy of Sciences, Beijing 100039 (China)

    2009-03-15

    In the present study, we investigated the mechanisms of apoptosis resistance and the roles of the phosphorylation of BRCA1, p21, the Bax/Bcl-2 protein ratio and cell cycle arrest in IR-induced apoptosis in MCF-7 cells. X-irradiation, in particular at low dose (1 Gy), but not carbon ion irradiation, had a significant antiproliferative effect on the growth of MCF-7 cells. 1 Gy X-irradiation resulted in G1 and G2 phase arrest, but 4 Gy induced a significant G1 block. In contrast, carbon ion irradiation resulted in a significant accumulation in the G2 phase. Concomitant with the phosphorylation of H2AX induced by DNA damage, carbon ion irradiation resulted in an approximately 1.9-2.8-fold increase in the phosphorylation of BRCA1 on serine residue 1524, significantly greater than that detected for X-irradiation. Carbon ion irradiation caused a dramatic increase in p21 expression and drastic decrease in Bax expression compared with X-irradiation. The data implicated that phosphorylation of BRCA1 on serine residue 1524 might, at least partially, induce p21 expression but repress Bax expression. Together, our results suggested that the phosphorylation of BRCA1 at Ser-1524 might contribute to the G2 phase arrest and might be an upstream signal involved in preventing apoptosis signal via upregulation of p21 and downregulation of the Bax/Bcl-2 ratio.

  14. Potential mechanisms involved in resistant phenotype of MCF-7 breast carcinoma cells to ionizing radiation induced apoptosis

    Science.gov (United States)

    Wang, Yan-ling; Zhang, Hong; Li, Ning; Wang, Xiao-hu; Hao, Ji-fang; Zhao, Wei-ping

    2009-03-01

    In the present study, we investigated the mechanisms of apoptosis resistance and the roles of the phosphorylation of BRCA1, p21, the Bax/Bcl-2 protein ratio and cell cycle arrest in IR-induced apoptosis in MCF-7 cells. X-irradiation, in particular at low dose (1 Gy), but not carbon ion irradiation, had a significant antiproliferative effect on the growth of MCF-7 cells. 1 Gy X-irradiation resulted in G1 and G2 phase arrest, but 4 Gy induced a significant G1 block. In contrast, carbon ion irradiation resulted in a significant accumulation in the G2 phase. Concomitant with the phosphorylation of H2AX induced by DNA damage, carbon ion irradiation resulted in an approximately 1.9-2.8-fold increase in the phosphorylation of BRCA1 on serine residue 1524, significantly greater than that detected for X-irradiation. Carbon ion irradiation caused a dramatic increase in p21 expression and drastic decrease in Bax expression compared with X-irradiation. The data implicated that phosphorylation of BRCA1 on serine residue 1524 might, at least partially, induce p21 expression but repress Bax expression. Together, our results suggested that the phosphorylation of BRCA1 at Ser-1524 might contribute to the G2 phase arrest and might be an upstream signal involved in preventing apoptosis signal via upregulation of p21 and downregulation of the Bax/Bcl-2 ratio.

  15. Effects of Oxymatrine on the Apoptosis of Human Esophageal Carcinoma Eca109 Cell Line and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    Yi JIN; Jianli HU; Qiong WANG; Zhenyu LI; Yeshan CHEN

    2008-01-01

    The effects of Oxymatrine (Oxy) on the proliferation and apoptosis of human esophageal carcinoma Eca109 cell line and the mechanism were investigated. The human esophageal carcinoma Eca109 cells were cultured in vitro. The Oxy-induced apoptosis of Eca109 cells was assayed by using flow cytometry. The expressions of p-ERK1/2, Cyclin D1, p21waf/cip1, Bax and Bcl-2 were detected by Western blot. Flow cytometry revealed that Oxy could induce the apoptosis of Eca109 cells. Western blot showed that Oxy of different concentrations suppressed the expressions of p-ERK1/2, cyclin D1 and Bc1-2, but up-regulated the expression of p21waf/cip1 and Bax, and the ratio of Bax/Bcl-2 was increased It was suggested the Oxy could induce the apoptosis of Eca109-cells, which might be related to the upregulation of p21waf/cip1 and the downregulation of p-ERK1/2 Cyclin D1 and p21waf/cip1. The possible pathway may be related to Bcl-2/Bax.

  16. Resveratrol induces apoptosis in human esophageal carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Hai-Bo Zhou; Yun Yan; Ya-Ni Sun; Ju-Ren Zhu

    2003-01-01

    AIM: To investigate the apoptosis in esophageal cancer cells induced by resveratrol, and the relation between this apoptosis and expression of Bcl-2 and Bax.METHODS: In in vitro experiments, MTr assay was used to determine the cell growth inhibitory rate. Transmission electron microscope and TUNEL staining method were used to quantitatively and qualitively detect the apoptosis status of esophageal cancer cell line EC-9706 before and after the resveratrol treatment. Immunohistochemical staining was used to detect the expression of apoptosis-regulated gene Bcl-2 and Bax.RESULTS: Resveratrol inhibited the growth of esophageal cancer cell line EC-9706 in a dose-and time-dependent manner. Resveratrol induced EC-9706 cells to undergo apoptosis with typically apoptotic characteristics, including morphological changes of chromatin condensation, chromatin crescent formation, nucleus fragmentation and apoptotic body formation. TUNEL assay showed that after the for 24 to 96 hours, the AIs were apparently increased with treated time (P<0.05). Immunohistochemical staining showed that after the treatment of EC-9706 cells with proteins were apparently reduced with treated time (P<0.05)and the PRs of Bax proteins were apparently increased with treated time (P<0.05).CONCLUSION: Resveratrol is able to induce the apoptosisin esophageal cancer. This apoptosis may be mediated by down-regulating the apoptosis-regulated gene Bcl-2 and upregulating the expression of apoptosis-regulated gene bax.

  17. Combinatorial chemopreventive effect of butyric acid, nicotinamide and calcium glucarate against the 7,12-dimethylbenz(a)anthracene induced mouse skin tumorigenesis attained by enhancing the induction of intrinsic apoptotic events.

    Science.gov (United States)

    Tiwari, Prakash; Sahay, Satya; Pandey, Manuraj; Qadri, Syed S Y H; Gupta, Krishna P

    2015-01-25

    We explored the basis of the combinatorial chemopreventive effect of butyric acid (BA), nicotinamide (NA) and calcium glucarate (CAG) on mouse skin exposed to 7,12-dimethylbenz(a)anthracene (DMBA). We studied the effects of topical application of DMBA in the presence or absence of BA, NA and CAG on the regulators of apoptosis. DMBA treatment suppressed Bax, Bax/Bcl-2 ratio, release of cyt c, Apaf1, caspase-9, -3 mediated apoptosis. Downregulation of p21 and upregulation of Bcl-2, mut p53 were also observed in only DMBA treated mice. Simultaneous application of BA, NA and CAG induced a mitochondria-mediated apoptosis, characterized by a rise in the Bax, Bax/Bcl-2 ratio, release of cyt c, upregulation of Apaf1 with down-stream activation of caspase-9, -3. Furthermore treatment with BA, NA and CAG demonstrated an upregulation of p21 and downregulation of Bcl-2, mut p53. But this effect was enhanced in the presence of all the three compounds together in combination. Chemoprevention by a combination of BA, NA and CAG by inducing the apoptosis, the natural cell death, suggest the importance of the potential combinational strategies capable of preventing skin tumor development. PMID:25478867

  18. 76 FR 15791 - National Poultry Improvement Plan and Auxiliary Provisions

    Science.gov (United States)

    2011-03-22

    ... enzyme-linked immunosorbent assay (ELISA) test,\\3\\ a polymerase chain ] reaction (PCR)-based test, or a...) H7L4S3. (3) DuPont Qualicon BAX Polymerase Chain Reaction (PCR)-based assay for Salmonella, DuPont.... In addition, our proposed changes to paragraph (b) of Sec. 145.14 indicated that the polymerase...

  19. Paclitaxel induces apoptosis in human gastric carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Hai-Bo Zhou; Ju-Ren Zhu

    2003-01-01

    AIM: To investigate the apoptosis in gastric cancer cells induced by paclitaxel, and the relation between this apoptosis and expression of Bcl-2 and Bax.METHODS: In in vitro experiments, MTT assay was used to determine the cell growth inhibitory rate. Transmission electron microscope and TUNEL staining method were used to quantitatively and qualitively detect the apoptosis status of gastric cancer cell line SGC-7901 before and after the paditaxel treatment. Immunohistochemical staining was used to detect the expression of apoptosis-regulated gene Bcl-2and Bax.RESULTS: Paclitaxel inhibited the growth of gastric cancer cell line SGC-7901 in a dose-and time-dependent manner.Paclitaxel induced SGC-7901 cells to undergo apoptosis with typically apoptotic characteristics, including morphological changes of chromatin condensation, chromatin crescent formation, nucleus fragmentation and apoptotic body formation. Paclitaxel could reduce the expression of apoptosis-regulated gene Bcl-2, and improve the expression of apoptosis-regulated gene Bax.CONCLUSION: Paclitaxel is able to induce the apoptosis in gastric cancer. This apoptosis may be mediated by downexpression of apoptosis-regulated gene Bcl-2 and upexpression of apoptosis-regulated gene Bax.

  20. ICT in ELT: How Did We Get Here and Where Are We Going?

    Science.gov (United States)

    Dudeney, Gavin; Hockly, Nicky

    2012-01-01

    This article looks at how specific developments in information and communication technologies (ICT) have impacted on ELT over the past three decades. Of particular interest is the effect on classroom practice, and on the types of materials available for teaching and learning. We take as our starting point Mark Warschauer's and Stephen Bax's…

  1. Experimental Study on the Preventive Mechanism of Salviae Miltiorrhizae Against Atherosclerosis in Rabbits Models

    Institute of Scientific and Technical Information of China (English)

    李树生; 万磊

    2004-01-01

    Summary: The preventive mechanism of salviae miltiorrhizae (SM) against experimental atherosclerosis (AS) in rabbits models was investigated. The experimental AS rabbit models were reproduced by feeding the high cholesterol diet. The changes of atherosclerotic plaques in normal group, model group and SM treated group were observed. The levels of serum TG, TC, HDL-C and LDL-C were determined. The immunohistochemistry was used to detect the expression of Bcl-2,Bax and IL-6 proteins in atherosclerotic plaques. The results showed that the level of serum TG in SM treated group was significantly lower than in model group (P<0.01). Immunohistochemistry revealed that the expression of Bcl-2, Bax ano IL-6 in model group was significantly higher than in normal group.In the SM group, the expression of Bcl-2 protein was up-regulated and that of Bax was down-regulated. It was suggested that SM could inhibit formation of AS in experimental rabbits. To decrease the expression of Bax and increase the expression of Bcl-2 protein may be one of the mechanisms of SM against atherosclerosis.

  2. Dicty_cDB: Contig-U05695-1 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available Populus trichocarpa clone Pop1-51M14, complete se... 36 0.29 4 ( DL264438 ) METHODS FOR ANALYZING GENES OF INDUSTRIAL...ETHODS FOR ANALYZING GENES OF INDUSTRIAL YEASTS. 44 6.3 1 ( DL130971 ) Bax-responsive genes for drug target

  3. Metabolism and Endocrinology

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    2011183 Effect of pioglitazone on the expressions of Bax and Bcl-2 protein in mouse osteoblasts. LI Jun-yan (李俊岩) ,et al. Dept Endocrinol,Heji Hosp, Changzhi Med Coll,Changzhi 046000. Chin J Endocrinol Metab 2011; 27(2):118-121.

  4. Apoptosis of Alveolar Wall Cells in Chronic Obstructive Pulmonary Disease Patients with Pulmonary Emphysema Is Involved in Emphysematous Changes

    Institute of Scientific and Technical Information of China (English)

    Hongmei LIU; Lijun MA; Jizhen WU; Kai WANG; Xianliang CHEN

    2009-01-01

    s of alveolar wall cells, espe-cially apoptosis of type-Ⅱ cells, may take part in the pathogenesis of emphysema. Up-regulation of Bax expression may be responsible for the apoptosis of alveolar wall cells in the COPD patients with pulmonary emphysema.

  5. Upregulation of p‑Akt by glial cell line‑derived neurotrophic factor ameliorates cell apoptosis in the hippocampus of rats with streptozotocin‑induced diabetic encephalopathy.

    Science.gov (United States)

    Cui, Weigang; Zhang, Yinghua; Lu, Derong; Ren, Mingxin; Yuan, Guoyan

    2016-01-01

    The loss of neurotrophic factor support has been shown to contribute to the development of the central nervous system. Glial cell line‑derived neurotrophic factor (GDNF), a potent neurotrophic factor, is closely associated with apoptosis and exerts neuroprotective effects on numerous populations of cells. However, the underlying mechanisms of these protective effects remain unknown. In the present study, a significant increase in Bax levels and DNA fragmentation was observed in the hippocampus obtained from the brains of diabetic rats 60 days after diabetes had been induced. The apoptotic changes were correlated with the loss of GDNF/Akt signaling. GDNF administration was found to reverse the diabetes‑induced Bax and DNA fragmentation changes. This was associated with an improvement in the level of p‑Akt/Akt. In addition, combination of GDNF with a specific inhibitor of the phosphoinositide 3‑kinase (PI3K)/Akt pathway, Wortmannin, significantly abrogated the effects of GDNF on the levels of p‑Akt/Akt, Bax and DNA fragmentation. However, a p38 mitogen‑activated proten kinase (MAPK) inhibitor, SB203580, had no effect on the expression of p‑Akt/Akt, Bax or DNA fragmentation. These results demonstrate the pivotal role of GDNF as well as the PI3K/Akt pathway, but not the MAPK pathway, in the prevention of diabetes‑induced neuronal apoptosis in the hippocampus. PMID:26549420

  6. The effects of unilateral varicose ovarian vein on antioxidant capacity and oocyte quality in rat ovary

    Directory of Open Access Journals (Sweden)

    Babatunde Adebayo Kehinde

    2016-08-01

    Conclusion: The results of this study show that reduced gene expression of Bmp-15, Gdf-9 and Hsp-27, increased gene expression of bax and an imbalance between pro-oxidant/ antioxidant ratio are few of the several mechanisms by which varicocele may lead to infertility in female.

  7. Ceftriaxone, a Beta-Lactam Antibiotic, Modulates Apoptosis Pathways and Oxidative Stress in a Rat Model of Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Bahareh Amin

    2014-01-01

    Full Text Available Purpose. In our previous study, ceftriaxone, a beta-lactam antibiotic, elicited antinociceptive effects in the chronic constriction injury (CCI of neuropathic pain. In this study, we assessed apoptosis and oxidative stress in the spinal cord of neuropathic rats treated with ceftriaxone. Methods. 45 male Wistar rats were divided as naïve, sham, normal saline-treated CCI rats, and CCI animals treated with the effective dose of ceftriaxone. Involvement of Bax, Bcl2, and caspases 3 and 9, important contributors of programmed cell death (apoptosis, was determined using western blotting at days 3 and 7. The markers of oxidative stress including malondialdehyde (MDA and reduced glutathione (GSH were measured on days 3 and 7. Results. Increased Bax/Bcl2 ratio and cleaved active forms of caspases 3 and 9 were observed in the spinal cord of CCI rats on day 3. Ceftriaxone attenuated the increased levels of Bax and cleaved forms of caspases 3 and 9, while it increased Bcl2 levels. Bax and active forms of caspases declined by day 7. Consequently, comparison among groups showed no difference at this time. CCI enhanced MDA and decreased GSH on days 3 and 7, while ceftriaxone protected against the CCI-induced oxidative stress. Conclusion. Our results suggest that ceftriaxone, an upregulator/activator of GLT1, could concomitantly reduce oxidative stress and apoptosis and producing its new analogs lacking antimicrobial activity may represent a novel approach for neuropathic pain treatment.

  8. Cardiolipin or MTCH2 can serve as tBID receptors during apoptosis.

    Science.gov (United States)

    Raemy, E; Montessuit, S; Pierredon, S; van Kampen, A H; Vaz, F M; Martinou, J-C

    2016-07-01

    During apoptosis, proapoptotic BAX and BAK trigger mitochondrial outer membrane (MOM) permeabilization by a mechanism that is not yet fully understood. BH3-only proteins such as tBID, together with lipids of the MOM, are thought to play a key role in BAX and BAK activation. In particular, cardiolipin (CL) has been shown to stimulate tBID-induced BAX activation in vitro. However, it is still unclear whether this process also relies on CL in the cell, or whether it is more dependent on MTCH2, a proposed receptor for tBID present in the MOM. To address this issue, we deleted both alleles of cardiolipin synthase in human HCT116 cells by homologous recombination, which resulted in a complete absence of CL. The CL-deficient cells were fully viable in glucose but displayed impaired oxidative phosphorylation and an inability to grow in galactose. Using these cells, we found that CL was not required for either tBID-induced BAX activation, or for apoptosis in response to treatment with TRAIL. Downregulation of MTCH2 in HCT116 cells also failed to prevent recruitment of tBID to mitochondria in apoptotic conditions. However, when both CL and MTCH2 were depleted, a significant reduction in tBID recruitment was observed, suggesting that in HCT116 cells, CL and MTCH2 can have redundant functions in this process. PMID:26794447

  9. Differential effects of two pro-apoptotic members of the Bcl-2 gene family on murine bone quality

    Science.gov (United States)

    Wise, Lisa Marie

    Bax and Hrk are pro-apoptotic members of the Bcl-2 gene family. Both Bax and Hrk have been previously implicated in ovarian cell survival. Effects on bone cells have also been studied in several members of the Bcl-2 gene family; thus, the focus of this work was to characterize the bone quality of mice deficient in Bax or Hrk. Bone quality of various age groups (3, 6, 12, 6 and 22 months) of Bax-knockout (KO) and Hrk-KO female mice were compared to age-matched control female mice. Additional groups of 6-month mice were ovariectomized (OVX) to determine whether effects are dependent on ovarian function. Dual energy x-ray absorptiometry was performed on all mice to determine bone mineral density (BMD). To evaluate bone mechanical properties, 3-point bending, torsion testing and femoral neck fracture were performed on femora, while compression was performed on individual vertebrae. Mechanical properties were rationalized through evaluation of structural (strut analysis, micro computed tomography), remodeling (histomorphometry, osteoclast staining) and material (back-scattered electron imaging, x-ray diffraction) properties. Aged Bax-KO mice do not experience the loss in BMD, bone mechanics and trabecular bone structural properties typically observed with age. Enhanced ovarian cell numbers in Bax-KO mice likely indirectly leads to this enhanced bone phenotype. Ovariectomy results in the loss of the enhanced trabecular bone phenotype, but does not affect the cortical bone phenotype. As such, cortical bone may be protected from typical OVX effects due to sustained osteoblast function in Bax-KO mice. By contrast, young Hrk-KO mice exhibit higher BMD and trabecular bone structural properties compared to control mice, coupled with a compromised mechanical integrity. This subtle transient osteopetrotic-like phenotype is likely influenced by a potentially augmented osteoblast survival, albeit with a compromised activity. This osteopetrotic-like phenotype, and the effect of Hrk

  10. Transcription of five p53- and Stat-3-Inducible genes after ionizing radiation

    International Nuclear Information System (INIS)

    Ionizing radiation (IR) produces temporal- and dose-dependent changes in multiple gene mRNA targets that are potential biomarkers of radiation dose. We confirmed IR-induced changes in expression of gadd45a, ddb-2, and cdkn1a downstream transcripts of p53 by quantitative reverse transcription-polymerase chain reaction (QRT-PCR) assay in total RNA samples from the whole blood of radiotherapy patients undergoing total-body irradiation [Amundson, S.A., Grace, M.B., McLeland, C.B., Epperly, M.W., Yeager, A., Zhan, Q., Greenberger, J.S., Fornace Jr., A.J., 2004. Human in vivo radiation-induced biomarkers: gene expression changes in radiotherapy patients. Cancer Res. 64, 6368-6371.]. We now confirm dose-dependent up-regulation of bax in addition to these p53-dependent transcripts, and bcl-2, a downstream transcript of Stat-3, in ex vivo irradiated blood samples from healthy unrelated volunteers. Together these biomarkers represent pathways involved in growth arrest, DNA damage, and apoptosis. The objectives of this study were to (1) investigate the relationship between baseline mRNA expression levels, and (2) define expression patterns in response to IR in a large cohort (n=20). Whole-blood samples were irradiated ex vivo to measure gene expression in samples from (i) three healthy donors over a broad dose range (0, 0.25, 0.50, 0.75, 1, 2, and 3 Gy), and (ii) 20 healthy donors at two doses, 0.25 and 2.5 Gy. Expression level variance (σ2) of baseline values (0 Gy) showed negligible inter-individual variation with all values ≤1.0. σ2values=0.50bax, 0.25 bcl-2, 0.73 gadd45a, 0.66 cdkn1a, and 1.0 ddb-2. Meaningful IR dose-responses were observed for bax, gadd45a, and ddb-2 profiles and the ratio of bax:bcl-2 mRNA expression over a broad dose range. QRT-PCR studies were extended in the lower dose range (0, 0.1, 0.5, 0.75, and 1 Gy). Results showed that bax:bcl-2 ratio initially favors bax expression at doses of <1Gy, with IR-induced dose responses observed between 1 and 3

  11. Protective Effects of Baicalin Against Learing and Memory Capacity of Mice with Cerebral Ischemia-reperfusion Injury%黄芩苷抗脑缺血小鼠学习记忆功能损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    李园园; 杨晖; 廖桂凤; 曾勇

    2011-01-01

    目的 探讨中药黄芩苷对脑缺血-再灌注模型小鼠学习记忆功能损伤的保护作用和机理.方法 将60只小鼠随机等分为脑缺血模型组、假手术组、黄芩苷组,采用经典Morris水迷宫法测试小鼠空间学习记忆能力,记录每天的潜伏期与游泳轨迹,同时运用蛋白印记的方法来检测小鼠纹状体中Bax 和Bcl-2蛋白水平的变化.结果 黄芩苷组小鼠水迷宫训练学习期的第4 天开始,逃避潜伏期缩短、错误次数减少,与模型组相比差异有统计学意义(P < 0.01);脑缺血模型组损伤4 d后,小鼠纹状体区神经细胞Bcl-2与Bax表达、Bax/Bcl-2比值都上调;黄芩苷组预处理可以分别下调Bax表达与Bax/Bcl-2比值,较模型组显著降低(P<0.01).结论 黄芩苷能有效预防脑缺血-再灌注致小鼠学习能力的损伤,其作用机制可能与Bax/Bcl-2改变有关.%Objective To investigate the protective effect and mechinasm of baicalin against the leaming and memory capacity of mice with cerebral ischemia-reperfusion injury. Methods Sixty Kunming mice were randomly divided into three groups: control group (n = 20) , reperfusion group (n = 20) and baicalin group (n = 20). Water maze of Morris was used to detect the learning and memory capacity, and latent period and swimming locus were recorded. Westem blot analysis was used to detect Bax and Bcl-2 protein expression in mice in each group. Resuls From the 4th day after Water maze training, the latent period was shortened and the error times were reduced in mice in Baicalin groups, and had significant difference with those in reperfusion group (P< 0.01 ). The protein expression of Bcl-2 and Bax was upregulated and the Bax/Bcl-2 ratio increased in corpus striatum of mice in reperfusion group 4 days after ischemia-reperfusion injury. Baicalin treatment significantly downregulated the protein expression of Bax and reduced Bax/Bcl-2 ratio after ischemia-reperfusion injury,compared with reperfusion

  12. Effect of fetal hypothyroidism on tolerance to ischemia-reperfusion injury in aged male rats: Role of nitric oxide.

    Science.gov (United States)

    Jeddi, Sajad; Zaman, Jalal; Ghasemi, Asghar

    2016-05-01

    Aging is associated with increased prevalence of cardiovascular disease. Thyroid hormone deficiency during fetal life decreases myocardial tolerance to ischemia-reperfusion (IR) injury in later life. The long-term effects of fetal hypothyroidism (FH) on response to IR injury in aged rats have not been well documented. The aim of this study was therefore to compare the effect of FH on tolerance to IR injury in young and aged male rats and to determine contribution of iNOS (inducible nitric oxide synthase), Bax, and Bcl-2. Pregnant female rats were divided into two groups: The FH group received water containing 0.025% 6-propyl-2-thiouracil during gestation and the controls consumed tap water. Isolated perfused hearts from young (3 months) and aged (12 months) rats were subjected to IR. Hemodynamic parameters, infarct size, and heart NOx (nitrite+nitrate) levels were measured; in addition, mRNA expression of iNOS, Bax, and Bcl-2 and their protein levels in heart were measured. Recovery of post-ischemic LVDP and ±dp/dt were lower and infarct sizes were higher than controls in aged FH rats (68.38 ± 6.7% vs. 50.5 ± 1.7%; P Bcl-2 was lower in both the young (350 and 240% for iNOS and Bax, respectively and 51% for Bcl-2) and aged rats (504 and 567% for iNOS and Bax, respectively and 67% for Bcl-2). Compared to controls, in FH rats protein levels of iNOS (37% for young and 45% for aged rats) and Bax (94% for young and 118% for aged rats) were higher while for Bcl-2 (36% for young and 62% for aged rats) were lower. After IR, in FH rats, aminoguanidine, a selective iNOS inhibitor, decreased mRNA expression of iNOS and Bax and increased expression of Bcl-2 in both young (65% and 58% for iNOS and Bax, respectively and 152% for Bcl-2) and aged rats (76% and 64% for iNOS and Bax, respectively and 222% for Bcl-2). In addition, in the heart of FH rats, aminoguanidine decreased protein levels of iNOS (47% for young and 60% for aged rats) and Bax (57% for young and 80% for

  13. Induction of Apoptosis and expression of Apoptosis-related gene products in response to radiation in murine tumors

    International Nuclear Information System (INIS)

    To analyze the involvement of apoptosis regulatory genes p53, p21waf1/cip1, bax and bcl-2 in induction of apoptosis by radiation in murine tumors. The radiation-sensitive ovarian carcinoma OCa-I and the radiation-resistant hepatocarcinoma HCa-I were used. Tumors, 8mm in diameter, were irradiated with 25Gy and at various times after irradiation, ranging from 1 to 48 h, were analyzed histologically for apoptosis and by western blot for alterations in the expression of these genes. The p53 status of the tumors were determined by the polymerase chain reaction-single strand conformation polymorphism assay. Both tumors were positive for wild-type p53. Radiation induced apoptosis in OCa-I but not in HCa-I. Apoptosis developed rapidly, peaked at 2 h after irradiation and returned to almost the background level at 48 h. In OCa-I radiation upregulated the expression of p53, p21waf1/cip1, and the bcl-2/bax ratio was decreased. In HCa-I radiation increased the expression of both p53 and p21waf1/cip1, although the increase of the latter was small. The bcl-2/bax ratio was greatly increased. In general the observed changes occurred within a few hours after irradiation, and either preceded or coincided with development of apoptosis. The development of apoptosis required upregulation of both p53 and p21waf1/cip1 as well as a decrease in bcl-2/bax ratio. In contrast, an increase in bcl-2/bax ratio prevented apoptosis in the presence of upregulated p53 and p21waf1/cip1. These findings identified the involvement of multiple oncogenes in apoptosis regulation in vivo and demonstrate the complexity that may be associated with the use of a single oncogene assessment for predicting the outcome of cancer therapy with cytotoxic agents. (author)

  14. Change in expression of apoptosis genes after hyperthermia, chemotherapy and radiotherapy in human colon cancer transplanted into nude mice

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate the change in expression of p53, Bcl-2, and Bax genes in human colon cancer cells transplanted into nude mice after hyperthermia,chemotherapy, radiotherapy, thermochemotherapy,thermoradiotherapy and thermochemoradiotherapy.METHODS: Human colon cancer cell line (HT29)was transplanted into the hind limbs of nude mice.Under laboratory simulated conditions of hyperthermia (43℃, 60 min), the actual radiation doses and doses of mitomycin C (MMC) were calculated in reference to the clinical radiotherapy for human rectal cancer and chemotherapy prescription for colon cancer. The mice were divided into 6 groups according to the treatment approaches: hyperthermia, chemotherapy,radiotherapy, thermochemotherapy, thermoradiotherapy,and thermochemoradiotherapy. The mice were sacrificed at different time points and the tumor tissue was taken for further procedures. The morphologic changes in membrane, cytoplasm and nuclei of tumor cells of p53, Bcl-2, and Bax after treatment, were observed by immunohistochemistry staining.RESULTS: All of the six treatment modalities downregulated the expression of p53, Bcl-2 and up-regulated the expression of Bax at different levels. The combined therapy of hyperthermia, with chemotherapy, and/or irradiation showed a greater effect on down-regulating the expression of p53 (0.208 ± 0.009 vs 0.155 ± 0.0115,P < 0.01) and Bcl-2 (0.086 ± 0.010 vs 0.026 ± 0.0170,P < 0.01) and up-regulating Bax expression (0.091 ±0.0013 vs 0.207 ±0.027, P < 0.01) compared with any single therapy.CONCLUSION: Hyperthermia enhances the effect of radio- and chemotherapy on tumors by changing the expression of apoptosis genes, such as p53, Bcl-2 and Bax.

  15. Supercritical carbon dioxide extraction of aromatic turmerone from Curcuma longa Linn. induces apoptosis through reactive oxygen species-triggered intrinsic and extrinsic pathways in human hepatocellular carcinoma HepG2 cells.

    Science.gov (United States)

    Cheng, Shao-Bin; Wu, Li-Chen; Hsieh, Yun-Chih; Wu, Chi-Hao; Chan, Yu-Ju; Chang, Li-Hsun; Chang, Chieh-Ming J; Hsu, Shih-Lan; Teng, Chieh-Lin; Wu, Chun-Chi

    2012-09-26

    The mechanisms underlying the antiproliferative and antitumor activities of aromatic turmerone (ar-turmerone), a volatile turmeric oil isolated from Curcuma longa Linn., have been largely unknown. In this study, 86% pure ar-turmerone was extracted by supercritical carbon dioxide and liquid-solid chromatography and its potential effects and molecular mechanisms on cell proliferation studied in human hepatocellular carcinoma cell lines. Ar-turmerone exhibited significant antiproliferative activity, with 50% inhibitory concentrations of 64.8 ± 7.1, 102.5 ± 11.5, and 122.2 ± 7.6 μg/mL against HepG2, Huh-7, and Hep3B cells, respectively. Ar-turmerone-induced apoptosis, confirmed by increased annexin V binding and DNA fragmentation, was accompanied by reactive oxygen species (ROS) production, mitochondrial membrane potential dissipation, increased Bax and p53 up-regulated modulator of apoptosis (PUMA) levels, Bax mitochondrial translocation, cytochrome c release, Fas and death receptor 4 (DR4) augmentation, and caspase-3, -8, and -9 activation. Exposure to caspase inhibitors, Fas-antagonistic antibody, DR4 antagonist, and furosemide (a blocker of Bax translocation) effectively abolished ar-turmerone-triggered apoptosis. Moreover, ar-turmerone stimulated c-Jun N-terminal kinase (JNK) and extracellular signal-related kinase (ERK) phosphorylation and activation; treatment with JNK and ERK inhibitors markedly reduced PUMA, Bax, Fas, and DR4 levels and reduced apoptosis but not ROS generation. Furthermore, antioxidants attenuated ar-turmerone-mediated ROS production; mitochondrial dysfunction; JNK and ERK activation; PUMA, Bax, Fas, and DR4 expression; and apoptosis. Taken together, these results suggest that ar-turmerone-induced apoptosis in HepG2 cells is through ROS-mediated activation of ERK and JNK kinases and triggers both intrinsic and extrinsic caspase activation, leading to apoptosis. On the basis of these observations, ar-turmerone deserves further investigation

  16. The effect of arsenic trioxide on human hepatoma cell line BEL-7402 culturedin vitro

    Institute of Scientific and Technical Information of China (English)

    You Lin Yang; Hong Yu Xu; Yuan Yuan Gao; Qiao Li Wu; Guang Qiang Gao

    2000-01-01

    AIM To study the effect of a wide range of concentration of arsenic trioxide on human hepatoma cell lineBEL-7402 and its mechanism.METHODS The BEL-7402 cells were treated with arsenic trioxide (a final concentration of 0.5, 1 and2 μmol/L, respectively) in various durations or for 4 successive days. The cell growth and proliferation wereobserved by cell counting and cell-growth curve. Morphologic changes were studied under electronmicroscopy. Flow cytometry was used to assay cell-DNA distribution and the protein expression of Bcl-2 andBax was detected by immunocytochemical method.RESULTS The cell growth was significantly inhibited by the different concentrations of arsenic trioxide asrevealed by cell counting and cell-growth curve. Arsenic trioxide treatment at 0.5, 1 and 2 μmol/L, resultedin a sub-G1 cell peak. The decreased G0/G1 phase cell and the increased percentage of S phase cell were observed by flow cytometer, suggesting that the inhibiting effect of arsernic trioxide on BEL-7402 cell lay inG0/G1 phase cell. Apoptotis-related morphology, such as intact cell membrane, nucleic condensation,apoptotic body formation, can be seen under the electron microscopy. High protein expression level of Bcl-2and Bax was detected in 1 and 2 μmol/L arsenic trioxide-treated cells, but that of Bax was more significant.Arsenic trioxide treatment at 0.5 μmol/L resulted in higher expression level of Bcl-2 and lower expressionlevel of Bax compared with control (P1<0.01, P2<0.01).CONCLUSION Arsenic trioxide not only inhibited the proliferation but also induced apoptosis of humanhepatoma cell line BEL-7402. The induced-apoptosis effect of 1 and 2 μmol/L arsenic trioxide was relative tothe expression level of Bcl-2 and Bax.

  17. Astragaloside IV, a novel antioxidant, prevents glucose-induced podocyte apoptosis in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Dingkun Gui

    Full Text Available Glucose-induced reactive oxygen species (ROS production initiates podocyte apoptosis, which represents a novel early mechanism leading to diabetic nephropathy (DN. Here, we tested the hypothesis that Astragaloside IV(AS-IV exerts antioxidant and antiapoptotic effects on podocytes under diabetic conditions. Apoptosis, albuminuria, ROS generation, caspase-3 activity and cleavage, as well as Bax and Bcl-2 mRNA and protein expression were measured in vitro and in vivo. Cultured podocytes were exposed to high glucose (HG with 50, 100 and 200 µg/ml of AS-IV for 24 h. AS-IV significantly attenuated HG-induced podocyte apoptosis and ROS production. This antiapoptotic effect was associated with restoration of Bax and Bcl-2 expression, as well as inhibition of caspase-3 activation and overexpression. In streptozotocin (STZ-induced diabetic rats, severe hyperglycemia and albuminuria were developed. Increased apoptosis, Bax expression, caspase-3 activity and cleavage while decreased Bcl-2 expression were detected in diabetic rats. However, pretreatment with AS-IV (2.5, 5, 10 mg·kg(-1·d(-1 for 14 weeks ameliorated podocyte apoptosis, caspase-3 activation, renal histopathology, podocyte foot process effacement, albuminuria and oxidative stress. Expression of Bax and Bcl-2 mRNA and protein in kidney cortex was partially restored by AS-IV pretreatment. These findings suggested AS-IV, a novel antioxidant, to prevent Glucose-Induced podocyte apoptosis partly through restoring the balance of Bax and Bcl-2 expression and inhibiting caspase-3 activation.

  18. Apoptosis of human primary gastric carcinoma cells induced by genistein

    Institute of Scientific and Technical Information of China (English)

    Hai-Bo Zhou; Juan-Juan Chen; Wen-Xia Wang; Jian-Ting Cai; Qin Du

    2004-01-01

    AIM: To investigate the apoptosis in primary gastric cancer cells induced by genistein, and the relationship between this apoptosis and expression of bcl-2 and bax.METHODS: MTT assay was used to determine the cell growth inhibitory rate in vitro. Transmission electron microscope and TUNEL staining were used to quantitatively and qualitatively detect the apoptosis of primary gastric cancer cells before and after genistein treatment. Immunohistochemical staining and RT-PCR were used to detect the expression of apoptosisassociated genes bcl-2 and bax.RESULTS: Genistein inhibited the growth of primary gastric cancer cells in dose-and time-dependent manner. Genistein induced primary gastric cancer cells to undergo apoptosis with typically apoptotic characteristics. TUNEL assay showed that after the treatment of primary gastric cancer cells with genistein for 24 to 96 h, the apoptotic rates of primary gastric cancer cells increased time-dependently. Immunohistochemical staining showed that after the treatment of primary gastric cancer cells with genistein for 24 to 96 h, the positivity rates of Bcl-2 proteins were apparently reduced with time and the positivity rates of Bax proteins were apparently increased with time. After exposed to genistein at 20 μmol/L for 24,48, 72 and 96 respectively, the density of bcl-2 mRNA decreased progressively and the density of bax mRNA increased progressively with elongation of time.CONCLUSION: Genistein is able to induce the apoptosis in primary gastric cancer cells. This apoptosis may be mediated by down-regulating the apoptosis- associated bcl-2 gene and up-regulating the expression of apoptosis-associated bax gene.

  19. Clostridium butyricum pretreatment attenuates cerebral ischemia/reperfusion injury in mice via anti-oxidation and anti-apoptosis.

    Science.gov (United States)

    Sun, Jing; Ling, Zongxin; Wang, Fangyan; Chen, Wenqian; Li, Haixiao; Jin, Jiangtao; Zhang, Huiqing; Pang, Mengqi; Yu, Junjie; Liu, Jiaming

    2016-02-01

    Probiotics participate actively in the neuropsychiatric disorders. However, their roles on ischemic stroke remain unclear. This study aims to determine whether Clostridium butyricum (C. butyricum) could attenuate cerebral ischemia/reperfusion (I/R) injury and its possible mechanisms. Male ICR mice were intragastrically pretreated with C. butyricum for 2 successive weeks, and then subjected to cerebral I/R injury induced by the bilateral common carotid artery occlusion (BCCAO) for 20min. After 24h of the reperfusion, neurological deficit scores were evaluated. Histopathological changes of the hippocampus neurons were observed using Hematoxylin and eosin (H&E) and TUNEL staining. Malondialdehyde (MDA) contents and superoxide dismutase (SOD) activities in the brain were detected. The expression of Caspase-3, Bax and Bcl-2 were investigated by Western blot and immunohistochemistry analysis. The butyrate contents in the brain were determined. Our results showed that cerebral I/R injury led to neurological deficit, increased levels of Caspase-3 and Bax and decreased Bcl-2/Bax ratio. C. butyricum significantly improved neurological deficit, relieved histopathologic change, decreased MDA contents and increased SOD activities in the I/R injury mice. After C. butyricum pretreatment, the expression of Caspase-3 and Bax were significantly decreased, the Bcl-2/Bax ratio was significantly increased, and butyrate contents in the brain were significantly increased. These findings suggested that C. butyricum is able to exert neuroprotective effects against I/R injury mice through anti-oxidant and anti-apoptotic mechanisms, and reversing decrease of butyrate contents in the brain might be involved in its neuroprotection. PMID:26733300

  20. Protective Effect and Mechanism of TGF - β1 on Intestinal Mucosa against IR Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    SUN Peichun; WU Wanqing; WU Gang

    2008-01-01

    Objective To investigate the protective effect and mechanism of TGF - 1 on intestinal mucosa against ischemia-reperfusion (I/R) injury, so as to provide new methods of clinical prevention from and dealing with intestine I/R injury and gut - derived multiple organ dysfunction syndrome(MODS). Methods 30 SD rats were randomly divided into 3 groups ( n = 10 each), A: namely sham - operation group ( group A) : superior mesenteric artery ( SMA ) was only isolated but not blocked; B: control group (group B), ischemia for 60 minutes, then reperfusion for 120 minutes, and administered with normal saline solution (NS) 0. 5ml through SMA 10 minutes before SMA blockage; C: experimental group (group C) : animals underwent the same procedure with group B except for taking TGF-β1 instead of NS. The contents of intestinal mucosa Chiu's sore, bacteria translocation, intestinal mucosa cellular apoptosis index, expression of bax mRNA and bcl - 2 mRNA and protein were measured. Results Compared with group A, the results from group B are as follows, the Chiu's score significantly increased, bacteria translocation increased, intestinal mucosa cellular apeptosis rate significantly increased, level of bax mRNA and Bax protein significantly increased, while level of intestinal mucosal bcl -2 mRNA and Bcl -2 protein significantly decreased. All the changes in group B were reversed significantly in group C. Conclusion TGF - 1 exerts a protective effect on the gut barrier against intestine I/R injury, perhaps via reversing injury - induced downregulation in bcl2 transcription and upregulation in bax transcription, with the result in modulating bcl -2 and bax protein expression and downregulation of the susceptibility to apoptosis of intestinal epithelial cells.

  1. Study on the Effects of Losartan on Cardiomyocyte Apoptosis and Gene Expression After Ischemia and Reperfusion in vivo in Rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Dongqing; YANG Liming; LIU Zhengxiang; MI Shizan

    2000-01-01

    In order to study the effects of losartan on cardiomyocyte apoptosis following ischemia (0.5 h) and reperfusion (48 h) in vivo and bcl-2 and bax gene expression, TUNEL staining method, immunohistochemistry and in situ hybridization histochemistry (ISHH) were used to monitor the apoptotic cells, mRNA and protein of gene expression, respectively. Image processing system was used to quantitively dispose the positive metric substance of both immunohistochemistry and ISHH through the average optical density (OD) value. The number of the apoptotic cells were 38±9 (control group), 0-1 (sham operation group) and 9±4 (losartan-treated group) in each visual field respectively with the difference among the groups being significant (P<0.001). OD values of bcl-2 (ISHH) were 0.07425±0.02029 (control group), 0.05961±0.009932 (sham operation group) and 0. 07619±0.01445 (losartan-treated group) respectively,while OD values of bcl-2 (immunohistochemistry) were 0.1374 ±0.01367 (control group),0.08510±0.01862 (sham operation group) and 0.1252±0.02064 (losartan-treated group), bcl-2gene expression was increased significantly in the control gro