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Sample records for stress generates ros

  1. Blue light irradiation-induced oxidative stress in vivo via ROS generation in rat gingival tissue.

    Science.gov (United States)

    Yoshida, Ayaka; Shiotsu-Ogura, Yukako; Wada-Takahashi, Satoko; Takahashi, Shun-suke; Toyama, Toshizo; Yoshino, Fumihiko

    2015-10-01

    It has been reported that oxidative stress with reactive oxygen species (ROS) generation is induced by blue light irradiation to a living body. Only limited research has been reported in dental field on the dangers of blue light, mostly focusing on cytotoxicity associated with heat injury of dental pulp. We thus performed an in vivo study on oral tissue exposed to blue light. ROS generated upon blue light irradiation of flavin adenine dinucleotide were measured by electron spin resonance spectroscopy. After blue light irradiation, the palatal gingiva of Wistar rats were isolated. Collected samples were subjected to biochemical analysis of lipid peroxidation and glutathione. Singlet oxygen was generated by blue light irradiation, but was significantly quenched in an N-acetyl-L-cysteine (NAC) concentration-dependent manner. Blue light significantly accelerated oxidative stress and increased the oxidized glutathione levels in gingival tissue. These effects were also inhibited by NAC pre-administration. The results suggest that blue light irradiation at clinical levels of tooth bleaching treatment may enhance lipid peroxidation by the induction of oxidative stress and the consumption of a significant amount of intracellular glutathione. In addition, NAC might be an effective supplement for the protection of oral tissues against blue light irradiation-induced oxidative damage. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Endoplasmic Reticulum Stress and Associated ROS

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    Hafiz Maher Ali Zeeshan

    2016-03-01

    Full Text Available The endoplasmic reticulum (ER is a fascinating network of tubules through which secretory and transmembrane proteins enter unfolded and exit as either folded or misfolded proteins, after which they are directed either toward other organelles or to degradation, respectively. The ER redox environment dictates the fate of entering proteins, and the level of redox signaling mediators modulates the level of reactive oxygen species (ROS. Accumulating evidence suggests the interrelation of ER stress and ROS with redox signaling mediators such as protein disulfide isomerase (PDI-endoplasmic reticulum oxidoreductin (ERO-1, glutathione (GSH/glutathione disuphide (GSSG, NADPH oxidase 4 (Nox4, NADPH-P450 reductase (NPR, and calcium. Here, we reviewed persistent ER stress and protein misfolding-initiated ROS cascades and their significant roles in the pathogenesis of multiple human disorders, including neurodegenerative diseases, diabetes mellitus, atherosclerosis, inflammation, ischemia, and kidney and liver diseases.

  3. Role of ER stress response in photodynamic therapy: ROS generated in different subcellular compartments trigger diverse cell death pathways

    Czech Academy of Sciences Publication Activity Database

    Moserová, Irena; Králová, Jarmila

    2012-01-01

    Roč. 7, č. 3 (2012), e32972 E-ISSN 1932-6203 R&D Projects: GA MŠk(CZ) LC06077; GA ČR GA203/09/1311; GA ČR(CZ) GAP303/11/1291 Institutional research plan: CEZ:AV0Z50520514 Keywords : photodynamic therapy * porphyrin derivatives * cell death * ER stress Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.730, year: 2012

  4. Ny forskning: Derfor virker ros ikke mod stress

    DEFF Research Database (Denmark)

    Pedersen, Pernille

    2015-01-01

    Ny forskning peger på, at stressede medarbejdere overhører din ros og anerkendelse, hvis de føler skam. Skam over ikke at kunne slå til på arbejdet. Vil du hjælpe en stresset medarbejder, skal du forebygge, at de føler sig skamfulde. Læs her anbefalinger til, hvordan du bedst hjælper din stressed...

  5. Chelerythrine induced cell death through ROS-dependent ER stress in human prostate cancer cells

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    Wu S

    2018-05-01

    Full Text Available Songjiang Wu, Yanying Yang, Feiping Li, Lifu Huang, Zihua Han, Guanfu Wang, Hongyuan Yu, Haiping Li Department of Urology, Enze Hospital of Taizhou Enze Medical Center (Group, Taizhou, China Introduction: Prostate cancer is the most common noncutaneous cancer and the second leading cause of cancer-related mortality worldwide and the third in USA in 2017. Chelerythrine (CHE, a naturalbenzo[c]phenanthridine alkaloid, formerly identified as a protein kinase C inhibitor, has also shown anticancer effect through a number of mechanisms. Herein, effect and mechanism of the CHE-induced apoptosis via reactive oxygen species (ROS-mediated endoplasmic reticulum (ER stress in prostate cancer cells were studied for the first time. Methods: In our present study, we investigated whether CHE induced cell viability decrease, colony formation inhibition, and apoptosis in a dose-dependent manner in PC-3 cells. In addition, we showed that CHE increases intracellular ROS and leads to ROS-dependent ER stress and cell apoptosis. Results: Pre-treatment with N-acetyl cysteine, an ROS scavenger, totally reversed the CHE-induced cancer cell apoptosis as well as ER stress activation, suggesting that the ROS generation was responsible for the anticancer effects of CHE. Conclusion: Taken together, our findings support one of the anticancer mechanisms by which CHE increased ROS accumulation in prostate cancer cells, thereby leading to ER stress and caused intrinsic apoptotic signaling. The study reveals that CHE could be a potential candidate for application in the treatment of prostate cancer. Keywords: chelerythrine, reactive oxygen species, endoplasmic reticulum stress, apoptosis, prostate cancer

  6. Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Seung Min, E-mail: smjeong@catholic.ac.kr [Department of Biochemistry, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Institute for Aging and Metabolic Diseases, College of Medicine, The Catholic University of Korea, Seoul 137-701 (Korea, Republic of); Hwang, Sunsook; Seong, Rho Hyun [School of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul 151-742 (Korea, Republic of)

    2016-03-11

    The transferrin receptor (TfR1) is upregulated in malignant cells and its expression is associated with cancer progression. Because of its pre-eminent role in cell proliferation, TfR1 has been an important target for the development of cancer therapy. Although TfR1 is highly expressed in pancreatic cancers, what it carries out in these refractory cancers remains poorly understood. Here we report that TfR1 supports mitochondrial respiration and ROS production in human pancreatic ductal adenocarcinoma (PDAC) cells, which is required for their tumorigenic growth. Elevated TfR1 expression in PDAC cells contributes to oxidative phosphorylation, which allows for the generation of ROS. Importantly, mitochondrial-derived ROS are essential for PDAC growth. However, exogenous iron supplement cannot rescue the defects caused by TfR1 knockdown. Moreover, we found that TfR1 expression determines PDAC cells sensitivity to oxidative stress. Together, our findings reveal that TfR1 can contribute to the mitochondrial respiration and ROS production, which have essential roles in growth and survival of pancreatic cancer. - Highlights: • Pancreatic ductal adenocarcinoma (PDAC) exhibits an elevated transferrin receptor (TfR1) expression in comparison with non-transformed pancreatic cells. • TfR1 is required for PDAC growth by regulating mitochondrial respiration and ROS production. • TfR1 functions as a determinant of cell viability to oxidative stress in PDAC cells.

  7. Transferrin receptor regulates pancreatic cancer growth by modulating mitochondrial respiration and ROS generation

    International Nuclear Information System (INIS)

    Jeong, Seung Min; Hwang, Sunsook; Seong, Rho Hyun

    2016-01-01

    The transferrin receptor (TfR1) is upregulated in malignant cells and its expression is associated with cancer progression. Because of its pre-eminent role in cell proliferation, TfR1 has been an important target for the development of cancer therapy. Although TfR1 is highly expressed in pancreatic cancers, what it carries out in these refractory cancers remains poorly understood. Here we report that TfR1 supports mitochondrial respiration and ROS production in human pancreatic ductal adenocarcinoma (PDAC) cells, which is required for their tumorigenic growth. Elevated TfR1 expression in PDAC cells contributes to oxidative phosphorylation, which allows for the generation of ROS. Importantly, mitochondrial-derived ROS are essential for PDAC growth. However, exogenous iron supplement cannot rescue the defects caused by TfR1 knockdown. Moreover, we found that TfR1 expression determines PDAC cells sensitivity to oxidative stress. Together, our findings reveal that TfR1 can contribute to the mitochondrial respiration and ROS production, which have essential roles in growth and survival of pancreatic cancer. - Highlights: • Pancreatic ductal adenocarcinoma (PDAC) exhibits an elevated transferrin receptor (TfR1) expression in comparison with non-transformed pancreatic cells. • TfR1 is required for PDAC growth by regulating mitochondrial respiration and ROS production. • TfR1 functions as a determinant of cell viability to oxidative stress in PDAC cells.

  8. Decitabine induces delayed reactive oxygen species (ROS) accumulation in leukemia cells and induces the expression of ROS generating enzymes.

    Science.gov (United States)

    Fandy, Tamer E; Jiemjit, Anchalee; Thakar, Manjusha; Rhoden, Paulette; Suarez, Lauren; Gore, Steven D

    2014-03-01

    Azanucleoside DNA methyltransferase (DNMT) inhibitors are currently approved by the U.S. Food and Drug Administration for treatment of myelodysplastic syndrome. The relative contributions of DNMT inhibition and other off-target effects to their clinical efficacy remain unclear. Data correlating DNA methylation reversal and clinical response have been conflicting. Consequently, it is necessary to investigate so-called off-target effects and their impact on cell survival and differentiation. Flow cytometry was used for cell cycle, apoptosis, and reactive oxygen species (ROS) accumulation analysis. Gene expression analysis was performed using real-time PCR. DNA methylation was detected by methylation-specific PCR. Mitochondrial membrane potential was analyzed using JC-1 dye staining. Western blotting was used for quantitative protein expression analysis. 5-Aza-2'-deoxycytidine (DAC) induced cell-cycle arrest and apoptosis in leukemia cells. p53 expression was dispensable for DAC-induced apoptosis. DAC induced delayed ROS accumulation in leukemia cells but not in solid tumor cells and p53 expression was dispensable for ROS increase. ROS increase was deoxycytidine kinase dependent, indicating that incorporation of DAC into nuclear DNA is required for ROS generation. ROS accumulation by DAC was caspase-independent and mediated the dissipation of the mitochondrial membrane potential. Concordantly, ROS scavengers diminished DAC-induced apoptosis. DAC induced the expression of different NADPH oxidase isoforms and upregulated Nox4 protein expression in an ATM-dependent manner, indicating the involvement of DNA damage signaling in Nox4 upregulation. These data highlight the importance of mechanisms other than DNA cytosine demethylation in modulating gene expression and suggest investigating the relevance of ROS accumulation to the clinical activity of DAC. ©2014 AACR

  9. Under fungal attack on a metalliferous soil: ROS or not ROS? Insights from Silene paradoxa L. growing under copper stress

    International Nuclear Information System (INIS)

    Taiti, Cosimo; Giorni, Elisabetta; Colzi, Ilaria; Pignattelli, Sara; Bazihizina, Nadia; Buccianti, Antonella; Luti, Simone; Pazzagli, Luigia; Mancuso, Stefano; Gonnelli, Cristina

    2016-01-01

    We investigated how the adaptation to metalliferous environments can influence the plant response to biotic stress. In a metallicolous and a non-metallicolous population of Silene paradoxa the induction of oxidative stress and the production of callose and volatiles were evaluated in the presence of copper and of the PAMP fungal protein cerato-platanin, separately and in combination. Our results showed incompatibility between the ordinary ROS-mediated response to fungal attack and the acquired mechanisms of preventing oxidative stress in the tolerant population. A similar situation was also demonstrated by the sensitive population growing in the presence of copper but, in this case, with a lack of certain responses, such as callose production. In addition, in terms of the joint behaviour of emitted volatiles, multivariate statistics showed that not only did the populations respond differently to the presence of copper or biotic stress, but also that the biotic and abiotic stresses interacted in different ways in the two populations. Our results demonstrated that the same incompatibility of hyperaccumulators in ROS-mediated biotic stress signals also seemed to be exhibited by the excluder metallophyte, but without the advantage of being able to rely on the elemental defence for plant protection from natural enemies. - Highlights: • Silene paradoxa plants from metalliferous and nonmetalliferous soil were studied. • Plants were exposed to Cerato-platanin in presence/absence of Cu in culture media. • ROS response was fully present in nonmetallicolous plants only in the absence of Cu. • Similar ROS response in metallicolous plants with or without Cu. - The adaptation to high concentrations of copper was found to interfere with the ordinary ROS-mediated response to fungal attack in an excluder metallophyte.

  10. Protective effects of andrographolide analogue AL-1 on ROS-induced RIN-mβ cell death by inducing ROS generation.

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    Guang-Rong Yan

    Full Text Available Oxidative stress is considered to be a major factor contributing to pathogenesis and progression of many diseases. A novel andrographolide-lipoic acid conjugate (AL-1 could protect pancreatic β-cells from reactive oxygen species (ROS-induced oxidative injury. However, its protective mechanism is still unclear. In this work, we used proteomics to identify AL-1-regulated proteins in β-cells and found that 13 of the 71 proteins regulated by AL-1 were closely associated with antioxidation. These differential proteins were mainly involved in the ERK1/2 and AKT1 signaling pathways. Functional investigation demonstrated that AL-1 exerted its protective effects on H2O2-induced cell death of β-cells by generating NADPH oxidase-dependent ROS to activate ERK1/2 and AKT1 signaling pathways. As a consequence, the expressions of antioxidant proteins including Trx1, Prx1 and Prx5, and anti-apoptotic proteins including PDCD6IP, prohibitin, galectin-1 and HSP were upregulated. AL-1 probably worked as a "vaccinum" to activate the cellular antioxidant system by inducing the generation of low concentration ROS which then reciprocally protected β-cells from oxidative damage caused by high-level ROS from H2O2. To the best of our knowledge, this is the first comprehensive proteomic analysis illustrating a novel molecular mechanism for the protective effects of antioxidants on β-cells from H2O2-induced cell death.

  11. Endogenous ROS levels in C. elegans under exogenous stress support revision of oxidative stress theory of life-history tradeoffs.

    Science.gov (United States)

    Smith, Samson W; Latta, Leigh C; Denver, Dee R; Estes, Suzanne

    2014-07-24

    The oxidative stress theory of life-history tradeoffs states that oxidative stress caused by damaging free radicals directly underpins tradeoffs between reproduction and longevity by altering the allocation of energetic resources between these tasks. We test this theory by characterizing the effects of exogenous oxidative insult and its interaction with thermal stress and diet quality on a suite of life-history traits and correlations in Caenorhabditis elegans nematodes. We also quantify demographic aging rates and endogenous reactive oxygen species (ROS) levels in live animals. Our findings indicate a tradeoff between investment in reproduction and antioxidant defense (somatic maintenance) consistent with theoretical predictions, but correlations between standard life-history traits yield little evidence that oxidative stress generates strict tradeoffs. Increasing oxidative insult, however, shows a strong tendency to uncouple positive phenotypic correlations and, in particular, to reduce the correlation between reproduction and lifespan. We also found that mild oxidative insult results in lower levels of endogenous ROS accompanied by hormetic changes in lifespan, demographic aging, and reproduction that disappear in combined-stress treatments--consistent with the oxidative stress theory of aging. Our findings demonstrate that oxidative stress is a direct contributor to life-history trait variation and that traditional tradeoffs are not necessary to invoke oxidative stress as a mediator of relationships between life-history traits, supporting previous calls for revisions to theory.

  12. Tunicamycin promotes apoptosis in leukemia cells through ROS generation and downregulation of survivin expression.

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    Lim, Eun Jin; Heo, Jeonghoon; Kim, Young-Ho

    2015-08-01

    Tunicamycin (TN), one of the endoplasmic reticulum stress inducers, has been reported to inhibit tumor cell growth and exhibit anticarcinogenic activity. However, the mechanism by which TN initiates apoptosis remains poorly understood. In the present study, we investigated the effect of TN on the apoptotic pathway in U937 cells. We show that TN induces apoptosis in association with caspase-3 activation, generation of reactive oxygen species (ROS), and downregulation of survivin expression. P38 MAPK (mitogen-activated protein kinase) and the generation of ROS signaling pathway play crucial roles in TN-induced apoptosis in U937 cells. We hypothesized that TN-induced activation of p38 MAPK signaling pathway is responsible for cell death. To test this hypothesis, we selectively inhibited MAPK during treatment with TN. Our data demonstrated that inhibitor of p38 (SB), but not ERK (PD) or JNK (SP), partially maintained apoptosis during treatment with TN. Pre-treatment with NAC and GSH markedly prevented cell death, suggesting a role for ROS in this process. Ectopic expression of survivin in U937 cells attenuated TN-induced apoptosis by suppression of caspase-3 cleavage, mitochondrial membrane potential, and cytochrome c release in U937 cells. Taken together, our results show that TN modulates multiple components of the apoptotic response of human leukemia cells and raise the possibility of a novel therapeutic strategy for hematological malignancies.

  13. Endogenous mechanisms of reactive oxygen species (ROS generation

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    Agata Sarniak

    2016-11-01

    Full Text Available The main cellular source of reactive oxygen species (ROS is mitochondrial respiratory chain and active NADPH responsible for “respiratory burst” of phagocytes. Whatsmore ROS are produced in endoplasmic reticulum, peroxisomes, with the participation of xanthine and endothelial oxidase and during autoxidation process of small molecules. Mitochondrial respiratory chain is the main cellular source of ROS. It is considered that in aerobic organisms ROS are mainly formed during normal oxygen metabolism, as byproducts of oxidative phosphorylation, during the synthesis of ATP. The intermembranous phagocyte enzyme – activated NADPH oxidase, responsible for the “respiratory burst” of phagocytes, which is another source of ROS, plays an important role in defense of organism against infections.The aim of this article is to resume actuall knowledge about structure and function of the mitochondrial electron transport chain in which ROS are the byproducts and about NADPH oxidase as well as the function of each of its components in the “respiratory burst” of phagocytes.

  14. ROS signaling and stomatal movement in plant responses to drought stress and pathogen attack.

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    Qi, Junsheng; Song, Chun-Peng; Wang, Baoshan; Zhou, Jianmin; Kangasjärvi, Jaakko; Zhu, Jian-Kang; Gong, Zhizhong

    2018-04-16

    Stomata, the pores formed by a pair of guard cells, are the main gateways for water transpiration and photosynthetic CO 2 exchange, as well as pathogen invasion in land plants. Guard cell movement is regulated by a combination of environmental factors including water status, light, CO 2 levels and pathogen attack, as well as endogenous signals such as abscisic acid and apoplastic reactive oxygen species (ROS). Under abiotic and biotic stress conditions, extracellular ROS are mainly produced by plasma membrane-localized NADPH oxidases, whereas intracellular ROS are produced in multiple organelles. These ROS form a sophisticated cellular signaling network, with the accumulation of apoplastic ROS an early hallmark of stomatal movement. Here, we review recent progress in understanding the molecular mechanisms of the ROS signaling network, primarily during drought stress and pathogen attack. We summarize the roles of apoplastic ROS in regulating stomatal movement, ABA and CO 2 signaling, and immunity responses. Finally, we discuss ROS accumulation and communication between organelles and cells. This information provides a conceptual framework for understanding how ROS signaling is integrated with various signaling pathways during plant responses to abiotic and biotic stress stimuli. This article is protected by copyright. All rights reserved.

  15. Generation of ROS mediated by mechanical waves (ultrasound) and its possible applications.

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    Duco, Walter; Grosso, Viviana; Zaccari, Daniel; Soltermann, Arnaldo T

    2016-10-15

    The thermal decomposition of 9,10 diphenylanthracene peroxide (DPAO 2 ) generates DPA and a mix of triplet and singlet molecular oxygen. For DPAO 2 the efficiency to produce singlet molecular oxygen is 0.35. On the other hand, it has shown that many thermal reactions can be carried out through the interaction of molecules with ultrasound. Ultrasound irradiation can create hydrodynamic stress (sonomechanical process), inertial cavitation (pyrolitic process) and long range effects mediated by radicals or ROS. Sonochemical reactions can be originated by pyrolytic like process, shock mechanical waves, thermal reactions and radical and ROS mediated reactions. Sonolysis of pure water can yield hydrogen or hydroxyl radicals and hydrogen peroxide (ROS). When DPAO 2 in 1,4 dioxane solution is treated with 20 or 24kHz and different power intensity the production of molecular singlet oxygen is observed. Specific scavengers like tetracyclone (TC) are used to demonstrate it. The efficiency now is 0.85 showing that the sonochemical process is much more efficient that the thermal one. Another endoperoxide, artemisinin was also studied. Unlike the concept of photosensitizer of photodynamic therapy, in spite of large amount of reported results in literature, the term sonosensitizer and the sonosensitization process are not well defined. We define sonosensitized reaction as one in which a chemical species decompose as consequence of cavitation phenomena producing ROS or other radicals and some other target species does undergo a chemical reaction. The concept could be reach rapidly other peroxides which are now under experimental studies. For artemisinin, an important antimalarian and anticancer drug, was established that ultrasound irradiation increases the effectiveness of the treatment but without any explanation. We show that artemisinin is an endoperoxide and behaves as a sonosensitizer in the sense of our definition. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Endogenous cytokinin overproduction modulates ROS homeostasis and decreases salt stress resistance in Arabidopsis thaliana

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    Yanping eWang

    2015-11-01

    Full Text Available Cytokinins in plants are crucial for numerous biological processes, including seed germination, cell division and differentiation, floral initiation and adaptation to abiotic stresses. The salt stress can promote reactive oxygen species (ROS production in plants which are highly toxic and ultimately results in oxidative stress. However, the correlation between endogenous cytokinin production and ROS homeostasis in responding to salt stress is poorly understood. In this study, we analyzed the correlation of overexpressing the cytokinin biosynthetic gene AtIPT8 (adenosine phosphate-isopentenyl transferase 8 and the response of salt stress in Arabidopsis. Overproduction of cytokinins, which was resulted by the inducible overexpression of AtIPT8, significantly inhibited the primary root growth and true leaf emergence, especially under the conditions of exogenous salt, glucose and mannitol treatments. Upon cytokinin overproduction, the salt stress resistance was declined, and resulted in less survival rates and chlorophyll content. Interestingly, ROS production was obviously increased with the salt treatment, accompanied by endogenously overproduced cytokinins. The activities of CAT and SOD, which are responsible for scavenging ROS, were also affected. Transcription profiling revealed that the differential expressions of ROS-producing and scavenging related genes, the photosynthesis-related genes and stress responsive genes were existed in transgenic plants of overproducing cytokinins. Our results suggested that broken in the homeostasis of cytokinins in plant cells could modulate the salt stress responses through a ROS-mediated regulation in Arabidopsis.

  17. Overexpressed cyclophilin B suppresses apoptosis associated with ROS and Ca2+ homeostasis after ER stress.

    Science.gov (United States)

    Kim, Jinhwan; Choi, Tae Gyu; Ding, Yan; Kim, Yeonghwan; Ha, Kwon Soo; Lee, Kyung Ho; Kang, Insug; Ha, Joohun; Kaufman, Randal J; Lee, Jinhwa; Choe, Wonchae; Kim, Sung Soo

    2008-11-01

    Prolonged accumulation of misfolded proteins in the endoplasmic reticulum (ER) results in ER stress-mediated apoptosis. Cyclophilins are protein chaperones that accelerate the rate of protein folding through their peptidyl-prolyl cis-trans isomerase (PPIase) activity. In this study, we demonstrated that ER stress activates the expression of the ER-localized cyclophilin B (CypB) gene through a novel ER stress response element. Overexpression of wild-type CypB attenuated ER stress-induced cell death, whereas overexpression of an isomerase activity-defective mutant, CypB/R62A, not only increased Ca(2+) leakage from the ER and ROS generation, but also decreased mitochondrial membrane potential, resulting in cell death following exposure to ER stress-inducing agents. siRNA-mediated inhibition of CypB expression rendered cells more vulnerable to ER stress. Finally, CypB interacted with the ER stress-related chaperones, Bip and Grp94. Taken together, we concluded that CypB performs a crucial function in protecting cells against ER stress via its PPIase activity.

  18. Rod and cone photoreceptor cells produce ROS in response to stress in a live retinal explant system.

    LENUS (Irish Health Repository)

    Bhatt, Lavinia

    2010-01-01

    that both rods and cones generated ROS in response to the stress of serum deprivation. Nox4 was the most abundantly expressed Nox in the photoreceptor layer, but Duox1 and Duox2 were also present at detectable levels, and as apocynin reduced the levels of ROS produced, this implied that these proteins may play some role in this production.

  19. The endogenous nitric oxide mediates selenium-induced phytotoxicity by promoting ROS generation in Brassica rapa.

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    Yi Chen

    Full Text Available Selenium (Se is suggested as an emerging pollutant in agricultural environment because of the increasing anthropogenic release of Se, which in turn results in phytotoxicity. The most common consequence of Se-induced toxicity in plants is oxidative injury, but how Se induces reactive oxygen species (ROS burst remains unclear. In this work, histofluorescent staining was applied to monitor the dynamics of ROS and nitric oxide (NO in the root of Brassica rapa under Se(IV stress. Se(IV-induced faster accumulation of NO than ROS. Both NO and ROS accumulation were positively correlated with Se(IV-induced inhibition of root growth. The NO accumulation was nitrate reductase (NR- and nitric oxide synthase (NOS-dependent while ROS accumulation was NADPH oxidase-dependent. The removal of NO by NR inhibitor, NOS inhibitor, and NO scavenger could alleviate Se(IV-induced expression of Br_Rbohs coding for NADPH oxidase and the following ROS accumulation in roots, which further resulted in the amelioration of Se(IV-induced oxidative injury and growth inhibition. Thus, we proposed that the endogenous NO played a toxic role in B. rapa under Se(IV stress by triggering ROS burst. Such findings can be used to evaluate the toxic effects of Se contamination on crop plants.

  20. Asperlin induces G{sub 2}/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    He, Long; Nan, Mei-Hua [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); Oh, Hyun Cheol [College of Medical and Life Sciences, Silla University, 100 Silladaehak-gil, Sasang-gu, Busan 617-736 (Korea, Republic of); Kim, Young Ho [College of Pharmacy, ChungNam National University, Yuseong, Daejeon, 305-764 (Korea, Republic of); Jang, Jae Hyuk [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); Erikson, Raymond Leo [Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138 (United States); Ahn, Jong Seog, E-mail: jsahn@kribb.re.kr [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); Kim, Bo Yeon, E-mail: bykim@kribb.re.kr [Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of); World Class Institute, KRIBB, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk 363-883 (Korea, Republic of)

    2011-06-10

    Highlights: {yields} A new anti-cancer effect of an antibiotics, asperlin, is exploited. {yields} Asperlin induced human cervical cancer cell apoptosis through ROS generation. {yields} Asperlin activated DNA-damage related ATM protein and cell cycle associated proteins. {yields} Asperlin could be developed as a new anti-cancer therapeutics. -- Abstract: We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-L-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells.

  1. Asperlin induces G2/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells

    International Nuclear Information System (INIS)

    He, Long; Nan, Mei-Hua; Oh, Hyun Cheol; Kim, Young Ho; Jang, Jae Hyuk; Erikson, Raymond Leo; Ahn, Jong Seog; Kim, Bo Yeon

    2011-01-01

    Highlights: → A new anti-cancer effect of an antibiotics, asperlin, is exploited. → Asperlin induced human cervical cancer cell apoptosis through ROS generation. → Asperlin activated DNA-damage related ATM protein and cell cycle associated proteins. → Asperlin could be developed as a new anti-cancer therapeutics. -- Abstract: We exploited the biological activity of an antibiotic agent asperlin isolated from Aspergillus nidulans against human cervical carcinoma cells. We found that asperlin dramatically increased reactive oxygen species (ROS) generation accompanied by a significant reduction in cell proliferation. Cleavage of caspase-3 and PARP and reduction of Bcl-2 could also be detected after asperlin treatment to the cells. An anti-oxidant N-acetyl-L-cysteine (NAC), however, blocked all the apoptotic effects of asperlin. The involvement of oxidative stress in asperlin induced apoptosis could be supported by the findings that ROS- and DNA damage-associated G2/M phase arrest and ATM phosphorylation were increased by asperlin. In addition, expression and phosphorylation of cell cycle proteins as well as G2/M phase arrest in response to asperlin were significantly blocked by NAC or an ATM inhibitor KU-55933 pretreatment. Collectively, our study proved for the first time that asperlin could be developed as a potential anti-cancer therapeutics through ROS generation in HeLa cells.

  2. Unravelling how plants benefit from ROS and NO reactions, while resisting oxidative stress.

    Science.gov (United States)

    Considine, Michael J; Sandalio, Luisa Maria; Foyer, Christine Helen

    2015-09-01

    Reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO), play crucial roles in the signal transduction pathways that regulate plant growth, development and defence responses, providing a nexus of reduction/oxidation (redox) control that impacts on nearly every aspect of plant biology. Here we summarize current knowledge and concepts that lay the foundations of a new vision for ROS/RNS functions – particularly through signalling hubs – for the next decade. Plants have mastered the art of redox control using ROS and RNS as secondary messengers to regulate a diverse range of protein functions through redox-based, post-translational modifications that act as regulators of molecular master-switches. Much current focus concerns the impact of this regulation on local and systemic signalling pathways, as well as understanding how such reactive molecules can be effectively used in the control of plant growth and stress responses. The spectre of oxidative stress still overshadows much of our current philosophy and understanding of ROS and RNS functions. While many questions remain to be addressed – for example regarding inter-organellar regulation and communication, the control of hypoxia and how ROS/RNS signalling is used in plant cells, not only to trigger acclimation responses but also to create molecular memories of stress – it is clear that ROS and RNS function as vital signals of living cells.

  3. Plant Growth-Promoting Rhizobacteria Enhance Salinity Stress Tolerance in Okra through ROS-Scavenging Enzymes

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    Sheikh Hasna Habib

    2016-01-01

    Full Text Available Salinity is a major environmental stress that limits crop production worldwide. In this study, we characterized plant growth-promoting rhizobacteria (PGPR containing 1-aminocyclopropane-1-carboxylate (ACC deaminase and examined their effect on salinity stress tolerance in okra through the induction of ROS-scavenging enzyme activity. PGPR inoculated okra plants exhibited higher germination percentage, growth parameters, and chlorophyll content than control plants. Increased antioxidant enzyme activities (SOD, APX, and CAT and upregulation of ROS pathway genes (CAT, APX, GR, and DHAR were observed in PGPR inoculated okra plants under salinity stress. With some exceptions, inoculation with Enterobacter sp. UPMR18 had a significant influence on all tested parameters under salt stress, as compared to other treatments. Thus, the ACC deaminase-containing PGPR isolate Enterobacter sp. UPMR18 could be an effective bioresource for enhancing salt tolerance and growth of okra plants under salinity stress.

  4. The effect of artichoke (Cynara scolymus L.) extract on ROS generation in HUVEC cells.

    Science.gov (United States)

    Juzyszyn, Z; Czerny, B; Pawlik, A; Droździk, M

    2008-09-01

    The effect of an artichoke extract on induced reactive oxygen species (ROS) generation in cultured human umbilical endothelial cells (HUVECs) and its reductive properties were evaluated. Preincubation of HUVEC cells with the artichoke extract at concentrations of 25-100 microg/mL for 24 h abolished ROS generation induced by LPS and oxyLDL as evaluated by the fluorescence intensity of 2',7'-dichlorofluorescein (DCF). Potent, concentration-dependent reductive properties of the artichoke extract were demonstrated by the reduction kinetics of cytochrome c in reference to ascorbate were also revealed. The results of the present study the warrant application of artichoke extracts as endothelium protecting agents.

  5. Macranthoidin B Modulates Key Metabolic Pathways to Enhance ROS Generation and Induce Cytotoxicity and Apoptosis in Colorectal Cancer

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    Xing Fan

    2018-04-01

    Full Text Available Background/Aims: Induction of oxidative stress and reactive oxygen species (ROS mediated-apoptosis have been utilized as effective strategies in anticancer therapy. Macranthoidin B (MB is a potent inducer of ROS-mediated apoptosis in cancer, but its mechanism of action is poorly understood. Method: Superoxide production with MB exposure in colorectal cancer (CRC cells was measured using lucigenin chemiluminescence and real-time PCR. MB’s inhibitory effect on proliferation and viability of CRC cells was determined by proliferation assays. MB’s effect on apoptosis of CRC cells was determined by Western blotting and annexin V-FITC/PI staining. MB’s effect on the growth of CRC xenografts in mice was assessed. An established metabolomics profiling platform combining ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS with gas chromatography-mass spectrometry (GC-MS was performed to determine MB’s effect on total metabolite variation in CRC cells. Results: We found that MB increases ROS generation via modulating key metabolic pathways. Using metabolomics profiling platform combining LC-MS with GC-MS, a total of 236 metabolites were identified in HCT-116 cells in which 31 metabolites were determined to be significantly regulated (p ≤ 0.05 after MB exposure. A number of key metabolites revealed by metabolomics analysis include glucose, fructose, citrate, arginine, phenylalanine, and S-adenosylhomocysteine (SAH, suggesting specific modulation of metabolism on carbohydrates, amino acids and peptides, lipids, nucleotide, cofactors and vitamins in HCT-116 CRC cells with MB treatment highly associated with apoptosis triggered by enhanced ROS and activated caspase-3. Conclusion: Our results demonstrate that MB represses CRC cell proliferation by inducing ROS-mediated apoptosis.

  6. Macranthoidin B Modulates Key Metabolic Pathways to Enhance ROS Generation and Induce Cytotoxicity and Apoptosis in Colorectal Cancer.

    Science.gov (United States)

    Fan, Xing; Rao, Jun; Zhang, Ziwei; Li, Dengfeng; Cui, Wenhao; Zhang, Jun; Wang, Hua; Tou, Fangfang; Zheng, Zhi; Shen, Qiang

    2018-01-01

    Induction of oxidative stress and reactive oxygen species (ROS) mediated-apoptosis have been utilized as effective strategies in anticancer therapy. Macranthoidin B (MB) is a potent inducer of ROS-mediated apoptosis in cancer, but its mechanism of action is poorly understood. Superoxide production with MB exposure in colorectal cancer (CRC) cells was measured using lucigenin chemiluminescence and real-time PCR. MB's inhibitory effect on proliferation and viability of CRC cells was determined by proliferation assays. MB's effect on apoptosis of CRC cells was determined by Western blotting and annexin V-FITC/PI staining. MB's effect on the growth of CRC xenografts in mice was assessed. An established metabolomics profiling platform combining ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS) with gas chromatography-mass spectrometry (GC-MS) was performed to determine MB's effect on total metabolite variation in CRC cells. We found that MB increases ROS generation via modulating key metabolic pathways. Using metabolomics profiling platform combining LC-MS with GC-MS, a total of 236 metabolites were identified in HCT-116 cells in which 31 metabolites were determined to be significantly regulated (p ≤ 0.05) after MB exposure. A number of key metabolites revealed by metabolomics analysis include glucose, fructose, citrate, arginine, phenylalanine, and S-adenosylhomocysteine (SAH), suggesting specific modulation of metabolism on carbohydrates, amino acids and peptides, lipids, nucleotide, cofactors and vitamins in HCT-116 CRC cells with MB treatment highly associated with apoptosis triggered by enhanced ROS and activated caspase-3. Our results demonstrate that MB represses CRC cell proliferation by inducing ROS-mediated apoptosis. © 2018 The Author(s). Published by S. Karger AG, Basel.

  7. Overload training inhibits phagocytosis and ROS generation of peritoneal macrophages: role of IGF-1 and MGF.

    Science.gov (United States)

    Xiao, Weihua; Chen, Peijie; Wang, Ru; Dong, Jingmei

    2013-01-01

    We tested the hypothesis that overload training inhibits the phagocytosis and the reactive oxygen species (ROS) generation of peritoneal macrophages (Mϕs), and that insulin-like growth factor-1(IGF-1) and mechano-growth factor (MGF) produced by macrophages may contribute to this process. Rats were randomized to two groups, sedentary control group (n = 10) and overload training group (n = 10). The rats of overload training group were subjected to 11 weeks of experimental training protocol. Blood sample was used to determine the content of hemoglobin, testosterone, and corticosterone. The phagocytosis and the ROS generation of Mϕs were measured by the uptake of neutral red and the flow cytometry, respectively. IGF-1 and MGF mRNA levels in Mϕs were determined by real-time PCR. In addition, we evaluated the effects of IGF-1 and MGF peptide on phagocytosis and ROS generation of Mϕs in vitro. The data showed that overload training significantly decreased the body weight (19.3 %, P overload training significantly decreased the phagocytosis (27 %, P overload training group increased significantly compared with the control group (21-fold and 92-fold, respectively; P overload training inhibits the phagocytosis and the ROS generation of peritoneal macrophages, and that MGF produced by macrophages may play a key role in this process. This may represent a novel mechanism of immune suppression induced by overload training.

  8. Possible involvement of ROS generation in vorinostat pretreatment induced enhancement of the antibacterial activity of ciprofloxacin

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    Masadeh MM

    2017-10-01

    Full Text Available Majed M Masadeh,1 Karem H Alzoubi,2 Sayer I Al-azzam,2 Ahlam M Al-buhairan3 1Department of Pharmaceutical Technology, 2Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Clinical Laboratory Sciences, King Saud University, Riyadh, Saudi Arabia Abstract: The mechanism underlying ciprofloxacin action involves interference with transcription and replication of bacterial DNA and, thus, the induction of double-strand breaks in DNA. It also involves elevated oxidative stress, which might contribute to bacterial cell death. Vorinostat was shown to induce oxidative DNA damage. The current work investigated a possible interactive effect of vorinostat on ciprofloxacin-induced cytotoxicity against a number of reference bacteria. Standard bacterial strains were Escherichia coli ATCC 35218, Staphylococcus aureus ATCC29213, Pseudomonas aeruginosa ATCC 9027, Staphylococcus epidermidis ATCC 12228, Acinetobacter baumannii ATCC 17978, Proteus mirabilis ATCC 12459, Klebsiella pneumoniae ATCC 13883, methicillin-resistant Staphylococcus aureus (MRSA (ATCC 43300, and Streptococcus pneumoniae (ATCC 25923. The antibacterial activity of ciprofloxacin, with or without pretreatment of bacterial cells by vorinostat, was examined using the disc diffusion procedure and determination of the minimum inhibitory concentration (MIC and zones of inhibition of bacterial growth. All tested bacterial strains showed sensitivity to ciprofloxacin. When pretreated with vorinostat, significantly larger zones of inhibition and smaller MIC values were observed in all bacterial strains compared to those treated with ciprofloxacin alone. In correlation, generation of reactive oxygen species (ROS induced by the antibacterial action of ciprofloxacin was enhanced by treatment of bacterial cells with vorinostat. Results showed the possible agonistic properties of vorinostat when used together with ciprofloxacin. This could be related to the

  9. Activation of the Small GTPase Rap1 Inhibits Choroidal Neovascularization by Regulating Cell Junctions and ROS Generation in Rats.

    Science.gov (United States)

    Li, Jiajia; Zhang, Rong; Wang, Caixia; Wang, Xin; Xu, Man; Ma, Jingxue; Shang, Qingli

    2018-03-30

    Choroidal neovascularization (CNV) is a common vision-threatening complication associated with many  fundus diseases. The retinal pigment epithelial (RPE) cell junction barrier has critical functions in preventing CNV, and oxidative stress can cause compromise of barrier integrity and induce angiogenesis. Rap1, a small guanosine triphosphatase (GTPase), is involved in regulating endothelial and epithelial cell junctions. In this work, we explored the function and mechanism of Rap1 in CNV in vivo. A laser-induced rat CNV model was developed. Rap1 was activated through intravitreal injection of the Rap1 activator 8CPT-2'-O-Me-cAMP (8CPT). At 14 days after laser treatment, CNV size in RPE/choroid flat mounts was measured by fluorescein isothiocyanate-dextran staining. Expression of vascular endothelial growth factor (VEGF) and cell junction proteins in RPE/choroid tissues were analyzed by western blots and quantitative real-time PCR assays. Reactive oxygen species (ROS) in RPE cells were detectedbydichloro-dihydro-fluorescein diacetate assays. The antioxidant apocynin was intraperitoneally injected into rats. Activating Rap1 by 8CPT significantly reduced CNV size and VEGF expression in the rat CNV model. Rap1 activation enhanced protein and mRNA levels of ZO-1 and occludin, two tight junction proteins in the RPE barrier. In addition, reducing ROS generation by injection of apocynin, a NADPH oxidase inhibitor, inhibited CNV formation. Rap1 activation reduced ROS generation and expression of NADPH oxidase 4. Rap1 activation inhibits CNV through regulating barrier integrity and ROS generation of RPE in vivo, and selectively activating Rap1 may be a way to reduce vision loss from CNV.

  10. Particulate matter exposure exacerbates high glucose-induced cardiomyocyte dysfunction through ROS generation.

    Directory of Open Access Journals (Sweden)

    Li Zuo

    Full Text Available Diabetes mellitus and fine particulate matter from diesel exhaust (DEP are both important contributors to the development of cardiovascular disease (CVD. Diabetes mellitus is a progressive disease with a high mortality rate in patients suffering from CVD, resulting in diabetic cardiomyopathy. Elevated DEP levels in the air are attributed to the development of various CVDs, presumably since fine DEP (<2.5 µm in diameter can be inhaled and gain access to the circulatory system. However, mechanisms defining how DEP affects diabetic or control cardiomyocyte function remain poorly understood. The purpose of the present study was to evaluate cardiomyocyte function and reactive oxygen species (ROS generation in isolated rat ventricular myocytes exposed overnight to fine DEP (0.1 µg/ml, and/or high glucose (HG, 25.5 mM. Our hypothesis was that DEP exposure exacerbates contractile dysfunction via ROS generation in cardiomyocytes exposed to HG. Ventricular myocytes were isolated from male adult Sprague-Dawley rats cultured overnight and sarcomeric contractile properties were evaluated, including: peak shortening normalized to baseline (PS, time-to-90% shortening (TPS(90, time-to-90% relengthening (TR(90 and maximal velocities of shortening/relengthening (±dL/dt, using an IonOptix field-stimulator system. ROS generation was determined using hydroethidine/ethidium confocal microscopy. We found that DEP exposure significantly increased TR(90, decreased PS and ±dL/dt, and enhanced intracellular ROS generation in myocytes exposed to HG. Further studies indicated that co-culture with antioxidants (0.25 mM Tiron and 0.5 mM N-Acetyl-L-cysteine completely restored contractile function in DEP, HG and HG+DEP-treated myocytes. ROS generation was blocked in HG-treated cells with mitochondrial inhibition, while ROS generation was blocked in DEP-treated cells with NADPH oxidase inhibition. Our results suggest that DEP exacerbates myocardial dysfunction in isolated

  11. Production of Superoxide in Bacteria Is Stress- and Cell State-Dependent: A Gating-Optimized Flow Cytometry Method that Minimizes ROS Measurement Artifacts with Fluorescent Dyes.

    Science.gov (United States)

    McBee, Megan E; Chionh, Yok H; Sharaf, Mariam L; Ho, Peiying; Cai, Maggie W L; Dedon, Peter C

    2017-01-01

    The role of reactive oxygen species (ROS) in microbial metabolism and stress response has emerged as a major theme in microbiology and infectious disease. Reactive fluorescent dyes have the potential to advance the study of ROS in the complex intracellular environment, especially for high-content and high-throughput analyses. However, current dye-based approaches to measuring intracellular ROS have the potential for significant artifacts. Here, we describe a robust platform for flow cytometric quantification of ROS in bacteria using fluorescent dyes, with ROS measurements in 10s-of-1000s of individual cells under a variety of conditions. False positives and variability among sample types (e.g., bacterial species, stress conditions) are reduced with a flexible four-step gating scheme that accounts for side- and forward-scattered light (morphological changes), background fluorescence, DNA content, and dye uptake to identify cells producing ROS. Using CellROX Green dye with Escherichia coli, Mycobacterium smegmatis , and Mycobacterium bovis BCG as diverse model bacteria, we show that (1) the generation of a quantifiable CellROX Green signal for superoxide, but not hydrogen peroxide-induced hydroxyl radicals, validates this dye as a superoxide detector; (2) the level of dye-detectable superoxide does not correlate with cytotoxicity or antibiotic sensitivity; (3) the non-replicating, antibiotic tolerant state of nutrient-deprived mycobacteria is associated with high levels of superoxide; and (4) antibiotic-induced production of superoxide is idiosyncratic with regard to both the species and the physiological state of the bacteria. We also show that the gating method is applicable to other fluorescent indicator dyes, such as the 5-carboxyfluorescein diacetate acetoxymethyl ester and 5-cyano-2,3-ditolyl tetrazolium chloride for cellular esterase and reductive respiratory activities, respectively. These results demonstrate that properly controlled flow cytometry coupled

  12. ROS signaling, oxidative stress and Nrf2 in pancreatic beta-cell function

    International Nuclear Information System (INIS)

    Pi Jingbo; Zhang Qiang; Fu Jingqi; Woods, Courtney G.; Hou Yongyong; Corkey, Barbara E.; Collins, Sheila; Andersen, Melvin E.

    2010-01-01

    This review focuses on the emerging evidence that reactive oxygen species (ROS) derived from glucose metabolism, such as H 2 O 2 , act as metabolic signaling molecules for glucose-stimulated insulin secretion (GSIS) in pancreatic beta-cells. Particular emphasis is placed on the potential inhibitory role of endogenous antioxidants, which rise in response to oxidative stress, in glucose-triggered ROS and GSIS. We propose that cellular adaptive response to oxidative stress challenge, such as nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant induction, plays paradoxical roles in pancreatic beta-cell function. On the one hand, induction of antioxidant enzymes protects beta-cells from oxidative damage and possible cell death, thus minimizing oxidative damage-related impairment of insulin secretion. On the other hand, the induction of antioxidant enzymes by Nrf2 activation blunts glucose-triggered ROS signaling, thus resulting in reduced GSIS. These two premises are potentially relevant to impairment of beta-cells occurring in the late and early stage of Type 2 diabetes, respectively. In addition, we summarized our recent findings that persistent oxidative stress due to absence of uncoupling protein 2 activates cellular adaptive response which is associated with impaired pancreatic beta-cell function.

  13. Platinum nanozymes recover cellular ROS homeostasis in an oxidative stress-mediated disease model

    Science.gov (United States)

    Moglianetti, Mauro; de Luca, Elisa; Pedone, Deborah; Marotta, Roberto; Catelani, Tiziano; Sartori, Barbara; Amenitsch, Heinz; Retta, Saverio Francesco; Pompa, Pier Paolo

    2016-02-01

    In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide dismutase, catalase, and peroxidase enzymes, with similar or even superior performance than natural enzymes, along with higher adaptability to the changes in environmental conditions. We then exploited their potent activity as radical scavenging materials in a cellular model of an oxidative stress-related disorder, namely human Cerebral Cavernous Malformation (CCM) disease, which is associated with a significant increase in intracellular ROS levels. Noteworthily, we found that Pt nanozymes can efficiently reduce ROS levels, completely restoring the cellular physiological homeostasis.In recent years, the use of nanomaterials as biomimetic enzymes has attracted great interest. In this work, we show the potential of biocompatible platinum nanoparticles (Pt NPs) as antioxidant nanozymes, which combine abundant cellular internalization and efficient scavenging activity of cellular reactive oxygen species (ROS), thus simultaneously integrating the functions of nanocarriers and antioxidant drugs. Careful toxicity assessment and intracellular tracking of Pt NPs proved their cytocompatibility and high cellular uptake, with compartmentalization within the endo/lysosomal vesicles. We have demonstrated that Pt NPs possess strong and broad antioxidant properties, acting as superoxide

  14. Causation by Diesel Exhaust Particles of Endothelial Dysfunctions in Cytotoxicity, Pro-inflammation, Permeability, and Apoptosis Induced by ROS Generation.

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    Tseng, Chia-Yi; Wang, Jhih-Syuan; Chao, Ming-Wei

    2017-10-01

    Epidemiological studies suggest that an increase of diesel exhaust particles (DEP) in ambient air corresponds to an increase in hospital-recorded myocardial infarctions within 48 h after exposure. Among the many theories to explain this data are endothelial dysfunction and translocation of DEP into vasculature. The mechanisms for such DEP-induced vascular permeability remain unknown. One of the major mechanisms underlying the effects of DEP is suggested to be oxidative stress. Experiments have shown that DEP induce the generation of reactive oxygen species (ROS), such as superoxide anion and H 2 O 2 in the HUVEC tube cells. Transcription factor Nrf2 is translocated to the cell nucleus, where it activates transcription of the antioxidative enzyme HO-1 and sequentially induces the release of vascular permeability factor VEGF-A. Furthermore, a recent study shows that DEP-induced intracellular ROS may cause the release of pro-inflammatory TNF-α and IL-6, which may induce endothelial permeability as well by promoting VEGF-A secretion independently of HO-1 activation. These results demonstrated that the adherens junction molecule, VE-cadherin, becomes redistributed from the membrane at cell-cell borders to the cytoplasm in response to DEP, separating the plasma membranes of adjacent cells. DEP were occasionally found in endothelial cell cytoplasm and in tube lumen. In addition, the induced ROS is cytotoxic to the endothelial tube-like HUVEC. Acute DEP exposure stimulates ATP depletion, followed by depolarization of their actin cytoskeleton, which sequentially inhibits PI3K/Akt activity and induces endothelial apoptosis. Nevertheless, high-dose DEP augments tube cell apoptosis up to 70 % but disrupts the p53 negative regulator Mdm2. In summary, exposure to DEP affects parameters influencing vasculature permeability and viability, i.e., oxidative stress and its upregulated antioxidative and pro-inflammatory responses, which sequentially induce vascular permeability

  15. Muramyl dipeptide (MDP) induces reactive oxygen species (ROS) generation via the NOD2/COX-2/NOX4 signaling pathway in human umbilical vein endothelial cells (HUVECs).

    Science.gov (United States)

    Kong, Ling-Jun; Liu, Xiao-Qian; Xue, Ying; Gao, Wei; Lv, Qian-Zhou

    2018-03-20

    Vascular endothelium dysfunction caused by oxidative stress accelerates the pathologic process of cardiovascular diseases. NOD2, an essential receptor of innate immune system, has been demonstrated to play a critical role in atherosclerosis. Here, the aim of our study was to investigate the effect and underlying molecular mechanism of muramyl dipeptide (MDP) on NOX4-mediated ROS generation in human umbilical vein endothelial cells (HUVECs). 2,7-dichlorofluorescein diacetate staining was to measure the intracellular ROS level and showed MDP promoted ROS production in a time- and dose-dependent manner. The mRNA and protein levels of NOX4 and COX-2 were detected by real-time PCR and western blot. Small interfering RNA (siRNA) was used to silence NOD2 or COX-2 gene expression and investigate the mechanism of NOD2-mediated signaling pathway in HUVECs. Data showed that MDP induced NOX4 and COX-2 expression in a time- and dose-dependent manner. NOD2 knock-down suppressed up-regulation of COX-2 and NOX4 in HUVECs treated with MDP. Furthermore, silence of COX-2 in HUVECs down-regulated the NOX4 expression after MDP stimulation. Collectively, we indicated that NOD2 played a leading role in MDP-induced COX-2/NOX4/ROS signaling pathway in HUVECs, which was a novel regulatory mechanism in the progress of ROS generation.

  16. ROS-mediated abiotic stress-induced programmed cell death in plants

    Directory of Open Access Journals (Sweden)

    Veselin ePetrov

    2015-02-01

    Full Text Available During the course of their ontogenesis, plants are continuously exposed to a large variety of abiotic stress factors which can damage tissues and jeopardize the survival of the organism unless properly countered. While animals can simply escape and thus evade stressors, plants as sessile organisms have developed complex strategies to withstand them. When the intensity of a detrimental factor is high, one of the defense programs employed by plants is the induction of programmed cell death (PCD. This is an active, genetically controlled process which is initiated to isolate and remove damaged tissues thereby ensuring the survival of the organism. The mechanism of PCD induction usually includes an increase in the levels of reactive oxygen species (ROS which are utilized as mediators of the stress signal. Abiotic stress-induced PCD is not only a process of fundamental biological importance, but also of considerable interest to agricultural practice as it has the potential to significantly influence crop yield. Therefore, numerous scientific enterprises have focused on elucidating the mechanisms leading to and controlling PCD in response to adverse conditions in plants. This knowledge may help to develop novel strategies to obtain more resilient crop varieties with improved tolerance and enhanced productivity. The aim of the present review is to summarize the recent advances in research on ROS-induced PCD related to abiotic stress and the role of the organelles in the process.

  17. Reactive oxygen species (ROS) and the heat stress response of Daphnia pulex: ROS-mediated activation of hypoxia-inducible factor 1 (HIF-1) and heat shock factor 1 (HSF-1) and the clustered expression of stress genes.

    Science.gov (United States)

    Klumpen, Eva; Hoffschröer, Nadine; Zeis, Bettina; Gigengack, Ulrike; Dohmen, Elias; Paul, Rüdiger J

    2017-01-01

    Heat stress in ectotherms involves direct (e.g. protein damage) and/or indirect effects (temperature-induced hypoxia and ROS formation), which cause activation of the transcription factors (TF) heat shock factor 1 (HSF-1) and/or hypoxia-inducible factor 1 (HIF-1). The present study focused on the links between stress (ROS) signals, nuclear (n) and cytoplasmic (c) HSF-1/HIF-1 levels, and stress gene expression on mRNA and protein levels (e.g. heat-shock protein 90, HSP90) upon acute heat and ROS (H 2 O 2 ) stress. Acute heat stress (30°C) evoked fluctuations in ROS level. Different feeding regimens, which affected the glutathione (GSH) level, allowed altering the frequency of ROS fluctuations. Other data showed fluctuation frequency to depend also on ROS production rate. The heat-induced slow or fast ROS fluctuations (at high or low GSH levels) evoked slow or fast fluctuations in the levels of nHIF-1α, nHSF-1 and gene products (mRNAs and protein), albeit after different time delays. Time delays to ROS fluctuations were, for example,shorter for nHIF-1α than for nHSF-1 fluctuations, and nHIF-1α fluctuations preceded and nHSF-1 fluctuations followed fluctuations in HSP90 mRNA level. Cytoplasmic TF levels either changed little (cHIF-1α) or showed a steady increase (cHSF-1). Applying acute H 2 O 2 stress (at 20°C) revealed effects on nHIF-1α and mRNA levels, but no significant effects on nHSF-1 level. Transcriptome data additionally showed coordinated fluctuations of mRNA levels upon acute heat stress, involving mRNAs for HSPs and other stress proteins, with all corresponding genes carrying DNA binding motifs for HIF-1 and HSF-1. This study provided evidence for promoting effects of ROS and HIF-1 on early haemoglobin, HIF-1α and HSP90 mRNA expressions upon heat or ROS stress. The increasing cHSF-1 level likely affected nHSF-1 level and later HSP90 mRNA expression. Heat stress evoked ROS fluctuations, with this stress signal forwarded via nHIF-1 and nHSF-1

  18. Mechanism of Cisplatin-Induced Cytotoxicity Is Correlated to Impaired Metabolism Due to Mitochondrial ROS Generation.

    Science.gov (United States)

    Choi, Yong-Min; Kim, Han-Kyul; Shim, Wooyoung; Anwar, Muhammad Ayaz; Kwon, Ji-Woong; Kwon, Hyuk-Kwon; Kim, Hyung Joong; Jeong, Hyobin; Kim, Hwan Myung; Hwang, Daehee; Kim, Hyung Sik; Choi, Sangdun

    2015-01-01

    The chemotherapeutic use of cisplatin is limited by its severe side effects. In this study, by conducting different omics data analyses, we demonstrated that cisplatin induces cell death in a proximal tubular cell line by suppressing glycolysis- and tricarboxylic acid (TCA)/mitochondria-related genes. Furthermore, analysis of the urine from cisplatin-treated rats revealed the lower expression levels of enzymes involved in glycolysis, TCA cycle, and genes related to mitochondrial stability and confirmed the cisplatin-related metabolic abnormalities. Additionally, an increase in the level of p53, which directly inhibits glycolysis, has been observed. Inhibition of p53 restored glycolysis and significantly reduced the rate of cell death at 24 h and 48 h due to p53 inhibition. The foremost reason of cisplatin-related cytotoxicity has been correlated to the generation of mitochondrial reactive oxygen species (ROS) that influence multiple pathways. Abnormalities in these pathways resulted in the collapse of mitochondrial energy production, which in turn sensitized the cells to death. The quenching of ROS led to the amelioration of the affected pathways. Considering these observations, it can be concluded that there is a significant correlation between cisplatin and metabolic dysfunctions involving mROS as the major player.

  19. Cadmium-induced teratogenicity: Association with ROS-mediated endoplasmic reticulum stress in placenta

    International Nuclear Information System (INIS)

    Wang, Zhen; Wang, Hua; Xu, Zhong Mei; Ji, Yan-Li; Chen, Yuan-Hua; Zhang, Zhi-Hui; Zhang, Cheng; Meng, Xiu-Hong; Zhao, Mei; Xu, De-Xiang

    2012-01-01

    The placenta is essential for sustaining the growth of the fetus. An increased endoplasmic reticulum (ER) stress has been associated with the impaired placental and fetal development. Cadmium (Cd) is a potent teratogen that caused fetal malformation and growth restriction. The present study investigated the effects of maternal Cd exposure on placental and fetal development. The pregnant mice were intraperitoneally injected with CdCl 2 (4.5 mg/kg) on gestational day 9. As expected, maternal Cd exposure during early limb development significantly increased the incidences of forelimb ectrodactyly in fetuses. An obvious impairment in the labyrinth, a highly developed tissue of blood vessels, was observed in placenta of mice treated with CdCl 2 . In addition, maternal Cd exposure markedly repressed cell proliferation and increased apoptosis in placenta. An additional experiment showed that maternal Cd exposure significantly upregulated the expression of GRP78, an ER chaperone. Moreover, maternal Cd exposure induced the phosphorylation of placental eIF2α, a downstream molecule of PERK signaling. In addition, maternal Cd exposure significantly increased the level of placental CHOP, another target of PERK signaling, indicating that the unfolded protein response (UPR) signaling was activated in placenta of mice treated with CdCl 2 . Interestingly, alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, significantly alleviated Cd-induced placental ER stress and UPR. Taken together, these results suggest that reactive oxygen species (ROS)-mediated ER stress might be involved in Cd-induced impairment on placental and fetal development. Antioxidants may be used as pharmacological agents to protect against Cd-induced fetal malformation and growth restriction. -- Highlights: ► Cd induces fetal malformation and growth restriction. ► Cd induced placental ER stress and UPR. ► PBN alleviates Cd-induced ER stress and UPR in placenta. ► ROS-mediated ER stress might

  20. Chemically Regulated ROS Generation from Gold Nanoparticles for Enzyme-Free Electrochemiluminescent Immunosensing.

    Science.gov (United States)

    Higashi, Yui; Mazumder, Joyotu; Yoshikawa, Hiroyuki; Saito, Masato; Tamiya, Eiichi

    2018-04-17

    In the present work, we report on an enzyme-free electrochemiluminescent (ECL) immunosensing scheme utilizing the catalytic generation of reactive oxygen species (ROS) from gold nanoparticles (AuNPs) (diameter ≥5 nm) dispersed in aqueous solutions of trishydroxymethylaminomethane (Tris). First, to examine this catalytic pathway in detail, the effects of various factors such as the AuNP size and concentration, dispersant type and concentration, and dissolved oxygen were investigated using the electrochemiluminescence (ECL) of luminol. It was found that the catalytic generation of ROS from AuNPs can be regulated chemically by altering conditions such as the type, concentration, and pH of the solution that the AuNPs are dispersed in. Under the best conditions studied in this work, the AuNPs displayed high catalytic activity toward ROS generation, with an estimated apparent turnover number per AuNP of 0.1 s -1 , comparable to those of several common peroxide-producing enzymes. Following these studies, this phenomenon was applied to develop a one-step enzyme-free ECL immunosensor based on sandwiching the target analyte using antibody-conjugated magnetic beads (MB) and AuNPs. Using IgA as a model analyte, the developed immunosensor was able to detect the target in the range of 1 ng/mL to 10 μg/mL, with the lower detection limit being comparable to those of commercial assays for the same target. Altering the antibodies used to modify the MB and AuNPs could further improve the detection limit as well as expand the applicability of this immunoassay to the detection of other analytes.

  1. Jolkinolide B induces apoptosis of colorectal carcinoma through ROS-ER stress-Ca2+-mitochondria dependent pathway.

    Science.gov (United States)

    Zhang, Jing; Wang, Yang; Zhou, Ye; He, Qing-Yu

    2017-10-31

    Colorectal carcinoma (CRC) remains one of the leading causes of death in cancer-related diseases. In this study, we aimed to investigate the anticancer effect of Jolkinolide B (JB), a bioactive diterpenoid component isolated from the dried roots of Euphorbia fischeriana Steud, on CRC cells and its underlying mechanisms. We found that JB suppressed the cell viability and colony formation of CRC cells, HT29 and SW620. Annexin V/PI assay revealed that JB induced apoptosis in CRC cells, which was further confirmed by the increased expression of cleaved-caspase3 and cleaved-PARP. iTRAQ-based quantitative proteomics was performed to identify JB-regulated proteins in CRC cells. Gene Ontology (GO) analysis revealed that these JB-regulated proteins were mainly involved in ER stress response, which was evidenced by the expression of ER stress marker proteins, HSP90, Bip and PDI. Moreover, we found that JB provoked the generation of reactive oxygen species (ROS), and that inhibition of the ROS generation with N-acetyl L-cysteine could reverse the JB-induced apoptosis. Confocal microscopy and flow cytometry showed that JB treatment enhanced intracellular and mitochondrial Ca 2+ level and JC-1 assay revealed a loss of mitochondrial membrane potential in CRC after JB treatment. The mitochondrial Ca 2+ uptake and depolarization can be blocked by Ruthenium Red (RuRed), an inhibitor of mitochondrial Ca 2+ uniporter. Taken together, we demonstrated that JB exerts its anticancer effect by ER stress-Ca 2+ -mitochondria signaling, suggesting the promising chemotherapeutic potential of JB for the treatment of CRC.

  2. PERK pathway is involved in oxygen-glucose-serum deprivation-induced NF-kB activation via ROS generation in spinal cord astrocytes.

    Science.gov (United States)

    Liu, Jinbo; Du, Lijian

    2015-11-13

    Mitochondrial dysfunction is a direct target of hypoxic/ischemic stress in astrocytes, which results in the increased production of reactive oxygen species (ROS). Previous reports showed that ROS can activate NF-kB in spinal cord astrocytes, which occurs as a secondary injury during the pathological process of spinal cord injury (SCI). Protein kinase RNA (PKR)-like ER kinase (PERK) plays an important role in mitochondrial dysfunction. To elucidate the specific role of PERK in hypoxic/ischemic-induced NF-kB activation in spinal astrocytes, we utilized an in vitro oxygen-glucose deprivation (OGD) model, which showed an enhanced formation of ROS and NF-kB activation. Knockdown of PERK resulted in reduced activation of PERK and ROS generation in astrocytes under OGD conditions. Notably, the knockdown of PERK also induced NF-kB activation in astrocytes. These data suggest that PERK is required for the hypoxic/ischemic-induced-dependent regulation of ROS and that it is involved in NF-kB activation in the astrocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Curcumin Induced Human Gastric Cancer BGC-823 Cells Apoptosis by ROS-Mediated ASK1-MKK4-JNK Stress Signaling Pathway

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    Tao Liang

    2014-09-01

    Full Text Available The signaling mediated by stress-activated MAP kinases (MAPK, c-Jun N-terminal kinase (JNK has well-established importance in cancer. In the present report, we investigated the effects of curcumin on the signaling pathway in human gastric cancer BGC-823 cells. Curcumin induced reactive oxygen species (ROS production and BGC-823 cells apoptosis. Inhibition of ROS generation by antioxidant (NAC or Trion significantly prevented curcumin-mediated apoptosis. Notably, we observed that curcumin activated ASK1, a MAPKKK that is oxidative stress sensitive and responsible to phosphorylation of JNK via triggering cascades, up-regulated an upstream effector of the JNK, MKK4, and phosphorylated JNK protein expression in BGC-823 cells. However, curcumin induced ASK1-MKK4-JNK signaling was attenuated by NAC. All the findings confirm the possibility that oxidative stress-activated ASK1-MKK4-JNK signaling cascade promotes the apoptotic response in curcumin-treated BGC-823 cells.

  4. Auranofin induces apoptosis by ROS-mediated ER stress and mitochondrial dysfunction and displayed synergistic lethality with piperlongumine in gastric cancer.

    Science.gov (United States)

    Zou, Peng; Chen, Minxiao; Ji, Jiansong; Chen, Weiqian; Chen, Xi; Ying, Shilong; Zhang, Junru; Zhang, Ziheng; Liu, Zhiguo; Yang, Shulin; Liang, Guang

    2015-11-03

    Gastric cancer (GC) is one of the leading causes of cancer mortality in the world. In addressing the need of treatments for relapsed disease, we report the identification of an existing U.S. Food and Drug Administration-approved small-molecule drug to repurpose for GC treatment. Auranofin (AF), clinically used to treat rheumatic arthritis, but it exhibited preclinical efficacy in GC cells. By increasing intracellular reactive oxygen species (ROS) levels, AF induces a lethal endoplasmic reticulum stress response and mitochondrial dysfunction in cultured GC cells. Blockage of ROS production reversed AF-induced ER stress and mitochondrial pathways activation as well as apoptosis. In addition, AF displays synergistic lethality with an ROS-generating agent piperlongumine, which is a natural product isolated from the long pepper Piper longum L. Taken together, this work provides a novel anticancer candidate for the treatment of gastric cancer. More importantly, it reveals that increased ROS generation might be an effective strategy in treating human gastric cancer.

  5. Ganoderma atrum polysaccharide ameliorates ROS generation and apoptosis in spleen and thymus of immunosuppressed mice.

    Science.gov (United States)

    Li, Wen-Juan; Li, Lu; Zhen, Weng-Ya; Wang, Le-Feng; Pan, Meng; Lv, Jia-Qian; Wang, Fan; Yao, Yu-Fei; Nie, Shao-Ping; Xie, Ming-Yong

    2017-01-01

    Ganoderma atrum polysaccharide (PSG-1) is a bioactive compound with antioxidant and immunomodulatory activities. The aim of this study was to determine the effect of PSG-1 on reactive oxygen species (ROS) generation and apoptosis in spleen and thymus of cyclophosphamide (CTX)-induced immunosuppressed mice. The results showed that PSG-1 protected mice against CTX-mediated immunosuppression, as evidenced by enhancing the ratios of thymus and spleen weights to body weight, promoting T cell and B cell survival, and increasing levels of TNF-α and IL-2. Apoptosis, ROS generation and lipid peroxidation in the immune organs of the immunosuppressed animals were ameliorated by PSG-1. The immune benefits of PSG-1 were associated with the enhancement of the activities of glutathione peroxidase, superoxide dismutase and catalase in the immune organs, implying that antioxidant activities of PSG-1 may play an important role in PSG-1-evoked immune protection. Taken together, these findings have demonstrated that PSG-1 may ameliorate CTX-induced immunosuppression through reducing apoptosis and oxidative damage in immunological system. Copyright © 2016. Published by Elsevier Ltd.

  6. Curcumin analog WZ35 induced cell death via ROS-dependent ER stress and G2/M cell cycle arrest in human prostate cancer cells

    International Nuclear Information System (INIS)

    Zhang, Xiuhua; Chen, Minxiao; Zou, Peng; Kanchana, Karvannan; Weng, Qiaoyou; Chen, Wenbo; Zhong, Peng; Ji, Jiansong; Zhou, Huiping; He, Langchong; Liang, Guang

    2015-01-01

    Prostate cancer is the most commonly diagnosed malignancy among men. The Discovery of new agents for the treatment of prostate cancer is urgently needed. Compound WZ35, a novel analog of the natural product curcumin, exhibited good anti-prostate cancer activity, with an IC 50 of 2.2 μM in PC-3 cells. However, the underlying mechanism of WZ35 against prostate cancer cells is still unclear. Human prostate cancer PC-3 cells and DU145 cells were treated with WZ35 for further proliferation, apoptosis, cell cycle, and mechanism analyses. NAC and CHOP siRNA were used to validate the role of ROS and ER stress, respectively, in the anti-cancer actions of WZ35. Our results show that WZ35 exhibited much higher cell growth inhibition than curcumin by inducing ER stress-dependent cell apoptosis in human prostate cells. The reduction of CHOP expression by siRNA partially abrogated WZ35-induced cell apoptosis. WZ35 also dose-dependently induced cell cycle arrest in the G2/M phase. Furthermore, we found that WZ35 treatment for 30 min significantly induced reactive oxygen species (ROS) production in PC-3 cells. Co-treatment with the ROS scavenger NAC completely abrogated the induction of WZ35 on cell apoptosis, ER stress activation, and cell cycle arrest, indicating an upstream role of ROS generation in mediating the anti-cancer effect of WZ35. Taken together, this work presents the novel anticancer candidate WZ35 for the treatment of prostate cancer, and importantly, reveals that increased ROS generation might be an effective strategy in human prostate cancer treatment. The online version of this article (doi:10.1186/s12885-015-1851-3) contains supplementary material, which is available to authorized users

  7. Deliberate ROS production and auxin synergistically trigger the asymmetrical division generating the subsidiary cells in Zea mays stomatal complexes.

    Science.gov (United States)

    Livanos, Pantelis; Galatis, Basil; Apostolakos, Panagiotis

    2016-07-01

    Subsidiary cell generation in Poaceae is an outstanding example of local intercellular stimulation. An inductive stimulus emanates from the guard cell mother cells (GMCs) towards their laterally adjacent subsidiary cell mother cells (SMCs) and triggers the asymmetrical division of the latter. Indole-3-acetic acid (IAA) immunolocalization in Zea mays protoderm confirmed that the GMCs function as local sources of auxin and revealed that auxin is polarly accumulated between GMCs and SMCs in a timely-dependent manner. Besides, staining techniques showed that reactive oxygen species (ROS) exhibit a closely similar, also time-dependent, pattern of appearance suggesting ROS implication in subsidiary cell formation. This phenomenon was further investigated by using the specific NADPH-oxidase inhibitor diphenylene iodonium, the ROS scavenger N-acetyl-cysteine, menadione which leads to ROS overproduction, and H2O2. Treatments with diphenylene iodonium, N-acetyl-cysteine, and menadione specifically blocked SMC polarization and asymmetrical division. In contrast, H2O2 promoted the establishment of SMC polarity and subsequently subsidiary cell formation in "younger" protodermal areas. Surprisingly, H2O2 favored the asymmetrical division of the intervening cells of the stomatal rows leading to the creation of extra apical subsidiary cells. Moreover, H2O2 altered IAA localization, whereas synthetic auxin analogue 1-napthaleneacetic acid enhanced ROS accumulation. Combined treatments with ROS modulators along with 1-napthaleneacetic acid or 2,3,5-triiodobenzoic acid, an auxin efflux inhibitor, confirmed the crosstalk between ROS and auxin functioning during subsidiary cell generation. Collectively, our results demonstrate that ROS are critical partners of auxin during development of Z. mays stomatal complexes. The interplay between auxin and ROS seems to be spatially and temporarily regulated.

  8. Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts.

    Science.gov (United States)

    Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Kwiatkowska, Aleksandra; Potocki, Leszek; Rawska, Ewa; Pabian, Sylwia; Kaplan, Jakub; Lewinska, Anna; Wnuk, Maciej

    2016-05-24

    Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages. The gains of chromosomes I, III and VI and significant changes in the gene copy number in nine functional gene categories involved in metabolic processes and stress responses were observed. Ethanol-mediated gains of YRF1 and CUP1 genes were the most accented. Ethanol also induced nucleolus fragmentation that confirms that nucleolus is a stress sensor in yeasts. Taken together, we postulate that wine yeasts of different origin may adapt to mild alcohol stress by shifts in intracellular redox state promoting growth capacity, upregulation of key regulators of longevity, namely sirtuins and changes in the dosage of genes involved in the telomere maintenance and ion detoxification.

  9. Endoplasmic reticulum-derived reactive oxygen species (ROS) is involved in toxicity of cell wall stress to Candida albicans.

    Science.gov (United States)

    Yu, Qilin; Zhang, Bing; Li, Jianrong; Zhang, Biao; Wang, Honggang; Li, Mingchun

    2016-10-01

    The cell wall is an important cell structure in both fungi and bacteria, and hence becomes a common antimicrobial target. The cell wall-perturbing agents disrupt synthesis and function of cell wall components, leading to cell wall stress and consequent cell death. However, little is known about the detailed mechanisms by which cell wall stress renders fungal cell death. In this study, we found that ROS scavengers drastically attenuated the antifungal effect of cell wall-perturbing agents to the model fungal pathogen Candida albicans, and these agents caused remarkable ROS accumulation and activation of oxidative stress response (OSR) in this fungus. Interestingly, cell wall stress did not cause mitochondrial dysfunction and elevation of mitochondrial superoxide levels. Furthermore, the iron chelator 2,2'-bipyridyl (BIP) and the hydroxyl radical scavengers could not attenuate cell wall stress-caused growth inhibition and ROS accumulation. However, cell wall stress up-regulated expression of unfold protein response (UPR) genes, enhanced protein secretion and promoted protein folding-related oxidation of Ero1, an important source of ROS production. These results indicated that oxidation of Ero1 in the endoplasmic reticulum (ER), rather than mitochondrial electron transport and Fenton reaction, contributed to cell wall stress-related ROS accumulation and consequent growth inhibition. Our findings uncover a novel link between cell wall integrity (CWI), ER function and ROS production in fungal cells, and shed novel light on development of strategies promoting the antifungal efficacy of cell wall-perturbing agents against fungal infections. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Generation of reactive oxygen species (ROS) is a key factor for stimulation of macrophage proliferation by ceramide 1-phosphate

    International Nuclear Information System (INIS)

    Arana, Lide; Gangoiti, Patricia; Ouro, Alberto; Rivera, Io-Guané; Ordoñez, Marta; Trueba, Miguel; Lankalapalli, Ravi S.; Bittman, Robert; Gomez-Muñoz, Antonio

    2012-01-01

    We previously demonstrated that ceramide 1-phosphate (C1P) is mitogenic for fibroblasts and macrophages. However, the mechanisms involved in this action were only partially described. Here, we demonstrate that C1P stimulates reactive oxygen species (ROS) formation in primary bone marrow-derived macrophages, and that ROS are required for the mitogenic effect of C1P. ROS production was dependent upon prior activation of NADPH oxidase by C1P, which was determined by measuring phosphorylation of the p40phox subunit and translocation of p47phox from the cytosol to the plasma membrane. In addition, C1P activated cytosolic calcium-dependent phospholipase A 2 and protein kinase C-α, and NADPH oxidase activation was blocked by selective inhibitors of these enzymes. These inhibitors, and inhibitors of ROS production, blocked the mitogenic effect of C1P. By using BHNB-C1P (a photolabile caged-C1P analog), we demonstrate that all of these C1P actions are caused by intracellular C1P. It can be concluded that the enzyme responsible for C1P-stimulated ROS generation in bone marrow-derived macrophages is NADPH oxidase, and that this enzyme is downstream of PKC-α and cPLA 2 -α in this pathway. -- Highlights: ► Ceramide 1-phosphate (C1P) stimulates reactive oxygen species (ROS) formation. ► The enzyme responsible for ROS generation by C1P in macrophages is NADPH oxidase. ► NADPH oxidase lies downstream of cPLA 2 -α and PKC-α in this pathway. ► ROS generation is essential for the stimulation of macrophage proliferation by C1P.

  11. Human Leukemic Cells performing Oxidative Phosphorylation (OXPHOS Generate an Antioxidant Response Independently of Reactive Oxygen species (ROS Production

    Directory of Open Access Journals (Sweden)

    Abrar Ul Haq Khan

    2016-01-01

    Full Text Available Tumor cell metabolism is altered during leukemogenesis. Cells performing oxidative phosphorylation (OXPHOS generate reactive oxygen species (ROS through mitochondrial activity. To limit the deleterious effects of excess ROS, certain gene promoters contain antioxidant response elements (ARE, e.g. the genes NQO-1 and HO-1. ROS induces conformational changes in KEAP1 and releases NRF2, which activates AREs. We show in vitro and in vivo that OXPHOS induces, both in primary leukemic cells and cell lines, de novo expression of NQO-1 and HO-1 and also the MAPK ERK5 and decreases KEAP1 mRNA. ERK5 activates the transcription factor MEF2, which binds to the promoter of the miR-23a–27a–24-2 cluster. Newly generated miR-23a destabilizes KEAP1 mRNA by binding to its 3′UTR. Lower KEAP1 levels increase the basal expression of the NRF2-dependent genes NQO-1 and HO-1. Hence, leukemic cells performing OXPHOS, independently of de novo ROS production, generate an antioxidant response to protect themselves from ROS.

  12. Shift in aggregation, ROS generation, antioxidative defense, lysozyme and acetylcholinesterase activities in the cells of an Indian freshwater sponge exposed to washing soda (sodium carbonate).

    Science.gov (United States)

    Mukherjee, Soumalya; Ray, Mitali; Ray, Sajal

    2016-09-01

    Washing soda, chemically identified as anhydrous sodium carbonate, is a popular cleaning agent among the rural and urban populations of India which often contaminates the freshwater ponds and lakes, the natural habitat of sponge Eunapius carteri. Present investigation deals with estimation of cellular aggregation, generation of ROS and activities of antioxidant enzymes, lysozyme and acetylcholinesterase in the cells of E. carteri under the environmentally realistic concentrations of washing soda. Prolonged treatment of washing soda inhibited the degree of cellular aggregation. Experimental exposure of 8 and 16mg/l of sodium carbonate for 48h elevated the physiological level of reactive oxygen species (ROS) generation in the agranulocytes, semigranulocytes and granulocytes of E. carteri, whereas, treatment of 192h inhibited the ROS generation in three cellular morphotypes. Activities of superoxide dismutase, catalase and glutathione-S-transferase were recorded to be inhibited under prolonged exposure of washing soda. Washing soda mediated inhibition of ROS generation and depletion in the activities of antioxidant enzymes were indicative to an undesirable shift in cytotoxic status and antioxidative defense in E. carteri. Inhibition in the activity of lysozyme under the treatment of sodium carbonate was suggestive to a severe impairment of the innate immunological efficiency of E. carteri distributed in the washing soda contaminated habitat. Washing soda mediated inhibition in the activity of acetylcholinesterase indicated its neurotoxicity in E. carteri. Washing soda, a reported environmental contaminant, affected adversely the immunophysiological status of E. carteri with reference to cellular aggregation, oxidative stress, antioxidative defense, lysozyme and acetylcholinesterase activity. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Non-thermal plasma induces mitochondria-mediated apoptotic signaling pathway via ROS generation in HeLa cells.

    Science.gov (United States)

    Li, Wei; Yu, K N; Ma, Jie; Shen, Jie; Cheng, Cheng; Zhou, Fangjian; Cai, Zhiming; Han, Wei

    2017-11-01

    Non-thermal plasma (NTP) has been proposed as a novel therapeutic method for anticancer treatment. Although increasing evidence suggests that NTP selectively induces apoptosis in some types of tumor cells, the molecular mechanisms underlying this phenomenon remain unclear. In this study, we further investigated possible molecular mechanisms for NTP-induced apoptosis of HeLa cells. The results showed that NTP exposure significantly inhibited the growth and viability of HeLa cells. Morphological observation and flow cytometry analysis demonstrated that NTP exposure induced HeLa cell apoptosis. NTP exposure also activated caspase-9 and caspase-3, which subsequently cleaved poly (ADP- ribose) polymerase. Furthermore, NTP exposure suppressed Bcl-2 expression, enhanced Bax expression and translocation to mitochondria, activated mitochondria-mediated apoptotic pathway, followed by the release of cytochrome c. Further studies showed that NTP treatment led to ROS generation, whereas blockade of ROS generation by N-acetyl-l-cysteine (NAC, ROS scavengers) significantly prevented NTP-induced mitochondrial alteration and subsequent apoptosis of HeLa cells via suppressing Bax translocation, cytochrome c and caspase-3 activation. Taken together, our results indicated that NTP exposure induced mitochondria-mediated intrinsic apoptosis of HeLa cells was activated by ROS generation. These findings provide insights to the therapeutic potential and clinical research of NTP as a novel tool in cervical cancer treatment. Copyright © 2017. Published by Elsevier Inc.

  14. ROS generation and multiple forms of mammalian mitochondrial glycerol-3-phosphate dehydrogenase

    Czech Academy of Sciences Publication Activity Database

    Mráček, Tomáš; Holzerová, Eliška; Drahota, Zdeněk; Kovářová, Nikola; Vrbacký, Marek; Ješina, Pavel; Houštěk, Josef

    2014-01-01

    Roč. 1837, č. 1 (2014), s. 98-111 ISSN 0005-2728 R&D Projects: GA ČR(CZ) GPP303/10/P227; GA MŠk(CZ) LL1204 Grant - others:Univerzita Karlova(CZ) 750213 Institutional support: RVO:67985823 Keywords : mitochondrial glycerol-3-phosphate dehydrogenase * ROS production * supercomplex * in-gel ROS detection Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.353, year: 2014

  15. Induction of apoptosis and antiproliferative activity of naringenin in human epidermoid carcinoma cell through ROS generation and cell cycle arrest.

    Directory of Open Access Journals (Sweden)

    Md Sultan Ahamad

    Full Text Available A natural predominant flavanone naringenin, especially abundant in citrus fruits, has a wide range of pharmacological activities. The search for antiproliferative agents that reduce skin carcinoma is a task of great importance. The objective of this study was to analyze the anti-proliferative and apoptotic mechanism of naringenin using MTT assay, DNA fragmentation, nuclear condensation, change in mitochondrial membrane potential, cell cycle kinetics and caspase-3 as biomarkers and to investigate the ability to induce reactive oxygen species (ROS initiating apoptotic cascade in human epidermoid carcinoma A431 cells. Results showed that naringenin exposure significantly reduced the cell viability of A431 cells (p<0.01 with a concomitant increase in nuclear condensation and DNA fragmentation in a dose dependent manner. The intracellular ROS generation assay showed statistically significant (p<0.001 dose-related increment in ROS production for naringenin. It also caused naringenin-mediated epidermoid carcinoma apoptosis by inducing mitochondrial depolarization. Cell cycle study showed that naringenin induced cell cycle arrest in G0/G1 phase of cell cycle and caspase-3 analysis revealed a dose dependent increment in caspase-3 activity which led to cell apoptosis. This study confirms the efficacy of naringenin that lead to cell death in epidermoid carcinoma cells via inducing ROS generation, mitochondrial depolarization, nuclear condensation, DNA fragmentation, cell cycle arrest in G0/G1 phase and caspase-3 activation.

  16. ALA/LA ameliorates glucose toxicity on HK-2 cells by attenuating oxidative stress and apoptosis through the ROS/p38/TGF-β1 pathway.

    Science.gov (United States)

    Jiang, Mingxia; Zhang, Haifen; Zhai, Lijie; Ye, Bianliang; Cheng, Yin; Zhai, Chengkai

    2017-11-16

    Growing evidence indicates that oxidative stress (OS) plays a pivotal role in Diabetic nephropathy (DN). In a previous study we demonstrated that ALA/LA protected HK-2 cells against high glucose-induced cytotoxicity. So we aimed to establish the glucose injury model of HK-2 cells and investigate the beneficial effects of ALA/LA on high glucose-induced excessive production of TGF-β1 and the possible mechanisms mediating the effects. The expression of OS markers in high glucose-induced HK-2 cells treated with ALA/LA., including the antioxidant enzymes and reactive oxygen species (ROS) production, as well as the apoptosis rate were assayed by ELISA and flow cytometry. The p38/transforming growth factor β 1 (TGF-β 1 ) signal pathway were measured by real-time RT-PCR and western blot. The modeling condition of glucose toxicity on HK-2 cells was at the glucose concentration of 40.9 mM. ALA/LA can significantly increase the activities of antioxidant enzymes and decrease ROS production stimulated by high glucose. The study also found that ALA/LA caused a decrease in the apoptosis rate and TGF-β 1 level of HK-2 cells under high glucose stress through the ROS/p38 pathway. ALA/LA exerts protective effects in vitro through inhibition of ROS generation, down regulation of the activation of the p38MAPK pathway and the expression of TGF-β 1 in HK-2 cells.

  17. ROS generation and MAPKs activation contribute to the Ni-induced testosterone synthesis disturbance in rat Leydig cells.

    Science.gov (United States)

    Han, Aijie; Zou, Lingyue; Gan, Xiaoqin; Li, Yu; Liu, Fangfang; Chang, Xuhong; Zhang, Xiaotian; Tian, Minmin; Li, Sheng; Su, Li; Sun, Yingbiao

    2018-06-15

    Nickel (Ni) can disorder testosterone synthesis in rat Leydig cells, whereas the mechanisms remain unclear. The aim of this study was to investigate the role of reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) in Ni-induced disturbance of testosterone synthesis in rat Leydig cells. The testosterone production and ROS levels were detected in Leydig cells. The mRNA and protein levels of testosterone synthetase, including StAR, CYP11A1, 3β-HSD, CYP17A1 and 17β-HSD, were determined. Effects of Ni on the ERK1/2, p38 and JNK MAPKs were also investigated. The results showed that Ni triggered ROS generation, consequently resulted in the decrease of testosterone synthetase expression and testosterone production in Leydig cells, which were then attenuated by ROS scavengers of N-acetylcysteine (NAC) and 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), indicating that ROS are involved in the Ni-induced testosterone biosynthesis disturbance. Meanwhile Ni activated the ERK1/2, p38 and JNK MAPKs. Furthermore, Ni-inhibited testosterone synthetase expression levels and testosterone secretion were all alleviated by co-treatment with MAPK specific inhibitors (U0126 and SB203580, respectively), implying that Ni inhibited testosterone synthesis through activating ERK1/2 and p38 MAPK signal pathways in Leydig cells. In conclusion, these findings suggest that Ni causes testosterone synthesis disorder, partly, via ROS and MAPK signal pathways. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Ethanol stimulates ROS generation by mitochondria through Ca2+ mobilization and increases GFAP content in rat hippocampal astrocytes.

    Science.gov (United States)

    González, Antonio; Pariente, José A; Salido, Ginés M

    2007-10-31

    We have employed rat hippocampal astrocytes in culture to investigate the effect of ethanol on reactive oxygen species (ROS) production as well as its effect on [Ca2+]c and GFAP expression. Cells were loaded with the fluorescent probes fura-2 and H2DCFDA for the determination of changes in [Ca2+]c and ROS production respectively, employing spectrofluorimetry. GFAP content was determined by immunocytochemistry and confocal scanning microscopy. Our results show ROS production in response to 50 mM ethanol, that was reduced in Ca2+-free medium (containing 0.5 mM EGTA) and in the presence of the intracellular Ca2+ chelator BAPTA (10 microM). The effect of ethanol on ROS production was significantly reduced in the presence of the alcohol dehydrogenase inhibitor 4-methylpyrazole (1 mM), and the antioxidants resveratrol (100 microM) or catalase (300 U/ml). Preincubation of astrocytes in the presence of 10 microM antimycin plus 10 microM oligomycin to inhibit mitochondria completely blocked ethanol-evoked ROS production. In addition, ethanol led to a sustained increase in [Ca2+]c that reached a constant level over the prestimulation values. Finally, incubation of astrocytes in the presence of ethanol increased the content of GFAP that was significantly reduced in the absence of extracellular Ca2+ and by resveratrol and catalase pretreatment. The data obtained in the present study suggest that astrocytes are able to metabolize ethanol, which induces two effects on intracellular homeostasis: an immediate response (Ca2+ release and ROS generation) and later changes involving GFAP expression. Both effects may underline various signaling pathways which are important for cell proliferation, differentiation and function.

  19. A novel copper complex induces ROS generation in doxorubicin resistant Ehrlich ascitis carcinoma cells and increases activity of antioxidant enzymes in vital organs in vivo

    International Nuclear Information System (INIS)

    Mookerjee, Ananda; Roy, Syamal; Choudhuri, Soumitra K; Basu, Jayati Mookerjee; Majumder, Surajit; Chatterjee, Shilpak; Panda, Gouri S; Dutta, Pranabananda; Pal, Smarajit; Mukherjee, Pratima; Efferth, Thomas

    2006-01-01

    In search of a suitable GSH-depleting agent, a novel copper complex viz., copper N-(2-hydroxyacetophenone) glycinate (CuNG) has been synthesized, which was initially found to be a potential resistance modifying agent and later found to be an immunomodulator in mice model in different doses. The objective of the present work was to decipher the effect of CuNG on reactive oxygen species (ROS) generation and antioxidant enzymes in normal and doxorubicin-resistant Ehrlich ascites carcinoma (EAC/Dox)-bearing Swiss albino mice. The effect of CuNG has been studied on ROS generation, multidrug resistance-associated protein1 (MRP1) expression and on activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). CuNG increased ROS generation and reduced MRP1 expression in EAC/Dox cells while only temporarily depleted glutathione (GSH) within 2 h in heart, kidney, liver and lung of EAC/Dox bearing mice, which were restored within 24 h. The level of liver Cu was observed to be inversely proportional to the level of GSH. Moreover, CuNG modulated SOD, CAT and GPx in different organs and thereby reduced oxidative stress. Thus nontoxic dose of CuNG may be utilized to reduce MRP1 expression and thus sensitize EAC/Dox cells to standard chemotherapy. Moreover, CuNG modulated SOD, CAT and and GPx activities to reduce oxidative stress in some vital organs of EAC/Dox bearing mice. CuNG treatment also helped to recover liver and renal function in EAC/Dox bearing mice. Based on our studies, we conclude that CuNG may be a promising candidate to sensitize drug resistant cancers in the clinic

  20. ROS and ROS-Mediated Cellular Signaling

    Directory of Open Access Journals (Sweden)

    Jixiang Zhang

    2016-01-01

    Full Text Available It has long been recognized that an increase of reactive oxygen species (ROS can modify the cell-signaling proteins and have functional consequences, which successively mediate pathological processes such as atherosclerosis, diabetes, unchecked growth, neurodegeneration, inflammation, and aging. While numerous articles have demonstrated the impacts of ROS on various signaling pathways and clarify the mechanism of action of cell-signaling proteins, their influence on the level of intracellular ROS, and their complex interactions among multiple ROS associated signaling pathways, the systemic summary is necessary. In this review paper, we particularly focus on the pattern of the generation and homeostasis of intracellular ROS, the mechanisms and targets of ROS impacting on cell-signaling proteins (NF-κB, MAPKs, Keap1-Nrf2-ARE, and PI3K-Akt, ion channels and transporters (Ca2+ and mPTP, and modifying protein kinase and Ubiquitination/Proteasome System.

  1. Reactive Oxygen Species Generation-Scavenging and Signaling during Plant-Arbuscular Mycorrhizal and Piriformospora indica Interaction under Stress Condition.

    Science.gov (United States)

    Nath, Manoj; Bhatt, Deepesh; Prasad, Ram; Gill, Sarvajeet S; Anjum, Naser A; Tuteja, Narendra

    2016-01-01

    A defined balance between the generation and scavenging of reactive oxygen species (ROS) is essential to utilize ROS as an adaptive defense response of plants under biotic and abiotic stress conditions. Moreover, ROS are not only a major determinant of stress response but also act as signaling molecule that regulates various cellular processes including plant-microbe interaction. In particular, rhizosphere constitutes the biologically dynamic zone for plant-microbe interactions which forms a mutual link leading to reciprocal signaling in both the partners. Among plant-microbe interactions, symbiotic associations of arbuscular mycorrhizal fungi (AMF) and arbuscular mycorrhizal-like fungus especially Piriformospora indica with plants are well known to improve plant growth by alleviating the stress-impacts and consequently enhance the plant fitness. AMF and P. indica colonization mainly enhances ROS-metabolism, maintains ROS-homeostasis, and thereby averts higher ROS-level accrued inhibition in plant cellular processes and plant growth and survival under stressful environments. This article summarizes the major outcomes of the recent reports on the ROS-generation, scavenging and signaling in biotic-abiotic stressed plants with AMF and P. indica colonization. Overall, a detailed exploration of ROS-signature kinetics during plant-AMF/ P. indica interaction can help in designing innovative strategies for improving plant health and productivity under stress conditions.

  2. Ebselen attenuates cisplatin-induced ROS generation through Nrf2 activation in auditory cells.

    Science.gov (United States)

    Kim, Se-Jin; Park, Channy; Han, A Lum; Youn, Myung-Ja; Lee, Jeong-Han; Kim, Yunha; Kim, Eun-Sook; Kim, Hyung-Jin; Kim, Jin-Kyung; Lee, Ho-Kyun; Chung, Sang-Young; So, Hongseob; Park, Raekil

    2009-05-01

    Ebselen, an organoselenium compound that acts as a glutathione peroxidase mimetic, has been demonstrated to possess antioxidant and anti-inflammatory activities. However, the molecular mechanism underlying this effect is not fully understood in auditory cells. The purpose of the present study is to investigate the protective effect of ebselen against cisplatin-induced toxicity in HEI-OC1 auditory cells, organotypic cultures of cochlear explants from two-day postnatal rats (P(2)) and adult Balb/C mice. Pretreatment with ebselen ameliorated apoptotic death induced by cisplatin in HEI-OC1 cells and organotypic cultures of Corti's organ. Ebselen pretreatment also significantly suppressed cisplatin-induced increases in intracellular reactive oxygen species (ROS), intracellular reactive nitrogen species (RNS) and lipid peroxidation levels. Ebselen dose-dependently increased the expression level of an antioxidant response element (ARE)-luciferase reporter in HEI-OC1 cells through the translocation of Nrf2 into the nucleus. Furthermore, we found that pretreatment with ebselen significantly restored Nrf2 function, whereas it ameliorated the cytotoxicity of cisplatin in cells transfectants with either a pcDNA3.1 (control) or a DN-Nrf2 (dominant-negative) plasmid. We also observed that Nrf2 activation by ebselen increased the expression of phase II antioxidant genes, including heme oxygenase (HO-1), NAD(P)H:quinine oxidoreductase, and gamma-glutamylcysteine synthetase (gamma-GCS). Treatment with ebselen resulted in an increased expression of HO-1 and intranuclear Nrf2 in hair cells of organotypic cultured cochlea. After intraperitoneal injection with cisplatin, auditory brainstem responses (ABRs) threshold was measured on 8th day in Balb/C mice. ABR threshold shift was marked occurred in mice injected with cisplatin (16 mg/kg, n=5; Click and 8-kHz stimuli, pebselen was not significantly changed. These results suggest that ebselen activates the Nrf2-ARE signaling pathway

  3. Tenuifolide B from Cinnamomum tenuifolium Stem Selectively Inhibits Proliferation of Oral Cancer Cells via Apoptosis, ROS Generation, Mitochondrial Depolarization, and DNA Damage.

    Science.gov (United States)

    Chen, Chung-Yi; Yen, Ching-Yu; Wang, Hui-Ru; Yang, Hui-Ping; Tang, Jen-Yang; Huang, Hurng-Wern; Hsu, Shih-Hsien; Chang, Hsueh-Wei

    2016-11-05

    The development of drugs that selectively kill oral cancer cells but are less harmful to normal cells still provide several challenges. In this study, the antioral cancer effects of tenuifolide B (TFB), extracted from the stem of the plant Cinnamomum tenuifolium are evaluated in terms of their effects on cancer cell viability, cell cycle analysis, apoptosis, oxidative stress, and DNA damage. Cell viability of oral cancer cells (Ca9-22 and CAL 27) was found to be significantly inhibited by TFB in a dose-responsive manner in terms of ATP assay, yielding IC 50 = 4.67 and 7.05 μM (24 h), but are less lethal to normal oral cells (HGF-1). Dose-responsive increases in subG1 populations as well as the intensities of flow cytometry-based annexin V/propidium iodide (PI) analysis and pancaspase activity suggested that apoptosis was inducible by TFB in these two types of oral cancer cells. Pretreatment with the apoptosis inhibitor (Z-VAD-FMK) reduced the annexin V intensity of these two TFB-treated oral cancer cells, suggesting that TFB induced apoptosis-mediated cell death to oral cancer cells. Cleaved-poly (ADP-ribose) polymerase (PARP) and cleaved-caspases 3, 8, and 9 were upregulated in these two TFB-treated oral cancer cells over time but less harmful for normal oral HGF-1 cells. Dose-responsive and time-dependent increases in reactive oxygen species (ROS) and decreases in mitochondrial membrane potential (MitoMP) in these two TFB-treated oral cancer cells suggest that TFB may generate oxidative stress as measured by flow cytometry. N -acetylcysteine (NAC) pretreatment reduced the TFB-induced ROS generation and further validated that ROS was relevant to TFB-induced cell death. Both flow cytometry and Western blotting demonstrated that the DNA double strand marker γH2AX dose-responsively increased in TFB-treated Ca9-22 cells and time-dependently increased in two TFB-treated oral cancer cells. Taken together, we infer that TFB can selectively inhibit cell proliferation of

  4. Alternative oxidase pathway optimizes photosynthesis during osmotic and temperature stress by regulating cellular ROS, malate valve and antioxidative systems

    Directory of Open Access Journals (Sweden)

    DINAKAR eCHALLABATHULA

    2016-02-01

    Full Text Available The present study reveals the importance of alternative oxidase (AOX pathway in optimizing photosynthesis under osmotic and temperature stress conditions in the mesophyll protoplasts of Pisum sativum. The responses of photosynthesis and respiration were monitored at saturating light intensity of 1000 µmoles m-2 s-1 at 25 oC under a range of sorbitol concentrations from 0.4 M to 1.0M to induce hyper-osmotic stress and by varying the temperature of the thermo-jacketed pre-incubation chamber from 25 oC to 10 oC to impose sub-optimal temperature stress. Compared to controls (0.4 M sorbitol and 25 OC, the mesophyll protoplasts showed remarkable decrease in NaHCO3-dependent O2 evolution (indicator of photosynthetic carbon assimilation, under both hyper-osmotic (1.0 M sorbitol and sub-optimal temperature stress conditions (10 OC, while the decrease in rates of respiratory O2 uptake were marginal. The capacity of AOX pathway increased significantly in parallel to increase in intracellular pyruvate and reactive oxygen species (ROS levels under both hyper-osmotic stress and sub-optimal temperature stress under the background of saturating light. The ratio of redox couple (Malate/OAA related to malate valve increased in contrast to the ratio of redox couple (GSH/GSSG related to antioxidative system during hyper-osmotic stress. Nevertheless, the ratio of GSH/GSSG decreased in the presence of sub-optimal temperature, while the ratio of Malate/OAA showed no visible changes. Also, the redox ratios of pyridine nucleotides increased under hyper-osmotic (NADH/NAD and sub-optimal temperature (NADPH/NADP stresses, respectively. However, upon restriction of AOX pathway by using salicylhydroxamic acid (SHAM, the observed changes in NaHCO3 dependent O2 evolution, cellular ROS, redox ratios of Malate/OAA, NAD(PH/NAD(P and GSH/GSSG were further aggravated under stress conditions with concomitant modulations in NADP-MDH and antioxidant enzymes. Taken together, the

  5. Oxygen Consumption and Usage During Physical Exercise: The Balance Between Oxidative Stress and ROS-Dependent Adaptive Signaling

    Science.gov (United States)

    Zhao, Zhongfu; Koltai, Erika; Ohno, Hideki; Atalay, Mustafa

    2013-01-01

    Abstract The complexity of human DNA has been affected by aerobic metabolism, including endurance exercise and oxygen toxicity. Aerobic endurance exercise could play an important role in the evolution of Homo sapiens, and oxygen was not important just for survival, but it was crucial to redox-mediated adaptation. The metabolic challenge during physical exercise results in an elevated generation of reactive oxygen species (ROS) that are important modulators of muscle contraction, antioxidant protection, and oxidative damage repair, which at moderate levels generate physiological responses. Several factors of mitochondrial biogenesis, such as peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), mitogen-activated protein kinase, and SIRT1, are modulated by exercise-associated changes in the redox milieu. PGC-1α activation could result in decreased oxidative challenge, either by upregulation of antioxidant enzymes and/or by an increased number of mitochondria that allows lower levels of respiratory activity for the same degree of ATP generation. Endogenous thiol antioxidants glutathione and thioredoxin are modulated with high oxygen consumption and ROS generation during physical exercise, controlling cellular function through redox-sensitive signaling and protein–protein interactions. Endurance exercise-related angiogenesis, up to a significant degree, is regulated by ROS-mediated activation of hypoxia-inducible factor 1α. Moreover, the exercise-associated ROS production could be important to DNA methylation and post-translation modifications of histone residues, which create heritable adaptive conditions based on epigenetic features of chromosomes. Accumulating data indicate that exercise with moderate intensity has systemic and complex health-promoting effects, which undoubtedly involve regulation of redox homeostasis and signaling. Antioxid. Redox Signal. 18, 1208–1246. PMID:22978553

  6. Modulation of Potassium Channel Activity in the Balance of ROS and ATP Production by Durum Wheat Mitochondria - An amazing defence tool against hyperosmotic stress

    Directory of Open Access Journals (Sweden)

    Daniela eTrono

    2015-12-01

    hyperosmotic stress (mannitol or NaCl, PmitoKATP was found to be activated by ROS, so inhibiting further large-scale ROS production according to a feedback mechanism; moreover, a stress-activated phospholipase A2 may generate FFAs, further activating the channel. In conclusion, a main property of PmitoKATP is the ability to keep in balance the control of harmful ROS with the mitochondrial/cellular bioenergetics, thus preserving ATP for energetic needs of cell defence under stress.

  7. A deficiency of apoptosis inducing factor (AIF in Harlequin mouse heart mitochondria paradoxically reduces ROS generation during ischemia-reperfusion

    Directory of Open Access Journals (Sweden)

    Qun eChen

    2014-07-01

    Full Text Available Background and Aims: AIF (apoptosis inducing factor is a flavin and NADH containing protein located within mitochondria required for optimal function of the respiratory chain. AIF may function as an antioxidant within mitochondria, yet when released from mitochondria it activates caspase-independent cell death. The Harlequin (Hq mouse has a markedly reduced content of AIF, providing an experimental model to query if the main role of AIF in the exacerbation of cell death is enhanced mitochondrial generation of reactive oxygen species (ROS or the activation of cell death programs. We asked if the ROS generation is altered in Hq heart mitochondria at baseline or following ischemia-reperfusion (IR.Methods: Buffer perfused mouse hearts underwent 30 min ischemia and 30 min reperfusion. Mitochondrial function including oxidative phosphorylation and H2O2 generation was measured. Immunoblotting was used to determine the contents of AIF and PAR [poly(ADP-ribose] in cell fractions.Results: There were no differences in the release of H2O2 between wild type (WT and Hq heart mitochondria at baseline. IR increased H2O2 generation from WT but not from Hq mitochondria compared to corresponding time controls. The complex I activity was decreased in WT but not in Hq mice following IR. The relocation of AIF from mitochondria to nucleus was increased in WT but not in Hq mice. IR activated PARP-1 only in WT mice. Cell injury was decreased in Hq mouse heart following in vitro IR.Conclusion: A deficiency of AIF within mitochondria does not increase ROS production during IR, indicating that AIF functions less as an antioxidant within mitochondria. The decreased cardiac injury in Hq mouse heart accompanied by less AIF translocation to the nucleus suggests that AIF relocation, rather than the AIF content within mitochondria, contributes to cardiac injury during IR.

  8. The SbMT-2 gene from a halophyte confers abiotic stress tolerance and modulates ROS scavenging in transgenic tobacco.

    Directory of Open Access Journals (Sweden)

    Amit Kumar Chaturvedi

    Full Text Available Heavy metals are common pollutants of the coastal saline area and Salicornia brachiata an extreme halophyte is frequently exposed to various abiotic stresses including heavy metals. The SbMT-2 gene was cloned and transformed to tobacco for the functional validation. Transgenic tobacco lines (L2, L4, L6 and L13 showed significantly enhanced salt (NaCl, osmotic (PEG and metals (Zn++, Cu++ and Cd++ tolerance compared to WT plants. Transgenic lines did not show any morphological variation and had enhanced growth parameters viz. shoot length, root length, fresh weight and dry weight. High seed germination percentage, chlorophyll content, relative water content, electrolytic leakage and membrane stability index confirmed that transgenic lines performed better under salt (NaCl, osmotic (PEG and metals (Zn++, Cu++ and Cd++ stress conditions compared to WT plants. Proline, H2O2 and lipid peroxidation (MDA analyses suggested the role of SbMT-2 in cellular homeostasis and H2O2 detoxification. Furthermore in vivo localization of H2O2 and O2-; and elevated expression of key antioxidant enzyme encoding genes, SOD, POD and APX evident the possible role of SbMT-2 in ROS scavenging/detoxification mechanism. Transgenic lines showed accumulation of Cu++ and Cd++ in root while Zn++ in stem under stress condition. Under control (unstressed condition, Zn++ was accumulated more in root but accumulation of Zn++ in stem under stress condition suggested that SbMT-2 may involve in the selective translocation of Zn++ from root to stem. This observation was further supported by the up-regulation of zinc transporter encoding genes NtZIP1 and NtHMA-A under metal ion stress condition. The study suggested that SbMT-2 modulates ROS scavenging and is a potential candidate to be used for phytoremediation and imparting stress tolerance.

  9. The SbMT-2 gene from a halophyte confers abiotic stress tolerance and modulates ROS scavenging in transgenic tobacco.

    Science.gov (United States)

    Chaturvedi, Amit Kumar; Patel, Manish Kumar; Mishra, Avinash; Tiwari, Vivekanand; Jha, Bhavanath

    2014-01-01

    Heavy metals are common pollutants of the coastal saline area and Salicornia brachiata an extreme halophyte is frequently exposed to various abiotic stresses including heavy metals. The SbMT-2 gene was cloned and transformed to tobacco for the functional validation. Transgenic tobacco lines (L2, L4, L6 and L13) showed significantly enhanced salt (NaCl), osmotic (PEG) and metals (Zn++, Cu++ and Cd++) tolerance compared to WT plants. Transgenic lines did not show any morphological variation and had enhanced growth parameters viz. shoot length, root length, fresh weight and dry weight. High seed germination percentage, chlorophyll content, relative water content, electrolytic leakage and membrane stability index confirmed that transgenic lines performed better under salt (NaCl), osmotic (PEG) and metals (Zn++, Cu++ and Cd++) stress conditions compared to WT plants. Proline, H2O2 and lipid peroxidation (MDA) analyses suggested the role of SbMT-2 in cellular homeostasis and H2O2 detoxification. Furthermore in vivo localization of H2O2 and O2-; and elevated expression of key antioxidant enzyme encoding genes, SOD, POD and APX evident the possible role of SbMT-2 in ROS scavenging/detoxification mechanism. Transgenic lines showed accumulation of Cu++ and Cd++ in root while Zn++ in stem under stress condition. Under control (unstressed) condition, Zn++ was accumulated more in root but accumulation of Zn++ in stem under stress condition suggested that SbMT-2 may involve in the selective translocation of Zn++ from root to stem. This observation was further supported by the up-regulation of zinc transporter encoding genes NtZIP1 and NtHMA-A under metal ion stress condition. The study suggested that SbMT-2 modulates ROS scavenging and is a potential candidate to be used for phytoremediation and imparting stress tolerance.

  10. A novel synthetic analog of militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells

    International Nuclear Information System (INIS)

    Yoon, Deok Hyo; Lim, Mi-Hee; Lee, Yu Ran; Sung, Gi-Ho; Lee, Tae-Ho; Jeon, Byeong Hwa; Cho, Jae Youl; Song, Won O.; Park, Haeil; Choi, Sunga; Kim, Tae Woong

    2013-01-01

    A synthetic Militarin analog-1[(2R,3R,4R,5R)-1,6-bis(4-(2,4,4-trimethylpentan-2-yl)phenoxy) hexane-2,3,4,5-tetraol] is a novel derivative of constituents from Cordyceps militaris, which has been used to treat a variety of chronic diseases including inflammation, diabetes, hyperglycemia and cancers. Here, we report for the first time the synthesis of Militarin analog-1 (MA-1) and the apoptotic mechanism of MA-1 against human lung cancer cell lines. Treatment with MA-1 significantly inhibited the viability of 3 human lung cancer cell lines. The inhibition of viability and growth in MA-1-treated A549 cells with an IC 50 of 5 μM were mediated through apoptosis induction, as demonstrated by an increase in DNA fragmentation, sub-G 0 /G 1 -DNA fraction, nuclear condensation, and phosphatidylserine exposure. The apoptotic cell death caused mitochondrial membrane permeabilization through regulation of expression of the Bcl-2 family proteins, leading to cytochrome c release in a time-dependent manner. Subsequently, the final stage of apoptosis, activation of caspase-9/-3 and cleavage of poly (ADP ribose) polymerase, was induced. Furthermore, A549 lung cancer cells were more responsive to MA-1 than a bronchial epithelial cell line (BEAS-2B), involving the rapid generation of reactive oxygen species (ROS), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation. The pharmacological inhibition of ROS generation and JNK/p38 MAPK exhibited attenuated DNA fragmentation in MA-1-induced apoptosis. Oral administration of MA-1 also retarded growth of A549 orthotopic xenografts. In conclusion, the present study indicates that the new synthetic derivative MA-1 triggers mitochondrial apoptosis through ROS generation and regulation of MAPKs and may be a potent therapeutic agent against human lung cancer. - Highlights: • We report a novel synthesized derivative, militarin analog-1 (MA-1). • MA-1-induced cancer cell death was triggered by the ROS

  11. A novel synthetic analog of militarin, MA-1 induces mitochondrial dependent apoptosis by ROS generation in human lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Deok Hyo; Lim, Mi-Hee [Department of Biochemistry, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Lee, Yu Ran [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Sung, Gi-Ho [Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Suwon 404-707 (Korea, Republic of); Lee, Tae-Ho [R and D Center, Dong-A Pharmaceutical Co, Ltd, Yongin 446-905 (Korea, Republic of); Jeon, Byeong Hwa [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Cho, Jae Youl [Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Song, Won O. [Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824 (United States); Park, Haeil [College of Pharmacy, Kangwon National University, Chuncheon 200-701 (Korea, Republic of); Choi, Sunga, E-mail: sachoi@cnu.ac.kr [Department of Physiology, School of Medicine, Chungnam National University, Daejeon 301-747 (Korea, Republic of); Kim, Tae Woong, E-mail: tawkim@kangwon.ac.kr [Department of Biochemistry, Kangwon National University, Chuncheon 200-701 (Korea, Republic of)

    2013-12-15

    A synthetic Militarin analog-1[(2R,3R,4R,5R)-1,6-bis(4-(2,4,4-trimethylpentan-2-yl)phenoxy) hexane-2,3,4,5-tetraol] is a novel derivative of constituents from Cordyceps militaris, which has been used to treat a variety of chronic diseases including inflammation, diabetes, hyperglycemia and cancers. Here, we report for the first time the synthesis of Militarin analog-1 (MA-1) and the apoptotic mechanism of MA-1 against human lung cancer cell lines. Treatment with MA-1 significantly inhibited the viability of 3 human lung cancer cell lines. The inhibition of viability and growth in MA-1-treated A549 cells with an IC{sub 50} of 5 μM were mediated through apoptosis induction, as demonstrated by an increase in DNA fragmentation, sub-G{sub 0}/G{sub 1}-DNA fraction, nuclear condensation, and phosphatidylserine exposure. The apoptotic cell death caused mitochondrial membrane permeabilization through regulation of expression of the Bcl-2 family proteins, leading to cytochrome c release in a time-dependent manner. Subsequently, the final stage of apoptosis, activation of caspase-9/-3 and cleavage of poly (ADP ribose) polymerase, was induced. Furthermore, A549 lung cancer cells were more responsive to MA-1 than a bronchial epithelial cell line (BEAS-2B), involving the rapid generation of reactive oxygen species (ROS), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation. The pharmacological inhibition of ROS generation and JNK/p38 MAPK exhibited attenuated DNA fragmentation in MA-1-induced apoptosis. Oral administration of MA-1 also retarded growth of A549 orthotopic xenografts. In conclusion, the present study indicates that the new synthetic derivative MA-1 triggers mitochondrial apoptosis through ROS generation and regulation of MAPKs and may be a potent therapeutic agent against human lung cancer. - Highlights: • We report a novel synthesized derivative, militarin analog-1 (MA-1). • MA-1-induced cancer cell death was triggered by

  12. ROSMOD: A Toolsuite for Modeling, Generating, Deploying, and Managing Distributed Real-time Component-based Software using ROS

    Directory of Open Access Journals (Sweden)

    Pranav Srinivas Kumar

    2016-09-01

    Full Text Available This paper presents the Robot Operating System Model-driven development tool suite, (ROSMOD an integrated development environment for rapid prototyping component-based software for the Robot Operating System (ROS middleware. ROSMOD is well suited for the design, development and deployment of large-scale distributed applications on embedded devices. We present the various features of ROSMOD including the modeling language, the graphical user interface, code generators, and deployment infrastructure. We demonstrate the utility of this tool with a real-world case study: an Autonomous Ground Support Equipment (AGSE robot that was designed and prototyped using ROSMOD for the NASA Student Launch competition, 2014–2015.

  13. Protective Effects of N-Acetyl Cysteine against Diesel Exhaust Particles-Induced Intracellular ROS Generates Pro-Inflammatory Cytokines to Mediate the Vascular Permeability of Capillary-Like Endothelial Tubes

    Science.gov (United States)

    Tseng, Chia-Yi; Chang, Jing-Fen; Wang, Jhih-Syuan; Chang, Yu-Jung; Gordon, Marion K.; Chao, Ming-Wei

    2015-01-01

    Exposure to diesel exhaust particles (DEP) is associated with pulmonary and cardiovascular diseases. Previous studies using in vitro endothelial tubes as a simplified model of capillaries have found that DEP-induced ROS increase vascular permeability with rearrangement or internalization of adherens junctional VE-cadherin away from the plasma membrane. This allows DEPs to penetrate into the cell and capillary lumen. In addition, pro-inflammatory cytokines are up-regulated and mediate vascular permeability in response to DEP. However, the mechanisms through which these DEP-induced pro-inflammatory cytokines increase vascular permeability remain unknown. Hence, we examined the ability of DEP to induce permeability of human umbilical vein endothelial cell tube cells to investigate these mechanisms. Furthermore, supplementation with NAC reduces ROS production following exposure to DEP. HUVEC tube cells contributed to a pro-inflammatory response to DEP-induced intracellular ROS generation. Endothelial oxidative stress induced the release of TNF-α and IL-6 from tube cells, subsequently stimulating the secretion of VEGF-A independent of HO-1. Our data suggests that DEP-induced intracellular ROS and release of the pro-inflammatory cytokines TNF- α and IL-6, which would contribute to VEGF-A secretion and disrupt cell-cell borders and increase vasculature permeability. Addition of NAC suppresses DEP-induced ROS efficiently and reduces subsequent damages by increasing endogenous glutathione. PMID:26148005

  14. Protective Effects of N-Acetyl Cysteine against Diesel Exhaust Particles-Induced Intracellular ROS Generates Pro-Inflammatory Cytokines to Mediate the Vascular Permeability of Capillary-Like Endothelial Tubes.

    Directory of Open Access Journals (Sweden)

    Chia-Yi Tseng

    Full Text Available Exposure to diesel exhaust particles (DEP is associated with pulmonary and cardiovascular diseases. Previous studies using in vitro endothelial tubes as a simplified model of capillaries have found that DEP-induced ROS increase vascular permeability with rearrangement or internalization of adherens junctional VE-cadherin away from the plasma membrane. This allows DEPs to penetrate into the cell and capillary lumen. In addition, pro-inflammatory cytokines are up-regulated and mediate vascular permeability in response to DEP. However, the mechanisms through which these DEP-induced pro-inflammatory cytokines increase vascular permeability remain unknown. Hence, we examined the ability of DEP to induce permeability of human umbilical vein endothelial cell tube cells to investigate these mechanisms. Furthermore, supplementation with NAC reduces ROS production following exposure to DEP. HUVEC tube cells contributed to a pro-inflammatory response to DEP-induced intracellular ROS generation. Endothelial oxidative stress induced the release of TNF-α and IL-6 from tube cells, subsequently stimulating the secretion of VEGF-A independent of HO-1. Our data suggests that DEP-induced intracellular ROS and release of the pro-inflammatory cytokines TNF- α and IL-6, which would contribute to VEGF-A secretion and disrupt cell-cell borders and increase vasculature permeability. Addition of NAC suppresses DEP-induced ROS efficiently and reduces subsequent damages by increasing endogenous glutathione.

  15. Overexpression of wheat ferritin gene TaFER-5B enhances tolerance to heat stress and other abiotic stresses associated with the ROS scavenging.

    Science.gov (United States)

    Zang, Xinshan; Geng, Xiaoli; Wang, Fei; Liu, Zhenshan; Zhang, Liyuan; Zhao, Yue; Tian, Xuejun; Ni, Zhongfu; Yao, Yingyin; Xin, Mingming; Hu, Zhaorong; Sun, Qixin; Peng, Huiru

    2017-01-14

    The yield of wheat (Triticum aestivum L.), an important crop, is adversely affected by heat stress in many regions of the world. However, the molecular mechanisms underlying thermotolerance are largely unknown. A novel ferritin gene, TaFER, was identified from our previous heat stress-responsive transcriptome analysis of a heat-tolerant wheat cultivar (TAM107). TaFER was mapped to chromosome 5B and named TaFER-5B. Expression pattern analysis revealed that TaFER-5B was induced by heat, polyethylene glycol (PEG), H 2 O 2 and Fe-ethylenediaminedi(o-hydroxyphenylacetic) acid (Fe-EDDHA). To confirm the function of TaFER-5B in wheat, TaFER-5B was transformed into the wheat cultivar Jimai5265 (JM5265), and the transgenic plants exhibited enhanced thermotolerance. To examine whether the function of ferritin from mono- and dico-species is conserved, TaFER-5B was transformed into Arabidopsis, and overexpression of TaFER-5B functionally complemented the heat stress-sensitive phenotype of a ferritin-lacking mutant of Arabidopsis. Moreover, TaFER-5B is essential for protecting cells against heat stress associated with protecting cells against ROS. In addition, TaFER-5B overexpression also enhanced drought, oxidative and excess iron stress tolerance associated with the ROS scavenging. Finally, TaFER-5B transgenic Arabidopsis and wheat plants exhibited improved leaf iron content. Our results suggest that TaFER-5B plays an important role in enhancing tolerance to heat stress and other abiotic stresses associated with the ROS scavenging.

  16. High-fat diet induces an initial adaptation of mitochondrial bioenergetics in the kidney despite evident oxidative stress and mitochondrial ROS production

    Science.gov (United States)

    Ruggiero, Christine; Ehrenshaft, Marilyn; Cleland, Ellen

    2011-01-01

    Obesity and metabolic syndrome are associated with an increased risk for several diabetic complications, including diabetic nephropathy and chronic kidney diseases. Oxidative stress and mitochondrial dysfunction are often proposed mechanisms in various organs in obesity models, but limited data are available on the kidney. Here, we fed a lard-based high-fat diet to mice to investigate structural changes, cellular and subcellular oxidative stress and redox status, and mitochondrial biogenesis and function in the kidney. The diet induced characteristic changes, including glomerular hypertrophy, fibrosis, and interstitial scarring, which were accompanied by a proinflammatory transition. We demonstrate evidence for oxidative stress in the kidney through 3-nitrotyrosine and protein radical formation on high-fat diet with a contribution from iNOS and NOX-4 as well as increased generation of mitochondrial oxidants on carbohydrate- and lipid-based substrates. The increased H2O2 emission in the mitochondria suggests altered redox balance and mitochondrial ROS generation, contributing to the overall oxidative stress. No major derailments were observed in respiratory function or biogenesis, indicating preserved and initially improved bioenergetic parameters and energy production. We suggest that, regardless of the oxidative stress events, the kidney developed an adaptation to maintain normal respiratory function as a possible response to an increased lipid overload. These findings provide new insights into the complex role of oxidative stress and mitochondrial redox status in the pathogenesis of the kidney in obesity and indicate that early oxidative stress-related changes, but not mitochondrial bioenergetic dysfunction, may contribute to the pathogenesis and development of obesity-linked chronic kidney diseases. PMID:21386058

  17. UVA-induced ROS generation inhibition by Oenothera paradoxa defatted seeds extract and subsequent cell death in human dermal fibroblasts.

    Science.gov (United States)

    Jaszewska, Edyta; Soin, Magdalena; Filipek, Agnieszka; Naruszewicz, Marek

    2013-09-05

    UVA radiation stimulates the production of reactive oxygen species (ROS), which react with lipids, proteins and other intracellular molecules leading to oxidative stress, cellular damage and ultimately cell death. There is, therefore, a growing need for substances exhibiting antioxidant activity, which may support repair mechanisms of the skin. This study evaluates the protective effect of the aqueous Oenothera paradoxa Hudziok defatted seeds extract, rich in polyphenolic compounds, against UVA (25 and 50J/cm(2))-induced changes in normal human dermal fibroblasts (NHDFs). The tested extract (0.1-10μg/ml) has decreased, in a concentration-dependent fashion, the UVA-induced release of lactate dehydrogenase (LDH) into the culture medium, the ROS production (with the use of 2',7'-dichlorodihydrofluorescein diacetate) and lipid peroxidation (utilizing redox reactions with ferrous ions) as compared to the control cells (incubated without the extract). Moreover, the extract increased the number of viable (calcein positive) cells decreasing the number of cells in late apoptosis (annexin V-FITC and propidium iodide positive). Thus our results show that O. paradoxa defatted seeds extract may be beneficial for the prevention of UVA skin damage. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Arsenite-induced ROS/RNS generation causes zinc loss and inhibits the activity of poly (ADP-ribose) polymerase-1

    OpenAIRE

    Wang, Feng; Zhou, Xixi; Liu, Wenlan; Sun, Xi; Chen, Chen; Hudson, Laurie G.; Liu, Ke Jian

    2013-01-01

    Arsenic enhances genotoxicity of other carcinogenic agents such as ultraviolet radiation and benzo[a]pyrene. Recent reports suggest that inhibition of DNA repair is an important aspect of arsenic co-carcinogenesis, and DNA repair proteins such as poly (ADP ribose) polymerase (PARP)-1 are direct molecular targets of arsenic. Although arsenic has been shown to generate reactive oxygen/nitrogen species (ROS/RNS), little is known about the role of arsenic-induced ROS/RNS in the mechanism underlyi...

  19. Alkynyl gold(I) complex triggers necroptosis via ROS generation in colorectal carcinoma cells.

    Science.gov (United States)

    Mármol, Inés; Virumbrales-Muñoz, María; Quero, Javier; Sánchez-de-Diego, Cristina; Fernández, Luis; Ochoa, Ignacio; Cerrada, Elena; Yoldi, Mª Jesús Rodríguez

    2017-11-01

    Given the rise of apoptosis-resistant tumors, there exist a growing interest in developing new drugs capable of inducing different types of cell death to reduce colorectal cancer-related death rates. As apoptosis and necroptosis do not share cellular machinery, necroptosis induction may have a great therapeutic potential on those apoptosis-resistant cancers, despite the inflammatory effects associated with it. We have synthesized an alkynyl gold(I) complex [Au(CC-2-NC 5 H 4 )(PTA)] whose anticancer effect was tested on the colorectal adenocarcinoma Caco-2 cell line. With regard to its mechanism of action, this gold complex enters the mitochondria and disrupts its normal function, leading to an increase in ROS production, which triggers necroptosis. Necroptosis induction has been found dependent of TNF-α (Tumor necrosisfactor α) and TNFR1(Tumor necrosisfactor receptor 1) binding, RIP1(Receptor-Interacting Protein 1) activation and NF-κB (Nuclear Factor Kappa-Light-Chain-Enhancer of Activated B Cells) signaling. Moreover, the antitumor potential of [Au(CC-2-NC 5 H 4 )(PTA)] has also been confirmed on the 3D cancer model spheroid. Overall, the obtained data show firstly that gold complexes might have the ability of inducing necroptosis, and secondarily that our compound [Au(CC-2-NC 5 H 4 )(PTA)] is an interesting alternative to current chemotherapy drugs in cases of apoptosis resistance. Copyright © 2017. Published by Elsevier Inc.

  20. Arsenite and monomethylarsonous acid generate oxidative stress response in human bladder cell culture

    International Nuclear Information System (INIS)

    Eblin, K.E.; Bowen, M.E.; Cromey, D.W.; Bredfeldt, T.G.; Mash, E.A.; Lau, S.S.; Gandolfi, A.J.

    2006-01-01

    Arsenicals have commonly been seen to induce reactive oxygen species (ROS) which can lead to DNA damage and oxidative stress. At low levels, arsenicals still induce the formation of ROS, leading to DNA damage and protein alterations. UROtsa cells, an immortalized human urothelial cell line, were used to study the effects of arsenicals on the human bladder, a site of arsenical bioconcentration and carcinogenesis. Biotransformation of As(III) by UROtsa cells has been shown to produce methylated species, namely monomethylarsonous acid [MMA(III)], which has been shown to be 20 times more cytotoxic. Confocal fluorescence images of UROtsa cells treated with arsenicals and the ROS sensing probe, DCFDA, showed an increase of intracellular ROS within five min after 1 μM and 10 μM As(III) treatments. In contrast, 50 and 500 nM MMA(III) required pretreatment for 30 min before inducing ROS. The increase in ROS was ameliorated by preincubation with either SOD or catalase. An interesting aspect of these ROS detection studies is the noticeable difference between concentrations of As(III) and MMA(III) used, further supporting the increased cytotoxicity of MMA(III), as well as the increased amount of time required for MMA(III) to cause oxidative stress. These arsenical-induced ROS produced oxidative DNA damage as evidenced by an increase in 8-hydroxyl-2'-deoxyguanosine (8-oxo-dG) with either 50 nM or 5 μM MMA(III) exposure. These findings provide support that MMA(III) cause a genotoxic response upon generation of ROS. Both As(III) and MMA(III) were also able to induce Hsp70 and MT protein levels above control, showing that the cells recognize the ROS and respond. As(III) rapidly induces the formation of ROS, possibly through it oxidation to As(V) and further metabolism to MMA(III)/(V). These studies provide evidence for a different mechanism of MMA(III) toxicity, one that MMA(III) first interacts with cellular components before an ROS response is generated, taking longer to

  1. Targeting TRPM2 in ROS-Coupled Diseases

    Directory of Open Access Journals (Sweden)

    Shinichiro Yamamoto

    2016-09-01

    Full Text Available Under pathological conditions such as inflammation and ischemia-reperfusion injury large amounts of reactive oxygen species (ROS are generated which, in return, contribute to the development and exacerbation of disease. The second member of the transient receptor potential (TRP melastatin subfamily, TRPM2, is a Ca2+-permeable non-selective cation channel, activated by ROS in an ADP-ribose mediated fashion. In other words, TRPM2 functions as a transducer that converts oxidative stress into Ca2+ signaling. There is good evidence that TRPM2 plays an important role in ROS-coupled diseases. For example, in monocytes the influx of Ca2+ through TRPM2 activated by ROS contributes to the aggravation of inflammation via chemokine production. In this review, the focus is on TRPM2 as a molecular linker between ROS and Ca2+ signaling in ROS-coupled diseases.

  2. Targeting TRPM2 in ROS-Coupled Diseases.

    Science.gov (United States)

    Yamamoto, Shinichiro; Shimizu, Shunichi

    2016-09-07

    Under pathological conditions such as inflammation and ischemia-reperfusion injury large amounts of reactive oxygen species (ROS) are generated which, in return, contribute to the development and exacerbation of disease. The second member of the transient receptor potential (TRP) melastatin subfamily, TRPM2, is a Ca(2+)-permeable non-selective cation channel, activated by ROS in an ADP-ribose mediated fashion. In other words, TRPM2 functions as a transducer that converts oxidative stress into Ca(2+) signaling. There is good evidence that TRPM2 plays an important role in ROS-coupled diseases. For example, in monocytes the influx of Ca(2+) through TRPM2 activated by ROS contributes to the aggravation of inflammation via chemokine production. In this review, the focus is on TRPM2 as a molecular linker between ROS and Ca(2+) signaling in ROS-coupled diseases.

  3. Modulation of ROS levels in fibroblasts by altering mitochondria regulates the process of wound healing.

    Science.gov (United States)

    Janda, Jaroslav; Nfonsam, Valentine; Calienes, Fernanda; Sligh, James E; Jandova, Jana

    2016-05-01

    Mitochondria are the major source of reactive oxygen species (ROS) in fibroblasts which are thought to be crucial regulators of wound healing with a potential to affect the expression of nuclear genes involved in this process. ROS generated by mitochondria are involved in all stages of tissue repair process but the regulation of ROS-generating system in fibroblasts still remains poorly understood. The purpose of this study was to better understand molecular mechanisms of how the regulation of ROS levels generated by mitochondria may influence the process of wound repair. Cybrid model system of mtDNA variations was used to study the functional consequences of altered ROS levels on wound healing responses in a uniform nuclear background of cultured ρ(0) fibroblasts. Mitochondrial ROS in cybrids were modulated by antioxidants that quench ROS to examine their ability to close the wound. Real-time PCR arrays were used to investigate whether ROS generated by specific mtDNA variants have the ability to alter expression of some key nuclear-encoded genes central to the wound healing response and oxidative stress. Our data suggest levels of mitochondrial ROS affect expression of some nuclear encoded genes central to wound healing response and oxidative stress and modulation of mitochondrial ROS by antioxidants positively affects in vitro process of wound closure. Thus, regulation of mitochondrial ROS-generating system in fibroblasts can be used as effective natural redox-based strategy to help treat non-healing wounds.

  4. The STAT3 inhibitor pimozide impedes cell proliferation and induces ROS generation in human osteosarcoma by suppressing catalase expression.

    Science.gov (United States)

    Cai, Nan; Zhou, Wei; Ye, Lan-Lan; Chen, Jun; Liang, Qiu-Ni; Chang, Gang; Chen, Jia-Jie

    2017-01-01

    Currently, there is a considerable need to develop new treatments for osteosarcoma (OS), a very aggressive bone cancer. The activation of STAT3 signaling is positively associated with poor prognosis and aggressive progression in OS patients. Our previous study reported that the FDA-approved antipsychotic drug pimozide had anti-tumor activity against hepatocellular carcinoma and prostate cancer cells by suppressing STAT3 activity. Therefore, the aim of this study was to investigate the specific effect of pimozide on OS cells and the underlying molecular mechanism. Pimozide inhibited cell proliferation, colony formation, and sphere formation capacities of the OS cells in a dose-dependent manner, inducing G0/G1 phase cell cycle arrest. Pimozide reduced the percentage of side population cells representing cancer stem-like cells and enhanced the sensitivity of OS cells to 5-FU induced proliferative inhibition. In addition, pimozide induced apoptosis of U2OS cells, which showed increased expression of cleaved-PARP, a marker of programmed cell death. Moreover, pimozide suppressed Erk signaling in OS cells. Importantly, pimozide induced ROS generation by downregulating the expression of the antioxidant enzyme catalase (CAT). NAC treatment partially reversed the ROS generation and cytotoxic effects induced by pimozide. CAT treatment attenuated the pimozide-induced proliferation inhibition. The decrease of CAT expression induced by pimozide was potentially mediated through the suppression of cellular STAT3 activity in OS cells. Thus, pimozide may be a novel STAT3 inhibitor that suppresses cellular STAT3 activity to inhibit OS cells or stem-like cells and is a novel potential anti-cancer agent in OS treatment.

  5. Neuroprotective Effect of Puerarin on Glutamate-Induced Cytotoxicity in Differentiated Y-79 Cells via Inhibition of ROS Generation and Ca(2+) Influx.

    Science.gov (United States)

    Wang, Ke; Zhu, Xue; Zhang, Kai; Wu, Zhifeng; Sun, Song; Zhou, Fanfan; Zhu, Ling

    2016-07-11

    Glutamate toxicity is estimated to be the key cause of photoreceptor degeneration in the pathogenesis of retinal degenerative diseases. Oxidative stress and Ca(2+) influx induced by glutamate are responsible for the apoptosis process of photoreceptor degeneration. Puerarin, a primary component of Kudzu root, has been widely used in the clinical treatment of retinal degenerative diseases in China for decades; however, the detailed molecular mechanism underlying this effect remains unclear. In this study, the neuroprotective effect of puerarin against glutamate-induced cytotoxicity in the differentiated Y-79 cells was first investigated through cytotoxicity assay. Then the molecular mechanism of this effect regarding anti-oxidative stress and Ca(2+) hemostasis was further explored with indirect immunofluorescence, flow cytometric analysis and western blot analysis. Our study showed that glutamate induced cell viability loss, excessive reactive oxygen species (ROS) generation, calcium overload and up-regulated cell apoptosis in differentiated Y-79 cells, which effect was significantly attenuated with the pre-treatment of puerarin in a dose-dependent manner. Furthermore, our data indicated that the neuroprotective effect of puerarin was potentially mediated through the inhibition of glutamate-induced activation of mitochondrial-dependent signaling pathway and calmodulin-dependent protein kinase II (CaMKII)-dependent apoptosis signal-regulating kinase 1(ASK-1)/c-Jun N-terminal kinase (JNK)/p38 signaling pathway. The present study supports the notion that puerarin may be a promising neuroprotective agent in the prevention of retinal degenerative diseases.

  6. ROS-mediated abiotic stress-induced programmed cell death in plants

    NARCIS (Netherlands)

    Petrov, Veselin; Hille, Jacob; Mueller-Rober, Bernd; Gechev, Tsanko S.

    2015-01-01

    During the course of their ontogenesis plants are continuously exposed to a large variety of abiotic stress factors which can damage tissues and jeopardize the survival of the organism unless properly countered. While animals can simply escape and thus evade stressors, plants as sessile organisms

  7. Pyrogallol, ROS generator inhibits As4.1 juxtaglomerular cells via cell cycle arrest of G2 phase and apoptosis

    International Nuclear Information System (INIS)

    Park, Woo Hyun; Han, Yong Hwan; Kim, Suhn Hee; Kim, Sung Zoo

    2007-01-01

    Pyrogallol as a catechin compound has been employed as an O 2 · - generator and often used to investigate the role of ROS in the biological system. Here, we investigated the in vitro effect of pyrogallol on cell growth, cell cycle and apoptosis in As4.1 juxtaglomerular cells. Dose-dependent inhibition of cell growth was observed with IC 50 of about 60 μM for 48 h using MTT assay. Pyrogallol (100 μM) did not alter intracellular H 2 O 2 level and catalase activity, but increased the intracellular O 2 · - level and decreased SOD activity in As4.1 cells. DNA flow cytometric analysis indicated that 50 and 100 μM pyrogallol significantly increased G2 phase cells as compared with those of pyrogallol-untreated cells. Also, pyrogallol induced apoptosis as evidenced by flow cytometric detection of sub-G1 DNA content, annexin V binding assay and DAPI staining. This apoptosis process was accompanied with the loss of mitochondrial transmembrane potential (ΔΨ m ), Bcl-2 decrease, caspase-3 activation and PARP cleavage. Pan caspase inhibitor (Z-VAD) could significantly rescue As4.1 cells from pyrogallol-induced cell death. But, the inhibitors of caspase-3, caspase-8, and caspase-9 did not prevent apoptotic events in pyrogallol-treated As4.1 cells. Taken together, we have demonstrated that an ROS inducer, pyrogallol inhibits the growth of As4.1 JG cells via cell cycle arrest and apoptosis, and suggest that the compound exhibits an anti-proliferative efficacy on these cells

  8. Oxidative stress activates the TRPM2-Ca2+-CaMKII-ROS signaling loop to induce cell death in cancer cells.

    Science.gov (United States)

    Wang, Qian; Huang, Lihong; Yue, Jianbo

    2017-06-01

    High intracellular levels of reactive oxygen species (ROS) cause oxidative stress that results in numerous pathologies, including cell death. Transient potential receptor melastatin-2 (TRPM2), a Ca 2+ -permeable cation channel, is mainly activated by intracellular adenosine diphosphate ribose (ADPR) in response to oxidative stress. Here we studied the role and mechanisms of TRPM2-mediated Ca 2+ influx on oxidative stress-induced cell death in cancer cells. We found that oxidative stress activated the TRPM2-Ca 2+ -CaMKII cascade to inhibit early autophagy induction, which ultimately led to cell death in TRPM2 expressing cancer cells. On the other hand, TRPM2 knockdown switched cells from cell death to autophagy for survival in response to oxidative stress. Moreover, we found that oxidative stress activated the TRPM2-CaMKII cascade to further induce intracellular ROS production, which led to mitochondria fragmentation and loss of mitochondrial membrane potential. In summary, our data demonstrated that oxidative stress activates the TRPM2-Ca 2+ -CaMKII-ROS signal loop to inhibit autophagy and induce cell death. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. ROS Hexapod

    Science.gov (United States)

    Davis, Kirsch; Bankieris, Derek

    2016-01-01

    As an intern project for NASA Johnson Space Center (JSC), my job was to familiarize myself and operate a Robotics Operating System (ROS). The project outcome converted existing software assets into ROS using nodes, enabling a robotic Hexapod to communicate to be functional and controlled by an existing PlayStation 3 (PS3) controller. Existing control algorithms and current libraries have no ROS capabilities within the Hexapod C++ source code when the internship started, but that has changed throughout my internship. Conversion of C++ codes to ROS enabled existing code to be compatible with ROS, and is now controlled using an existing PS3 controller. Furthermore, my job description was to design ROS messages and script programs that enabled assets to participate in the ROS ecosystem by subscribing and publishing messages. Software programming source code is written in directories using C++. Testing of software assets included compiling code within the Linux environment using a terminal. The terminal ran the code from a directory. Several problems occurred while compiling code and the code would not compile. So modifying code to where C++ can read the source code were made. Once the code was compiled and ran, the code was uploaded to Hexapod and then controlled by a PS3 controller. The project outcome has the Hexapod fully functional and compatible with ROS and operates using the PlayStation 3 controller. In addition, an open source software (IDE) Arduino board will be integrated into the ecosystem with designing circuitry on a breadboard to add additional behavior with push buttons, potentiometers and other simple elements in the electrical circuitry. Other projects with the Arduino will be a GPS module, digital clock that will run off 22 satellites to show accurate real time using a GPS signal and an internal patch antenna to communicate with satellites. In addition, this internship experience has led me to pursue myself to learn coding more efficiently and

  10. Oxidative stress provokes distinct transcriptional responses in the stress-tolerant atr7 and stress-sensitive loh2 Arabidopsis thaliana mutants as revealed by multi-parallel quantitative real-time PCR analysis of ROS marker and antioxidant genes.

    Science.gov (United States)

    Mehterov, Nikolay; Balazadeh, Salma; Hille, Jacques; Toneva, Valentina; Mueller-Roeber, Bernd; Gechev, Tsanko

    2012-10-01

    The Arabidopsis thaliana atr7 mutant is tolerant to oxidative stress induced by paraquat (PQ) or the catalase inhibitor aminotriazole (AT), while its original background loh2 and wild-type plants are sensitive. Both, AT and PQ, which stimulate the intracellular formation of H₂O₂ or superoxide anions, respectively, trigger cell death in loh2 but do not lead to visible damage in atr7. To study gene expression during oxidative stress and ROS-induced programmed cell death, two platforms for multi-parallel quantitative real-time PCR (qRT-PCR) analysis of 217 antioxidant and 180 ROS marker genes were employed. The qRT-PCR analyses revealed AT- and PQ-induced expression of many ROS-responsive genes mainly in loh2, confirming that an oxidative burst plays a role in the activation of the cell death in this mutant. Some of the genes were specifically regulated by either AT or PQ, serving as markers for particular types of ROS. Genes significantly induced by both AT and PQ in loh2 included transcription factors (ANAC042/JUB1, ANAC102, DREB19, HSFA2, RRTF1, ZAT10, ZAT12, ethylene-responsive factors), signaling compounds, ferritins, alternative oxidases, and antioxidant enzymes. Many of these genes were upregulated in atr7 compared to loh2 under non-stress conditions at the first time point, indicating that higher basal levels of ROS and higher antioxidant capacity in atr7 are responsible for the enhanced tolerance to oxidative stress and suggesting a possible tolerance against multiple stresses of this mutant. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  11. Role of Mitochondrial Reverse Electron Transport in ROS Signaling: Potential Roles in Health and Disease

    Directory of Open Access Journals (Sweden)

    Filippo Scialò

    2017-06-01

    Full Text Available Reactive Oxygen Species (ROS can cause oxidative damage and have been proposed to be the main cause of aging and age-related diseases including cancer, diabetes and Parkinson's disease. Accordingly, mitochondria from old individuals have higher levels of ROS. However, ROS also participate in cellular signaling, are instrumental for several physiological processes and boosting ROS levels in model organisms extends lifespan. The current consensus is that low levels of ROS are beneficial, facilitating adaptation to stress via signaling, whereas high levels of ROS are deleterious because they trigger oxidative stress. Based on this model the amount of ROS should determine the physiological effect. However, recent data suggests that the site at which ROS are generated is also instrumental in determining effects on cellular homeostasis. The best example of site-specific ROS signaling is reverse electron transport (RET. RET is produced when electrons from ubiquinol are transferred back to respiratory complex I, reducing NAD+ to NADH. This process generates a significant amount of ROS. RET has been shown to be instrumental for the activation of macrophages in response to bacterial infection, re-organization of the electron transport chain in response to changes in energy supply and adaptation of the carotid body to changes in oxygen levels. In Drosophila melanogaster, stimulating RET extends lifespan. Here, we review what is known about RET, as an example of site-specific ROS signaling, and its implications for the field of redox biology.

  12. Resolving Contributions of Oxygen-Consuming and ROS-Generating Enzymes at the Synapse

    Directory of Open Access Journals (Sweden)

    Engy A. Abdel-Rahman

    2016-01-01

    Full Text Available Disruption of cellular redox homeostasis is implicated in a wide variety of pathologic conditions and aging. A fundamental factor that dictates such balance is the ratio between mitochondria-mediated complete oxygen reduction into water and incomplete reduction into superoxide radical by mitochondria and NADPH oxidase (NOX enzymatic activity. Here we determined mitochondrial as well as NOX-dependent rates of oxygen consumption in parallel with H2O2 generation in freshly isolated synaptosomes using high resolution respirometry combined with fluorescence or electrochemical sensory. Our results indicate that although synaptic mitochondria exhibit substantially higher respiratory activities (8–82-fold greater than NOX oxygen consumption depending on mitochondrial respiratory state, NADPH-dependent oxygen consumption is associated with greater H2O2 production (6-7-fold higher NOX-H2O2. We also show that, in terms of the consumed oxygen, while synaptic mitochondria “leaked” 0.71%±0.12 H2O2 during NAD+-linked resting, 0.21%±0.04 during NAD+-linked active respiration, and 0.07%±0.02 during FAD+-linked active respiration, NOX converted 38%±13 of O2 into H2O2. Our results indicate that NOX rather than mitochondria is the major source of synaptic H2O2. The present approach may assist in the identification of redox-modulating synaptic factors that underlie a variety of physiological and pathological processes in neurons.

  13. Surface modification of amorphous nanosilica particles suppresses nanosilica-induced cytotoxicity, ROS generation, and DNA damage in various mammalian cells

    International Nuclear Information System (INIS)

    Yoshida, Tokuyuki; Yoshioka, Yasuo; Matsuyama, Keigo; Nakazato, Yasutaro; Tochigi, Saeko; Hirai, Toshiro; Kondoh, Sayuri; Nagano, Kazuya; Abe, Yasuhiro; Kamada, Haruhiko; Tsunoda, Shin-ichi; Nabeshi, Hiromi; Yoshikawa, Tomoaki; Tsutsumi, Yasuo

    2012-01-01

    Highlights: ► There is increasing concern regarding the potential health risks of nanomaterials. ► We evaluated the effect of surface properties of nanomaterials on cellular responses. ► We showed that the surface properties play an important in determining its safety. ► These data provide useful information for producing safer nanomaterials. -- Abstract: Recently, nanomaterials have been utilized in various fields. In particular, amorphous nanosilica particles are increasingly being used in a range of applications, including cosmetics, food technology, and medical diagnostics. However, there is concern that the unique characteristics of nanomaterials might induce undesirable effects. The roles played by the physical characteristics of nanomaterials in cellular responses have not yet been elucidated precisely. Here, by using nanosilica particles (nSPs) with a diameter of 70 nm whose surface was either unmodified (nSP70) or modified with amine (nSP70-N) or carboxyl groups (nSP70-C), we examined the relationship between the surface properties of nSPs and cellular responses such as cytotoxicity, reactive oxygen species (ROS) generation, and DNA damage. To compare the cytotoxicity of nSP70, nSP70-N, or nSP70-C, we examined in vitro cell viability after nSP treatment. Although the susceptibility of each cell line to the nSPs was different, nSP70-C and nSP70-N showed lower cytotoxicity than nSP70 in all cell lines. Furthermore, the generation of ROS and induction of DNA damage in nSP70-C- and nSP70-N-treated cells were lower than those in nSP70-treated cells. These results suggest that the surface properties of nSP70 play an important role in determining its safety, and surface modification of nSP70 with amine or carboxyl groups may be useful for the development of safer nSPs. We hope that our results will contribute to the development of safer nanomaterials.

  14. Impact of solar UV radiation on toxicity of ZnO nanoparticles through photocatalytic reactive oxygen species (ROS) generation and photo-induced dissolution

    Science.gov (United States)

    The present study investigated the impact of solar UV radiation on ZnO nanoparticle toxicity through photocatalytic ROS generation and photo-induced dissolution. Toxicity of ZnO nanoparticles to Daphnia magna was examined under laboratory light versus simulated solar UV radiatio...

  15. Increased Expression of the Innate Immune Receptor TLR10 in Obesity and Type-2 Diabetes: Association with ROS-Mediated Oxidative Stress.

    Science.gov (United States)

    Sindhu, Sardar; Akhter, Nadeem; Kochumon, Shihab; Thomas, Reeby; Wilson, Ajit; Shenouda, Steve; Tuomilehto, Jaakko; Ahmad, Rasheed

    2018-01-01

    Metabolic diseases such as obesity and type-2 diabetes (T2D) are known to be associated with chronic low-grade inflammation called metabolic inflammation together with an oxidative stress milieu found in the expanding adipose tissue. The innate immune Toll-like receptors (TLR) such as TLR2 and TLR4 have emerged as key players in metabolic inflammation; nonetheless, TLR10 expression in the adipose tissue and its significance in obesity/T2D remain unclear. TLR10 gene expression was determined in the adipose tissue samples from healthy non-diabetic and T2D individuals, 13 each, using real-time RT-PCR. TLR10 protein expression was determined by immunohistochemistry, confocal microscopy, and flow cytometry. Regarding in vitro studies, THP-1 cells, peripheral blood mononuclear cells (PBMC), or primary monocytes were treated with hydrogen peroxide (H2O2) for induction of reactive oxygen species (ROS)-mediated oxidative stress. Superoxide dismutase (SOD) activity was measured using a commercial kit. Data (mean±SEM) were compared using unpaired student's t-test and Pobesity as well as T2D which correlated with body mass index (BMI). ROS-mediated oxidative stress induced high levels of TLR10 gene/protein expression in monocytic cells and PBMC. In these cells, oxidative stress induced a time-dependent increase in SOD activity. Pre-treatment of cells with anti-oxidants/ROS scavengers diminished the expression of TLR10. ROS-induced TLR10 expression involved the nuclear factor-kappaB (NF-κB)/mitogen activated protein kinase (MAPK) signaling as well as endoplasmic reticulum (ER) stress. H2O2-induced oxidative stress interacted synergistically with palmitate to trigger the expression of TLR10 which associated with enhanced expression of proinflammatory cytokines/chemokine. Oxidative stress induces the expression of TLR10 which may represent an immune marker for metabolic inflammation. © 2018 The Author(s). Published by S. Karger AG, Basel.

  16. Arsenite-induced ROS/RNS generation causes zinc loss and inhibits the activity of poly(ADP-ribose) polymerase-1.

    Science.gov (United States)

    Wang, Feng; Zhou, Xixi; Liu, Wenlan; Sun, Xi; Chen, Chen; Hudson, Laurie G; Jian Liu, Ke

    2013-08-01

    Arsenic enhances the genotoxicity of other carcinogenic agents such as ultraviolet radiation and benzo[a]pyrene. Recent reports suggest that inhibition of DNA repair is an important aspect of arsenic cocarcinogenesis, and DNA repair proteins such as poly(ADP ribose) polymerase (PARP)-1 are direct molecular targets of arsenic. Although arsenic has been shown to generate reactive oxygen/nitrogen species (ROS/RNS), little is known about the role of arsenic-induced ROS/RNS in the mechanism underlying arsenic inhibition of DNA repair. We report herein that arsenite-generated ROS/RNS inhibits PARP-1 activity in cells. Cellular exposure to arsenite, as well as hydrogen peroxide and NONOate (nitric oxide donor), decreased PARP-1 zinc content, enzymatic activity, and PARP-1 DNA binding. Furthermore, the effects of arsenite on PARP-1 activity, DNA binding, and zinc content were partially reversed by the antioxidant ascorbic acid, catalase, and the NOS inhibitor, aminoguanidine. Most importantly, arsenite incubation with purified PARP-1 protein in vitro did not alter PARP-1 activity or DNA-binding ability, whereas hydrogen peroxide or NONOate retained PARP-1 inhibitory activity. These results strongly suggest that cellular generation of ROS/RNS plays an important role in arsenite inhibition of PARP-1 activity, leading to the loss of PARP-1 DNA-binding ability and enzymatic activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Curcumin enhances the effects of irinotecan on colorectal cancer cells through the generation of reactive oxygen species and activation of the endoplasmic reticulum stress pathway.

    Science.gov (United States)

    Huang, Yan-Feng; Zhu, Da-Jian; Chen, Xiao-Wu; Chen, Qi-Kang; Luo, Zhen-Tao; Liu, Chang-Chun; Wang, Guo-Xin; Zhang, Wei-Jie; Liao, Nv-Zhu

    2017-06-20

    Although initially effective against metastatic colorectal cancer (CRC), irinotecan-based chemotherapy leads to resistance and adverse toxicity. Curcumin is well known for its anti-cancer effects in many cancers, including CRC. Here, we describe reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress as important mechanisms by which curcumin enhances irinotecan's effects on CRC cells. CRC cell lines were treated with curcumin and/or irinotecan for 24 h, and then evaluated using cell proliferation assays, cell apoptosis assays, cell cycle analysis, intracellular Ca2+ measurements, ROS measurements and immunoblotting for key ER stress-related proteins. We found that cell viability was inhibited and apoptosis was increased, accompanied by ROS generation and ER stress activation in CRC cells treated with curcumin alone or in combination with irinotecan. Blocking ROS production attenuated the expression of two markers of ER stress: binding of immunoglobulin protein (BIP) and CCAAT/enhancer-binding protein homologous protein (CHOP). Blocking CHOP expression using RNA interference also inhibited ROS generation. These results demonstrated that curcumin could enhance the effects of irinotecan on CRC cells by inhibiting cell viability and inducing cell cycle arrest and apoptosis, and that these effects may be mediated, in part, by ROS generation and activation of the ER stress pathway.

  18. ROS signalling - specificity is required

    DEFF Research Database (Denmark)

    Møller, Ian M; Sweetlove, Lee J

    2010-01-01

    Reactive oxygen species (ROS) production increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 might induce a general stress response, but it does not have...... the required specificity to selectively regulate nuclear genes required for dealing with localized stress, e.g. in chloroplasts or mitochondria. Here we argue that peptides deriving from proteolytic breakdown of oxidatively damaged proteins have the requisite specificity to act as secondary ROS messengers...... and regulate source-specific genes and in this way contribute to retrograde ROS signalling during oxidative stress. Likewise, unmodified peptides deriving from the breakdown of redundant proteins could help coordinate organellar and nuclear gene expression...

  19. Strawberry-Tree Honey Induces Growth Inhibition of Human Colon Cancer Cells and Increases ROS Generation: A Comparison with Manuka Honey.

    Science.gov (United States)

    Afrin, Sadia; Forbes-Hernandez, Tamara Y; Gasparrini, Massimiliano; Bompadre, Stefano; Quiles, José L; Sanna, Gavino; Spano, Nadia; Giampieri, Francesca; Battino, Maurizio

    2017-03-11

    Honey is a natural product known to modulate several biological activities including cancer. The aim of the present study was to examine the phytochemical content and the antioxidant activity of Strawberry tree ( Arbutus unedo ) honey (STH) and its cytotoxic properties against human colon adenocarcinoma (HCT-116) and metastatic (LoVo) cell lines in comparison with Manuka ( Leptospermum scoparium ) honey (MH). Several unifloral STH and MH were analyzed for their phenolic, flavonoid, amino acid and protein contents, as well as their radical scavenging activities. STH from the Berchidda area showed the highest amount of phenolic, flavonoid, amino acid and protein content, and antioxidant capacity compared to MH. Both STH and MH induced cytotoxicity and cell death in a dose- and time-dependent manner in HCT-116 and LoVo cells, with less toxicity on non-cancer cells. Compared to MH, STH showed more effect at lower concentrations on HCT-116 and LoVo cells. In addition, both honeys increased intracellular reactive oxygen species (ROS) generation. In HCT-116 cells, STH and MH induced similar ROS production but in LoVo cells STH induced a higher percentage of ROS compared to MH. Our results indicate that STH and MH can induce cell growth inhibition and ROS generation in colon adenocarcinoma and metastatic cells, which could be due to the presence of phytochemicals with antioxidant properties. These preliminary results are interesting and suggest a potential chemopreventive action which could be useful for further studies in order to develop chemopreventive agents for colon cancer.

  20. Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release

    Science.gov (United States)

    Zorov, Dmitry B.; Juhaszova, Magdalena; Sollott, Steven J.

    2014-01-01

    Byproducts of normal mitochondrial metabolism and homeostasis include the buildup of potentially damaging levels of reactive oxygen species (ROS), Ca2+, etc., which must be normalized. Evidence suggests that brief mitochondrial permeability transition pore (mPTP) openings play an important physiological role maintaining healthy mitochondria homeostasis. Adaptive and maladaptive responses to redox stress may involve mitochondrial channels such as mPTP and inner membrane anion channel (IMAC). Their activation causes intra- and intermitochondrial redox-environment changes leading to ROS release. This regenerative cycle of mitochondrial ROS formation and release was named ROS-induced ROS release (RIRR). Brief, reversible mPTP opening-associated ROS release apparently constitutes an adaptive housekeeping function by the timely release from mitochondria of accumulated potentially toxic levels of ROS (and Ca2+). At higher ROS levels, longer mPTP openings may release a ROS burst leading to destruction of mitochondria, and if propagated from mitochondrion to mitochondrion, of the cell itself. The destructive function of RIRR may serve a physiological role by removal of unwanted cells or damaged mitochondria, or cause the pathological elimination of vital and essential mitochondria and cells. The adaptive release of sufficient ROS into the vicinity of mitochondria may also activate local pools of redox-sensitive enzymes involved in protective signaling pathways that limit ischemic damage to mitochondria and cells in that area. Maladaptive mPTP- or IMAC-related RIRR may also be playing a role in aging. Because the mechanism of mitochondrial RIRR highlights the central role of mitochondria-formed ROS, we discuss all of the known ROS-producing sites (shown in vitro) and their relevance to the mitochondrial ROS production in vivo. PMID:24987008

  1. The Effects of Aronia melanocarpa ‘Viking’ Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling

    Directory of Open Access Journals (Sweden)

    Mithun Ghosh

    2018-03-01

    Full Text Available This study aimed to determine the anti-osteoclastogenic effects of extracts from Aronia melanocarpa ‘Viking’ (AM and identify the underlying mechanisms in vitro. Reactive oxygen species (ROS are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW 264.7 cells in a dose-dependent manner and exhibited strong radical scavenging activity. The extracts also attenuated the number of tartrate-resistant acid phosphatase (TRAP-positive multinucleated osteoclasts. To attain molecular insights, the effect of the extracts on the signaling pathways induced by receptor activator of nuclear factor kappa B ligand (RANKL were also investigated. RANKL triggers many transcription factors through the activation of mitogen-activated protein kinase (MAPK and ROS, leading to the induction of osteoclast-specific genes. The extracts significantly suppressed RANKL-induced activation of MAPKs, such as extracellular signal-regulated kinase (ERK, c-Jun-N-terminal kinase (JNK and p38 and consequently led to the downregulation of c-Fos and nuclear factor of activated T cells 1 (NFATc1 protein expression which ultimately suppress the activation of the osteoclast-specific genes, cathepsin K, TRAP, calcitonin receptor and integrin β3. In conclusion, our findings suggest that AM extracts inhibited RANKL-induced osteoclast differentiation by downregulating ROS generation and inactivating JNK/ERK/p38, nuclear factor kappa B (NF-κB-mediated c-Fos and NFATc1 signaling pathway.

  2. The Effects of Aronia melanocarpa 'Viking' Extracts in Attenuating RANKL-Induced Osteoclastic Differentiation by Inhibiting ROS Generation and c-FOS/NFATc1 Signaling.

    Science.gov (United States)

    Ghosh, Mithun; Kim, In Sook; Lee, Young Min; Hong, Seong Min; Lee, Taek Hwan; Lim, Ji Hong; Debnath, Trishna; Lim, Beong Ou

    2018-03-08

    This study aimed to determine the anti-osteoclastogenic effects of extracts from Aronia melanocarpa 'Viking' (AM) and identify the underlying mechanisms in vitro. Reactive oxygen species (ROS) are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW 264.7 cells in a dose-dependent manner and exhibited strong radical scavenging activity. The extracts also attenuated the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. To attain molecular insights, the effect of the extracts on the signaling pathways induced by receptor activator of nuclear factor kappa B ligand (RANKL) were also investigated. RANKL triggers many transcription factors through the activation of mitogen-activated protein kinase (MAPK) and ROS, leading to the induction of osteoclast-specific genes. The extracts significantly suppressed RANKL-induced activation of MAPKs, such as extracellular signal-regulated kinase (ERK), c-Jun- N -terminal kinase (JNK) and p38 and consequently led to the downregulation of c-Fos and nuclear factor of activated T cells 1 (NFATc1) protein expression which ultimately suppress the activation of the osteoclast-specific genes, cathepsin K, TRAP, calcitonin receptor and integrin β₃. In conclusion, our findings suggest that AM extracts inhibited RANKL-induced osteoclast differentiation by downregulating ROS generation and inactivating JNK/ERK/p38, nuclear factor kappa B (NF-κB)-mediated c-Fos and NFATc1 signaling pathway.

  3. A Role of Fluoride on Free Radical Generation and Oxidative Stress in BV-2 Microglia Cells

    Directory of Open Access Journals (Sweden)

    Xi Shuhua

    2012-01-01

    Full Text Available The generation of ROS and lipid peroxidation has been considered to play an important role in the pathogenesis of chronic fluoride toxicity. In the present study, we observed that fluoride activated BV-2 microglia cell line by observing OX-42 expression in immunocytochemistry. Intracellular superoxide dismutase (SOD, glutathione (GSH, malondialdehyde (MDA, reactive oxygen species (ROS, superoxide anions (O2∙-, nitric oxide synthase (NOS, nitrotyrosine (NT and nitric oxide (NO, NOS in cell medium were determined for oxidative stress assessment. Our study found that NaF of concentration from 5 to 20 mg/L can stimuli BV-2 cells to change into activated microglia displaying upregulated OX-42 expression. SOD activities significantly decreased in fluoride-treated BV-2 cells as compared with control, and MDA concentrations and contents of ROS and O2∙- increased in NaF-treated cells. Activities of NOS in cells and medium significantly increased with fluoride concentrations in a dose-dependent manner. NT concentrations also increased significantly in 10 and 50 mg/L NaF-treated cells compared with the control cells. Our present study demonstrated that toxic effects of fluoride on the central nervous system possibly partly ascribed to activiting of microglia, which enhanced oxidative stress induced by ROS and reactive nitrogen species.

  4. Increased Expression of the Innate Immune Receptor TLR10 in Obesity and Type-2 Diabetes: Association with ROS-Mediated Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Sardar Sindhu

    2018-01-01

    Full Text Available Background/Aims: Metabolic diseases such as obesity and type-2 diabetes (T2D are known to be associated with chronic low-grade inflammation called metabolic inflammation together with an oxidative stress milieu found in the expanding adipose tissue. The innate immune Toll-like receptors (TLR such as TLR2 and TLR4 have emerged as key players in metabolic inflammation; nonetheless, TLR10 expression in the adipose tissue and its significance in obesity/T2D remain unclear. Methods: TLR10 gene expression was determined in the adipose tissue samples from healthy non-diabetic and T2D individuals, 13 each, using real-time RT-PCR. TLR10 protein expression was determined by immunohistochemistry, confocal microscopy, and flow cytometry. Regarding in vitro studies, THP-1 cells, peripheral blood mononuclear cells (PBMC, or primary monocytes were treated with hydrogen peroxide (H2O2 for induction of reactive oxygen species (ROS-mediated oxidative stress. Superoxide dismutase (SOD activity was measured using a commercial kit. Data (mean±SEM were compared using unpaired student’s t-test and P<0.05 was considered significant. Results: The adipose tissue TLR10 gene/protein expression was found to be significantly upregulated in obesity as well as T2D which correlated with body mass index (BMI. ROS-mediated oxidative stress induced high levels of TLR10 gene/protein expression in monocytic cells and PBMC. In these cells, oxidative stress induced a time-dependent increase in SOD activity. Pre-treatment of cells with anti-oxidants/ROS scavengers diminished the expression of TLR10. ROS-induced TLR10 expression involved the nuclear factor-kappaB (NF-κB/mitogen activated protein kinase (MAPK signaling as well as endoplasmic reticulum (ER stress. H2O2-induced oxidative stress interacted synergistically with palmitate to trigger the expression of TLR10 which associated with enhanced expression of proinflammatory cytokines/chemokine. Conclusion: Oxidative stress

  5. Detection of ROS Induced Proteomic Signatures by Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Brian McDonagh

    2017-07-01

    Full Text Available Reversible and irreversible post-translational modifications (PTMs induced by endogenously generated reactive oxygen species (ROS in regulatory enzymes and proteins plays an essential role in cellular signaling. Almost all cellular processes including metabolism, transcription, translation and degradation have been identified as containing redox regulated proteins. Specific redox modifications of key amino acids generated by ROS offers a dynamic and versatile means to rapidly alter the activity or functional structure of proteins in response to biochemical, environmental, genetic and pathological perturbations. How the proteome responds to these stimuli is of critical importance in oxidant physiology, as it can regulate the cell stress response by reversible and irreversible PTMs, affecting protein activity and protein-protein interactions. Due to the highly labile nature of many ROS species, applying redox proteomics can provide a signature footprint of the ROS species generated. Ideally redox proteomic approaches would allow; (1 the identification of the specific PTM, (2 identification of the amino acid residue that is modified and (3 the percentage of the protein containing the PTM. New developments in MS offer the opportunity of a more sensitive targeted proteomic approach and retrospective data analysis. Subsequent bioinformatics analysis can provide an insight into the biochemical and physiological pathways or cell signaling cascades that are affected by ROS generation. This mini-review will detail current redox proteomic approaches to identify and quantify ROS induced PTMs and the subsequent effects on cellular signaling.

  6. ROS and calcium signaling mediated pathways involved in stress responses of the marine microalgae Dunaliella salina to enhanced UV-B radiation.

    Science.gov (United States)

    Zhang, Xinxin; Tang, Xuexi; Wang, Ming; Zhang, Wei; Zhou, Bin; Wang, You

    2017-08-01

    UV-B ray has been addressed to trigger common metabolic responses on marine microalgae, however, the upstream events responsible for these changes in marine microalgae are poorly understood. In the present study, a species of marine green microalgae Dunaliella salina was exposed to a series of enhanced UV-B radiation ranging from 0.25 to 1.00 KJ·m -2 per day. The role of ROS and calcium signaling in the D. salina responses to UV-B was discussed. Results showed that enhanced UV-B radiation markedly decreased the cell density in a dose-dependent manner, but the contents of protein and glycerol that were essential for cell growth increased. It suggested that it was cell division instead of cell growth that UV-B exerted negative effects on. The subcellular damages on nuclei and plasmalemma further evidenced the hypothesis. The nutrient absorption was affected with UV-B exposure, and the inhibition on PO 4 3- uptake was more serious compared to NO 3 - uptake. UV-B radiation promoted reactive oxygen species (ROS) formation and thiobarbituric acid reactive substances (TBARS) contents, decreased the redox status and altered the antioxidant enzyme activities. The addition of the ROS scavenger and the glutathione biosynthesis precursor N-acetyl-l-cysteine (NAC) alleviated the stress degree, implying ROS-mediated pathway was involved in the stress response to UV-B radiation. Transient increase in Ca 2+ -ATPase was triggered simultaneously with UV-B exposure. Meanwhile, the addition of an intracellular free calcium chelator aggravated the damage of cell division, but exogenous calcium and ion channel blocker applications did not, inferring that endogenously initiated calcium signaling played roles in response to UV-B. Cross-talk analysis showed a relatively clear relationship between ROS inhibition and Ca 2+ -ATPase suppression, and a relation between Ca 2+ inhibition and GPx activity change was also observed. It was thus presumed that ROS-coupled calcium signaling via the

  7. Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.

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    Azhar R Hussain

    Full Text Available BACKGROUND: We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL. In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4', 5-trihydroxystilbene, a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL cells in causing inhibition of cell viability and inducing apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS. Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect. CONCLUSION/SIGNIFICANCE: Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway.

  8. Strawberry-Tree Honey Induces Growth Inhibition of Human Colon Cancer Cells and Increases ROS Generation: A Comparison with Manuka Honey

    Directory of Open Access Journals (Sweden)

    Sadia Afrin

    2017-03-01

    Full Text Available Honey is a natural product known to modulate several biological activities including cancer. The aim of the present study was to examine the phytochemical content and the antioxidant activity of Strawberry tree (Arbutus unedo honey (STH and its cytotoxic properties against human colon adenocarcinoma (HCT-116 and metastatic (LoVo cell lines in comparison with Manuka (Leptospermum scoparium honey (MH. Several unifloral STH and MH were analyzed for their phenolic, flavonoid, amino acid and protein contents, as well as their radical scavenging activities. STH from the Berchidda area showed the highest amount of phenolic, flavonoid, amino acid and protein content, and antioxidant capacity compared to MH. Both STH and MH induced cytotoxicity and cell death in a dose- and time-dependent manner in HCT-116 and LoVo cells, with less toxicity on non-cancer cells. Compared to MH, STH showed more effect at lower concentrations on HCT-116 and LoVo cells. In addition, both honeys increased intracellular reactive oxygen species (ROS generation. In HCT-116 cells, STH and MH induced similar ROS production but in LoVo cells STH induced a higher percentage of ROS compared to MH. Our results indicate that STH and MH can induce cell growth inhibition and ROS generation in colon adenocarcinoma and metastatic cells, which could be due to the presence of phytochemicals with antioxidant properties. These preliminary results are interesting and suggest a potential chemopreventive action which could be useful for further studies in order to develop chemopreventive agents for colon cancer.

  9. Novel derivative of aminobenzenesulfonamide (3c) induces apoptosis in colorectal cancer cells through ROS generation and inhibits cell migration.

    Science.gov (United States)

    Al-Khayal, Khayal; Alafeefy, Ahmed; Vaali-Mohammed, Mansoor-Ali; Mahmood, Amer; Zubaidi, Ahmed; Al-Obeed, Omar; Khan, Zahid; Abdulla, Maha; Ahmad, Rehan

    2017-01-03

    Colorectal cancer (CRC) is the 3 rd most common type of cancer worldwide. New anti-cancer agents are needed for treating late stage colorectal cancer as most of the deaths occur due to cancer metastasis. A recently developed compound, 3c has shown to have potent antitumor effect; however the mechanism underlying the antitumor effect remains unknown. 3c-induced inhibition of proliferation was measured in the absence and presence NAC using MTT in HT-29 and SW620 cells and xCELLigence RTCA DP instrument. 3c-induced apoptotic studies were performed using flow cytometry. 3c-induced redox alterations were measured by ROS production using fluorescence plate reader and flow cytometry and mitochondrial membrane potential by flow cytometry; NADPH and GSH levels were determined by colorimetric assays. Bcl2 family protein expression and cytochrome c release and PARP activation was done by western blotting. Caspase activation was measured by ELISA. Cell migration assay was done using the real time xCELLigence RTCA DP system in SW620 cells and wound healing assay in HT-29. Many anticancer therapeutics exert their effects by inducing reactive oxygen species (ROS). In this study, we demonstrate that 3c-induced inhibition of cell proliferation is reversed by the antioxidant, N-acetylcysteine, suggesting that 3c acts via increased production of ROS in HT-29 cells. This was confirmed by the direct measurement of ROS in 3c-treated colorectal cancer cells. Additionally, treatment with 3c resulted in decreased NADPH and glutathione levels in HT-29 cells. Further, investigation of the apoptotic pathway showed increased release of cytochrome c resulting in the activation of caspase-9, which in turn activated caspase-3 and -6. 3c also (i) increased p53 and Bax expression, (ii) decreased Bcl2 and BclxL expression and (iii) induced PARP cleavage in human colorectal cancer cells. Confirming our observations, NAC significantly inhibited induction of apoptosis, ROS production, cytochrome c

  10. Reynolds stress and shear flow generation

    DEFF Research Database (Denmark)

    Korsholm, Søren Bang; Michelsen, Poul; Naulin, V.

    2001-01-01

    The so-called Reynolds stress may give a measure of the self-consistent flow generation in turbulent fluids and plasmas by the small-scale turbulent fluctuations. A measurement of the Reynolds stress can thus help to predict flows, e.g. shear flows in plasmas. This may assist the understanding...... of improved confinement scenarios such as H-mode confinement regimes. However, the determination of the Reynolds stress requires measurements of the plasma potential, a task that is difficult in general and nearly impossible in hot plasmas in large devices. In this work we investigate an alternative method......, based on density measurements, to estimate the Reynolds stress, and demonstrate the validity range of this quantity, which we term the pseudo-Reynolds stress. The advantage of such a quantity is that accurate measurements of density fluctuations are much easier to obtain experimentally. Prior...

  11. The chalcone flavokawain B induces G2/M cell-cycle arrest and apoptosis in human oral carcinoma HSC-3 cells through the intracellular ROS generation and downregulation of the Akt/p38 MAPK signaling pathway.

    Science.gov (United States)

    Hseu, You-Cheng; Lee, Meng-Shiou; Wu, Chi-Rei; Cho, Hsin-Ju; Lin, Kai-Yuan; Lai, Guan-Hua; Wang, Sheng-Yang; Kuo, Yueh-Hsiung; Kumar, K J Senthil; Yang, Hsin-Ling

    2012-03-07

    Chalcones have been described to represent cancer chemopreventive food components that are rich in fruits and vegetables. In this study, we examined the anti-oral cancer effect of flavokawain B (FKB), a naturally occurring chalcone isolated from Alpinia pricei (shell gingers), and revealed its molecular mechanism of action. Treatment of human oral carcinoma (HSC-3) cells with FKB (1.25-10 μg/mL; 4.4-35.2 μM) inhibited cell viability and caused G(2)/M arrest through reductions in cyclin A/B1, Cdc2, and Cdc25C levels. Moreover, FKB treatment resulted in the induction of apoptosis, which was associated with DNA fragmentation, mitochondria dysfunction, cytochrome c and AIF release, caspase-3 and caspase-9 activation, and Bcl-2/Bax dysregulation. Furthermore, increased Fas activity and procaspase-8, procaspase-4, and procaspase-12 cleavages were accompanied by death receptor and ER-stress, indicating the involvement of mitochondria, death-receptor, and ER-stress signaling pathways. FKB induces apoptosis through ROS generation as evidenced by the upregulation of oxidative-stress markers HO-1/Nrf2. This mechanism was further confirmed by the finding that the antioxidant N-acetylcysteine (NAC) significantly blocked ROS generation and consequently inhibited FKB-induced apoptosis. Moreover, FKB downregulated the phosphorylation of Akt and p38 MAPK, while their inhibitors LY294002 and SB203580, respectively, induced G(2)/M arrest and apoptosis. The profound reduction in cell number was observed in combination treatment with FKB and Akt/p38 MAPK inhibitors, indicating that the disruption of Akt and p38 MAPK cascades plays a functional role in FKB-induced G(2)/M arrest and apoptosis in HSC-3 cells.

  12. PKCδ phosphorylation is an upstream event of GSK3 inactivation-mediated ROS generation in TGF-β1-induced senescence.

    Science.gov (United States)

    Byun, H-O; Jung, H-J; Kim, M-J; Yoon, G

    2014-09-01

    Transforming growth factor β1 (TGF-β1) induces Mv1Lu cell senescence through inactivating glycogen synthase kinase 3 (GSK3), thereby inactivating complex IV and increasing intracellular ROS. In the present study, we identified protein kinase C delta (PKCδ) as an upstream regulator of GSK3 inactivation in this mechanism of TGF-β1-induced senescence. When Mv1Lu cells were exposed to TGF-β1, PKCδ phosphorylation simultaneously increased with GSK3 phosphorylation, and then AKT and ERK were phosphorylated. AKT phosphorylation and Smad signaling were independent of GSK3 phosphorylation, but ERK phosphorylation was downstream of GSK3 inactivation. TGF-β1-triggered GSK3 phosphorylation was blocked by inhibition of PKCδ, using its pharmacological inhibitor, Rottlerin, or overexpression of a dominant negative PKCδ mutant, but GSK3 inhibition with SB415286 did not alter PKCδ phosphorylation. Activation of PKCδ by PMA delayed cell growth and increased intracellular ROS level, but did not induce senescent phenotypes. In addition, overexpression of wild type or a constitutively active PKCδ mutant was enough to delay cell growth and decrease the mitochondrial oxygen consumption rate and complex IV activity, but weakly induce senescence. However, PMA treatment on Mv1Lu cells, which overexpress wild type and constitutively active PKCδ mutants, effectively induced senescence. These results indicate that PKCδ plays a key role in TGF-β1-induced senescence of Mv1Lu cells through the phosphorylation of GSK3, thereby triggering mitochondrial complex IV dysfunction and intracellular ROS generation.

  13. N,N-dimethyl phytosphingosine induces caspase-8-dependent cytochrome c release and apoptosis through ROS generation in human leukemia cells

    International Nuclear Information System (INIS)

    Kim, Byeong Mo; Choi, Yun Jung; Han, Youngsoo; Yun, Yeon-Sook; Hong, Sung Hee

    2009-01-01

    N,N-dimethyl phytosphingosine (DMPS) blocks the conversion of sphingosine to sphingosine-1-phosphate (S1P) by the enzyme sphingosine kinase (SK). In this study, we elucidated the apoptotic mechanisms of DMPS action on a human leukemia cell line using functional pharmacologic and genetic approaches. First, we demonstrated that DMPS-induced apoptosis is evidenced by nuclear morphological change, distinct internucleosomal DNA fragmentation, and an increased sub-G1 cell population. DMPS treatment led to the activation of caspase-9 and caspase-3, accompanied by the cleavage of poly(ADP-ribose) polymerase (PARP) and led to cytochrome c release, depolarization of the mitochondrial membrane potential, and downregulation of the anti-apoptotic members of the bcl-2 family. Ectopic expression of bcl-2 and bcl-xL conferred resistance of HL-60 cells to DMPS-induced cell death, suggesting that DMPS-induced apoptosis occurs predominantly through the activation of the intrinsic mitochondrial pathway. We also observed that DMPS activated the caspase-8-Bid-Bax pathway and that the inhibition of caspase-8 by z-IETD-fmk or small interfering RNA suppressed the cleavage of Bid, cytochrome c release, caspase-3 activation, and apoptotic cell death. In addition, cells subjected to DMPS exhibited significantly increased reactive oxygen species (ROS) generation, and ROS scavengers, such as quercetin and Tiron, but not N-acetylcysteine (NAC), inhibited DMPS-induced activations of caspase-8, -3 and subsequent apoptotic cell death, indicating the role of ROS in caspase-8-mediated apoptosis. Taken together, these results indicate that caspase-8 acts upstream of caspase-3, and that the caspase-8-mediated mitochondrial pathway is important in DMPS-induced apoptosis. Our results also suggest that ROS are critical regulators of caspase-8-mediated apoptosis in DMPS-treated leukemia cells.

  14. Effect of release of dopamine on iron transformations and reactive oxygen species (ROS) generation under conditions typical of coastal waters.

    Science.gov (United States)

    Sun, Yingying; Pham, A Ninh; Waite, T David

    2018-01-24

    Seasonally persistent blooms of Ulvaria obscura var. blyttii, the prominent species present in green tides in the northern Pacific and Atlantic, have been well documented in recent decades. The synthesis and release of dopamine (DA) by Ulvaria obscura var. blyttii has been proposed to be associated with the suppression and inhibition of the growth of other organisms competing for limited resources. To better understand the potential benefits obtained from the release of DA, the transformation of DA as well its concomitant impact on the local seawater environment are investigated in this study. The results show that, despite several toxic quinones being produced during the oxidation of DA, aminochrome (DAC) is likely to be the only quinone playing an allelopathic role in view of its expected accumulation in the surrounding environment. As a consequence of the direct oxidation of DA and DA induced generation of 5,6-dihydroxyindole (DHI), high concentrations of H 2 O 2 accumulate over time, especially in the presence of elements including iron, calcium and magnesium. The oxidative stress to other organisms induced by the release of DA may be particularly detrimental as a result of H 2 O 2 induced reduction in photosynthesis, inactivation of antioxidant systems or even the generation of ˙OH. DA induced iron mobilization may benefit the continuously persistent blooms of Ulvaria obscura var. blyttii or even the whole community via alleviation in iron deficiency within the bloom region.

  15. Nrf2-induced antioxidant protection: a promising target to counteract ROS-mediated damage in neurodegenerative disease?

    NARCIS (Netherlands)

    de Vries, H.E.; Witte, M.; Hondius, D.; Rozemuller, A.J.M.; Drukarch, B.; Hoozemans, J.J.M.; van Horssen, J.

    2008-01-01

    Neurodegenerative diseases share various pathological features, such as accumulation of aberrant protein aggregates, microglial activation, and mitochondrial dysfunction. These pathological processes are associated with generation of reactive oxygen species (ROS), which cause oxidative stress and

  16. Oxidative stress and inflammation generated DNA damage by exposure to air pollution particles

    DEFF Research Database (Denmark)

    Møller, Peter; Danielsen, Pernille Høgh; Karottki, Dorina Gabriela

    2014-01-01

    at different locations (spatial variability), times (temporal variability) or particle size fraction across different experimental systems of acellular conditions, cultured cells, animals and humans. Nevertheless, there is substantial variation in the genotoxic, inflammation and oxidative stress potential......Generation of oxidatively damaged DNA by particulate matter (PM) is hypothesized to occur via production of reactive oxygen species (ROS) and inflammation. We investigated this hypothesis by comparing ROS production, inflammation and oxidatively damaged DNA in different experimental systems...... investigating air pollution particles. There is substantial evidence indicating that exposure to air pollution particles was associated with elevated levels of oxidatively damaged nucleobases in circulating blood cells and urine from humans, which is supported by observations of elevated levels of genotoxicity...

  17. Downregulation of blood-brain barrier phenotype by proinflammatory cytokines involves NADPH oxidase-dependent ROS generation: consequences for interendothelial adherens and tight junctions.

    Directory of Open Access Journals (Sweden)

    Keith D Rochfort

    Full Text Available Blood-brain barrier (BBB dysfunction is an integral feature of neurological disorders and involves the action of multiple proinflammatory cytokines on the microvascular endothelial cells lining cerebral capillaries. There is still however, considerable ambiguity throughout the scientific literature regarding the mechanistic role(s of cytokines in this context, thereby warranting a comprehensive in vitro investigation into how different cytokines may cause dysregulation of adherens and tight junctions leading to BBB permeabilization.The present study employs human brain microvascular endothelial cells (HBMvECs to compare/contrast the effects of TNF-α and IL-6 on BBB characteristics ranging from the expression of interendothelial junction proteins (VE-cadherin, occludin and claudin-5 to endothelial monolayer permeability. The contribution of cytokine-induced NADPH oxidase activation to altered barrier phenotype was also investigated.In response to treatment with either TNF-α or IL-6 (0-100 ng/ml, 0-24 hrs, our studies consistently demonstrated significant dose- and time-dependent decreases in the expression of all interendothelial junction proteins examined, in parallel with dose- and time-dependent increases in ROS generation and HBMvEC permeability. Increased expression and co-association of gp91 and p47, pivotal NADPH oxidase subunits, was also observed in response to either cytokine. Finally, cytokine-dependent effects on junctional protein expression, ROS generation and endothelial permeability could all be attenuated to a comparable extent using a range of antioxidant strategies, which included ROS depleting agents (superoxide dismutase, catalase, N-acetylcysteine, apocynin and targeted NADPH oxidase blockade (gp91 and p47 siRNA, NSC23766.A timely and wide-ranging investigation comparing the permeabilizing actions of TNF-α and IL-6 in HBMvECs is presented, in which we demonstrate how either cytokine can similarly downregulate the

  18. ROS signalling – Specificity is required

    DEFF Research Database (Denmark)

    Møller, Ian Max; Sweetlove, Lee J

    2011-01-01

    The production of reactive oxygen species (ROS) increases in plants under stress. ROS can damage cellular components, but they can also act in signal transduction to help the cell counteract the oxidative damage in the stressed compartment. H2O2 may induce a general stress response, but it does...... messengers and regulate source-specific genes and in this way contribute to retrograde ROS signalling during oxidative stress. (This is a new project funded by FNU) References: Møller, I.M. & Sweetlove, L.J. 2010. ROS signalling – Specificity is required. Trends Plant Sci. 15: 370-374...... not have the required specificity to selectively regulate nuclear genes required for dealing with localized stress, e.g., in chloroplasts or mitochondria. We here argue that peptides deriving from proteolytic breakdown of oxidatively damaged proteins have the requisite specificity to act as secondary ROS...

  19. Phytoextract of Indian mustard seeds acts by suppressing the generation of ROS against acetaminophen-induced hepatotoxicity in HepG2 cells.

    Science.gov (United States)

    Parikh, Harita; Pandita, Nancy; Khanna, Aparna

    2015-07-01

    Indian mustard [Brassica juncea (L.) Czern. & Coss. (Brassicaceae)] is reported to possess diverse pharmacological properties. However, limited information is available concerning its hepatoprotective activity and mechanism of action. To study the protective mechanism of mustard seed extract against acetaminophen (APAP) toxicity in a hepatocellular carcinoma (HepG2) cell line. Hepatotoxicity models were established using APAP (2.5-22.5 mM) based on the cytotoxicity profile. An antioxidant-rich fraction from mustard seeds was extracted and evaluated for its hepatoprotective potential. The mechanism of action was elucidated using various in vitro antioxidant assays, the detection of intracellular generation of reactive oxygen species (ROS), and cell cycle analysis. The phytoconstituents isolated via HPLC-DAD were also evaluated for hepatoprotective activity. Hydromethanolic seed extract exhibited hepatoprotective activity in post- and pre-treatment models of 20 mM APAP toxicity and restored the elevated levels of liver indices to normal values (p DAD analysis revealed the presence quercetin, vitamin E, and catechin, which exhibited hepatoprotective activity. A phytoextract of mustard seeds acts by suppressing the generation of ROS in response to APAP toxicity.

  20. NPRL-Z-1, as a new topoisomerase II poison, induces cell apoptosis and ROS generation in human renal carcinoma cells.

    Science.gov (United States)

    Wu, Szu-Ying; Pan, Shiow-Lin; Xiao, Zhi-Yan; Hsu, Jui-Ling; Chen, Mei-Chuan; Lee, Kuo-Hsiung; Teng, Che-Ming

    2014-01-01

    NPRL-Z-1 is a 4β-[(4"-benzamido)-amino]-4'-O-demethyl-epipodophyllotoxin derivative. Previous reports have shown that NPRL-Z-1 possesses anticancer activity. Here NPRL-Z-1 displayed cytotoxic effects against four human cancer cell lines (HCT 116, A549, ACHN, and A498) and exhibited potent activity in A498 human renal carcinoma cells, with an IC50 value of 2.38 µM via the MTT assay. We also found that NPRL-Z-1 induced cell cycle arrest in G1-phase and detected DNA double-strand breaks in A498 cells. NPRL-Z-1 induced ataxia telangiectasia-mutated (ATM) protein kinase phosphorylation at serine 1981, leading to the activation of DNA damage signaling pathways, including Chk2, histone H2AX, and p53/p21. By ICE assay, the data suggested that NPRL-Z-1 acted on and stabilized the topoisomerase II (TOP2)-DNA complex, leading to TOP2cc formation. NPRL-Z-1-induced DNA damage signaling and apoptotic death was also reversed by TOP2α or TOP2β knockdown. In addition, NPRL-Z-1 inhibited the Akt signaling pathway and induced reactive oxygen species (ROS) generation. These results demonstrated that NPRL-Z-1 appeared to be a novel TOP2 poison and ROS generator. Thus, NPRL-Z-1 may present a significant potential anticancer candidate against renal carcinoma.

  1. The sulfated laminarin triggers a stress transcriptome before priming the SA- and ROS-dependent defenses during grapevine's induced resistance against Plasmopara viticola.

    Directory of Open Access Journals (Sweden)

    Adrien Gauthier

    Full Text Available Grapevine (Vitis vinifera is susceptible to many pathogens which cause significant losses to viticulture worldwide. Chemical control is available, but agro-ecological concerns have raised interest in alternative methods, especially in triggering plant immunity by elicitor treatments. The β-glucan laminarin (Lam and its sulfated derivative (PS3 have been previously demonstrated to induce resistance in grapevine against downy mildew (Plasmopara viticola. However, if Lam elicits classical grapevine defenses such as oxidative burst, pathogenesis-related (PR-proteins and phytoalexin production, PS3 triggered grapevine resistance via a poorly understood priming phenomenon. The aim of this study was to identify the molecular mechanisms of the PS3-induced resistance. For this purpose we studied i the signaling events and transcriptome reprogramming triggered by PS3 treatment on uninfected grapevine, ii grapevine immune responses primed by PS3 during P. viticola infection. Our results showed that i PS3 was unable to elicit reactive oxygen species (ROS production, cytosolic Ca(2+ concentration variations, mitogen-activated protein kinase (MAPK activation but triggered a long lasting plasma membrane depolarization in grapevine cells, ii PS3 and Lam shared a common stress-responsive transcriptome profile that partly overlapped the salicylate- (SA and jasmonate-(JA-dependent ones. After P. viticola inoculation, PS3 specifically primed the SA- and ROS-dependent defense pathways leading to grapevine induced resistance against this biotroph. Interestingly pharmacological approaches suggested that the plasma membrane depolarization and the downstream ROS production are key events of the PS3-induced resistance.

  2. ATP mediates NADPH oxidase/ROS generation and COX-2/PGE2 expression in A549 cells: role of P2 receptor-dependent STAT3 activation.

    Directory of Open Access Journals (Sweden)

    Shin-Ei Cheng

    Full Text Available BACKGROUND: Up-regulation of cyclooxygenase (COX-2 and its metabolite prostaglandin E(2 (PGE(2 are frequently implicated in lung inflammation. Extracellular nucleotides, such as ATP have been shown to act via activation of P2 purinoceptors, leading to COX-2 expression in various inflammatory diseases, such as lung inflammation. However, the mechanisms underlying ATP-induced COX-2 expression and PGE(2 release remain unclear. PRINCIPAL FINDINGS: Here, we showed that ATPγS induced COX-2 expression in A549 cells revealed by western blot and real-time PCR. Pretreatment with the inhibitors of P2 receptor (PPADS and suramin, PKC (Gö6983, Gö6976, Ro318220, and Rottlerin, ROS (Edaravone, NADPH oxidase [diphenyleneiodonium chloride (DPI and apocynin], Jak2 (AG490, and STAT3 [cucurbitacin E (CBE] and transfection with siRNAs of PKCα, PKCι, PKCμ, p47(phox, Jak2, STAT3, and cPLA(2 markedly reduced ATPγS-induced COX-2 expression and PGE(2 production. In addition, pretreatment with the inhibitors of P2 receptor attenuated PKCs translocation from the cytosol to the membrane in response to ATPγS. Moreover, ATPγS-induced ROS generation and p47(phox translocation was also reduced by pretreatment with the inhibitors of P2 receptor, PKC, and NADPH oxidase. On the other hand, ATPγS stimulated Jak2 and STAT3 activation which were inhibited by pretreatment with PPADS, suramin, Gö6983, Gö6976, Ro318220, GF109203X, Rottlerin, Edaravone, DPI, and apocynin in A549 cells. SIGNIFICANCE: Taken together, these results showed that ATPγS induced COX-2 expression and PGE(2 production via a P2 receptor/PKC/NADPH oxidase/ROS/Jak2/STAT3/cPLA(2 signaling pathway in A549 cells. Increased understanding of signal transduction mechanisms underlying COX-2 gene regulation will create opportunities for the development of anti-inflammation therapeutic strategies.

  3. Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium.

    Science.gov (United States)

    Harijith, Anantha; Pendyala, Srikanth; Ebenezer, David L; Ha, Alison W; Fu, Panfeng; Wang, Yue-Ting; Ma, Ke; Toth, Peter T; Berdyshev, Evgeny V; Kanteti, Prasad; Natarajan, Viswanathan

    2016-08-01

    Hyperoxia-induced lung injury adversely affects ICU patients and neonates on ventilator assisted breathing. The underlying culprit appears to be reactive oxygen species (ROS)-induced lung damage. The major contributor of hyperoxia-induced ROS is activation of the multiprotein enzyme complex NADPH oxidase. Sphingosine-1-phosphate (S1P) signaling is known to be involved in hyperoxia-mediated ROS generation; however, the mechanism(s) of S1P-induced NADPH oxidase activation is unclear. Here, we investigated various steps in the S1P signaling pathway mediating ROS production in response to hyperoxia in lung endothelium. Of the two closely related sphingosine kinases (SphKs)1 and 2, which synthesize S1P from sphingosine, only Sphk1(-/-) mice conferred protection against hyperoxia-induced lung injury. S1P is metabolized predominantly by S1P lyase and partial deletion of Sgpl1 (Sgpl1(+/-)) in mice accentuated lung injury. Hyperoxia stimulated S1P accumulation in human lung microvascular endothelial cells (HLMVECs), and downregulation of S1P transporter spinster homolog 2 (Spns2) or S1P receptors S1P1&2, but not S1P3, using specific siRNA attenuated hyperoxia-induced p47(phox) translocation to cell periphery and ROS generation in HLMVECs. These results suggest a role for Spns2 and S1P1&2 in hyperoxia-mediated ROS generation. In addition, p47(phox) (phox:phagocyte oxidase) activation and ROS generation was also reduced by PF543, a specific SphK1 inhibitor in HLMVECs. Our data indicate a novel role for Spns2 and S1P1&2 in the activation of p47(phox) and production of ROS involved in hyperoxia-mediated lung injury in neonatal and adult mice. Copyright © 2016 the American Physiological Society.

  4. Roles of ROS mediated oxidative stress and DNA damage in 3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide-induced immunotoxicity of Sprague-Dawley rats.

    Science.gov (United States)

    Gao, Hui; Wang, Di; Zhang, Shun; Xu, Mengjing; Yang, Wei; Yan, Peipei; Liu, Yang; Luo, Xiao; Wu, Hailei; Yao, Ping; Yan, Hong; Liu, Liegang

    2015-11-01

    3-methyl-2-quinoxalin benzenevinylketo-1, 4-dioxide (Quinocetone, QCT) has been broadly used to treat dysentery and promote animal growth in food producing animals. However, its potential toxicity could not been neglected as parts of safety assessment according to the acceptable guidelines for QCT administration. In this study, the immunotoxicity of QCT was investigated in male Sprague-Dawley (SD) rats following a 28-day oral exposure at doses of 0, 50, 800, and 2400 mg/kg/day. The food consumption, body weight gain and relative spleen weight were significantly decreased by QCT in a dose-dependent manner. Treatment of rats with QCT also notably suppressed the T-cell proliferation and natural killer (NK) cell activity, accompanied by intracellular reactive oxygen species (ROS) accumulation, antioxidant system inhibition and DNA damage enhancement. Thus, the primary finding of this study is that QCT exposure (2400 mg/kg/day) could cause immunotoxicity in SD rats due to ROS mediated oxidative stress and DNA damage. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Pinus densiflora leaf essential oil induces apoptosis via ROS generation and activation of caspases in YD-8 human oral cancer cells.

    Science.gov (United States)

    Jo, Jeong-Rang; Park, Ju Sung; Park, Yu-Kyoung; Chae, Young Zoo; Lee, Gyu-Hee; Park, Gy-Young; Jang, Byeong-Churl

    2012-04-01

    The leaf of Pinus (P.) densiflora, a pine tree widely distributed in Asian countries, has been used as a traditional medicine. In the present study, we investigated the anticancer activity of essential oil, extracted by steam distillation, from the leaf of P. densiflora in YD-8 human oral squamous cell carcinoma (OSCC) cells. Treatment of YD-8 cells with P. densiflora leaf essential oil (PLEO) at 60 µg/ml for 8 h strongly inhibited proliferation and survival and induced apoptosis. Notably, treatment with PLEO led to generation of ROS, activation of caspase-9, PARP cleavage, down-regulation of Bcl-2, and phosphorylation of ERK-1/2 and JNK-1/2 in YD-8 cells. Treatment with PLEO, however, did not affect the expression of Bax, XIAP and GRP78. Importantly, pharmaco-logical inhibition studies demonstrated that treatment with vitamin E (an anti-oxidant) or z-VAD-fmk (a pan-caspase inhibitor), but not with PD98059 (an ERK-1/2 inhibitor) or SP600125 (a JNK-1/2 inhibitor), strongly suppressed PLEO-induced apoptosis in YD-8 cells and reduction of their survival. Vitamin E treatment further blocked activation of caspase-9 and Bcl-2 down-regulation induced by PLEO. Thus, these results demonstrate firstly that PLEO has anti-proliferative, anti-survival and pro-apoptotic effects on YD-8 cells and the effects are largely due to the ROS-dependent activation of caspases.

  6. Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines.

    Science.gov (United States)

    Park, S H; Sung, J H; Kim, E J; Chung, N

    2015-02-01

    Pancreatic cancer is the fourth leading cause of cancer death. Gemcitabine is widely used as a chemotherapeutic agent for the treatment of pancreatic cancer, but the prognosis is still poor. Berberine, an isoquinoline alkaloid extracted from a variety of natural herbs, possesses a variety of pharmacological properties including anticancer effects. In this study, we investigated the anticancer effects of berberine and compared its use with that of gemcitabine in the pancreatic cancer cell lines PANC-1 and MIA-PaCa2. Berberine inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. After berberine treatment, the G1 phase of PANC-1 cells increased by 10% compared to control cells, and the G1 phase of MIA-PaCa2 cells was increased by 2%. Whereas gemcitabine exerts antiproliferation effects through S-phase arrest, our results showed that berberine inhibited proliferation by inducing G1-phase arrest. Berberine-induced apoptosis of PANC-1 and MIA-PaCa2 cells increased by 7 and 2% compared to control cells, respectively. Notably, berberine had a greater apoptotic effect in PANC-1 cells than gemcitabine. Upon treatment of PANC-1 and MIA-PaCa2 with berberine at a half-maximal inhibitory concentration (IC50), apoptosis was induced by a mechanism that involved the production of reactive oxygen species (ROS) rather than caspase 3/7 activation. Our findings showed that berberine had anti-cancer effects and may be an effective drug for pancreatic cancer chemotherapy.

  7. Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines

    International Nuclear Information System (INIS)

    Park, S.H.; Sung, J.H.; Kim, E.J.; Chung, N.

    2014-01-01

    Pancreatic cancer is the fourth leading cause of cancer death. Gemcitabine is widely used as a chemotherapeutic agent for the treatment of pancreatic cancer, but the prognosis is still poor. Berberine, an isoquinoline alkaloid extracted from a variety of natural herbs, possesses a variety of pharmacological properties including anticancer effects. In this study, we investigated the anticancer effects of berberine and compared its use with that of gemcitabine in the pancreatic cancer cell lines PANC-1 and MIA-PaCa2. Berberine inhibited cell growth in a dose-dependent manner by inducing cell cycle arrest and apoptosis. After berberine treatment, the G1 phase of PANC-1 cells increased by 10% compared to control cells, and the G1 phase of MIA-PaCa2 cells was increased by 2%. Whereas gemcitabine exerts antiproliferation effects through S-phase arrest, our results showed that berberine inhibited proliferation by inducing G1-phase arrest. Berberine-induced apoptosis of PANC-1 and MIA-PaCa2 cells increased by 7 and 2% compared to control cells, respectively. Notably, berberine had a greater apoptotic effect in PANC-1 cells than gemcitabine. Upon treatment of PANC-1 and MIA-PaCa2 with berberine at a half-maximal inhibitory concentration (IC 50 ), apoptosis was induced by a mechanism that involved the production of reactive oxygen species (ROS) rather than caspase 3/7 activation. Our findings showed that berberine had anti-cancer effects and may be an effective drug for pancreatic cancer chemotherapy

  8. Sodium orthovanadate associated with pharmacological doses of ascorbate causes an increased generation of ROS in tumor cells that inhibits proliferation and triggers apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Günther, T-hat nia Mara Fischer; Kviecinski, Maicon Roberto; Baron, Carla Cristine; Felipe, Karina Bettega; Farias, Mirelle Sifroni; Ourique da Silva, Fabiana; Bücker, Nádia Cristina Falcão [Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis (Brazil); Pich, Claus Tröger [Campus de Araranguá, Universidade Federal de Santa Catarina, Araranguá (Brazil); Ferreira, Eduardo Antonio [Universidade de Brasília, Faculdade de Ceilândia, DF (Brazil); Filho, Danilo Wilhelm [Departamento de Ecologia e Zoologia, Universidade Federal de Santa Catarina, Florianópolis (Brazil); Verrax, Julien; Calderon, Pedro Buc [Toxicology and Cancer Biology Research Group, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels (Belgium); Pedrosa, Rozangela Curi, E-mail: rozangelapedrosa@gmail.com [Departamento de Bioquímica, Universidade Federal de Santa Catarina, Florianópolis (Brazil)

    2013-01-18

    Graphical abstract: -- Abstract: Pharmacological doses of ascorbate were evaluated for its ability to potentiate the toxicity of sodium orthovanadate (Na{sub 3}VO{sub 4}) in tumor cells. Cytotoxicity, inhibition of cell proliferation, generation of ROS and DNA fragmentation were assessed in T24 cells. Na{sub 3}VO{sub 4} was cytotoxic against T24 cells (EC{sub 50} = 5.8 μM at 24 h), but in the presence of ascorbate (100 μM) the EC{sub 50} fell to 3.3 μM. Na{sub 3}VO{sub 4} plus ascorbate caused a strong inhibition of cell proliferation (up to 20%) and increased the generation of ROS (4-fold). Na{sub 3}VO{sub 4} did not directly cleave plasmid DNA, at this aspect no synergism was found occurring between Na{sub 3}VO{sub 4} and ascorbate once the resulting action of the combination was no greater than that of both substances administered separately. Cells from Ehrlich ascites carcinoma-bearing mice were used to determine the activity of antioxidant enzymes, the extent of the oxidative damage and the type of cell death. Na{sub 3}VO{sub 4} alone, or combined with ascorbate, increased catalase activity, but only Na{sub 3}VO{sub 4} plus ascorbate increased superoxide dismutase activity (up to 4-fold). Oxidative damage on proteins and lipids was higher due to the treatment done with Na{sub 3}VO{sub 4} plus ascorbate (2–3-fold). Ascorbate potentiated apoptosis in tumor cells from mice treated with Na{sub 3}VO{sub 4}. The results indicate that pharmacological doses of ascorbate enhance the generation of ROS induced by Na{sub 3}VO{sub 4} in tumor cells causing inhibition of proliferation and apoptosis. Apoptosis induced by orthovanadate and ascorbate is closer related to inhibition on Bcl-xL and activation of Bax. Our data apparently rule out a mechanism of cell demise p53-dependent or related to Cdk2 impairment.

  9. Evaluation of the use of reactive oxygen species (ROS generated through oxyion® technology in strawberry (Fragaria × ananassa (Duchesne ex Weston Duchesne ex Rozier cv. Monterrey storage

    Directory of Open Access Journals (Sweden)

    Rafael Andres Ramirez

    2018-04-01

    Full Text Available Reactive oxygen species (ROS play a key role in oxidative stress processes at the biological level. In most cases the presence of these chemical species is undesirable due to the impact they have on tissues and cellular structures, however, their effects can be used to control the incidence of microorganisms responsible for deterioration processes in fruits and vegetables. In the present study the feasibility of combining low temperature storage with the presence of reactive oxygen species generated using Oxyion® technology to control the deterioration process in strawberry (Fragaria X ananassa was studied. The treatments used were as follows: control storage (4°C ± 2°C without Oxyion® and ROS storage (4°C ± 2°C with Oxyion®, for two product categories according to weight and maturation state according to NTC 4103 (ICONTEC, 1997. The variables were monitored with measuring points at 1, 3, 5, 7, 10 and 15 days after harvest in percentage of loss of mass, soluble solids, respiratory intensity, acidity, resistance, color and ethylene and significant interactions among variables. At the conclusion of the study, Oxyion® technology was found to have statistically significant differences compared to control, and have allowed to less weight loss, higher resistance and lower exogenous ethylene production, extending the life of strawberry cv. Monterrey in a 40% during storage, additionally the losses by action of microorganisms present in strawberries surface were reduced considerably, generating a positive precedent in the processes of storage and conservation of fruits for Colombia.

  10. CO-releasing molecules CORM2 attenuates angiotensin II-induced human aortic smooth muscle cell migration through inhibition of ROS/IL-6 generation and matrix metalloproteinases-9 expression

    Directory of Open Access Journals (Sweden)

    Ming-Horng Tsai

    2017-08-01

    Full Text Available Ang II has been involved in the pathogenesis of cardiovascular diseases, and matrix metalloproteinase-9 (MMP-9 induced migration of human aortic smooth muscle cells (HASMCs is the most common and basic pathological feature. Carbon monoxide (CO, a byproduct of heme breakdown by heme oxygenase, exerts anti-inflammatory effects in various tissues and organ systems. In the present study, we aimed to investigate the effects and underlying mechanisms of carbon monoxide releasing molecule-2 (CORM-2 on Ang II-induced MMP-9 expression and cell migration of HASMCs. Ang II significantly up-regulated MMP-9 expression and cell migration of HASMCs, which was inhibited by transfection with siRNA of p47phox, Nox2, Nox4, p65, angiotensin II type 1 receptor (AT1R and pretreatment with the inhibitors of NADPH oxidase, ROS, and NF-κB. In addition, Ang II also induced NADPH oxidase/ROS generation and p47phox translocation from the cytosol to the membrane. Moreover, Ang II-induced oxidative stress and MMP-9-dependent cell migration were inhibited by pretreatment with CORM-2. Finally, we observed that Ang II induced IL-6 release in HASMCs via AT1R, but not AT2R, which could further caused MMP-9 secretion and cell migration. Pretreatment with CORM-2 reduced Ang II-induced IL-6 release. In conclusion, CORM-2 inhibits Ang II-induced HASMCs migration through inactivation of suppression of NADPH oxidase/ROS generation, NF-κB inactivation and IL-6/MMP-9 expression. Thus, application of CO, especially CORM-2, is a potential countermeasure to reverse the pathological changes of various cardiovascular diseases. Further effects aimed at identifying novel antioxidant and anti-inflammatory substances protective for heart and blood vessels that targeting CO and establishment of well-designed in vivo models properly evaluating the efficacy of these agents are needed. Keywords: Angiotensin II, Carbon monoxide, Human aortic smooth muscle cell, Inflammation, Matrix metallopeptidase

  11. Soybean salt tolerance 1 (GmST1 reduces ROS production, enhances ABA sensitivity and abiotic stress tolerance in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Shuxin eRen

    2016-04-01

    Full Text Available Abiotic stresses, including high soil salinity, significantly reduce crop production worldwide. Salt tolerance in plants is a complex trait and is regulated by multiple mechanisms. Understanding the mechanisms and dissecting the components on their regulatory pathways will provide new insights, leading to novel strategies for the improvement of salt tolerance in agricultural and economic crops of importance. Here we report that soybean salt tolerance 1, named GmST1, exhibited strong tolerance to salt stress in the Arabidopsis transgenic lines. The GmST1-overexpressed Arabidopsis also increased sensitivity to ABA and decreased production of reactive oxygen species (ROS under salt stress. In addition, GmST1 significantly improved drought tolerance in Arabidopsis transgenic lines. GmST1 belongs to a 3-prime part of Glyma.03g171600 gene in the current version of soybean genome sequence annotation. However, comparative RT-PCR analysis around Glyma.03g171600 genomic region confirmed that GmST1 might serve as an intact gene in soybean leaf tissues. Unlike Glyma.03g171600 which was not expressed in leaves, GmST1 was strongly induced by salt treatment in the leaf tissues. By promoter analysis, a TATA box was detected to be positioned close to GmST1 start codon and a putative ABRE and a DRE cis-acting elements were identified at about 1kb upstream of GmST1 gene. The data also indicated that GmST1-transgenic lines survived under drought stress and showed a significantly lower water loss than non-transgenic lines. In summary, our results suggest that overexpression of GmST1 significantly improves Arabidopsis tolerance to both salt and drought stresses and the gene may be a potential candidate for genetic engineering of salt- and drought-tolerant crops.

  12. Plant responses to water stress

    Science.gov (United States)

    Kar, Rup Kumar

    2011-01-01

    Terrestrial plants most often encounter drought stress because of erratic rainfall which has become compounded due to present climatic changes.Responses of plants to water stress may be assigned as either injurious change or tolerance index. One of the primary and cardinal changes in response to drought stress is the generation of reactive oxygen species (ROS), which is being considered as the cause of cellular damage. However, recently a signaling role of such ROS in triggering the ROS scavenging system that may confer protection or tolerance against stress is emerging. Such scavenging system consists of antioxidant enzymes like SOD, catalase and peroxidases, and antioxidant compounds like ascorbate, reduced glutathione; a balance between ROS generation and scavenging ultimately determines the oxidative load. As revealed in case of defence against pathogen, signaling via ROS is initiated by NADPH oxidase-catalyzed superoxide generation in the apoplastic space (cell wall) followed by conversion to hydrogen peroxide by the activity of cell wall-localized SOD. Wall peroxidase may also play role in ROS generation for signaling. Hydrogen peroxide may use Ca2+ and MAPK pathway as downstream signaling cascade. Plant hormones associated with stress responses like ABA and ethylene play their role possibly via a cross talk with ROS towards stress tolerance, thus projecting a dual role of ROS under drought stress. PMID:22057331

  13. Anticancer potential of Conium maculatum extract against cancer cells in vitro: Drug-DNA interaction and its ability to induce apoptosis through ROS generation.

    Science.gov (United States)

    Mondal, Jesmin; Panigrahi, Ashis Kumar; Khuda-Bukhsh, Anisur Rahman

    2014-08-01

    Conium maculatum extract is used as a traditional medicine for cervix carcinoma including homeopathy. However, no systematic work has so far been carried out to test its anti-cancer potential against cervix cancer cells in vitro. Thus, in this study, we investigated whether ethanolic extract of conium is capable of inducing cytotoxicity in different normal and cancer cell lines including an elaborate study in HeLa cells. Conium's effects on cell cycle, reactive oxygen species (ROS) accumulation, mitochondrial membrane potential (MMP) and apoptosis, if any, were analyzed through flow cytometry. Whether Conium could damage DNA and induce morphological changes were also determined microscopically. Expression of different proteins related to cell death and survival was critically studied by western blotting and ELISA methods. If Conium could interact directly with DNA was also determined by circular dichroism (CD) spectroscopy. Conium treatment reduced cell viability and colony formation at 48 h and inhibited cell proliferation, arresting cell cycle at sub-G stage. Conium treatment lead to increased generation of reactive oxygen species (ROS) at 24 h, increase in MMP depolarization, morphological changes and DNA damage in HeLa cells along with externalization of phosphatidyl serine at 48 hours. While cytochrome c release and caspase-3 activation led HeLa cells toward apoptosis, down-regulation of Akt and NFkB inhibited cellular proliferation, indicating the signaling pathway to be mediated via the mitochondria-mediated caspase-3-dependent pathway. CD-spectroscopy revealed that Conium interacted with DNA molecule. Overall results validate anti-cancer potential of Conium and provide support for its use in traditional systems of medicine.

  14. Transcriptomic analysis reveals importance of ROS and phytohormones in response to short-term salinity stress in Populus tomentosa

    Directory of Open Access Journals (Sweden)

    Lingyu eZheng

    2015-09-01

    Full Text Available Populus tomentosa (Chinese white poplar is well adapted to various extreme environments, and is considered an important species to study the effects of salinity stress on poplar trees. To decipher the mechanism of poplar’s rapid response to short-term salinity stress, we firstly detected the changes in H2O2 and hormone, and then profiled the gene expression pattern of ten-week-old seedling roots treated with 200 mM NaCl for 0, 6, 12 and 24 hours (h by RNA-seq on the Illumina-Solexa platform. Physiological determination showed that the significant increase in H2O2 began at 6 h, while that in hormone ABA was at 24 h, under salt stress. Compared with controls (0 h, 3991, 4603 and 4903 genes were up regulated, and 1408, 2206 and 3461 genes were down regulated (adjusted P-value ≤ 0.05 and |log2Ratio|≥1 at 6, 12, and 24 h time points, respectively. The Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway annotation revealed that the differentially expressed genes (DEGs were highly enriched in hormone- and reactive oxygen species-related biological processes, including ‘response to oxidative stress or abiotic stimulus’, ‘peroxidase activity’, ‘regulation of transcription’, ‘hormone synthetic and metabolic process’, ‘hormone signal transduction’, ‘antioxidant activity’ and ‘transcription factor activity’. Moreover, K-means clustering demonstrated that DEGs (total RPKM value>12 from four time points could be categorized into four kinds of expression trends: quick up/down over 6 h or 12 h, and slow up/down over 24 h. Of these, DEGs involved in H2O2- and hormone- producing and signal-related genes were further enriched in this analysis, which indicated that the two kinds of small molecules, hormones and H2O2, play pivotal roles in the short-term salt stress response in poplar. This study provides a basis for future studies of the molecular adaptation of poplar and other tree species to salinity

  15. ROS and RNS in plant physiology: an overview.

    Science.gov (United States)

    Del Río, Luis A

    2015-05-01

    The production of reactive oxygen species (ROS) is the unavoidable consequence of aerobic life. ROS is a collective term that includes both oxygen radicals, like superoxide (O 2. -) and hydroxyl (·OH) radicals, and other non-radicals such as hydrogen peroxide (H2O2), singlet oxygen ((1)O2 or (1)Δg), etc. In plants, ROS are produced in different cell compartments and are oxidizing species, particularly hydroxyl radicals and singlet oxygen, that can produce serious damage in biological systems (oxidative stress). However, plant cells also have an array of antioxidants which, normally, can scavenge the excess oxidants produced and so avoid deleterious effects on the plant cell bio-molecules. The concept of 'oxidative stress' was re-evaluated in recent years and the term 'oxidative signalling' was created. This means that ROS production, apart from being a potentially harmful process, is also an important component of the signalling network that plants use for their development and for responding to environmental challenges. It is known that ROS play an important role regulating numerous biological processes such as growth, development, response to biotic and environmental stresses, and programmed cell death. The term reactive nitrogen species (RNS) includes radicals like nitric oxide (NO· ) and nitric dioxide (NO2.), as well as non-radicals such as nitrous acid (HNO2) and dinitrogen tetroxide (N2O4), among others. RNS are also produced in plants although the generating systems have still not been fully characterized. Nitric oxide (NO·) has an important function as a key signalling molecule in plant growth, development, and senescence, and RNS, like ROS, also play an important role as signalling molecules in the response to environmental (abiotic) stress. Similarly, NO· is a key mediator, in co-operation with ROS, in the defence response to pathogen attacks in plants. ROS and RNS have been demonstrated to have an increasingly important role in biology and medicine

  16. Breviscapine ameliorates CCl4‑induced liver injury in mice through inhibiting inflammatory apoptotic response and ROS generation.

    Science.gov (United States)

    Liu, Yu; Wen, Pei-Hao; Zhang, Xin-Xue; Dai, Yang; He, Qiang

    2018-05-02

    Acute liver injury is characterized by fibrosis, inflammation and apoptosis, leading to liver failure, cirrhosis or cancer and affecting the clinical outcome in the long term. However, no effective therapeutic strategy is currently available. Breviscapine, a mixture of flavonoid glycosides, has been reported to have multiple biological functions. The present study aimed to investigate the effects of breviscapine on acute liver injury induced by CCl4 in mice. C57BL/6 mice were subjected to intraperitoneal injection with CCl4 for 8 weeks with or without breviscapine (15 or 30 mg/kg). Mice treated with CCl4 developed acute liver injury, as evidenced by histological analysis, Masson trichrome and Sirius Red staining, accompanied with elevated levels of alanine aminotransferase and aspartate aminotransferase. Furthermore, increases in pro‑inflammatory cytokines, chemokines and apoptotic factors, including caspase‑3 and poly(ADP ribose) polymerase‑2 (PARP‑2), were observed. Breviscapine treatment significantly and dose‑dependently reduced collagen deposition and the fibrotic area. Inflammatory cytokines were downregulated by breviscapine through inactivating Toll‑like receptor 4/nuclear factor-κB signaling pathways. In addition, co‑administration of breviscapine with CCl4 decreased the apoptotic response by enhancing B‑cell lymphoma-2 (Bcl‑2) levels, while reducing Bcl‑2‑associated X protein, apoptotic protease activating factor 1, caspase‑3 and PARP activity. Furthermore, CCl4‑induced oxidative stress was blocked by breviscapine through improving anti‑oxidants and impeding mitogen‑activated protein kinase pathways. The present study highlighted that breviscapine exhibited liver‑protective effects against acute hepatic injury induced by CCl4 via suppressing inflammation and apoptosis.

  17. [Cell surface peroxidase--generator of superoxide anion in wheat root cells under wound stress].

    Science.gov (United States)

    Chasov, A V; Gordon, L Kh; Kolesnikov, O P; Minibaeva, F V

    2002-01-01

    Development of wound stress in excised wheat roots is known to be accompanied with an increase in reactive oxygen species (ROS) production, fall of membrane potential, release of K+ from cells, alkalization of extracellular solution, changes in respiration and metabolism of structural lipids. Dynamics of superoxide release correlates with changes in other physiological parameters, indicating the cross-reaction of these processes. Activity of peroxidase in extracellular solution after a 1 h incubation and removal of roots was shown to be stimulated by the range of organic acids, detergents, metals, and to be inhibited by cyanide. Superoxide production was sensitive to the addition of Mn2+ and H2O2. Increase in superoxide production correlates with the enhancement of peroxidase activity at the application of organic acids and detergents. The results obtained indicate that cell surface peroxidase is one of the main generators of superoxide in wounded wheat root cells. Different ways of stimulation of the ROS producing activity in root cells is supposed. By controlling superoxide and hydrogen peroxide formation, the cell surface peroxidase can control the adaptation processes in stressed plant cells.

  18. Dual Role of ROS as Signal and Stress Agents: Iron Tips the Balance in favor of Toxic Effects

    Directory of Open Access Journals (Sweden)

    Elena Gammella

    2016-01-01

    Full Text Available Iron is essential for life, while also being potentially harmful. Therefore, its level is strictly monitored and complex pathways have evolved to keep iron safely bound to transport or storage proteins, thereby maintaining homeostasis at the cellular and systemic levels. These sequestration mechanisms ensure that mildly reactive oxygen species like anion superoxide and hydrogen peroxide, which are continuously generated in cells living under aerobic conditions, keep their physiologic role in cell signaling while escaping iron-catalyzed transformation in the highly toxic hydroxyl radical. In this review, we describe the multifaceted systems regulating cellular and body iron homeostasis and discuss how altered iron balance may lead to oxidative damage in some pathophysiological settings.

  19. Cytotoxic effects induced by interferon-ω gene lipofection through ROS generation and mitochondrial membrane potential disruption in feline mammary carcinoma cells.

    Science.gov (United States)

    Villaverde, Marcela Solange; Targovnik, Alexandra Marisa; Miranda, María Victoria; Finocchiaro, Liliana María Elena; Glikin, Gerardo Claudio

    2016-08-01

    Progress in comparative oncology promises advances in clinical cancer treatments for both companion animals and humans. In this context, feline mammary carcinoma (FMC) cells have been proposed as a suitable model to study human breast cancer. Based on our previous data about the advantages of using type I interferon gene therapy over the respective recombinant DNA derived protein, the present work explored the effects of feline interferon-ω gene (fIFNω) transfer on FMC cells. Three different cell variants derived from a single spontaneous highly aggressive FMC tumor were successfully established and characterized. Lipofection of the fIFNω gene displayed a significant cytotoxic effect on the three cell variants. The extent of the response was proportional to ROS generation, mitochondrial membrane potential disruption and calcium uptake. Moreover, a lower sensitivity to the treatment correlated with a higher malignant phenotype. Our results suggest that fIFNω lipofection could offer an alternative approach in veterinary oncology with equal or superior outcome and with less adverse effects than recombinant fIFNω therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Inertial effects on the stress generation of active fluids

    Science.gov (United States)

    Takatori, S. C.; Brady, J. F.

    2017-09-01

    Suspensions of self-propelled bodies generate a unique mechanical stress owing to their motility that impacts their large-scale collective behavior. For microswimmers suspended in a fluid with negligible particle inertia, we have shown that the virial swim stress is a useful quantity to understand the rheology and nonequilibrium behaviors of active soft matter systems. For larger self-propelled organisms such as fish, it is unclear how particle inertia impacts their stress generation and collective movement. Here we analyze the effects of finite particle inertia on the mechanical pressure (or stress) generated by a suspension of self-propelled bodies. We find that swimmers of all scales generate a unique swim stress and Reynolds stress that impact their collective motion. We discover that particle inertia plays a similar role as confinement in overdamped active Brownian systems, where the reduced run length of the swimmers decreases the swim stress and affects the phase behavior. Although the swim and Reynolds stresses vary individually with the magnitude of particle inertia, the sum of the two contributions is independent of particle inertia. This points to an important concept when computing stresses in computer simulations of nonequilibrium systems: The Reynolds and the virial stresses must both be calculated to obtain the overall stress generated by a system.

  1. Effects of ultrafine diesel exhaust particles on oxidative stress generation and dopamine metabolism in PC-12 cells.

    Science.gov (United States)

    Kim, Yong-Dae; Lantz-McPeak, Susan M; Ali, Syed F; Kleinman, Michael T; Choi, Young-Sook; Kim, Heon

    2014-05-01

    A major constituent of urban air pollution is diesel exhaust, a complex mixture of gases, chemicals, and particles. Recent evidence suggests that exposure to air pollution can increase the risk of a fatal stroke, cause cerebrovascular damage, and induce neuroinflammation and oxidative stress that may trigger neurodegenerative diseases, such as Parkinson's disease. The specific aim of this study was to determine whether ultrafine diesel exhaust particles (DEPs), the particle component of exhaust from diesel engines, can induce oxidative stress and effect dopamine metabolism in PC-12 cells. After 24 h exposure to DEPs of 200 nm or smaller, cell viability, ROS and nitric oxide (NO(2)) generation, and levels of dopamine (DA) and its metabolites, (dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)), were evaluated. Results indicated cell viability was not significantly changed by DEP exposure. However, ROS showed dramatic dose-dependent changes after DEP exposure (2.4 fold increase compared to control at 200 μg/mL). NO(2) levels were also dose-dependently increased after DEP exposure. Although not in a dose-dependent manner, upon DEP exposure, intracellular DA levels were increased while DOPAC and HVA levels decreased when compared to control. Results suggest that ultrafine DEPs lead to dopamine accumulation in the cytoplasm of PC-12 cells, possibly contributing to ROS formation. Further studies are warranted to elucidate this mechanism. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  2. The effectiveness of laser diode induction to Carica Papaya L. chlorophyll extract to be ROS generating in the photodynamic inactivation mechanisms for C.albicans biofilms

    International Nuclear Information System (INIS)

    Astuty, S Dewi; Baktir, A

    2017-01-01

    Research on the effectiveness of photo inactivation of C.albicans biofilms led by a-PDT system mediated by chlorophyll-diode-laser-induced was done. This research was done using in vitro technique in order to effectively determine chlorophyll extract of ROS-generated Carica Papaya L. using in situ technique. This technique induced laser diode on different dose and C. albicans with reduced degree. This research is a preliminary study in efforts to find anew sensitizer agent candidate made of chlorophyll extract and antifungal of Carica Papaya L. The effectiveness of eradication has been tested with MDA’s content and OD of biomass biofilms as well as analyzed using ANOVA and Tukey Test (α=0.05). The characteristic of chlorophyll extract of Carica Papaya L. has maximum absorptions on blue areas (λ max = 420 nm) and red areas (λ max = 670 nm). The MIC value of Carica Papaya L. ’s chlorophyll extract against C. albicans planktonic and biofilms cell is 63.8 μM and 31.9 μM respectively. The result shows that treatment using laser which was combined with chlorophyll extract is more effective than that with laser only or chlorophyll extract only. The treatment using laser combined with chlorophyll extract obtained more than 65% (α=0.05) (more than that of negative control) for P 2 L 1 group with OD 595 0.915. The MDA’s content showed that group of laser which was mediated with chlorophyll extract had larger values than group of laser or chlorophyll extract only. (paper)

  3. Interphase and intergranular stress generation in carbon steels

    International Nuclear Information System (INIS)

    Oliver, E.C.; Daymond, M.R.; Withers, P.J.

    2004-01-01

    Neutron diffraction spectra have been acquired during tensile straining of high and low carbon steels, in order to compare the evolution of internal stress in ferritic steel with and without a reinforcing phase. In low carbon steel, the generation of intergranular stresses predominates, while in high carbon steel similar intergranular stresses among ferrite grain families are superposed upon a large redistribution of stress between phases. Comparison is made to calculations using elastoplastic self-consistent and finite element methods

  4. Abrus agglutinin promotes irreparable DNA damage by triggering ROS generation followed by ATM-p73 mediated apoptosis in oral squamous cell carcinoma.

    Science.gov (United States)

    Sinha, Niharika; Panda, Prashanta K; Naik, Prajna P; Das, Durgesh N; Mukhopadhyay, Subhadip; Maiti, Tapas K; Shanmugam, Muthu K; Chinnathambi, Arunachalam; Zayed, M E; Alharbi, Sulaiman A; Sethi, Gautam; Agarwal, Rajesh; Bhutia, Sujit K

    2017-11-01

    Oral cancer, a type of head and neck cancer, is ranked as one of the top most malignancies in India. Herein, we evaluated the anticancer efficacy of Abrus agglutinin (AGG), a plant lectin, in oral squamous cell carcinoma. AGG selectively inhibited cell growth, and caused cell cycle arrest and mitochondrial apoptosis through a reactive oxygen species (ROS)-mediated ATM-p73 dependent pathway in FaDu cells. AGG-induced ROS accumulation was identified as the major mechanism regulating apoptosis, DNA damage and DNA-damage response, which were significantly reversed by ROS scavenger N-acetylcysteine (NAC). Moreover, AGG was found to interact with mitochondrial manganese-dependent superoxide dismutase that might inhibit its activity and increase ROS in FaDu cells. In oral cancer p53 is mutated, thus we focused on p73; AGG resulted in p73 upregulation and knock down of p73 caused a decrease in AGG-induced apoptosis. Interestingly, AGG-dependent p73 expression was found to be regulated by ROS, which was reversed by NAC treatment. A reduction in the level of p73 in AGG-treated shATM cells was found to be associated with a decreased apoptosis. Moreover, administration of AGG (50 μg/kg body weight) significantly inhibited the growth of FaDu xenografts in athymic nude mice. In immunohistochemical analysis, the xenografts from AGG-treated mice displayed a decrease in PCNA expression and an increase in caspase-3 activation as compared to the controls. In conclusion, we established a connection among ROS, ATM and p73 in AGG-induced apoptosis, which might be useful in enhancing the therapeutic targeting of p53 deficient oral squamous cell carcinoma. © 2017 Wiley Periodicals, Inc.

  5. Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2

    Energy Technology Data Exchange (ETDEWEB)

    Chiou, Shyh-Shin, E-mail: chiouss@kmu.edu.tw [Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan (China); Department of Pediatrics, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, 807 Kaohsiung 807, Taiwan (China); Wang, Sophie Sheng-Wen; Wu, Deng-Chyang [Department of Gastroenterology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan (China); Lin, Ying-Chu [School of Dentistry, College of Dentistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Kao, Li-Pin [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 807 Kaohsiung 807, Taiwan (China)

    2013-07-26

    We report here that the Jun dimerization protein 2 (JDP2) plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS). JDP2 associates with Nrf2 and MafK (Nrf2-MafK) to increase the transcription of antioxidant response element-dependent genes. Oxidative-stress-inducing reagent led to an increase in the intracellular accumulation of ROS and cell proliferation in Jdp2 knock-out mouse embryonic fibroblasts. In Jdp2-Cre mice mated with reporter mice, the expression of JDP2 was restricted to granule cells in the brain cerebellum. The induced pluripotent stem cells (iPSC)-like cells were generated from DAOY medulloblastoma cell by introduction of JDP2, and the defined factor OCT4. iPSC-like cells expressed stem cell-like characteristics including alkaline phosphatase activity and some stem cell markers. However, such iPSC-like cells also proliferated rapidly, became neoplastic, and potentiated cell malignancy at a later stage in SCID mice. This study suggests that medulloblastoma cells can be reprogrammed successfully by JDP2 and OCT4 to become iPSC-like cells. These cells will be helpful for studying the generation of cancer stem cells and ROS homeostasis.

  6. Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2

    Directory of Open Access Journals (Sweden)

    Naoto Yamaguchi

    2013-07-01

    Full Text Available We report here that the Jun dimerization protein 2 (JDP2 plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2 and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS. JDP2 associates with Nrf2 and MafK (Nrf2-MafK to increase the transcription of antioxidant response element-dependent genes. Oxidative-stress-inducing reagent led to an increase in the intracellular accumulation of ROS and cell proliferation in Jdp2 knock-out mouse embryonic fibroblasts. In Jdp2-Cre mice mated with reporter mice, the expression of JDP2 was restricted to granule cells in the brain cerebellum. The induced pluripotent stem cells (iPSC-like cells were generated from DAOY medulloblastoma cell by introduction of JDP2, and the defined factor OCT4. iPSC-like cells expressed stem cell-like characteristics including alkaline phosphatase activity and some stem cell markers. However, such iPSC-like cells also proliferated rapidly, became neoplastic, and potentiated cell malignancy at a later stage in SCID mice. This study suggests that medulloblastoma cells can be reprogrammed successfully by JDP2 and OCT4 to become iPSC-like cells. These cells will be helpful for studying the generation of cancer stem cells and ROS homeostasis.

  7. Negative life events and symptoms of depression and anxiety: stress causation and/or stress generation

    OpenAIRE

    Phillips, Anna C.; Carroll, Douglas; Der, Geoffrey

    2015-01-01

    Background and Objectives: Stressful life events are known to contribute to development of depression, however, it is possible this link is bi-directional. The present study examined whether such stress generation effects are greater than the effects of stressful life events on depression, and whether stress generation is also evident with anxiety. Design: Participants were two large age cohorts (N = 732 aged 44 years; N = 705 aged 63 years) from the West of Scotland Twenty-07 study. Methods:...

  8. Stress analysis of steam generator row-1 tubes

    International Nuclear Information System (INIS)

    Kim, Woo Gon; Ryu, Woo Seog; Lee, Ho Jin; Kim, Sung Chung

    2000-01-01

    Residual stresses induced in U-bending and tube-to-tubesheet joining processes of PWR's steam generator row-1 tube were measured by X-ray method and Hole-Drilling Method(HDM). The stresses resulting from the internal pressure and the temperature gradient in the steam generator were also estimated theoretically. In U-bent regions, the residual stresses at extrados were induced with compressive stress(-), and its maximum value reached -319 Mpa in axial direction at ψ=0 .deg. in position. Maximum tensile residual stress of 170 MPa was found to be at the flank side at position of ψ=90 deg., i.e., at apex region. In tube-to-tubesheet joining methods, the residual stresses induced by the explosive joint method were found to be lower than that by the mechanical roll method. The gradient of residual stress along the expanded tube was highest at the transition region, and the residual stress in circumferential direction was found to be higher than the residual stress in axial direction. Hoop stress due to an internal pressure between primary and secondary side was analyzed to be 76 MPa and thermal stress was 45 MPa

  9. Oxidatively generated DNA/RNA damage in psychological stress states

    DEFF Research Database (Denmark)

    Jørgensen, Anders

    2013-01-01

    age-related somatic disorders. The overall aim of the PhD project was to investigate the relation between psychopathology, psychological stress, stress hormone secretion and oxidatively generated DNA and RNA damage, as measured by the urinary excretion of markers of whole-body DNA/RNA oxidation (8...... between the 24 h urinary cortisol excretion and the excretion of 8-oxodG/8-oxoGuo, determined in the same samples. Collectively, the studies could not confirm an association between psychological stress and oxidative stress on nucleic acids. Systemic oxidatively generated DNA/RNA damage was increased......Both non-pathological psychological stress states and mental disorders are associated with molecular, cellular and epidemiological signs of accelerated aging. Oxidative stress on nucleic acids is a critical component of cellular and organismal aging, and a suggested pathogenic mechanism in several...

  10. 7-ketocholesterol induces apoptosis of MC3T3-E1 cells associated with reactive oxygen species generation, endoplasmic reticulum stress and caspase-3/7 dependent pathway

    Directory of Open Access Journals (Sweden)

    Yuta Sato

    2017-03-01

    Full Text Available Type 2 diabetes mellitus (T2DM is associated with an increased risk of bone fractures without reduction of bone mineral density. The cholesterol oxide 7-ketocholesterol (7KCHO has been implicated in numerous diseases such as atherosclerosis, Alzheimer's disease, Parkinson's disease, cancer, age-related macular degeneration and T2DM. In the present study, 7KCHO decreased the viability of MC3T3-E1 cells, increased reactive oxygen species (ROS production and apoptotic rate, and upregulated the caspase-3/7 pathway. Furthermore, these effects of 7KCHO were abolished by pre-incubation of the cells with N-acetylcysteine (NAC, an ROS inhibitor. Also, 7KCHO enhanced the mRNA expression of two endoplasmic reticulum (ER stress markers; CHOP and GRP78, in MC3T3-E1 cells. Pre-incubation of the cells with NAC suppressed the 7KCHO-induced upregulation of CHOP, but not GRP78. In conclusion, we demonstrated that 7KCHO induced apoptosis of MC3T3-E1 cells associated with ROS generation, ER stress, and caspase-3/7 activity, and the effects of 7KCHO were abolished by the ROS inhibitor NAC. These findings may provide new insight into the relationship between oxysterol and pathophysiology of osteoporosis seen in T2DM.

  11. Capilliposide Isolated from Lysimachia capillipes Hemsl. Induces ROS Generation, Cell Cycle Arrest, and Apoptosis in Human Nonsmall Cell Lung Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Zheng-hua Fei

    2014-01-01

    Full Text Available Several data has reported that capilliposide, extracted from a traditional Chinese medicine, Lysimachia capillipes Hemsl. (LC could exhibit inhibitory effect on cell proliferation in various cancers. The current study investigated the antitumor efficacy of Capilliposide and elucidated its potential molecular mechanism involved in vivo and vitro. Our results indicated that LC capilliposide inhibited proliferation of lung cancer cells in a dose-dependent manner. LC capilliposide induced cell cycle arrest at the S stage and enhanced apoptosis in NSCLC cells. Treatment with LC capilliposide increased the intracellular level of ROS, which activated the mitochondrial apoptotic pathway. Blockage of ROS by NAC highly reversed the effect of LC capilliposide on apoptosis. Xenograft tumor growth was significantly lower in the LC-treated group compared with the untreated control group (P<0.05. The results also show that LC treatment does not produce any overt signs of acute toxicity in vivo. These findings demonstrate that LC capilliposide could exert an anti-tumor effect on NSCLC through mitochondrial-mediated apoptotic pathway and the activation of ROS is involved.

  12. Evaluation of stresses generated in steel finger joint of bridge by X-ray stress measurement

    International Nuclear Information System (INIS)

    Kohri, Ami; Kawano, Yutaka; Nishido, Takayuki

    2017-01-01

    In a steel bridge, the evaluation of the stress generated in the finger joint without a gap to absorb temperature change can be an index when evaluating the remaining life. This study chose as the object the finger joint of a diagonal bridge, where the generated stress state is considered to be more complicated, prepared a finger joint test specimen that simulated an actual part, and performed a load test. For judgment, FEM analysis, non-destructive X-ray stress measurement, and measurement of the generated stress using strain gauge were applied. Compared with the FEM analysis results, the difference in the stress value was generated due to the difference in the contact state, but the trends of the stress distribution were equivalent. In addition, the same measurement value as the strain gauge was obtained, and the validity of the X-ray stress measurement method was confirmed. As a result, it was found that the stress measurement method by X-ray is effective for measuring the generated stress including the residual stress of the finger joint without gap at a bridge. (A.O.)

  13. The stress field and transient stress generation at shallow depths in the Canadian shield

    International Nuclear Information System (INIS)

    Hasegawa, H.S.

    1984-01-01

    A prominent feature of the stress field in eastern Canada is the high horizontal stress at shallow depths. Possible causative factors to this shallow stress field are remanent stresses from a previous tectonic orogeny, plate tectonic stresses and glacial-related stresses (glacial drag and flexual stress). The inherent difficulty in differentiating residual from current stress is one of the reasons why the relative contributions to the stress field from the phenomena described above are not properly understood. Maximum stress-strain changes an underground vault is likely to encounter from natural phenomena should occur when the periphery of the advancing or retreating glacier is near the vault. Theoretical calculations indicate that lithospheric flexure, differential postglacial uplift and possibly glacial drag may be able to generate significant horizontal stresses around a vault. In order to calculate the earthquake potential of these induced stress changes, the ambient tectonic stress field should also be included and a suitable failure criterion (e.g. Coulomb-Mohr) used. For earthquakes to generate appreciable stress-strain concentrations near a vault; the seismic signal must contain appreciable energy at appropriate frequencies (wavelengths comparable to vault dimensions) and be of appreciable duration; the particle velocity must be high (> 10 cm/s), induced strain is a function of particle velocity; and, the hypocentre must be less than half a fault length from the vault for residual deformation (strain and tilt) to be significant. The most severe case is when the causative fault intersects the vault

  14. Modelling of thermal stress in vapor generator supports

    International Nuclear Information System (INIS)

    Halpert, S.; Vazquez, L.

    1997-01-01

    To assure safety and availability of a nuclear power plant components or equipment stress analysis are done. When thermal loads are involved it's necessary to know the temperature field of the component or equipment. This paper describes the structural analysis of a steam generator lug with thermal load including the model used for computer simulation and presents the evolution of the temperature profile, the stress intensity and principal stress during start up and shut down of a nuclear power reactor. Temperature field obtained from code calculation show good agreement with the experimental data while stress analysis results are in agreement with a preview estimation. (author) [es

  15. The role of reactive oxygen species (ROS and cytochrome P-450 2E1 in the generation of carcinogenic etheno-DNA adducts

    Directory of Open Access Journals (Sweden)

    Kirsten Linhart

    2014-01-01

    Full Text Available Exocyclic etheno-DNA adducts are mutagenic and carcinogenic and are formed by the reaction of lipidperoxidation (LPO products such as 4-hydoxynonenal or malondialdehyde with DNA bases. LPO products are generated either via inflammation driven oxidative stress or via the induction of cytochrome P-450 2E1 (CYP2E1. In the liver CYP2E1 is induced by various compounds including free fatty acids, acetone and ethanol. Increased levels of CYP2E1 and thus, oxidative stress are observed in the liver of patients with non-alcoholic steatohepatitis (NASH as well as in the chronic alcoholic. In addition, chronic ethanol ingestion also increases CYP2E1 in the mucosa of the oesophagus and colon. In all these tissues CYP2E1 correlates significantly with the levels of carcinogenic etheno-DNA adducts. In contrast, in patients with non-alcoholic steatohepatitis (NASH hepatic etheno-DNA adducts do not correlate with CYP2E1 indicating that in NASH etheno-DNA adducts formation is predominately driven by inflammation rather than by CYP2E1 induction. Since etheno-DNA adducts are strong mutagens producing various types of base pair substitution mutations as well as other types of genetic damage, it is strongly believed that they are involved in ethanol mediated carcinogenesis primarily driven by the induction of CYP2E1.

  16. Stress generation by myosin minifilaments in actin bundles

    International Nuclear Information System (INIS)

    Dasanayake, Nilushi L; Carlsson, Anders E

    2013-01-01

    Forces and stresses generated by the action of myosin minifilaments are analyzed in idealized computer-generated actin bundles, and compared to results for isotropic actin networks. The bundles are generated as random collections of actin filaments in two dimensions with constrained orientations, crosslinked and attached to two fixed walls. Myosin minifilaments are placed on actin filament pairs and allowed to move and deform the network so that it exerts forces on the walls. The vast majority of simulation runs end with contractile minifilament stress, because minifilaments rotate into energetically stable contractile configurations. This process is aided by the bending and stretching of actin filaments, which accomodate minifilament rotation. Stresses for bundles are greater than those for isotropic networks, and antiparallel filaments generate more tension than parallel filaments. The forces transmitted by the actin network to the walls of the simulation cell often exceed the tension in the minifilament itself. (paper)

  17. Negative life events and symptoms of depression and anxiety: stress causation and/or stress generation.

    Science.gov (United States)

    Phillips, Anna C; Carroll, Douglas; Der, Geoff

    2015-01-01

    Stressful life events are known to contribute to development of depression; however, it is possible this link is bidirectional. The present study examined whether such stress generation effects are greater than the effects of stressful life events on depression, and whether stress generation is also evident with anxiety. Participants were two large age cohorts (N = 732 aged 44 years; N = 705 aged 63 years) from the West of Scotland Twenty-07 study. Stressful life events, depression, and anxiety symptoms were measured twice five years apart. Cross-lagged panel analysis examined the mutual influences of stressful life events on depression and on anxiety over time. Life events predicted later depressive symptomatology (p = .01), but the depression predicting life events relationship was less strong (p = .06), whereas earlier anxiety predicted life events five years later (p = .001). There was evidence of sex differences in the extent to which life events predicted later anxiety. This study provides evidence of stress causation for depression and weaker evidence for stress generation. In contrast, there was strong evidence of stress generation for anxiety but weaker evidence for stress causation, and that differed for men and women.

  18. Does the stress generation hypothesis apply to eating disorders?: an examination of stress generation in eating, depressive, and anxiety symptoms.

    Science.gov (United States)

    Bodell, Lindsay P; Hames, Jennifer L; Holm-Denoma, Jill M; Smith, April R; Gordon, Kathryn H; Joiner, Thomas E

    2012-12-15

    The stress generation hypothesis posits that individuals actively contribute to stress in their lives. Although stress generation has been studied frequently in the context of depression, few studies have examined whether this stress generation process is unique to depression or whether it occurs in other disorders. Although evidence suggests that stress contributes to the development of eating disorders, it is unclear whether eating disorders contribute to subsequent stress. A prospective design was used to examine the influence of eating disorder symptoms on negative life stressors. Two hundred and ninety female undergraduates completed questionnaires at two time points that examined eating disorder, depressive and anxiety symptoms and the presence of negative life events. Regression analyses found that while eating disorder symptoms (i.e. bulimic symptoms and drive for thinness) were independent, significant predictors of negative life events, they did not predict negative life events above and beyond symptoms of depression. Limitations include the use of self-report measures and a college-based sample, which may limit generalizability of the results. Findings suggest that if stress generation is present in individuals with symptoms of eating disorders, it is likely attributable to symptoms of depression. Thus, it may be important for clinicians to target depressive symptoms in order to reduce the frequency of negative life stressors among individuals with eating disorders. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. CysLT1 receptor-induced human airway smooth muscle cells proliferation requires ROS generation, EGF receptor transactivation and ERK1/2 phosphorylation

    Directory of Open Access Journals (Sweden)

    Capra Valérie

    2006-03-01

    Full Text Available Abstract Background Cysteine-containing leukotrienes (cysteinyl-LTs are pivotal inflammatory mediators that play important roles in the pathophysiology of asthma, allergic rhinitis, and other inflammatory conditions. In particular, cysteinyl-LTs exert a variety of effects with relevance to the aetiology of asthma such as smooth muscle contraction, eosinophil recruitment, increased microvascular permeability, enhanced mucus secretion and decreased mucus transport and, finally, airway smooth muscle cells (ASMC proliferation. We used human ASMC (HASMC to identify the signal transduction pathway(s of the leukotriene D4 (LTD4-induced DNA synthesis. Methods Proliferation of primary HASMC was measured by [3H]thymidine incorporation. Phosphorylation of EGF receptor (EGF-R and ERK1/2 was assessed with a polyclonal anti-EGF-R or anti-phosphoERKl/2 monoclonal antibody. A Ras pull-down assay kit was used to evaluate Ras activation. The production of reactive oxygen species (ROS was estimated by measuring dichlorodihydrofluorescein (DCF oxidation. Results We demonstrate that in HASMC LTD4-stimulated thymidine incorporation and potentiation of EGF-induced mitogenic signaling mostly depends upon EGF-R transactivation through the stimulation of CysLT1-R. Accordingly, we found that LTD4 stimulation was able to trigger the increase of Ras-GTP and, in turn, to activate ERK1/2. We show here that EGF-R transactivation was sensitive to pertussis toxin (PTX and phosphoinositide 3-kinase (PI3K inhibitors and that it occurred independently from Src activity, despite the observation of a strong impairment of LTD4-induced DNA synthesis following Src inhibition. More interestingly, CysLT1-R stimulation increased the production of ROS and N-acetylcysteine (NAC abolished LTD4-induced EGF-R phosphorylation and thymidine incorporation. Conclusion Collectively, our data demonstrate that in HASMC LTD4 stimulation of a Gi/o coupled CysLT1-R triggers the transactivation of the EGF

  20. SkiROS

    DEFF Research Database (Denmark)

    Rovida, Francesco; Schou, Casper; Andersen, Rasmus Skovgaard

    During the last decades, the methods for intuitive task level programming of robots have become a fundamental point of interest for industrial application. The paper in hand presents SkiROS (Skill-based Robot Operating System) a novel software architecture based on the skills paradigm. The skill ...... of a flexible, highly modular system for the development of cognitive robot tasks....

  1. ROS Installation and Commissioning

    CERN Multimedia

    Gorini, B

    The ATLAS Readout group (a sub-group of TDAQ) has now completed the installation and commissioning of all of the Readout System (ROS) units. Event data from ATLAS is initially handled by detector specific hardware and software, but following a Level 1 Accept the data passes from the detector specific Readout Drivers (RODs) to the ROS, the first stage of the central ATLAS DAQ. Within the final ATLAS TDAQ system the ROS stores the data and on request makes it available to the Level 2 Trigger (L2) processors and to the Event Builder (EB) as required. The ROS is implemented as a large number of PCs housing custom built cards (ROBINs) and running custom multi-threaded software. Each ROBIN card (shown below) contains buffer memories to store the data, plus a field programmable gate array ( FPGA ) and an embedded PowerPC processor for management of the memories and data requests, and is implemented as a 64-bit 66 MHz PCI card. Both the software and the ROBIN cards have been designed and developed by the Readout g...

  2. Laser-induced generation of pure tensile stresses

    International Nuclear Information System (INIS)

    Niemz, M.H.; Lin, C.P.; Pitsillides, C.; Cui, J.; Doukas, A.G.; Deutsch, T.F.

    1997-01-01

    While short compressive stresses can readily be produced by laser ablation, the generation of pure tensile stresses is more difficult. We demonstrate that a 90 degree prism made of polyethylene can serve to produce short and pure tensile stresses. A compressive wave is generated by ablating a thin layer of strongly absorbing ink on one surface of the prism with a Q-switched frequency-doubled Nd:YAG laser. The compressive wave driven into the prism is reflected as a tensile wave by the polyethylene-air interface at its long surface. The low acoustic impedance of polyethylene makes it ideal for coupling tensile stresses into liquids. In water, tensile stresses up to -200bars with a rise time of the order of 20 ns and a duration of 100 ns are achieved. The tensile strength of water is determined for pure tensile stresses lasting for 100 ns only. The technique has potential application in studying the initiation of cavitation in liquids and in comparing the effect of compressive and tensile stress transients on biological media. copyright 1997 American Institute of Physics

  3. Cardioprotection of CAPE-oNO2 against myocardial ischemia/reperfusion induced ROS generation via regulating the SIRT1/eNOS/NF-κB pathway in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Dejuan Li

    2018-05-01

    Full Text Available Caffeic acid phenethyl ester (CAPE could ameliorate myocardial ischemia/reperfusion injury (MIRI by various mechanisms, but there hadn’t been any reports on that CAPE could regulate silent information regulator 1 (SIRT1 and endothelial nitric oxide synthase (eNOS to exert cardioprotective effect. The present study aimed to investigate the cardioprotective potential of caffeic acid o-nitro phenethyl ester (CAPE-oNO2 on MIRI and the possible mechanism based on the positive control of CAPE. The SD rats were subjected to left coronary artery ischemia /reperfusion (IR and the H9c2 cell cultured in hypoxia/reoxygenation (HR to induce the MIRI model. Prior to the procedure, vehicle, CAPE or CAPE-oNO2 were treated in the absence or presence of a SIRT1 inhibitor nicotinamide (NAM and an eNOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME. In vivo, CAPE and CAPE-oNO2 conferred a cardioprotective effect as shown by reduced myocardial infarct size, cardiac marker enzymes and structural abnormalities. From immunohistochemical and sirius red staining, above two compounds ameliorated the TNF-α release and collagen deposition of IR rat hearts. They could agitate SIRT1 and eNOS expression, and consequently enhance NO release and suppress NF-κB signaling, to reduce the malondialdehyde content and cell necrosis. In vitro, they could inhibit HR-induced H9c2 cell apoptosis and ROS generation by activating SIRT1/eNOS pathway and inhabiting NF-κB expression. Emphatically, CAPE-oNO2 presented the stronger cardioprotection than CAPE both in vivo and in vitro. However, NAM and L-NAME eliminated the CAPE-oNO2-mediated cardioprotection by restraining SIRT1 and eNOS expression, respectively. It suggested that CAPE-oNO2 ameliorated MIRI by suppressing the oxidative stress, inflammatory response, fibrosis and necrocytosis via the SIRT1/eNOS/NF-κB pathway.

  4. The role of mitochondrial ROS in the aging brain.

    Science.gov (United States)

    Stefanatos, Rhoda; Sanz, Alberto

    2018-03-01

    The brain is the most complex human organ, consuming more energy than any other tissue in proportion to its size. It relies heavily on mitochondria to produce energy and is made up of mitotic and postmitotic cells that need to closely coordinate their metabolism to maintain essential bodily functions. During aging, damaged mitochondria that produce less ATP and more reactive oxygen species (ROS) accumulate. The current consensus is that ROS cause oxidative stress, damaging mitochondria and resulting in an energetic crisis that triggers neurodegenerative diseases and accelerates aging. However, in model organisms, increasing mitochondrial ROS (mtROS) in the brain extends lifespan, suggesting that ROS may participate in signaling that protects the brain. Here, we summarize the mechanisms by which mtROS are produced at the molecular level, how different brain cells and regions produce different amounts of mtROS, and how mtROS levels change during aging. Finally, we critically discuss the possible roles of ROS in aging as signaling molecules and damaging agents, addressing whether age-associated increases in mtROS are a cause or a consequence of aging. © 2017 Federation of European Biochemical Societies.

  5. The ROS Workshop

    CERN Multimedia

    Francis, D.

    The first week of February saw the taking place of the ReadOut Subsystem (ROS) workshop. The ROS is the subsystem of the Trigger, DAQ & DCS project which receives and buffers data from the detector ReadOut Drivers (RODs). On request it then provides a subset of this buffered data, the so-called Regions of Interest (RoI), to the Level 2 trigger. Using the subsequent Level 2 trigger decision, the ROS either removes the buffered event data from its buffers or sends the full event data to the Event Filter for further processing. The workshop took place over a four-day period at a location in the Jura. The average daily attendance was twenty people, which mainly represented the five main ATLAS institutes currently engaged in this Trigger, DAQ & DCS activity. The aim of the workshop was to bring to an end the current prototyping activities in this area and launch the next, final, phase of prototyping. This new phase of prototyping will build on the successful activities of the previous phase and will focus...

  6. The residual stress evaluation for expansion process of steam generator tubes

    International Nuclear Information System (INIS)

    King, C.-S.; Lee, S.-C.; Shim, D.-N.

    2004-01-01

    The reliability of a nuclear power plant is affected by the reliability of steam generator tube and the reliability of steam generator tube is affected by stress corrosion cracking(SCC). Many steam generator tubes were experiencing stress corrosion cracking and stress corrosion cracking is affected material characteristics, corrosive environments and added stresses. The added stresses have the manufacturing stresses and operating stresses, the manufacturing stresses include the residual stresses generating in the tube manufacture and tube expanding procedure. We will investigate for influence which affected to residual stresses with tube plastic deformation method and measurement region. (author)

  7. ROS-related redox regulation and signaling in plants.

    Science.gov (United States)

    Noctor, Graham; Reichheld, Jean-Philippe; Foyer, Christine H

    2017-07-18

    As sessile oxygenic organisms with a plastic developmental programme, plants are uniquely positioned to exploit reactive oxygen species (ROS) as powerful signals. Plants harbor numerous ROS-generating pathways, and these oxidants and related redox-active compounds have become tightly embedded into plant function and development during the course of evolution. One dominant view of ROS-removing systems sees them as beneficial antioxidants battling to keep damaging ROS below dangerous levels. However, it is now established that ROS are a necessary part of subcellular and intercellular communication in plants and that some of their signaling functions require ROS-metabolizing systems. For these reasons, it is suggested that "ROS processing systems" would be a more accurate term than "antioxidative systems" to describe cellular components that are most likely to interact with ROS and, in doing so, transmit oxidative signals. Within this framework, our update provides an overview of the complexity and compartmentation of ROS production and removal. We place particular emphasis on the importance of ROS-interacting systems such as the complex cellular thiol network in the redox regulation of phytohormone signaling pathways that are crucial for plant development and defense against external threats. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Androgen receptor requires JunD as a coactivator to switch on an oxidative stress generation pathway in prostate cancer cells.

    Science.gov (United States)

    Mehraein-Ghomi, Farideh; Basu, Hirak S; Church, Dawn R; Hoffmann, F Michael; Wilding, George

    2010-06-01

    Relatively high oxidative stress levels in the prostate are postulated to be a major factor for prostate carcinogenesis and prostate cancer (CaP) progression. We focused on elucidating metabolic pathways of oxidative stress generation in CaP cells. Previously, we showed that the transcription factor JunD is essential for androgen-induced reactive oxygen species (ROS) production in androgen-dependent human CaP cells. We also recently showed that androgen induces the first and regulatory enzyme spermidine/spermine N1-acetyltransferase (SSAT) in a polyamine catabolic pathway that produces copious amounts of metabolic ROS. Here, we present coimmunoprecipitation and Gaussia luciferase reconstitution assay data that show that JunD forms a complex with androgen-activated androgen receptor (AR) in situ. Our chromatin immunoprecipitation assay data show that JunD binds directly to a specific SSAT promoter sequence only in androgen-treated LNCaP cells. Using a vector containing a luciferase reporter gene connected to the SSAT promoter and a JunD-silenced LNCaP cell line, we show that JunD is essential for androgen-induced SSAT gene expression. The elucidation of JunD-AR complex inducing SSAT expression leading to polyamine oxidation establishes the mechanistic basis of androgen-induced ROS production in CaP cells and opens up a new prostate-specific target for CaP chemopreventive/chemotherapeutic drug development. Copyright 2010 AACR.

  9. Impact physiologique et pathologique du stress oxydant chez le cheval

    OpenAIRE

    De Moffarts, Brieuc; Kirschvink, Nathalie; Pincemail, Joël; Lekeux, Pierre

    2005-01-01

    Oxidative stress has become of increasing interest in research and in equine and human medicine. If the pro-oxidant burden overwhelms the endogenous antioxidant defence of the organism, the arising imbalance between pro- and antioxidants is defined as oxidative stress. Different pathways might increase the generation of reactive oxygen species ( ROS) and results in oxidative stress. In physiological conditions, like during moderated exercise, the balance between ROS production and antioxidant...

  10. Stress analysis of HTR-10 steam generator heat exchanging tubes

    International Nuclear Information System (INIS)

    Dong Jianling; Zhang Xiaohang; Yin Dejian; Fu Jiyang

    2001-01-01

    Steam Generator (SG) heat exchanging tubes of 10 MW High Temperature Gas Cooled Reactor (HTR-10) are protective screens between the primary loop of helium with radioactivity and the secondary loop of feeding water and steam without radioactivity. Water and steam will enter into the primary loop when rupture of the heat exchanging tubes occurs, which lead to increase of the primary loop pressure and discharge of radioactive materials. Therefore it is important to guarantee the integrity of the tubes. The tube structure is spiral tube with small bending radius, which make it impossible to test with volumetric in-service detection. For such kind of spiral tube, using LBB concept to guarantee the integrity of the tubes is an important option. The author conducts stress analysis and calculation of HTR-10 SG heat exchanging tubes using the FEM code of piping stress analysis, PIPESTRESS. The maximum stress and the dangerous positions are obtained

  11. Characterization of residual stresses generated during inhomogeneous plastic deformation

    DEFF Research Database (Denmark)

    Lorentzen, T.; Faurholdt, T.; Clausen, B.

    1998-01-01

    Residual stresses generated by macroscopic inhomogeneous plastic deformation are predicted by an explicit finite element (FE) technique. The numerical predictions are evaluated by characterizing the residual elastic strains by neutron diffraction using two different (hkl) reflections. Intergranular...... compare well and verify the capability of the numerical technique as well as the possibilities of experimental validation using neutron diffraction. The presented experimental and numerical approach will subsequently be utilized for the evaluation of more complicated plastic deformation processes...

  12. Free radicals, reactive oxygen species, oxidative stress and its classification.

    Science.gov (United States)

    Lushchak, Volodymyr I

    2014-12-05

    Reactive oxygen species (ROS) initially considered as only damaging agents in living organisms further were found to play positive roles also. This paper describes ROS homeostasis, principles of their investigation and technical approaches to investigate ROS-related processes. Especial attention is paid to complications related to experimental documentation of these processes, their diversity, spatiotemporal distribution, relationships with physiological state of the organisms. Imbalance between ROS generation and elimination in favor of the first with certain consequences for cell physiology has been called "oxidative stress". Although almost 30years passed since the first definition of oxidative stress was introduced by Helmut Sies, to date we have no accepted classification of oxidative stress. In order to fill up this gape here classification of oxidative stress based on its intensity is proposed. Due to that oxidative stress may be classified as basal oxidative stress (BOS), low intensity oxidative stress (LOS), intermediate intensity oxidative stress (IOS), and high intensity oxidative stress (HOS). Another classification of potential interest may differentiate three categories such as mild oxidative stress (MOS), temperate oxidative stress (TOS), and finally severe (strong) oxidative stress (SOS). Perspective directions of investigations in the field include development of sophisticated classification of oxidative stresses, accurate identification of cellular ROS targets and their arranged responses to ROS influence, real in situ functions and operation of so-called "antioxidants", intracellular spatiotemporal distribution and effects of ROS, deciphering of molecular mechanisms responsible for cellular response to ROS attacks, and ROS involvement in realization of normal cellular functions in cellular homeostasis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Pre-treatment of soybean plants with calcium stimulates ROS responses and mitigates infection by Sclerotinia sclerotiorum.

    Science.gov (United States)

    Arfaoui, Arbia; El Hadrami, Abdelbasset; Daayf, Fouad

    2018-01-01

    Considering the high incidence of white mold caused by Sclerotinia sclerotiorum in a variety of field crops and vegetables, different control strategies are needed to keep the disease under economical threshold. This study assessed the effect of foliar application of a calcium formulation on disease symptoms, oxalic acid production, and on the oxidative stress metabolism in soybean plants inoculated with each of two isolates of the pathogen that have contrasting aggressiveness (HA, highly-aggressive versus WA, weakly-aggressive). Changes in reactive oxygen species (ROS) levels in soybean plants inoculated with S. sclerotiorum isolates were assessed at 6, 24, 48 and 72 h post inoculation (hpi). Generation of ROS including hydrogen peroxide (H 2 O 2 ), anion superoxide (O 2 - ) and hydroxyl radical (OH) was evaluated. Inoculation with the WA isolate resulted in more ROS accumulation compared to the HA isolate. Pre-treatment with the calcium formulation restored ROS production in plants inoculated with the HA isolate. We also noted a marked decrease in oxalic acid content in the leaves inoculated with the HA isolate in presence of calcium, which coincided with an increase in plant ROS production. The expression patterns of genes involved in ROS detoxification in response to the calcium treatments and/or inoculation with S. Sclerotiorum isolates were monitored by RT-qPCR. All of the tested genes showed a higher expression in response to inoculation with the WA isolate. The expression of most genes tested peaked at 6 hpi, which preceded ROS accumulation in the soybean leaves. Overall, these data suggest that foliar application of calcium contributes to a decrease in oxalic acid production and disease, arguably via modulation of the ROS metabolism. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Stress corrosion cracking experience in steam generators at Bruce NGS

    International Nuclear Information System (INIS)

    King, P.J.; Gonzalez, F.; Brown, J.

    1993-01-01

    In late 1990 and through 1991, units 1 and 2 at the Bruce A Nuclear Generating Station (BNGS-A) experienced a number of steam generator tube leaks. Tube failures were identified by eddy current to be circumferential cracks at U-bend supports on the hot-leg side of the boilers. In late 1991, tubes were removed from these units for failure characterization. Two active failure modes were found: corrosion fatigue in both units 1 and 2 and stress corrosion cracking (SCC) in unit 2. In unit 2, lead was found in deposits, on tubes, and in cracks, and the cracking was mixed-mode: transgranular and intergranular. This convincingly indicated the involvement of lead in the stress corrosion cracking failures. A program of inspection and tube removals was carried out to investigate more fully the extent of the problem. This program found significant cracking only in lead-affected boilers in unit 2, and also revealed a limited extent of non-lead-related intergranular stress corrosion cracking in other boilers and units. Various aspects of the failures and tube examinations are presented in this paper. Included is discussion of the cracking morphology, measured crack size distributions, and chemical analysis of tube surfaces, crack faces, and deposits -- with particular emphasis on lead

  15. Numerical analysis of stress fields generated by quenching process

    Directory of Open Access Journals (Sweden)

    A. Bokota

    2011-04-01

    Full Text Available In work the presented numerical models of tool steel hardening processes take into account mechanical phenomena generated by thermalphenomena and phase transformations. In the model of mechanical phenomena, apart from thermal, plastic and structural strain, alsotransformations plasticity was taken into account. The stress and strain fields are obtained using the solution of the Finite Elements Method of the equilibrium equation in rate form. The thermophysical constants occurring in constitutive relation depend on temperature and phase composite. For determination of plastic strain the Huber-Misses condition with isotropic strengthening was applied whereas fordetermination of transformation plasticity a modified Leblond model was used. In order to evaluate the quality and usefulness of thepresented models a numerical analysis of stresses and strains associated hardening process of a fang lathe of cone shaped made of tool steel was carried out.

  16. Potential Use of Spin Traps to Control ROS in Antipollution Cosmetics—A Review

    Directory of Open Access Journals (Sweden)

    Prashant D. Sawant

    2018-01-01

    Full Text Available Pollution from air and sunlight has adverse effects on human health, particularly skin health. It creates oxidative stress, which results in skin diseases, including skin cancer and aging. Different types of antioxidants are used as preventative actives in skin-care products. However, they have some limitations as they also scavenge oxygen. Recently, spin traps are being explored to trap free radicals before these radicals generating more free radicals (cascading effect and not the oxygen molecules. However, not all spin traps can be used in the topical cosmetic skin-care products due to their toxicity and regulatory issues. The present review focuses on the different pathways of reactive oxygen species (ROS generation due to pollution and the potential use of spin traps in anti-pollution cosmetics to control ROS.

  17. The Candida albicans stress response gene Stomatin-Like Protein 3 is implicated in ROS-induced apoptotic-like death of yeast phase cells.

    Directory of Open Access Journals (Sweden)

    Karen A Conrad

    Full Text Available The ubiquitous presence of SPFH (Stomatin, Prohibitin, Flotillin, HflK/HflC proteins in all domains of life suggests that their function would be conserved. However, SPFH functions are diverse with organism-specific attributes. SPFH proteins play critical roles in physiological processes such as mechanosensation and respiration. Here, we characterize the stomatin ORF19.7296/SLP3 in the opportunistic human pathogen Candida albicans. Consistent with the localization of stomatin proteins, a Slp3p-Yfp fusion protein formed visible puncta along the plasma membrane. We also visualized Slp3p within the vacuolar lumen. Slp3p primary sequence analyses identified four putative S-palmitoylation sites, which may facilitate membrane localization and are conserved features of stomatins. Plasma membrane insertion sequences are present in mammalian and nematode SPFH proteins, but are absent in Slp3p. Strikingly, Slp3p was present in yeast cells, but was absent in hyphal cells, thus categorizing it as a yeast-phase specific protein. Slp3p membrane fluorescence significantly increased in response to cellular stress caused by plasma membrane, cell wall, oxidative, or osmotic perturbants, implicating SLP3 as a general stress-response gene. A slp3Δ/Δ homozygous null mutant had no detected phenotype when slp3Δ/Δ mutants were grown in the presence of a variety of stress agents. Also, we did not observe a defect in ion accumulation, filamentation, endocytosis, vacuolar structure and function, cell wall structure, or cytoskeletal structure. However, SLP3 over-expression triggered apoptotic-like death following prolonged exposure to oxidative stress or when cells were induced to form hyphae. Our findings reveal the cellular localization of Slp3p, and for the first time associate Slp3p function with the oxidative stress response.

  18. Soybean Salt Tolerance 1 (GmST1) Reduces ROS Production, Enhances ABA Sensitivity, and Abiotic Stress Tolerance in Arabidopsis thaliana.

    Science.gov (United States)

    Ren, Shuxin; Lyle, Chimera; Jiang, Guo-Liang; Penumala, Abhishek

    2016-01-01

    Abiotic stresses, including high soil salinity, significantly reduce crop production worldwide. Salt tolerance in plants is a complex trait and is regulated by multiple mechanisms. Understanding the mechanisms and dissecting the components on their regulatory pathways will provide new insights, leading to novel strategies for the improvement of salt tolerance in agricultural and economic crops of importance. Here we report that soybean salt tolerance 1, named GmST1, exhibited strong tolerance to salt stress in the Arabidopsis transgenic lines. The GmST1-overexpressed Arabidopsis also increased sensitivity to ABA and decreased production of reactive oxygen species under salt stress. In addition, GmST1 significantly improved drought tolerance in Arabidopsis transgenic lines. GmST1 belongs to a 3-prime part of Glyma.03g171600 gene in the current version of soybean genome sequence annotation. However, comparative reverse transcription-polymerase chain reaction analysis around Glyma.03g171600 genomic region confirmed that GmST1 might serve as an intact gene in soybean leaf tissues. Unlike Glyma.03g171600 which was not expressed in leaves, GmST1 was strongly induced by salt treatment in the leaf tissues. By promoter analysis, a TATA box was detected to be positioned close to GmST1 start codon and a putative ABRE and a DRE cis-acting elements were identified at about 1 kb upstream of GmST1 gene. The data also indicated that GmST1-transgenic lines survived under drought stress and showed a significantly lower water loss than non-transgenic lines. In summary, our results suggest that overexpression of GmST1 significantly improves Arabidopsis tolerance to both salt and drought stresses and the gene may be a potential candidate for genetic engineering of salt- and drought-tolerant crops.

  19. Particle-bound reactive oxygen species (PB-ROS) emissions and formation pathways in residential wood smoke under different combustion and aging conditions

    Science.gov (United States)

    Zhou, Jun; Zotter, Peter; Bruns, Emily A.; Stefenelli, Giulia; Bhattu, Deepika; Brown, Samuel; Bertrand, Amelie; Marchand, Nicolas; Lamkaddam, Houssni; Slowik, Jay G.; Prévôt, André S. H.; Baltensperger, Urs; Nussbaumer, Thomas; El-Haddad, Imad; Dommen, Josef

    2018-05-01

    Wood combustion emissions can induce oxidative stress in the human respiratory tract by reactive oxygen species (ROS) in the aerosol particles, which are emitted either directly or formed through oxidation in the atmosphere. To improve our understanding of the particle-bound ROS (PB-ROS) generation potential of wood combustion emissions, a suite of smog chamber (SC) and potential aerosol mass (PAM) chamber experiments were conducted under well-determined conditions for different combustion devices and technologies, different fuel types, operation methods, combustion regimes, combustion phases, and aging conditions. The PB-ROS content and the chemical properties of the aerosols were quantified by a novel ROS analyzer using the DCFH (2',7'-dichlorofluorescin) assay and a high-resolution time-of-flight aerosol mass spectrometer (HR-ToF-AMS). For all eight combustion devices tested, primary PB-ROS concentrations substantially increased upon aging. The level of primary and aged PB-ROS emission factors (EFROS) were dominated by the combustion device (within different combustion technologies) and to a greater extent by the combustion regimes: the variability within one device was much higher than the variability of EFROS from different devices. Aged EFROS under bad combustion conditions were ˜ 2-80 times higher than under optimum combustion conditions. EFROS from automatically operated combustion devices were on average 1 order of magnitude lower than those from manually operated devices, which indicates that automatic combustion devices operated at optimum conditions to achieve near-complete combustion should be employed to minimize PB-ROS emissions. The use of an electrostatic precipitator decreased the primary and aged ROS emissions by a factor of ˜ 1.5 which is however still within the burn-to-burn variability. The parameters controlling the PB-ROS formation in secondary organic aerosol were investigated by employing a regression model, including the fractions of

  20. Oxidative stress provokes distinct transcriptional responses in the stress-tolerant atr7 and stress-sensitive loh2 Arabidopsis thaliana mutants as revealed by multi-parallel quantitative real-time PCR analysis of ROS marker and antioxidant genes

    NARCIS (Netherlands)

    Mehterov, Nikolay; Balazadeh, Salma; Hille, Jacques; Toneva, Valentina; Mueller-Roeber, Bernd; Gechev, Tsanko

    2012-01-01

    The Arabidopsis thaliana atr7 mutant is tolerant to oxidative stress induced by paraquat (PQ) or the catalase inhibitor aminotriazole (AT), while its original background loh2 and wild-type plants are sensitive. Both, AT and PQ which stimulate the intracellular formation of H2O2 or superoxide anions,

  1. Acculturation-Related Stress and Mental Health Outcomes among Three Generations of Hispanic Adolescents

    Science.gov (United States)

    Cervantes, Richard C.; Padilla, Amado M.; Napper, Lucy E.; Goldbach, Jeremy T.

    2013-01-01

    Stress associated with acculturation and minority status among Hispanic youth is understudied. Using survey data from the Hispanic Stress Inventory-Adolescent Version (HSI-A), we examined psychosocial stress across eight domains including family economic stress and acculturation-gap stress in a national sample of three generations (first, second,…

  2. Learning ROS for robotics programming

    CERN Document Server

    Martinez, Aaron

    2013-01-01

    The book will take an easy-to-follow and engaging tutorial approach, providing a practical and comprehensive way to learn ROS.If you are a robotic enthusiast who wants to learn how to build and program your own robots in an easy-to-develop, maintainable and shareable way, ""Learning ROS for Robotics Programming"" is for you. In order to make the most of the book, you should have some C++ programming background, knowledge of GNU/Linux systems, and computer science in general. No previous background on ROS is required, since this book provides all the skills required. It is also advisable to hav

  3. Normal personality traits, rumination and stress generation among early adolescent girls

    OpenAIRE

    Stroud, Catherine B.; Sosoo, Effua E.; Wilson, Sylia

    2015-01-01

    This study examined associations between personality and stress generation. Expanding upon prior work, we examined (a) the role of Positive Emotionality (PE), Negative Emotionality (NE), and Constraint (CON), and their lower-order facets, as predictors of acute and chronic interpersonal stress generation; (b) whether personality moderated effects of rumination on stress generation; and (c) whether personality increased exposure to independent (uncontrollable) stress. These questions were exam...

  4. Optimal ROS Signaling Is Critical for Nuclear Reprogramming

    Directory of Open Access Journals (Sweden)

    Gang Zhou

    2016-05-01

    Full Text Available Efficient nuclear reprogramming of somatic cells to pluripotency requires activation of innate immunity. Because innate immune activation triggers reactive oxygen species (ROS signaling, we sought to determine whether there was a role of ROS signaling in nuclear reprogramming. We examined ROS production during the reprogramming of doxycycline (dox-inducible mouse embryonic fibroblasts (MEFs carrying the Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc [OSKM] into induced pluripotent stem cells (iPSCs. ROS generation was substantially increased with the onset of reprogramming. Depletion of ROS via antioxidants or Nox inhibitors substantially decreased reprogramming efficiency. Similarly, both knockdown and knockout of p22phox—a critical subunit of the Nox (1–4 complex—decreased reprogramming efficiency. However, excessive ROS generation using genetic and pharmacological approaches also impaired reprogramming. Overall, our data indicate that ROS signaling is activated early with nuclear reprogramming, and optimal levels of ROS signaling are essential to induce pluripotency.

  5. β-Elemene piperazine derivatives induce apoptosis in human leukemia cells through downregulation of c-FLIP and generation of ROS.

    Directory of Open Access Journals (Sweden)

    Zhiying Yu

    Full Text Available β-Elemene is an active component of the herb medicine Curcuma Wenyujin with reported antitumor activity. To improve its antitumor ability, five novel piperazine derivatives of β-elemene, 13-(3-methyl-1-piperazinyl-β-elemene (DX1, 13-(cis-3,5-dimethyl-1-piperazinyl-β-elemene (DX2, 13-(4-ethyl-1-piperazinyl-β-elemene (DX3, 13-(4-isopropyl-1-piperazinyl-β-elemene (DX4 and 13-piperazinyl-β-elemene (DX5, were synthesized. The antiproliferative and apoptotic effects of these derivatives were determined in human leukemia HL-60, NB4, K562 and HP100-1 cells. DX1, DX2 and DX5, which contain a secondary amino moiety, were more active in inhibiting cell growth and in inducing apoptosis than DX3 and DX4. The apoptosis induction ability of DX1 was associated with the generation of hydrogen peroxide (H(2O(2, a decrease of mitochondrial membrane potential (MMP, and the activation of caspase-8. Pretreatment with the antioxidants N-acetylcysteine and catalase completely blocked DX1-induced H(2O(2 production, but only partially its activation of caspase-8 and induction of apoptosis. HL-60 cells were more sensitive than its H(2O(2-resistant subclone HP100-1 cells to DX1-induced apoptosis. The activation of caspase-8 by these compounds was correlated with the decrease in the levels of cellular FLICE-inhibitory protein (c-FLIP. The proteasome inhibitor MG-132 augmented the decrease in c-FLIP levels and apoptosis induced by these derivatives. FADD- and caspase-8-deficient Jurkat subclones have a decreased response to DX1-induced apoptosis. Our data indicate that these novel β-elemene piperazine derivatives induce apoptosis through the decrease in c-FLIP levels and the production of H(2O(2 which leads to activation of both death receptor- and mitochondrial-mediated apoptotic pathways.

  6. Rap1 signaling is required for suppression of Ras-generated reactive oxygen species and protection against oxidative stress in T lymphocytes

    NARCIS (Netherlands)

    Remans, Philip H. J.; Gringhuis, Sonja I.; van Laar, Jacob M.; Sanders, Marjolein E.; Papendrecht-van der Voort, Ellen A. M.; Zwartkruis, Fried J. T.; Levarht, E. W. Nivine; Rosas, Marcela; Coffer, Paul J.; Breedveld, Ferdinand C.; Bos, Johannes L.; Tak, Paul P.; Verweij, Cornelis L.; Reedquist, Kris A.

    2004-01-01

    Transient production of reactive oxygen species (ROS) plays an important role in optimizing transcriptional and proliferative responses to TCR signaling in T lymphocytes. Conversely, chronic oxidative stress leads to decreased proliferative responses and enhanced transcription of inflammatory gene

  7. Stress relief treatment of Alloy 600 steam generator tubing

    International Nuclear Information System (INIS)

    Rooyen, D. van; Cragnolino, C.

    1994-01-01

    The intergranular stress corrosion cracking (IGSCC) of Alloy 600 tubing in the primary side of operating steam generators is the subject of this investigation. The objective of the program was to examine the feasibility of heat treatment to alleviate the IGSCC problem. In addition to this, tests were also performed to examine the IGSCC susceptibility of nuclear grade Alloy 600 tubing obtained from various sources. Examination of temperature-time combinations that may hold potential for improved IGSCC resistance of the transition regions of tubes expanded into tube sheet holes was done. The combinations fall in two categories. One is of short duration and relatively high temperature, where induction is the best method of heating because the treatment only lasts from some tens of seconds to a few minutes. The other is carried out in a lower temperature range and lasts for several hours. This latter combination of temperatures and times is considered for the so-called global heat treatment of entire tube sheet. To assess the effect of these treatments, reverse U-bend testing in high purity deaerated water containing an overpressure of hydrogen was employed and several heats of Alloy 600 were compared in tests at 365 degrees C, which is well above actual operating temperatures of steam generators, but provides an accelerated test procedure. Results of furnace heating in the range of 550-610 degrees C indicated improvement in IGSCC resistance, with best performance after a heat treatment at 610 degrees C for nine hours. In addition to stress relief, carbide precipitation can also occur, and their relative contributions to the improvement is discussed

  8. Upregulated ROS production induced by the proteasome inhibitor MG-132 on XBP1 gene expression and cell apoptosis in Tca-8113 cells.

    Science.gov (United States)

    Chen, Hai-ying; Ren, Xiao-yan; Wang, Wei-hua; Zhang, Ying-xin; Chen, Shuang-feng; Zhang, Bin; Wang, Le-xin

    2014-07-01

    Exposure of Tca-8113 cells to proteasome inhibitor carbobenzoxy-Leu-Leu-leucinal (MG-132) causing apoptosis is associated with endoplasmic reticulum (ER) stress. X-box-binding protein-1 (XBP1) is an important regulator of a subset of genes active during ER stress, which is related to cell survival and is required for tumor growth. The present study is to evaluate the effect of MG-132 on ROS production, XBP1 gene expression, tumor necrosis factor receptor-associated factor 2 (TRAF2), ASK1 and c-jun protein expression in tongue squamous cell carcinoma cell line Tca-8113 cells. ROS production was measured by reactive oxygen species assay. X-box binding protein-1 (XBP1) mRNA was analyzed by real-time-PCR, TRAF2, ASK1 and c-jun protein were investigated by western blot and immunocytochemistry respectively. The result indicated that ROS production, TRAF2, ASK1 and c-jun were elevated in MG-132 treated cells. Giving ROS scavenger N-acetyl-L-cysteine (NAC) largely prevented the effects of MG-132. Furthermore, treating with MG-132 lead to decreased XBP1 mRNA expression but could not completely block the expression of XBP1. Taken together, these findings provide the evidence that MG-132 induced ER stress lead to Tca-8113 cells apoptosis through ROS generation and TRAF2-ASK1-JNK signal pathway activation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. Normal personality traits, rumination and stress generation among early adolescent girls

    Science.gov (United States)

    Stroud, Catherine B.; Sosoo, Effua E.; Wilson, Sylia

    2017-01-01

    This study examined associations between personality and stress generation. Expanding upon prior work, we examined (a) the role of Positive Emotionality (PE), Negative Emotionality (NE), and Constraint (CON), and their lower-order facets, as predictors of acute and chronic interpersonal stress generation; (b) whether personality moderated effects of rumination on stress generation; and (c) whether personality increased exposure to independent (uncontrollable) stress. These questions were examined in a one-year study of 126 adolescent girls (M age = 12.39 years) using contextual stress interviews. NE predicted increases in acute and chronic interpersonal stress generation, but not independent stress. NE, CON and affiliative PE each moderated the effect of rumination on chronic interpersonal stress generation. These effects were driven by particular lower-order traits. PMID:28845067

  10. Stress generation and hierarchical fracturing in reactive systems

    Science.gov (United States)

    Jamtveit, B.; Iyer, K.; Royne, A.; Malthe-Sorenssen, A.; Mathiesen, J.; Feder, J.

    2007-12-01

    Hierarchical fracture patterns are the result of a slowly driven fracturing process that successively divides the rocks into smaller domains. In quasi-2D systems, such fracture patterns are characterized by four sided domains, and T-junctions where new fractures stop at right angles to pre-existing fractures. We describe fracturing of mm to dm thick enstatite layers in a dunite matrix from the Leka ophiolite complex in Norway. The fracturing process is driven by expansion of the dunite matrix during serpentinization. The cumulative distributions of fracture lengths show a scaling behavior that lies between a log - normal and power law (fractal) distribution. This is consistent with a simple fragmentation model in which domains are divided according to a 'top hat' distribution of new fracture positions within unfractured domains. Reaction-assisted hierarchical fracturing is also likely to be responsible for other (3-D) structures commonly observed in serpentinized ultramafic rocks, including the mesh-textures observed in individual olivine grains, and the high abundance of rectangular domains at a wide range of scales. Spectacular examples of 3-D hierarchical fracture patterns also form during the weathering of basaltic intrusions (dolerites). Incipient chemical weathering of dolerites in the Karoo Basin in South Africa occurs around water- filled fractures, originally produced by thermal contraction or by externally imposed stresses. This chemical weathering causes local expansion of the rock matrix and generates elastic stresses. On a mm to cm scale, these stresses lead to mechanical layer-by-layer spalling, producing the characteristic spheroidal weathering patterns. However, our field observations and computer simulations demonstrate that in confined environments, the spalling process alone is unable to relieve the elastic stresses. In such cases, chemical weathering drives a much larger scale hierarchical fracturing process in which fresh dolerite undergoes a

  11. Co-Rumination Exacerbates Stress Generation among Adolescents with Depressive Symptoms.

    Science.gov (United States)

    Rose, Amanda J; Glick, Gary C; Smith, Rhiannon L; Schwartz-Mette, Rebecca A; Borowski, Sarah K

    2017-07-01

    Through stress generation, individuals' own thoughts and behaviors can actually lead to increases in their experience of stress. Unfortunately, stress generation is especially common among individuals who are already suffering from elevated depressive symptoms. However, despite the acknowledgement that some individuals with depressive symptoms generate greater stress than others, few studies have identified specific factors that could exacerbate stress generation among individuals with depressive symptoms. The present study examines co-rumination as a factor that might exacerbate stress generation among adolescents with depressive symptoms using a short-term longitudinal design. Considering these processes among adolescents was critical given that many youth experience increases in depressive symptoms at this developmental stage and that co-rumination also becomes more common at adolescence. Participants were 628 adolescents (326 girls; 302 boys) who reported on their depressive symptoms, experiences of stress, and co-rumination with a best friend. Interpersonal stressors (peer and family stress) and non-interpersonal stressors (school and sports stress) were assessed. Consistent with past research, adolescents with depressive symptoms experienced greater interpersonal and non-interpersonal stress over time. Importantly, co-rumination interacted with both depressive symptoms and gender in predicting increases in peer stress. Depressive symptoms predicted the generation of peer stress only for girls who reported high levels of co-rumination with friends. Implications for protecting youth with depressive symptoms against stress generation are discussed.

  12. ROS dependent copper toxicity in Hydra-biochemical and molecular study.

    Science.gov (United States)

    Zeeshan, Mohammed; Murugadas, Anbazhagan; Ghaskadbi, Surendra; Rajendran, Ramasamy Babu; Akbarsha, Mohammad Abdulkader

    2016-01-01

    Copper, an essential microelement, is known to be toxic to aquatic life at concentrations higher than that could be tolerated. Copper-induced oxidative stress has been documented in vitro, yet the in vivo effects of metal-induced oxidative stress have not been extensively studied in the lower invertebrates. The objective of the present study has been to find the effect of ROS-mediated toxicity of environmentally relevant concentrations of copper at organismal and cellular levels in Hydra magnipapillata. Exposure to copper at sublethal concentrations (0.06 and 0.1mg/L) for 24 or 48h resulted in generation of significant levels of intracellular reactive oxygen species (ROS). We infer that the free radicals here originate predominantly at the lysosomes but partly at the mitochondria also as visualized by H2-DHCFDA staining. Quantitative real-time PCR of RNA extracted from copper-exposed polyps revealed dose-dependent up-regulation of all antioxidant response genes (CAT, SOD, GPx, GST, GR, G6PD). Concurrent increase of Hsp70 and FoxO genes suggests the ability of polyps to respond to stress, which at 48h was not the same as at 24h. Interestingly, the transcript levels of all genes were down-regulated at 48h as compared to 24h incubation period. Comet assay indicated copper as a powerful genotoxicant, and the DNA damage was dose- as well as duration-dependent. Western blotting of proteins (Bax, Bcl-2 and caspase-3) confirmed ROS-mediated mitochondrial cell death in copper-exposed animals. These changes correlated well with changes in morphology, regeneration and aspects of reproduction. Taken together, the results indicate increased production of intracellular ROS in Hydra on copper exposure. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Complex I and complex III inhibition specifically increase cytosolic hydrogen peroxide levels without inducing oxidative stress in HEK293 cells

    NARCIS (Netherlands)

    Forkink, M.; Basit, F.; Teixeira, J.; Swarts, H.G.; Koopman, W.J.H.; Willems, P.H.G.M.

    2015-01-01

    Inhibitor studies with isolated mitochondria demonstrated that complex I (CI) and III (CIII) of the electron transport chain (ETC) can act as relevant sources of mitochondrial reactive oxygen species (ROS). Here we studied ROS generation and oxidative stress induction during chronic (24h) inhibition

  14. The medial tibial stress syndrome score: Item generation for a new ...

    African Journals Online (AJOL)

    The medial tibial stress syndrome score: Item generation for a new patient reported outcome measure. ... instrument that evaluates injury severity and treatment effects for medial tibial stress syndrome (MTSS) patients. ... from 32 Countries:.

  15. Obesity and Age-Related Changes in Markers of Oxidative Stress and Inflammation Across Four Generations

    NARCIS (Netherlands)

    Hulsegge, Gerben; Herber-Gast, Gerrie-Cor M; Spijkerman, Annemieke M W; Picavet, H. Susan J; van der Schouw, Yvonne T; Bakker, Stephan J L; Gansevoort, Ron T; Dollé, Martijn E T; Smit, Henriette A; Monique Verschuren, W M

    OBJECTIVE: The prevalence of obesity increases with age and is higher in each younger generation (unfavorable generation shift). This may influence patterns of oxidative stress and inflammation. Age-related changes and generation shifts in markers of oxidative stress and inflammation were

  16. Obesity and Age-Related Changes in Markers of Oxidative Stress and Inflammation Across Four Generations

    NARCIS (Netherlands)

    Hulsegge, Gerben; Herber-Gast, Gerrie-Cor M; Spijkerman, Annemieke M W; Susan, H; Picavet, J; van der Schouw, Yvonne T; Bakker, Stephan J L; Gansevoort, Ron T; Dollé, Martijn E T; Smit, Henriette A; Monique Verschuren, W M

    ObjectiveThe prevalence of obesity increases with age and is higher in each younger generation (unfavorable generation shift). This may influence patterns of oxidative stress and inflammation. Age-related changes and generation shifts in markers of oxidative stress and inflammation were

  17. Vulnerability-specific stress generation: An examination of negative cognitive and interpersonal styles

    OpenAIRE

    Liu, Richard T.; Alloy, Lauren B.; Mastin, Becky M.; Choi, Jimmy Y.; Boland, Elaine M.; Jenkins, Abby L.

    2014-01-01

    Although there is substantial evidence documenting the stress generation effect in depression (i.e., the tendency for depression-prone individuals to experience higher rates of life stress to which they contribute), additional research is required to advance current understanding of the specific types of dependent stress (i.e., events influenced by characteristics and attendant behaviors of the individual) relevant to this effect. The present study tested an extension of the stress generation...

  18. Calcium and ROS: A mutual interplay

    Science.gov (United States)

    Görlach, Agnes; Bertram, Katharina; Hudecova, Sona; Krizanova, Olga

    2015-01-01

    Calcium is an important second messenger involved in intra- and extracellular signaling cascades and plays an essential role in cell life and death decisions. The Ca2+ signaling network works in many different ways to regulate cellular processes that function over a wide dynamic range due to the action of buffers, pumps and exchangers on the plasma membrane as well as in internal stores. Calcium signaling pathways interact with other cellular signaling systems such as reactive oxygen species (ROS). Although initially considered to be potentially detrimental byproducts of aerobic metabolism, it is now clear that ROS generated in sub-toxic levels by different intracellular systems act as signaling molecules involved in various cellular processes including growth and cell death. Increasing evidence suggests a mutual interplay between calcium and ROS signaling systems which seems to have important implications for fine tuning cellular signaling networks. However, dysfunction in either of the systems might affect the other system thus potentiating harmful effects which might contribute to the pathogenesis of various disorders. PMID:26296072

  19. A reaction-diffusion model of ROS-induced ROS release in a mitochondrial network.

    Directory of Open Access Journals (Sweden)

    Lufang Zhou

    2010-01-01

    Full Text Available Loss of mitochondrial function is a fundamental determinant of cell injury and death. In heart cells under metabolic stress, we have previously described how the abrupt collapse or oscillation of the mitochondrial energy state is synchronized across the mitochondrial network by local interactions dependent upon reactive oxygen species (ROS. Here, we develop a mathematical model of ROS-induced ROS release (RIRR based on reaction-diffusion (RD-RIRR in one- and two-dimensional mitochondrial networks. The nodes of the RD-RIRR network are comprised of models of individual mitochondria that include a mechanism of ROS-dependent oscillation based on the interplay between ROS production, transport, and scavenging; and incorporating the tricarboxylic acid (TCA cycle, oxidative phosphorylation, and Ca(2+ handling. Local mitochondrial interaction is mediated by superoxide (O2.- diffusion and the O2.(--dependent activation of an inner membrane anion channel (IMAC. In a 2D network composed of 500 mitochondria, model simulations reveal DeltaPsi(m depolarization waves similar to those observed when isolated guinea pig cardiomyocytes are subjected to a localized laser-flash or antioxidant depletion. The sensitivity of the propagation rate of the depolarization wave to O(2.- diffusion, production, and scavenging in the reaction-diffusion model is similar to that observed experimentally. In addition, we present novel experimental evidence, obtained in permeabilized cardiomyocytes, confirming that DeltaPsi(m depolarization is mediated specifically by O2.-. The present work demonstrates that the observed emergent macroscopic properties of the mitochondrial network can be reproduced in a reaction-diffusion model of RIRR. Moreover, the findings have uncovered a novel aspect of the synchronization mechanism, which is that clusters of mitochondria that are oscillating can entrain mitochondria that would otherwise display stable dynamics. The work identifies the

  20. Polymorphic ROS scavenging revealed by CCCP in a lizard

    Science.gov (United States)

    Olsson, Mats; Wilson, Mark; Isaksson, Caroline; Uller, Tobias

    2009-07-01

    Ingestion of antioxidants has been argued to scavenge circulating reactive molecules (e.g., free radicals), play a part in mate choice (by mediating access to this important resource), and perhaps increase life span. However, recent work has come to question these relationships. We have shown elsewhere in the polychromatic lizard, Ctenophorus pictus, that diet supplementation of carotenoids as antioxidants does not depress circulating natural reactive oxygen species (ROS) levels and leads to no corresponding improvement of color traits. However, a much stronger test would be to experimentally manipulate the ROS levels themselves and assess carotenoid-induced ROS depression. Here, we achieve this by using carbonyl cyanide 3-chlorophenylhydrazone, which elevates superoxide (SO) formation approximately threefold at 10 μM in this model system. We then look for depressing effects on ROS of the carotenoids in order to assess whether ‘super-production’ of SO makes carotenoid effects on elevated ROS levels detectable. The rationale for this treatment was that if not even such elevated levels of SO are reduced by carotenoid supplementation, the putative link carotenoids, ROS depression, and mate quality (in terms of antioxidant capacity) is highly questionable. We conclude that there is no significant effect of carotenoids on mean SO levels even at the induced ROS levels. However, our results showed a significant interaction effect between carotenoid treatment and male color, with red males having higher ROS levels than yellow males. We suggest that this may be because different pigments are differently involved in the generation of the integumental colors in the two morphs with concomitant effects on ROS depletion depending on carotenoid uptake or allocation to coloration and antioxidation.

  1. PO2 cycling reduces diaphragm fatigue by attenuating ROS formation.

    Science.gov (United States)

    Zuo, Li; Diaz, Philip T; Chien, Michael T; Roberts, William J; Kishek, Juliana; Best, Thomas M; Wagner, Peter D

    2014-01-01

    Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr) followed by a high oxygen level (550 Torr), can reduce intracellular reactive oxygen species (ROS) as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe) was used to monitor muscular ROS production in real time with confocal microscopy during a lower PO2 condition. In the control group with no PO2 cycling, intracellular ROS formation did not appear during the first 15 min of the low PO2 period. However, after 20 min of low PO2, ROS levels increased significantly by ∼30% compared to baseline, and this increase continued until the end of the 30 min low PO2 condition. Conversely, muscles treated with PO2 cycling showed a complete absence of enhanced fluorescence emission throughout the entire low PO2 period. Furthermore, PO2 cycling-treated diaphragm exhibited increased fatigue resistance during prolonged low PO2 period compared to control. Thus, our data suggest that PO2 cycling mitigates diaphragm fatigue during prolonged low PO2. Although the exact mechanism for this protection remains to be elucidated, it is likely that through limiting excessive ROS levels, PO2 cycling initiates ROS-related antioxidant defenses.

  2. PO2 cycling reduces diaphragm fatigue by attenuating ROS formation.

    Directory of Open Access Journals (Sweden)

    Li Zuo

    Full Text Available Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr followed by a high oxygen level (550 Torr, can reduce intracellular reactive oxygen species (ROS as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe was used to monitor muscular ROS production in real time with confocal microscopy during a lower PO2 condition. In the control group with no PO2 cycling, intracellular ROS formation did not appear during the first 15 min of the low PO2 period. However, after 20 min of low PO2, ROS levels increased significantly by ∼30% compared to baseline, and this increase continued until the end of the 30 min low PO2 condition. Conversely, muscles treated with PO2 cycling showed a complete absence of enhanced fluorescence emission throughout the entire low PO2 period. Furthermore, PO2 cycling-treated diaphragm exhibited increased fatigue resistance during prolonged low PO2 period compared to control. Thus, our data suggest that PO2 cycling mitigates diaphragm fatigue during prolonged low PO2. Although the exact mechanism for this protection remains to be elucidated, it is likely that through limiting excessive ROS levels, PO2 cycling initiates ROS-related antioxidant defenses.

  3. European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).

    Science.gov (United States)

    Egea, Javier; Fabregat, Isabel; Frapart, Yves M; Ghezzi, Pietro; Görlach, Agnes; Kietzmann, Thomas; Kubaichuk, Kateryna; Knaus, Ulla G; Lopez, Manuela G; Olaso-Gonzalez, Gloria; Petry, Andreas; Schulz, Rainer; Vina, Jose; Winyard, Paul; Abbas, Kahina; Ademowo, Opeyemi S; Afonso, Catarina B; Andreadou, Ioanna; Antelmann, Haike; Antunes, Fernando; Aslan, Mutay; Bachschmid, Markus M; Barbosa, Rui M; Belousov, Vsevolod; Berndt, Carsten; Bernlohr, David; Bertrán, Esther; Bindoli, Alberto; Bottari, Serge P; Brito, Paula M; Carrara, Guia; Casas, Ana I; Chatzi, Afroditi; Chondrogianni, Niki; Conrad, Marcus; Cooke, Marcus S; Costa, João G; Cuadrado, Antonio; My-Chan Dang, Pham; De Smet, Barbara; Debelec-Butuner, Bilge; Dias, Irundika H K; Dunn, Joe Dan; Edson, Amanda J; El Assar, Mariam; El-Benna, Jamel; Ferdinandy, Péter; Fernandes, Ana S; Fladmark, Kari E; Förstermann, Ulrich; Giniatullin, Rashid; Giricz, Zoltán; Görbe, Anikó; Griffiths, Helen; Hampl, Vaclav; Hanf, Alina; Herget, Jan; Hernansanz-Agustín, Pablo; Hillion, Melanie; Huang, Jingjing; Ilikay, Serap; Jansen-Dürr, Pidder; Jaquet, Vincent; Joles, Jaap A; Kalyanaraman, Balaraman; Kaminskyy, Danylo; Karbaschi, Mahsa; Kleanthous, Marina; Klotz, Lars-Oliver; Korac, Bato; Korkmaz, Kemal Sami; Koziel, Rafal; Kračun, Damir; Krause, Karl-Heinz; Křen, Vladimír; Krieg, Thomas; Laranjinha, João; Lazou, Antigone; Li, Huige; Martínez-Ruiz, Antonio; Matsui, Reiko; McBean, Gethin J; Meredith, Stuart P; Messens, Joris; Miguel, Verónica; Mikhed, Yuliya; Milisav, Irina; Milković, Lidija; Miranda-Vizuete, Antonio; Mojović, Miloš; Monsalve, María; Mouthuy, Pierre-Alexis; Mulvey, John; Münzel, Thomas; Muzykantov, Vladimir; Nguyen, Isabel T N; Oelze, Matthias; Oliveira, Nuno G; Palmeira, Carlos M; Papaevgeniou, Nikoletta; Pavićević, Aleksandra; Pedre, Brandán; Peyrot, Fabienne; Phylactides, Marios; Pircalabioru, Gratiela G; Pitt, Andrew R; Poulsen, Henrik E; Prieto, Ignacio; Rigobello, Maria Pia; Robledinos-Antón, Natalia; Rodríguez-Mañas, Leocadio; Rolo, Anabela P; Rousset, Francis; Ruskovska, Tatjana; Saraiva, Nuno; Sasson, Shlomo; Schröder, Katrin; Semen, Khrystyna; Seredenina, Tamara; Shakirzyanova, Anastasia; Smith, Geoffrey L; Soldati, Thierry; Sousa, Bebiana C; Spickett, Corinne M; Stancic, Ana; Stasia, Marie José; Steinbrenner, Holger; Stepanić, Višnja; Steven, Sebastian; Tokatlidis, Kostas; Tuncay, Erkan; Turan, Belma; Ursini, Fulvio; Vacek, Jan; Vajnerova, Olga; Valentová, Kateřina; Van Breusegem, Frank; Varisli, Lokman; Veal, Elizabeth A; Yalçın, A Suha; Yelisyeyeva, Olha; Žarković, Neven; Zatloukalová, Martina; Zielonka, Jacek; Touyz, Rhian M; Papapetropoulos, Andreas; Grune, Tilman; Lamas, Santiago; Schmidt, Harald H H W; Di Lisa, Fabio; Daiber, Andreas

    2017-10-01

    The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  4. European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS

    Directory of Open Access Journals (Sweden)

    Javier Egea

    2017-10-01

    Full Text Available The European Cooperation in Science and Technology (COST provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.

  5. β-Cell protection and antidiabetic activities of Crassocephalum crepidioides (Asteraceae) Benth. S. Moore extract against alloxan-induced oxidative stress via regulation of apoptosis and reactive oxygen species (ROS).

    Science.gov (United States)

    Bahar, Entaz; Akter, Kazi-Marjahan; Lee, Geum-Hwa; Lee, Hwa-Young; Rashid, Harun-Or; Choi, Min-Kyung; Bhattarai, Kashi Raj; Hossain, Mir Mohammad Monir; Ara, Joushan; Mazumder, Kishor; Raihan, Obayed; Chae, Han-Jung; Yoon, Hyonok

    2017-03-29

    Medicinal plants are becoming more popular in the treatment of various diseases because of the adverse effects of the current therapy, especially antioxidant plant components such as phenols and flavonoids have a protective role against oxidative stress-induced degenerative diseases like diabetes. Thus, the purpose of this study was to investigate β-cell protection and antidiabetic activities of Crassocephalum crepidioides (Asteraceae) Benth. S. Moore. The in-vitro study was conducted by the pancreatic β-cell culture and α-amylase inhibition technique which includes two methods, namely starch-iodine method and 3,5-dinitrosalicylic acid (DNSA) method. On the other hand, the in-vivo study was performed by oral glucose tolerance test (OGTT) method and alloxan-induced diabetes method by using Wistar albino rat. At the end pancreatic specimens were removed and processed for histopathological study. The plant extract showed significant (*p < 0.05, **p < 0.01) effect on hyperglycemia as compared to standard (Gliclazide) in OGTT. The plant extract showed efficient protection activity of pancreatic β-cell from cell death in INS-1 cell line by significantly reduced (*p < 0.05, **p < 0.01) the levels alloxan-induced apoptosis and intracellular reactive oxygen species (ROS) accumulation. In addition, the plant extract showed a significant (*p < 0.05, **p < 0.01) effect on hyperglycemia by increases in percent of β-cells present in each islet (45% - 60%) compared to the diabetic group. The result showed that C. crepidioides had β-cell protection and antidiabetic activities in pancreatic β-cell culture and Wistar albino rat.

  6. ROS (Robot Operating System) für Automotive

    OpenAIRE

    Bubeck, Alexander

    2014-01-01

    - Introduction into the Robot Operating System - Open Source in the automotive industries - Application of ROS in the automotive industry - ROS navigation - ROS with real time control - ROS in the embedded world - Outlook: ROS 2.0 - Summary

  7. Residual stresses generated in F-522 steel by different machining processes

    International Nuclear Information System (INIS)

    Gracia-Navas, V.; Ferreres, I.; Maranon, J. A.; Garcia-Rosales, C.; Gil-Sevillano, J.

    2005-01-01

    Machining operations induce plastic deformation and heat generation in the near surface area of the machined part, giving rise to residual stresses. Depending on their magnitude and sign, these stresses can be detrimental or beneficial to the service life of the part. The final stress state depends on the machining process applied, as well as on the machining parameters. Therefore, the establishment of adequate machining guidelines requires the measurement of the residual stresses generated both at the surface and inside the material. in this work, the residual stresses generated in F-522 steel by two hard turning (conventional and laser assisted) and two grinding (production and finishing) processes were measured by X-ray diffraction. Additionally, depth profiles of the volume fraction of retained austenite, microstructure and nano hardness were obtained in order to correlate those results with the residual stress state obtained for each machining process. It has been observed that turning generates tensile stresses in the surface while grinding causes compressive stresses. Below the surface grinding generates weak tensile or nearly null stresses whereas turning generates strong compressive stresses. These results show that the optimum mechanising process (disregarding economical considerations) implies the combination of turning plus elimination of a small thickness by final grinding. (Author) 19 refs

  8. Discrimination and Acculturative Stress among First-Generation Dominicans

    Science.gov (United States)

    Dawson, Beverly Araujo; Panchanadeswaran, Subadra

    2010-01-01

    The present study examined the relationship between discriminatory experiences and acculturative stress levels among a sample of 283 Dominican immigrants. Findings from a linear regression analysis revealed that experiences of daily racial discrimination and major racist events were significant predictors of acculturative stress after controlling…

  9. The Effect of Creep on the Residual Stresses Generated During Silicon Sheet Growth

    Science.gov (United States)

    Hutchinson, J. W.; Lambropoulos, J. C.

    1984-01-01

    The modeling of stresses generated during the growth of thin silicon sheets at high speeds is an important part of the EFG technique since the experimental measurement of the stresses is difficult and prohibitive. The residual stresses which arise in such a growth process lead to serious problems which make thin Si ribbons unsuitable for fabrication. The constitutive behavior is unrealistic because at high temperature (close to the melting point) Si exhibits considerable creep which significantly relaxes the residual stresses. The effect of creep on the residual stresses generated during the growth of Si sheets at high speeds was addressed and the basic qualitative effect of creep are reported.

  10. Oxidative Stress, Bone Marrow Failure, and Genome Instability in Hematopoietic Stem Cells

    Directory of Open Access Journals (Sweden)

    Christine Richardson

    2015-01-01

    Full Text Available Reactive oxygen species (ROS can be generated by defective endogenous reduction of oxygen by cellular enzymes or in the mitochondrial respiratory pathway, as well as by exogenous exposure to UV or environmental damaging agents. Regulation of intracellular ROS levels is critical since increases above normal concentrations lead to oxidative stress and DNA damage. A growing body of evidence indicates that the inability to regulate high levels of ROS leading to alteration of cellular homeostasis or defective repair of ROS-induced damage lies at the root of diseases characterized by both neurodegeneration and bone marrow failure as well as cancer. That these diseases may be reflective of the dynamic ability of cells to respond to ROS through developmental stages and aging lies in the similarities between phenotypes at the cellular level. This review summarizes work linking the ability to regulate intracellular ROS to the hematopoietic stem cell phenotype, aging, and disease.

  11. Drought-induced trans-generational tradeoff between stress tolerance and defence: consequences for range limits?

    OpenAIRE

    Alsdurf, Jacob D.; Ripley, Tayler J.; Matzner, Steven L.; Siemens, David H.

    2013-01-01

    Areas just across species range boundaries are often stressful, but even with ample genetic variation within and among range-margin populations, adaptation towards stress tolerance across range boundaries often does not occur. Adaptive trans-generational plasticity should allow organisms to circumvent these problems for temporary range expansion; however, range boundaries often persist. To investigate this dilemma, we drought stressed a parent generation of Boechera stricta (A.Gray) A. L?ve &...

  12. Stress analysis and fatigue life prediction for a U-bend steam generator tube

    International Nuclear Information System (INIS)

    Cheng Weili; Finnie, I.

    1996-01-01

    An analysis is carried out to determine the stresses in a steam generator tube that failed by fatigue. Using data available for the failed tube and for failures in two similar steam generators, the magnitudes of the alternating and mean stresses produced during operation are estimated. The cause for the early fatigue failure is shown to be the high mean stress caused by denting of the tube in the location where it passed through the tube sheet. (orig.)

  13. Internal stress distribution for generating closure domains in laser-irradiated Fe–3%Si(110) steels

    International Nuclear Information System (INIS)

    Iwata, Keiji; Imafuku, Muneyuki; Orihara, Hideto; Sakai, Yusuke; Ohya, Shin-Ichi; Suzuki, Tamaki; Shobu, Takahisa; Akita, Koichi; Ishiyama, Kazushi

    2015-01-01

    Internal stress distribution for generating closure domains occurring in laser-irradiated Fe–3%Si(110) steels was investigated using high-energy X-ray analysis and domain theory based on the variational principle. The measured triaxial stresses inside the specimen were compressive and the stress in the rolling direction became more dominant than stresses in the other directions. The calculations based on the variational principle of magnetic energy for closure domains showed that the measured triaxial stresses made the closure domains more stable than the basic domain without closure domains. The experimental and calculation results reveal that the laser-introduced internal stresses result in the occurrence of the closure domains

  14. A longitudinal examination of stress generation in depressive and anxiety disorders.

    Science.gov (United States)

    Uliaszek, Amanda A; Zinbarg, Richard E; Mineka, Susan; Craske, Michelle G; Griffith, James W; Sutton, Jonathan M; Epstein, Alyssa; Hammen, Constance

    2012-02-01

    The current study compared two competing theories of the stress generation model of depression (stress causation vs. stress continuation) using interview-based measures of episodic life stress, as well as interpersonal and noninterpersonal chronic life stress. We also expanded on past research by examining anxiety disorders as well as depressive disorders. In addition, we examined the role of neuroticism and extraversion in these relationships. Participants were 627 adolescents enrolled in a two-site, longitudinal study of risk factors for depressive and anxiety disorders. Baseline and follow-up assessments were approximately one year apart. Results supported the stress causation theory for episodic stress generation for anxiety disorders, with neuroticism partially accounting for this relationship. The stress causation theory was also supported for depression, but only for more moderate to severe stressors; neuroticism partially accounted for this relationship as well. Finally, we found evidence for interpersonal and noninterpersonal chronic life stress continuation in both depressive and anxiety disorders. The present findings have implications regarding the specificity of the stress generation model to depressive disorders, as well as variables involved in the stress generation process. PsycINFO Database Record (c) 2012 APA, all rights reserved.

  15. Contact Stress Generation on the UHMWPE Tibial Insert

    Directory of Open Access Journals (Sweden)

    S. Petrović Savić

    2014-12-01

    Full Text Available Total knee replacement (TKR is considered, during last years, as a very successful surgical technique for removing knee joint deformities and eliminating pain caused by cartilage damage. In literature, as primary causes for knee joint endoprothesis damage are cited complex movements which cause occurrences of complex stress conditions, sagital radius conformity, sliding, types of materials etc. Aim of this study is analysis of contact stresses that occur on tibial implant for 15°, 45° and 60° knee flexion and 50 kg, 75 kg, 100 kg and 125 kg weight. Knee joint prosthesis model and finite elements method (FEM analysis are done in software Catia V5. For this analysis we used ultra-high molecular weight polyethylene (UHMWPE for tibial implant material and AISI 316, AISI 317, AISI 321, 17-4PH, CoCrMo, Ti6Al4V and SAE A-286 for femoral component materials. Results show that area of maximal contact stress is identified in medial and lateral part of tibial implant. Von Mises stress values vary regarding of flexion degree and weight, but values are approximate for types of chosen materials. Contact stress location corresponds to damage that occur on tibial implant during exploitation.

  16. Thermal and stress analyses in thermoelectric generator with tapered and rectangular pin configurations

    International Nuclear Information System (INIS)

    Yilbas, Bekir Sami; Akhtar, S.S.; Sahin, A.Z.

    2016-01-01

    Thermal stress developed in thermoelectric generators is critical for long service applications. High temperature gradients, due to a large temperature difference across the junctions, causes excessive stress levels developed in the device pins and electrodes at the interfaces. In the present study, a thermoelectric generator with horizontal pin configuration is considered and thermal stress analysis in the device is presented. Ceramic wafer is considered to resemble the high temperature plate and copper electrodes are introduced at the pin junctions to reduce the electrical resistance between the pins and the high and low temperature junction plates during the operation. Finite element code is used to simulate temperature and stress fields in the thermoelectric generator. In the simulations, convection and radiation losses from the thermoelectric pins are considered and bismuth telluride pin material with and without tapering is incorporated. It is found that von Mises stress attains high values at the interface between the hot and cold junctions and the copper electrodes. Thermal stress developed in tapered pin configuration attains lower values than that of rectangular pin cross-section. - Highlights: • Different cold junction temperatures improves thermoelectric generator performance. • von Mises stress remains high across copper electrodes and hot junction ceramics. • von Mises stress reduces along pin length towards cold junction. • Pin tapering lowers stress levels in thermoelectric generator.

  17. Edaravone, an ROS Scavenger, Ameliorates Photoreceptor Cell Death after Experimental Retinal Detachment

    Science.gov (United States)

    Roh, Mi In; Murakami, Yusuke; Thanos, Aristomenis; Miller, Joan W.

    2011-01-01

    Purpose. To investigate whether edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, would be neuroprotective against photoreceptor cell death in a rat model of retinal detachment (RD). Methods. RD was induced in adult Brown Norway rats by subretinal injection of sodium hyaluronate. Edaravone (3, 5, or 10 mg/kg) or physiologic saline was administered intraperitoneally once a day until death on day 3 or 5. Oxidative stress in the retina was assessed by 4-hydroxynonenal staining or ELISA for protein carbonyl content. Photoreceptor death was assessed by TUNEL and measurement of the outer nuclear layer thickness. Western blot analysis and caspase activity assays were performed. Inflammatory cytokine secretion and inflammatory cell infiltration were evaluated by ELISA and immunostaining, respectively. Results. RD resulted in increased generation of ROS. Treatment with 5 mg/kg edaravone significantly reduced the ROS level, along with a decrease in TUNEL-positive cells in the photoreceptor layer. A caspase assay also confirmed decreased activation of caspase-3, -8, and -9 in RD treated with edaravone. The level of the antiapoptotic Bcl-2 was increased in detached retinas after edaravone treatment, whereas the levels of the stress-activated p-ERK1/2 were decreased. In addition, edaravone treatment resulted in a significant decrease in the levels of TNF-α, MCP-1, and macrophage infiltration. Conclusions. Oxidative stress plays an important role in photoreceptor cell death after RD. Edaravone treatment may aid in preventing photoreceptor cell death after RD by suppressing ROS-induced photoreceptor damage. PMID:21310909

  18. Modelling of stresses generated in steels by phase transformations

    International Nuclear Information System (INIS)

    Dudek, K.; Glowacki, M.; Pietrzyk, M.

    1999-01-01

    Numerical model describing stresses arising during phase transformations in steels products is presented. The full model consists of three components. The first component uses finite element solution of Fourier equation for an evaluation of the temperature field inside the sample. The second component predicts kinetics of phase transformation occurring during cooling of steel products. Coupling of these two components allows prediction of structure and properties of final products at room temperature. The third component uses elastic-plastic finite element model for prediction of stresses caused by non-uniform temperatures and by changes of volume during transformations. Typical results of simulations performed for cooling of rails after hot rolling are presented. (author)

  19. Menadione triggers cell death through ROS-dependent mechanisms involving PARP activation without requiring apoptosis.

    Science.gov (United States)

    Loor, Gabriel; Kondapalli, Jyothisri; Schriewer, Jacqueline M; Chandel, Navdeep S; Vanden Hoek, Terry L; Schumacker, Paul T

    2010-12-15

    Low levels of reactive oxygen species (ROS) can function as redox-active signaling messengers, whereas high levels of ROS induce cellular damage. Menadione generates ROS through redox cycling, and high concentrations trigger cell death. Previous work suggests that menadione triggers cytochrome c release from mitochondria, whereas other studies implicate the activation of the mitochondrial permeability transition pore as the mediator of cell death. We investigated menadione-induced cell death in genetically modified cells lacking specific death-associated proteins. In cardiomyocytes, oxidant stress was assessed using the redox sensor RoGFP, expressed in the cytosol or the mitochondrial matrix. Menadione elicited rapid oxidation in both compartments, whereas it decreased mitochondrial potential and triggered cytochrome c redistribution to the cytosol. Cell death was attenuated by N-acetylcysteine and exogenous glutathione or by overexpression of cytosolic or mitochondria-targeted catalase. By contrast, no protection was observed in cells overexpressing Cu,Zn-SOD or Mn-SOD. Overexpression of antiapoptotic Bcl-X(L) protected against staurosporine-induced cell death, but it failed to confer protection against menadione. Genetic deletion of Bax and Bak, cytochrome c, cyclophilin D, or caspase-9 conferred no protection against menadione-induced cell death. However, cells lacking PARP-1 showed a significant decrease in menadione-induced cell death. Thus, menadione induces cell death through the generation of oxidant stress in multiple subcellular compartments, yet cytochrome c, Bax/Bak, caspase-9, and cyclophilin D are dispensable for cell death in this model. These studies suggest that multiple redundant cell death pathways are activated by menadione, but that PARP plays an essential role in mediating each of them. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. A Molecular Web: Endoplasmic Reticulum Stress, Inflammation and Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Namrata eChaudhari

    2014-07-01

    Full Text Available Execution of fundamental cellular functions demands regulated protein folding homeostasis. Endoplasmic reticulum (ER is an active organelle existing to implement this function by folding and modifying secretory and membrane proteins. Loss of protein folding homeostasis is central to various diseases and budding evidences suggest ER stress as being a major contributor in the development or pathology of a diseased state besides other cellular stresses. The trigger for diseases may be diverse but, inflammation and/or ER stress may be basic mechanisms increasing the severity or complicating the condition of the disease. Chronic ER stress and activation of the unfolded protein response (UPR through endogenous or exogenous insults may result in impaired calcium and redox homeostasis, oxidative stress via protein overload thereby also influencing vital mitochondrial functions. Calcium released from the ER augments the production of mitochondrial Reactive Oxygen Species (ROS. Toxic accumulation of ROS within ER and mitochondria disturb fundamental organelle functions. Sustained ER stress is known to potentially elicit inflammatory responses via UPR pathways. Additionally, ROS generated through inflammation or mitochondrial dysfunction could accelerate ER malfunction. Dysfunctional UPR pathways has been associated with a wide range of diseases including several neurodegenerative diseases, stroke, metabolic disorders, cancer, inflammatory disease, diabetes mellitus, cardiovascular disease and others. In this review we have discussed the UPR signaling pathways, and networking between ER stress induced inflammatory pathways, oxidative stress and mitochondrial signaling events which further induce or exacerbate ER stress.

  1. The Synchronous Generators Rated Speed’s Influence on Electromagnetic Stresses and on Costs

    Directory of Open Access Journals (Sweden)

    Elisabeta Spunei

    2013-09-01

    Full Text Available During the design of synchronous generators is very important to establish the values of their electromagnetic stresses. The specific literature recommends that these stress values are to be chosen from the curves obtained during experimental design, where the independent values are the polar pitch and the number of pole pairs. The authors of this work propose a method of finding the dependency between the electromagnetic stress and the synchronous generator rated speed to rapidly estimate the stresses in a given interval of rated speed values.

  2. Etiologies of sperm oxidative stress

    Directory of Open Access Journals (Sweden)

    Parvin Sabeti

    2016-04-01

    Full Text Available Sperm is particularly susceptible to reactive oxygen species (ROS during critical phases of spermiogenesis. However, the level of seminal ROS is restricted by seminal antioxidants which have beneficial effects on sperm parameters and developmental potentials. Mitochondria and sperm plasma membrane are two major sites of ROS generation in sperm cells. Besides, leukocytes including polymer phonuclear (PMN leukocytes and macrophages produce broad category of molecules including oxygen free radicals, non-radical species and reactive nitrogen species. Physiological role of ROS increase the intracellular cAMP which then activate protein kinase in male reproductive system. This indicates that spermatozoa need small amounts of ROS to acquire the ability of nuclear maturation regulation and condensation to fertilize the oocyte. There is a long list of intrinsic and extrinsic factors which can induce oxidative stress to interact with lipids, proteins and DNA molecules. As a result, we have lipid peroxidation, DNA fragmentation, axonemal damage, denaturation of the enzymes, over generation of superoxide in the mitochondria, lower antioxidant activity and finally abnormal spermatogenesis. If oxidative stress is considered as one of the main cause of DNA damage in the germ cells, then there should be good reason for antioxidant therapy in these conditions

  3. Radiation oxidative stress in cancer induction and prevention

    International Nuclear Information System (INIS)

    Meher, Prabodha Kumar; Mishra, Kaushala Prasad

    2017-01-01

    Exposure of cells to ionizing radiation causes generation of intracellular reactive oxygen species (ROS) which are implicated in the mechanism of carcinogenesis. Molecular steps involved in the transformation of normal cells to cancer cells have been enigmatic but generally believed to arise from aberration in cellular redox homeostasis. In normal cell function, a delicate balance is maintained between ROS generated in the metabolic process and level of endogenous antioxidant defense. ROS are known to regulate various cellular functions, such as cell division, signal transduction, and apoptosis. Cells experience oxidative stress when excess production of ROS occurs inside a cell upon exposure to external stress or agents. This redox imbalance affects the cellular functions due to DNA strand breaks, chromosomal aberrations, gene mutations, alteration in signal transduction, and inhibition of apoptosis leading to induction of cancer and other diseases. Radiation-induced ROS are involved in initiation and promotion of carcinogenesis. Therefore, detoxification of ROS by exogenous antioxidants including dietary polyphenols offers an important strategy for cancer prevention. Recent research results have shown that resistance of cancer stem cells to therapies is linked to low level of ROS. Interestingly, in vitro and in vivo experiments have reported that radiotherapy- and chemotherapy-induced ROS in cytosol sensitize the tumor cells to death, resulting in tumor growth retardation. This review is an attempt to delineate mechanisms of ROS in carcinogenesis and prevention by dietary compounds. Natural polyphenols and dietary antioxidants hold potential to prevent cancer. Interventions in ROS-mediated signal alteration, apoptosis activation, and modulation of epigenetic processes may offer effective cancer prevention strategy. (author)

  4. Study of scratch-induced stress corrosion cracking for steam generator tubes and scratch control

    International Nuclear Information System (INIS)

    Meng, F.; Xu, X.; Liu, X.; Wang, J.

    2014-01-01

    This paper introduces field cases for scratch-induced stress corrosion cracking (SISCC) of steam generator tubes in PWR and current studies in laboratories. According to analysis result of broke tubes, scratches caused intergranular stress corrosion cracking (IGSCC) with outburst. The effect of microstructure for nickel-base alloys, residual stresses caused by scratching process and water chemistry on SISCC and possible mechanism of SISCC are discussed. The result shows that scratch-induced microstructure evolution contributes to SISCC significantly. The causes of scratches during steam generator tubing manufacturing and installation process are stated and improved reliability with scratch control is highlighted for steam generator tubes in newly built nuclear power plants. (author)

  5. Study of scratch-induced stress corrosion cracking for steam generator tubes and scratch control

    Energy Technology Data Exchange (ETDEWEB)

    Meng, F.; Xu, X.; Liu, X. [Shanghai Nuclear Engineering Research and Design Institute, Shanghai (China); Wang, J. [Chinese Academy of Sciences, Institute of Metal Research, Shenyang (China)

    2014-07-01

    This paper introduces field cases for scratch-induced stress corrosion cracking (SISCC) of steam generator tubes in PWR and current studies in laboratories. According to analysis result of broke tubes, scratches caused intergranular stress corrosion cracking (IGSCC) with outburst. The effect of microstructure for nickel-base alloys, residual stresses caused by scratching process and water chemistry on SISCC and possible mechanism of SISCC are discussed. The result shows that scratch-induced microstructure evolution contributes to SISCC significantly. The causes of scratches during steam generator tubing manufacturing and installation process are stated and improved reliability with scratch control is highlighted for steam generator tubes in newly built nuclear power plants. (author)

  6. Two Prospective Studies of Changes in Stress Generation across Depressive Episodes in Adolescents and Emerging Adults

    Science.gov (United States)

    Morris, Matthew C.; Kouros, Chrystyna D.; Hellman, Natalie; Rao, Uma; Garber, Judy

    2014-01-01

    The stress generation hypothesis was tested in two different longitudinal studies examining relations between weekly depression symptom ratings and stress levels in adolescents and emerging adults at varied risk for depression. Participants in Study 1 included 240 adolescents who differed with regard to their mother’s history of depressive disorders. Youth were assessed annually across 6 years (Grades 6 through 12). Consistent with the depression autonomy model, higher numbers of prior major depressive episodes (MDEs) were associated with weaker stress generation effects, such that higher levels of depressive symptoms predicted increases in levels of dependent stressors for adolescents with ≤ 2 prior MDEs, but depressive symptoms were not significantly related to dependent stress levels for youth with ≥ 3 prior MDEs. In Study 2, participants were 32 remitted-depressed and 36 never-depressed young adults who completed a psychosocial stress task to determine cortisol reactivity and were re-assessed for depression and stress approximately eight months later. Stress generation effects were moderated by cortisol responses to a laboratory psychosocial stressor, such that individuals with higher cortisol responses exhibited a pattern consistent with the depression autonomy model, whereas individuals with lower cortisol responses showed a pattern more consistent with the depression sensitization model. Finally, comparing across the two samples, stress generation effects were weaker for older participants and for those with more prior MDEs. The complex, multi-factorial relation between stress and depression is discussed. PMID:25422968

  7. Transient thermal stresses in an orthotropic finite rectangular plate due to arbitrary surface heat-generations

    International Nuclear Information System (INIS)

    Sugano, Y.

    1980-01-01

    The transient thermal stresses in an orthotropic finite rectangular plate due to arbitrary surface heat-generations on two edges are studied by means of the Airy stress function. The purposes of this paper are to present a method of determing the transient thermal stresses in an orthographic rectangular plate with four edges of distinct thermal boundary condition of the third kind which exactly satisfy the traction-free conditions of shear stress over all boundaries including four corners of the plate, and to consider the effects of the anisotropies of material properties and the convective heat transfer on the upper and lower surfaces on the thermal stress distribution. (orig.)

  8. Involvement of reactive oxygen species (ROS) in the induction of genetic instability by radiation

    International Nuclear Information System (INIS)

    Tominaga, Hideyuki; Kodama, Seiji; Suzuki, Keiji; Watanabe, Masami; Matsuda, Naoki

    2004-01-01

    Radiation generates reactive oxygen species (ROS) that interact with cellular molecules, including DNA, lipids, and proteins. To know how ROS contribute to the induction of genetic instability, we examined the effect of the anti-ROS condition, using both ascorbic acid phosphate (APM) treatment or a low oxygen condition, on the induction of delayed reproductive cell death and delayed chromosome aberrations. The primary surviving colonies of mouse m5S-derived cl. 2011-14 cells irradiated with 6 Gy of X-rays were replated and allowed to form secondary colonies. The anti-ROS treatments were applied to either preirradiation culture or postirradiation cultures for primary or secondary colony formation. Both anti-ROS conditions relieved X-ray-induced acute cell killing to a similar extent. These anti-ROS conditions also relieved genetic instability when those conditions were applied during primary colony formation. However, no effect was observed when the conditions were applied during preirradiation culture and secondary colony formation. We also demonstrated that the amounts of ROS in X-ray-irradiated cells rapidly increase and then decrease at 6 hr postirradiation, and the levels of ROS then gradually decrease to a baseline within 2 weeks. The APM treatment kept the ROS production at a lower level than an untreated control. These results suggest that the cause of genetic instability might be fixed by ROS during a 2-week postirradiation period. (author)

  9. Ancestral Exposure to Stress Generates New Behavioral Traits and a Functional Hemispheric Dominance Shift.

    Science.gov (United States)

    Ambeskovic, Mirela; Soltanpour, Nasrin; Falkenberg, Erin A; Zucchi, Fabiola C R; Kolb, Bryan; Metz, Gerlinde A S

    2017-03-01

    In a continuously stressful environment, the effects of recurrent prenatal stress (PS) accumulate across generations and generate new behavioral traits in the absence of genetic variation. Here, we investigated if PS or multigenerational PS across 4 generations differentially affect behavioral traits, laterality, and hemispheric dominance in male and female rats. Using skilled reaching and skilled walking tasks, 3 findings support the formation of new behavioral traits and shifted laterality by multigenerational stress. First, while PS in the F1 generation did not alter paw preference, multigenerational stress in the F4 generation shifted paw preference to favor left-handedness only in males. Second, multigenerational stress impaired skilled reaching and skilled walking movement abilities in males, while improving these abilities in females beyond the levels of controls. Third, the shift toward left-handedness in multigenerationally stressed males was accompanied by increased dendritic complexity and greater spine density in the right parietal cortex. Thus, cumulative multigenerational stress generates sexually dimorphic left-handedness and dominance shift toward the right hemisphere in males. These findings explain the origins of apparently heritable behavioral traits and handedness in the absence of DNA sequence variations while proposing epigenetic mechanisms. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Downregulation of the taurine transporter TauT during hypo-osmotic stress in NIH3T3 mouse fibroblasts

    DEFF Research Database (Denmark)

    Hansen, Daniel Bloch; Friis, Martin Barfred; Hoffmann, Else Kay

    2012-01-01

    The present work was initiated to investigate regulation of the taurine transporter TauT by reactive oxygen species (ROS) and the tonicity-responsive enhancer binding protein (TonEBP) in NIH3T3 mouse fibroblasts during acute and long-term (4 h) exposure to low-sodium/hypo-osmotic stress. Taurine...... are significantly increased following hyperosmotic exposure. Swelling-induced ROS production in NIH3T3 fibroblasts is generated by NOX4 and by increasing total ROS, by either exogenous application of H(2)O(2) or overexpressing NOX4, we demonstrate that TonEBP activity and taurine influx are regulated negatively...... by ROS under hypo-osmotic, low-sodium conditions, whereas the TauT mRNA level is unaffected. Acute exposure to ROS reduces taurine uptake as a result of modulated TauT transport kinetics. Thus, swelling-induced ROS production could account for the reduced taurine uptake under low...

  11. Stress identification in steam generator tubes from profile measurements

    International Nuclear Information System (INIS)

    Andrieux, S.; Voldoire, F.

    1993-01-01

    An identification method devoted to the determination of stresses in tubes, by means of profile measurements, provided by on site non-destructive evaluations, is presented here. From the only available data (the radial displacement w on the inner wall), the computation of the strains, and consequently the stresses in the elastoplastic range, is made within the framework of the shell theory. For this purpose, we need to determine the associated curvature w'': this step is an ill-posed problem, because of the lack of continuity with respect to the discrete data. This difficulty is overridden by means of an appropriate regularization procedure. The predictive ability of the method has been tested by comparison with direct simulations; we present an industrial application. (author)

  12. Ionized gas (plasma) delivery of reactive oxygen species (ROS) into artificial cells

    International Nuclear Information System (INIS)

    Hong, Sung-Ha; Jenkins, A Toby A; Szili, Endre J; Short, Robert D

    2014-01-01

    This study was designed to enhance our understanding of how reactive oxygen species (ROS), generated ex situ by ionized gas (plasma), can affect the regulation of signalling processes within cells. A model system, comprising of a suspension of phospholipid vesicles (cell mimics) encapsulating a ROS reporter, was developed to study the plasma delivery of ROS into cells. For the first time it was shown that plasma unequivocally delivers ROS into cells over a sustained period and without compromising cell membrane integrity. An important consideration in cell and biological assays is the presence of serum, which significantly reduced the transfer efficiency of ROS into the vesicles. These results are key to understanding how plasma treatments can be tailored for specific medical or biotechnology applications. Further, the phospholipid vesicle ROS reporter system may find use in other studies involving the application of free radicals in biology and medicine. (fast track communication)

  13. Ionized gas (plasma) delivery of reactive oxygen species (ROS) into artificial cells

    Science.gov (United States)

    Hong, Sung-Ha; Szili, Endre J.; Jenkins, A. Toby A.; Short, Robert D.

    2014-09-01

    This study was designed to enhance our understanding of how reactive oxygen species (ROS), generated ex situ by ionized gas (plasma), can affect the regulation of signalling processes within cells. A model system, comprising of a suspension of phospholipid vesicles (cell mimics) encapsulating a ROS reporter, was developed to study the plasma delivery of ROS into cells. For the first time it was shown that plasma unequivocally delivers ROS into cells over a sustained period and without compromising cell membrane integrity. An important consideration in cell and biological assays is the presence of serum, which significantly reduced the transfer efficiency of ROS into the vesicles. These results are key to understanding how plasma treatments can be tailored for specific medical or biotechnology applications. Further, the phospholipid vesicle ROS reporter system may find use in other studies involving the application of free radicals in biology and medicine.

  14. Vulnerability-specific stress generation: An examination of negative cognitive and interpersonal styles

    Science.gov (United States)

    Liu, Richard T.; Alloy, Lauren B.; Mastin, Becky M.; Choi, Jimmy Y.; Boland, Elaine M.; Jenkins, Abby L.

    2014-01-01

    Although there is substantial evidence documenting the stress generation effect in depression (i.e., the tendency for depression-prone individuals to experience higher rates of life stress to which they contribute), additional research is required to advance current understanding of the specific types of dependent stress (i.e., events influenced by characteristics and attendant behaviors of the individual) relevant to this effect. The present study tested an extension of the stress generation hypothesis, in which the content of dependent stress that is produced by depression-prone individuals is contingent upon, and matches, the nature of their particular vulnerabilities. This extension was tested within the context of two cognitive models (i.e., hopelessness theory [Abramson, Metalsky, & Alloy, 1989] and Cole’s [1990, 1991] competency-based model) and two interpersonal models (i.e., Swann’s [1987] self-verification theory and Coyne’s [1976] interpersonal theory) of depression. Overall, support was obtained for vulnerability-specific stress generation. Specifically, in analyses across vulnerability domains, evidence of stress-generation specificity was found for all domain-specific cognitive vulnerabilities except self-perceived social competence. The within-domain analyses for cognitive vulnerabilities produced more mixed results, but were largely supportive. Additionally, excessive reassurance-seeking was specifically predictive of dependent stress in the social domain, and moderated, but did not mediate, the relation between negative inferential styles overall and in the interpersonal domain and their corresponding generated stress. Finally, no evidence was found for a stress generation effect with negative feedback-seeking. PMID:24679143

  15. Crosstalk between Rac1-mediated actin regulation and ROS production.

    Science.gov (United States)

    Acevedo, Alejandro; González-Billault, Christian

    2018-02-20

    The small RhoGTPase Rac1 is implicated in a variety of events related to actin cytoskeleton rearrangement. Remarkably, another event that is completely different from those related to actin regulation has the same relevance; the Rac1-mediated production of reactive oxygen species (ROS) through NADPH oxidases (NOX). Each outcome involves different Rac1 downstream effectors; on one hand, events related to the actin cytoskeleton require Rac1 to bind to WAVEs proteins and PAKs that ultimately promote actin branching and turnover, on the other, NOX-derived ROS production demands active Rac1 to be bound to a cytosolic activator of NOX. How Rac1-mediated signaling ends up promoting actin-related events, NOX-derived ROS, or both is poorly understood. Rac1 regulators, including scaffold proteins, are known to exert tight control over its functions. Hence, evidence of Rac1 regulatory events leading to both actin remodeling and NOX-mediated ROS generation are discussed. Moreover, cellular functions linked to physiological and pathological conditions that exhibit crosstalk between Rac1 outcomes are analyzed, while plausible roles in neuronal functions (and dysfunctions) are highlighted. Together, discussed evidence shed light on cellular mechanisms which requires Rac1 to direct either actin- and/or ROS-related events, helping to understand crucial roles of Rac1 dual functionality. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Phenotypic effects of salt and heat stress over three generations in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Léonie Suter

    Full Text Available Current and predicted environmental change will force many organisms to adapt to novel conditions, especially sessile organisms such as plants. It is therefore important to better understand how plants react to environmental stress and to what extent genotypes differ in such responses. It has been proposed that adaptation to novel conditions could be facilitated by heritable epigenetic changes induced by environmental stress, independent of genetic variation. Here we assessed phenotypic effects of heat and salt stress within and across three generations using four highly inbred Arabidopsis thaliana genotypes (Col, Cvi, Ler and Sha. Salt stress generally decreased fitness, but genotypes were differently affected, suggesting that susceptibility of A. thaliana to salt stress varies among genotypes. Heat stress at an early rosette stage had less detrimental effects but accelerated flowering in three out of four accessions. Additionally, we found three different modes of transgenerational effects on phenotypes, all harboring the potential of being adaptive: heat stress in previous generations induced faster rosette growth in Sha, both under heat and control conditions, resembling a tracking response, while in Cvi, the phenotypic variance of several traits increased, resembling diversified bet-hedging. Salt stress experienced in earlier generations altered plant architecture of Sha under salt but not control conditions, similar to transgenerational phenotypic plasticity. However, transgenerational phenotypic effects depended on the type of stress as well as on genotype, suggesting that such effects may not be a general response leading to adaptation to novel environmental conditions in A. thaliana.

  17. Residual stresses associated with the hydraulic expansion of steam generator tubing into tubesheets

    International Nuclear Information System (INIS)

    Middlebrooks, W.B.; Harrod, D.L.; Gold, R.E.

    1993-01-01

    Various methods are being used to expand heat transfer tubes into the thick tubesheets of nuclear steam generators. The residual stresses in the as-expanded tubes and methods for reducing these stresses are important because of the role which residual stresses play in stress corrosion cracking and stress assisted corrosion of the tubing. Of the various expansion processes, the hydraulic expansion process is most amenable to analytical study. This paper presents results on the residual stresses and strains in hydraulically expanded tubes and the tubesheet as computed by two different finite element codes with three different finite element models and by a theoretical incremental analysis method. The calculations include a sensitivity analysis to assess the effects of the expansion variables and the effect of stress relief heat treatments. (orig.)

  18. Middleware Interoperability for Robotics: A ROS-YARP Framework

    Directory of Open Access Journals (Sweden)

    Plinio Moreno

    2016-10-01

    Full Text Available Middlewares are fundamental tools for progress in research and applications in robotics. They enable the integration of multiple heterogeneous sensing and actuation devices, as well as providing general purpose modules for key robotics functions (kinematics, navigation, planning. However, no existing middleware yet provides a complete set of functionalities for all robotics applications, and many robots may need to rely on more than one framework. This paper focuses on the interoperability between two of the most prevalent middleware in robotics: YARP and ROS. Interoperability between middlewares should ideally allow users to execute existing software without the necessity of: (i changing the existing code, and (ii writing hand-coded ``bridges'' for each use-case. We propose a framework enabling the communication between existing YARP modules and ROS nodes for robotics applications in an automated way. Our approach generates the ``bridging gap'' code from a configuration file, connecting YARP ports and ROS topics through code-generated YARP Bottles. %%The configuration file must describe: (i the sender entities, (ii the way to group and convert the information read from the sender, (iii the structure of the output message and (iv the receiving entity. Our choice for the many inputs to one output is the most common use-case in robotics applications, where examples include filtering, decision making and visualization. %We support YARP/ROS and ROS/YARP sender/receiver configurations, which are demonstrated in a humanoid on wheels robot that uses YARP for upper body motor control and visual perception, and ROS for mobile base control and navigation algorithms.

  19. The role and effect of residual stress on pore generation during anodization of aluminium thin films

    International Nuclear Information System (INIS)

    Liao, M.W.; Chung, C.K.

    2013-01-01

    Highlights: •Al films of varying residual stress were prepared by sputtering. •Variation of the residual stress in the Al films influences pore growth during anodization. •The change in average pore size with residual stress is fairly small. •Interaction of residual stress with oxide growth stress leads to change in structure. •Residual tensile stress increases the pore density of porous alumina. -- Abstract: The role and effect of residual stress on pore generation of anodized aluminium oxide (AAO) have been investigated into anodizing the various-residual-stresses aluminium films. The plane stresses were characterised by X-ray diffraction with sin 2 ψ method. The pore density roughly linearly increased with residual stress from 64.6 (−132.5 MPa) to 90.5 pores/μm 2 (135.9 MPa). However, the average pore size around 40 nm was not changed significantly except for the rougher film. The tensile residual stress lessened the compressive oxide growth stress to reduce AAO plastic deformation for higher pore density. The findings provide new foundations for realizing AAO films on silicon

  20. Thinking Across Generations: Unique Contributions of Maternal Early Life and Prenatal Stress to Infant Physiology.

    Science.gov (United States)

    Gray, Sarah A O; Jones, Christopher W; Theall, Katherine P; Glackin, Erin; Drury, Stacy S

    2017-11-01

    Respiratory sinus arrhythmia (RSA) is a parasympathetic-mediated biomarker of self-regulation linked to lifespan mental and physical health outcomes. Intergenerational impacts of mothers' exposure to prenatal stress have been demonstrated, but evidence for biological embedding of maternal preconception stress, including adverse childhood experiences (ACEs), on infant RSA is lacking. We examine the independent effects of maternal ACEs and prenatal stress on infant RSA, seeking to broaden the understanding of the earliest origins of mental and physical health risk. Mothers reported on ACEs and prenatal stress. RSA was recorded in a sample of 167 4-month-old infants (49% female and 51% male) during a dyadic stressor, the Still Face Paradigm. Independent contributions of maternal ACEs and prenatal stress to infant RSA were observed. High maternal ACEs were associated with lower RSA, whereas prenatal stress was associated with failure to recover following the stressor. Sex but not race differences were observed. Prenatal stress was associated with higher RSA among boys but lower RSA among girls. Infants' RSA is affected by mothers' life course experiences of stress, with ACEs predicting a lower set point and prenatal stress dampening recovery from stress. For prenatal stress but not ACEs, patterns vary across sex. Findings underscore that stress-reducing interventions for pregnant women or those considering pregnancy may lead to decreased physical and mental health risk across generations. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  1. Matrine pretreatment improves cardiac function in rats with diabetic cardiomyopathy via suppressing ROS/TLR-4 signaling pathway.

    Science.gov (United States)

    Liu, Zhong-wei; Wang, Jun-kui; Qiu, Chuan; Guan, Gong-chang; Liu, Xin-hong; Li, Shang-jian; Deng, Zheng-rong

    2015-03-01

    Matrine is an alkaloid from Sophora alopecuroides L, which has shown a variety of pharmacological activities and potential therapeutic value in cardiovascular diseases. In this study we examined the protective effects of matrine against diabetic cardiomyopathy (DCM) in rats. Male SD rats were injected with streptozotocin (STZ) to induce DCM. One group of DCM rats was pretreated with matrine (200 mg·kg(-1)·d(-1), po) for 10 consecutive days before STZ injection. Left ventricular function was evaluated using invasive hemodynamic examination, and myocardiac apoptosis was assessed. Primary rat myocytes were used for in vitro experiments. Intracellular ROS generation, MDA content and GPx activity were determined. Real-time PCR and Western blotting were performed to detect the expression of relevant mRNAs and proteins. DCM rats exhibited abnormally elevated non-fasting blood glucose levels at 4 weeks after STZ injection, and LV function impairment at 16 weeks. The cardiac tissues of DCM rats showed markedly increased apoptosis, excessive ROS production, and activation of TLR-4/MyD-88/caspase-8/caspase-3 signaling. Pretreatment with matrine significantly decreased non-fasting blood glucose levels and improved LV function in DCM rats, which were associated with reducing apoptosis and ROS production, and suppressing TLR-4/MyD-88/caspase-8/caspase-3 signaling in cardiac tissues. Incubation in a high-glucose medium induced oxidative stress and activation of TLR-4/MyD-88 signaling in cultured myocytes in vitro, which were significantly attenuated by pretreatment with N-acetylcysteine. Excessive ROS production in DCM activates the TLR-4/MyD-88 signaling, resulting in cardiomyocyte apoptosis, whereas pretreatment with matrine improves cardiac function via suppressing ROS/TLR-4 signaling pathway.

  2. Study of residual stresses generated in machining of AISI 4340 steel

    International Nuclear Information System (INIS)

    Reis, W.P. dos; Fonseca, M.P. Cindra; Serrao, L.F.; Chuvas, T.C.; Oliveira, L.C.

    2010-01-01

    Among the mechanical construction steels, AISI 4340 has good harden ability, while combining high strength with toughness and good fatigue strength, making it excellent for application in the metalworking industry, where it can work at different levels and types of requests. Residual stresses are generated in almost all processes of mechanical manufacturing. In this study, the residual stresses generated in different machining processes and heat treatment hardening of AISI 4340 were analyzed by X-ray diffraction, by the sen 2 ψ method, using Crκβ radiation and compared. All samples, except for turned and cut by EDM, presented compressive residual stresses in the surface with various magnitudes. (author)

  3. A discrete stress-strength interference model based on universal generating function

    International Nuclear Information System (INIS)

    An Zongwen; Huang Hongzhong; Liu Yu

    2008-01-01

    Continuous stress-strength interference (SSI) model regards stress and strength as continuous random variables with known probability density function. This, to some extent, results in a limitation of its application. In this paper, stress and strength are treated as discrete random variables, and a discrete SSI model is presented by using the universal generating function (UGF) method. Finally, case studies demonstrate the validity of the discrete model in a variety of circumstances, in which stress and strength can be represented by continuous random variables, discrete random variables, or two groups of experimental data

  4. Evaluation of the residual stress field in a steam generator end tube after hydraulic expansion

    International Nuclear Information System (INIS)

    Thiel, F.; Kang, S.; Chabrerie, J.

    1994-01-01

    This paper presents a finite element elastoplastic model of a nuclear steam generator end tube, used to evaluate the residual stress field existing after hydraulic expansion of the tube into the tubesheet of the heat exchanger. This model has been tested against an experimental hydraulic expansion, carried out on full scale end tubes. The operation was monitored thanks to strain gages localized on the outer surface of the tubes, subjected to elastoplastic deformations. After a presentation of the expansion test and the description of the numerical model, the authors compare the stress fields issues from the gages and from the model. The comparison shows a good agreement. These results allow them to calculate the stress field resulting from normal operating conditions, while taking into account a correct initial state of stress. Therefore the authors can improve the understanding of the behavior of a steam generator end tube, with respect to stress corrosion cracking and crack growth

  5. The Role of Reactive Oxygen Species (ROS in the Biological Activities of Metallic Nanoparticles

    Directory of Open Access Journals (Sweden)

    Ahmed Abdal Dayem

    2017-01-01

    Full Text Available Nanoparticles (NPs possess unique physical and chemical properties that make them appropriate for various applications. The structural alteration of metallic NPs leads to different biological functions, specifically resulting in different potentials for the generation of reactive oxygen species (ROS. The amount of ROS produced by metallic NPs correlates with particle size, shape, surface area, and chemistry. ROS possess multiple functions in cellular biology, with ROS generation a key factor in metallic NP-induced toxicity, as well as modulation of cellular signaling involved in cell death, proliferation, and differentiation. In this review, we briefly explained NP classes and their biomedical applications and describe the sources and roles of ROS in NP-related biological functions in vitro and in vivo. Furthermore, we also described the roles of metal NP-induced ROS generation in stem cell biology. Although the roles of ROS in metallic NP-related biological functions requires further investigation, modulation and characterization of metallic NP-induced ROS production are promising in the application of metallic NPs in the areas of regenerative medicine and medical devices.

  6. PO2 Cycling Reduces Diaphragm Fatigue by Attenuating ROS Formation

    OpenAIRE

    Zuo, Li; Diaz, Philip T.; Chien, Michael T.; Roberts, William J.; Kishek, Juliana; Best, Thomas M.; Wagner, Peter D.

    2014-01-01

    Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr) followed by a high oxygen level (550 Torr), can reduce intracellular reactive oxygen species (ROS) as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe) was used to monito...

  7. Robot operating system (ROS) the complete reference

    CERN Document Server

    The objective of this book is to provide the reader with a comprehensive coverage on the Robot Operating Systems (ROS) and latest related systems, which is currently considered as the main development framework for robotics applications. The book includes twenty-seven chapters organized into eight parts. Part 1 presents the basics and foundations of ROS. In Part 2, four chapters deal with navigation, motion and planning. Part 3 provides four examples of service and experimental robots. Part 4 deals with real-world deployment of applications. Part 5 presents signal-processing tools for perception and sensing. Part 6 provides software engineering methodologies to design complex software with ROS. Simulations frameworks are presented in Part 7. Finally, Part 8 presents advanced tools and frameworks for ROS including multi-master extension, network introspection, controllers and cognitive systems. This book will be a valuable companion for ROS users and developers to learn more ROS capabilities and features.   ...

  8. Class I review of LOFT steam generator stress and fatigue life analysis report

    International Nuclear Information System (INIS)

    Fors, R.M.; Silverman, S.

    1977-01-01

    Review of the LOFT steam generator stress and fatigue life analysis report is presented. Deficiencies were found which will require evaluation and in some areas reanalysis. The effects of these deficiencies upon the steam generator will include: to further reduce the allowable ΔP across the tubesheet for the abnormal design case of pressure on primary; and to reduce the allowable number of LOCE transients at some locations of the steam generator from the numbers listed in the stress report and to increase them at other locations

  9. Stress relief to prevent stress corrosion in the transition region of expanded Alloy 600 steam-generator tubing. Final report

    International Nuclear Information System (INIS)

    Woodward, J.; van Rooyen, D.

    1983-05-01

    The feasibility of preventing primary side roll transition cracking has been investigated, using induction heating to attain stress relief of expanded Ni-Cr-Fe Alloy 600 steam generator tubing. Work on rolled tubing and U-bends has shown that temperatures with which stress relief can be obtained range from 700 to 850 0 C, with lower temperatures in this range requiring longer times at temperature to provide the requisite reduction in residual stresses. No work has yet been done outside this range. Preliminary tests, using induction heating, have been carried out on a mock tube sheet assembly, designed to the dimensions of a typical steam generator, and have identified the type of heating/cooling cycle that would occur in the tube sheet during a stress relief operation. Preliminary results show that the times to reach the higher temperatures in the range observed to give stress relief, of the order of 850 0 C, can be as short as 8 seconds, and less with optimum coil design and power control

  10. Stress corrosion cracking susceptibility of steam generator tubing on secondary side in restricted flow areas

    International Nuclear Information System (INIS)

    Fulger, M.; Lucan, D.; Radulescu, M.; Velciu, L.

    2003-01-01

    Nuclear steam generator tubes operate in high temperature water and on the secondary side in restricted flow areas many nonvolatile impurities accidentally introduced into circuit tend to concentrate. The concentration process leads to the formation of highly aggressive alkaline or acid solutions in crevices, and these solutions can cause stress corrosion cracking (SCC) on stressed tube materials. Even though alloy 800 has shown to be highly resistant to general corrosion in high temperature water, it has been found that the steam generator tubes may crack during service from the primary and/or secondary side. Stress corrosion cracking is still a serious problem occurring on outside tubes in operating steam generators. The purpose of this study was to evaluate the environmental factors affecting the stress corrosion cracking of steam generators tubing. The main test method was the exposure for 1000 hours into static autoclaves of plastically stressed C-rings of Incoloy 800 in caustic solutions (10% NaOH) and acidic chloride solutions because such environments may sometimes form accidentally in crevices on secondary side of tubes. Because the kinetics of corrosion of metals is indicated by anodic polarization curves, in this study, some stressed specimens were anodically polarized in caustic solutions in electrochemical cell, and other in chloride acidic solutions. The results presented as micrographs, potentiokinetic curves, and electrochemical parameters have been compared to establish the SCC behavior of Incoloy 800 in such concentrated environments. (authors)

  11. Drought-induced trans-generational tradeoff between stress tolerance and defence: consequences for range limits?

    Science.gov (United States)

    Alsdurf, Jacob D; Ripley, Tayler J; Matzner, Steven L; Siemens, David H

    2013-01-01

    Areas just across species range boundaries are often stressful, but even with ample genetic variation within and among range-margin populations, adaptation towards stress tolerance across range boundaries often does not occur. Adaptive trans-generational plasticity should allow organisms to circumvent these problems for temporary range expansion; however, range boundaries often persist. To investigate this dilemma, we drought stressed a parent generation of Boechera stricta (A.Gray) A. Löve & D. Löve, a perennial wild relative of Arabidopsis, representing genetic variation within and among several low-elevation range margin populations. Boechera stricta is restricted to higher, moister elevations in temperate regions where generalist herbivores are often less common. Previous reports indicate a negative genetic correlation (genetic tradeoff) between chemical defence allocation and abiotic stress tolerance that may prevent the simultaneous evolution of defence and drought tolerance that would be needed for range expansion. In growth chamber experiments, the genetic tradeoff became undetectable among offspring sib-families whose parents had been drought treated, suggesting that the stress-induced trans-generational plasticity may circumvent the genetic tradeoff and thus enable range expansion. However, the trans-generational effects also included a conflict between plastic responses (environmental tradeoff); offspring whose parents were drought treated were more drought tolerant, but had lower levels of glucosinolate toxins that function in defence against generalist herbivores. We suggest that either the genetic or environmental tradeoff between defence allocation and stress tolerance has the potential to contribute to range limit development in upland mustards.

  12. Generation of sheared poloidal flows via Reynolds stress and transport barrier physics

    International Nuclear Information System (INIS)

    Hidalgo, C.; Pedrosa, M.A.; Sanchez, E.; Balbin, R.; Lopez-Fraguas, A.; Milligen, B. van; Silva, C.; Fernandes, H.; Varandas, C.A.F.; Riccardi, C.; Carrozza, R.; Fontanesi, M.; Carreras, B.A.; Garcia, L.

    2000-01-01

    A view of the latest experimental results and progress in the understanding of the role of poloidal flows driven by fluctuations via Reynolds stress is given. Reynolds stress shows a radial gradient close to the velocity shear layer location in tokamaks and stellarators, indicating that this mechanism may drive significant poloidal flows in the plasma boundary. Observation of the generation of ExB sheared flows via Reynolds stress at the ion Bernstein resonance layer has been noticed in toroidal magnetized plasmas. The experimental evidence of sheared ExB flows linked to the location of rational surfaces in stellarator plasmas might be interpreted in terms of Reynolds stress sheared driven flows. These results show that ExB sheared flows driven by fluctuations can play an important role in the generation of transport barriers. (author)

  13. Oxidative stress in cancer and fibrosis: Opportunity for therapeutic intervention with antioxidant compounds, enzymes, and nanoparticles

    Directory of Open Access Journals (Sweden)

    Jingga Morry

    2017-04-01

    Full Text Available Oxidative stress, mainly contributed by reactive oxygen species (ROS, has been implicated in pathogenesis of several diseases. We review two primary examples; fibrosis and cancer. In fibrosis, ROS promote activation and proliferation of fibroblasts and myofibroblasts, activating TGF-β pathway in an autocrine manner. In cancer, ROS account for its genomic instability, resistance to apoptosis, proliferation, and angiogenesis. Importantly, ROS trigger cancer cell invasion through invadopodia formation as well as extravasation into a distant metastasis site. Use of antioxidant supplements, enzymes, and inhibitors for ROS-generating NADPH oxidases (NOX is a logical therapeutic intervention for fibrosis and cancer. We review such attempts, progress, and challenges. Lastly, we review how nanoparticles with inherent antioxidant activity can also be a promising therapeutic option, considering their additional feature as a delivery platform for drugs, genes, and imaging agents.

  14. Transient thermal stresses in circular cylinder under intermittently sudden heat generation

    International Nuclear Information System (INIS)

    Sugano, Y.; Saito, K.; Takeuti, Y.

    1975-01-01

    The thermal stresses associated with the transient temperature distribution arising in a circular cylinder under intermittently changing sudden heat generation over a finite band and with heat loss to a surrounding medium on the remainder of the cylinder surface are exactly analysed. For the first time the temperature field in a circular cylinder under sudden heat generation over a finite band of the cylinder surface is determined by combined use of Fourier cosine, Laplace transforms in axial position and time, respectively. Secondly it is assumed that the temperature fields in a circular cylinder subjected to heat generation Qsub(i) (i=0, 1, 2, ...) independently over a finite band are given by T 0 (r,z,t), T 1 (r,z,t), T 2 (r,z,t),... respectively. Tsub(i)(r,z,t) indicates the temperature field before the i-th heat generation Qsub(i). The thermal stresses associated with the temperature field described above are analysed by using the Hoyle stress functions. Numerical calculations are carried out for the extensive case of the ratio of the heat-generating length to the diameter of cylinder. It is found that the time in which the maximum stresses occur on the cylinder surface does not depend on the heat-generating length-to-diameter ratio

  15. Hericium erinaceus Inhibits TNF-α-Induced Angiogenesis and ROS Generation through Suppression of MMP-9/NF-κB Signaling and Activation of Nrf2-Mediated Antioxidant Genes in Human EA.hy926 Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Hebron C. Chang

    2016-01-01

    Full Text Available Hericium erinaceus (HE is an edible mushroom that has been shown to exhibit anticancer and anti-inflammatory activities. We investigated the antiangiogenic and antioxidant potentials of ethanol extracts of HE in human endothelial (EA.hy926 cells upon tumor necrosis factor-α- (TNF-α- stimulation (10 ng/mL. The underlying molecular mechanisms behind the pharmacological efficacies were elucidated. We found that noncytotoxic concentrations of HE (50–200 μg/mL significantly inhibited TNF-α-induced migration/invasion and capillary-like tube formation of endothelial cells. HE treatment suppressed TNF-α-induced activity and/or overexpression of matrix metalloproteinase-9 (MMP-9 and intercellular adhesion molecule-1 (ICAM-1. Furthermore, HE downregulated TNF-α-induced nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB followed by suppression of I-κB (inhibitor-κB degradation. Data from fluorescence microscopy illustrated that increased intracellular ROS production upon TNF-α-stimulation was remarkably inhibited by HE pretreatment in a dose-dependent manner. Notably, HE triggered antioxidant gene expressions of heme oxygenase-1 (HO-1, γ-glutamylcysteine synthetase (γ-GCLC, and glutathione levels, which may contribute to inhibition of ROS. Increased antioxidant status was associated with upregulated nuclear translocation and transcriptional activation of NF-E2 related factor-2 (Nrf2 in HE treated cells. Our findings conclude that antiangiogenic and anti-inflammatory activities of H. erinaceus may contribute to its anticancer property through modulation of MMP-9/NF-κB and Nrf2-antioxidant signaling pathways.

  16. Hericium erinaceus Inhibits TNF-α-Induced Angiogenesis and ROS Generation through Suppression of MMP-9/NF-κB Signaling and Activation of Nrf2-Mediated Antioxidant Genes in Human EA.hy926 Endothelial Cells.

    Science.gov (United States)

    Chang, Hebron C; Yang, Hsin-Ling; Pan, Jih-Hao; Korivi, Mallikarjuna; Pan, Jian-You; Hsieh, Meng-Chang; Chao, Pei-Min; Huang, Pei-Jane; Tsai, Ching-Tsan; Hseu, You-Cheng

    2016-01-01

    Hericium erinaceus (HE) is an edible mushroom that has been shown to exhibit anticancer and anti-inflammatory activities. We investigated the antiangiogenic and antioxidant potentials of ethanol extracts of HE in human endothelial (EA.hy926) cells upon tumor necrosis factor-α- (TNF-α-) stimulation (10 ng/mL). The underlying molecular mechanisms behind the pharmacological efficacies were elucidated. We found that noncytotoxic concentrations of HE (50-200 μg/mL) significantly inhibited TNF-α-induced migration/invasion and capillary-like tube formation of endothelial cells. HE treatment suppressed TNF-α-induced activity and/or overexpression of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). Furthermore, HE downregulated TNF-α-induced nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB) followed by suppression of I-κB (inhibitor-κB) degradation. Data from fluorescence microscopy illustrated that increased intracellular ROS production upon TNF-α-stimulation was remarkably inhibited by HE pretreatment in a dose-dependent manner. Notably, HE triggered antioxidant gene expressions of heme oxygenase-1 (HO-1), γ-glutamylcysteine synthetase (γ-GCLC), and glutathione levels, which may contribute to inhibition of ROS. Increased antioxidant status was associated with upregulated nuclear translocation and transcriptional activation of NF-E2 related factor-2 (Nrf2) in HE treated cells. Our findings conclude that antiangiogenic and anti-inflammatory activities of H. erinaceus may contribute to its anticancer property through modulation of MMP-9/NF-κB and Nrf2-antioxidant signaling pathways.

  17. On methods for the detection of reactive oxygen species generation by human spermatozoa: analysis of the cellular responses to catechol oestrogen, lipid aldehyde, menadione and arachidonic acid.

    Science.gov (United States)

    Aitken, R J; Smith, T B; Lord, T; Kuczera, L; Koppers, A J; Naumovski, N; Connaughton, H; Baker, M A; De Iuliis, G N

    2013-03-01

    Oxidative stress is known to have a major impact on human sperm function and, as a result, there is a need to develop sensitive methods for measuring reactive oxygen species (ROS) generation by these cells. A variety of techniques have been developed for this purpose including chemiluminescence (luminol and lucigenin), flow cytometry (MitoSOX Red, dihydroethidium, 4,5-diaminofluorescein diacetate and 2',7'-dichlorodihydrofluorescein diacetate) and spectrophotometry (nitroblue tetrazolium). The relative sensitivity of these assays and their comparative ability to detect ROS generated in different subcellular compartments of human spermatozoa, have not previously been investigated. To address this issue, we have compared the performance of these assays when ROS generation was triggered with a variety of reagents including 2-hydroxyestradiol, menadione, 4-hydroxynonenal and arachidonic acid. The results revealed that menadione predominantly induced release of ROS into the extracellular space where these metabolites could be readily detected by luminol-peroxidase and, to a lesser extent, 2',7'-dichlorodihydrofluorescein. However, such sensitivity to extracellular ROS meant that these assays were particularly vulnerable to interference by leucocytes. The remaining reagents predominantly elicited ROS generation by the sperm mitochondria and could be optimally detected by MitoSOX Red and DHE. Examination of spontaneous ROS generation by defective human spermatozoa revealed that MitoSOX Red was the most effective indicator of oxidative stress, thereby emphasizing the general importance of mitochondrial dysregulation in the aetiology of defective sperm function. © 2013 American Society of Andrology and European Academy of Andrology.

  18. Optimizing the Universal Robots ROS driver

    DEFF Research Database (Denmark)

    Andersen, Thomas Timm

    improvement both in terms of faster reaction as well as making it possible to control the robot using either ros_control or ordinary joint speed commands, which is required for many types of sensory based control like visual servoing. The developed driver is compared to the drivers already existing in the ROS...

  19. Heat priming induces trans-generational tolerance to high temperature stress in wheat

    Directory of Open Access Journals (Sweden)

    Xiao eWang

    2016-04-01

    Full Text Available Wheat plants are very sensitive to high temperature stress during grain filling. Effects of heat priming applied to the first generation on tolerance of the successive generation to post-anthesis high temperature stress were investigated. Compared with the progeny of non-heat primed plants (NH, the progeny of heat-primed plants (PH possessed higher grain yield, leaf photosynthesis and activities of antioxidant enzymes and lower cell membrane damage under high temperature stress. In the transcriptome profile, 1430 probes showed obvious difference in expression between PH and NH. These genes were related to signal transduction, transcription, energy, defense, and protein destination and storage, respectively. The gene encoding the lysine-specific histone demethylase 1 (LSD1 which was involved in histone demethylation related to epigenetic modification was up-regulated in the PH compared with NH. The proteome analysis indicated that the proteins involved in photosynthesis, energy production and protein destination and storage were up-regulated in the PH compared with NH. In short, thermos-tolerance was induced through heritable epigenetic alternation and signaling transduction, both processes further triggered prompt modifications of defense related responses in anti-oxidation, transcription, energy production, and protein destination and storage in the progeny of the primed plants under high temperature stress. It was concluded that trans-generation thermo-tolerance was induced by heat priming in the first generation, and this might be an effective measure to cope with severe high-temperature stresses during key growth stages in wheat production.

  20. Numerical simulations on the temperature gradient and thermal stress of a thermoelectric power generator

    International Nuclear Information System (INIS)

    Wu, Yongjia; Ming, Tingzhen; Li, Xiaohua; Pan, Tao; Peng, Keyuan; Luo, Xiaobing

    2014-01-01

    Highlights: • An appropriate ceramic plate thickness is effective in alleviating the thermal stress. • A smaller distance between thermo-pins can help prolong lifecycle of the TE module. • Either a thicker or a thinner copper conducting strip effectively reduces thermal stress. • A suitable tin soldering thickness will alleviate thermal stress intensity and increase thermal efficiency. - Abstract: Thermoelectric generator is a device taking advantage of the temperature difference in thermoelectric material to generate electric power, where the higher the temperature difference of the hot-cold ends, the higher the efficiency will be. However, higher temperature or higher heat flux upon the hot end will cause strong thermal stress which will negatively influence the lifecycle of the thermoelectric module. This phenomenon is very common in industrial applications but seldom has research work been reported. In this paper, numerical analysis on the thermodynamics and thermal stress performance of the thermoelectric module has been performed, considering the variation on the thickness of materials; the influence of high heat flux on thermal efficiency, power output, and thermal stress has been examined. It is found that under high heat flux imposing upon the hot end, the thermal stress is so strong that it has a decisive effect on the life expectation of the device. To improve the module’s working condition, different geometrical configurations are tested and the optimum sizes are achieved. Besides, the side effects on the efficiency, power output, and open circuit voltage output of the thermoelectric module are taken into consideration

  1. European contribution to the study of ROS

    DEFF Research Database (Denmark)

    Egea, Javier; Fabregat, Isabel; Frapart, Yves M

    2017-01-01

    of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still...... generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination...

  2. Prenatal stress programs neuroendocrine stress responses and affective behaviors in second generation rats in a sex-dependent manner.

    Science.gov (United States)

    Grundwald, Natalia J; Brunton, Paula J

    2015-12-01

    An adverse environment in early life is often associated with dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis and higher rates of mood disorders in adulthood. In rats, exposure to social stress during pregnancy results in hyperactive HPA axis responses to stress in the adult offspring and heightened anxiety behavior in the males, but not the females. Here we tested whether, without further intervention, the effects of prenatal stress (PNS) in the first filial generation (F1) are transmitted to the F2 generation via the maternal line. F1 control and PNS female rats were mated with control males and housed under non-stress conditions throughout pregnancy. HPA axis responses to acute stress, anxiety- and depressive-like behavior were assessed in the adult F2 offspring. ACTH and corticosterone responses to an acute stressor were markedly enhanced in F2 PNS females compared with controls. This was associated with greater corticotropin releasing hormone (Crh) mRNA expression in the paraventricular nucleus and reduced hippocampal glucocorticoid (Gr) and mineralocorticoid receptor (Mr) mRNA expression. Conversely, in the F2 PNS males, HPA axis responses to acute stress were attenuated and hippocampal Gr mRNA expression was greater compared with controls. F2 PNS males exhibited heightened anxiety-like behavior (light-dark box and elevated plus maze) compared with F2 control males. Anxiety-like behavior did not differ between F2 control and PNS females during metestrus/diestrus, however at proestrus/estrus, F2 control females displayed a reduction in anxiety-like behavior, but this effect was not observed in the F2 PNS females. Heightened anxiety in the F2 PNS males was associated with greater Crh mRNA expression in the central nucleus of the amygdala compared with controls. Moreover, Crh receptor-1 (Crhr1) mRNA expression was significantly increased, whereas Crhr2 mRNA was significantly decreased in discrete regions of the amygdala in F2 PNS males compared

  3. ROS Are Required for Mouse Spermatogonial Stem Cell Self-Renewal

    OpenAIRE

    Morimoto, Hiroko; Iwata, Kazumi; Ogonuki, Narumi; Inoue, Kimiko; Ogura, Atsuo; Kanatsu-Shinohara, Mito; Morimoto, Takeshi; Yabe-Nishimura, Chihiro; Shinohara, Takashi

    2013-01-01

    Reactive oxygen species (ROS) generation is implicated in stem cell self-renewal in several tissues but is thought to be detrimental for spermatogenesis as well as spermatogonial stem cells (SSCs). Using cultured SSCs, we show that ROS are generated via the AKT and MEK signaling pathways under conditions where the growth factors glial cell line-derived neurotrophic factor and fibroblast growth factor 2 drive SSC self-renewal and, instead, stimulate self-renewal at physiological levels. SSCs d...

  4. Stress corrosion cracking of the tubing materials for nuclear steam generators in an environment containing lead

    International Nuclear Information System (INIS)

    Kim, Kyung Mo; Kim, Uh Chul; Lee, Eun Hee; Hwang, Seong Sik

    2004-01-01

    Steam generator tube materials show a high susceptibility to stress corrosion cracking (SCC) in an environment containing lead species and some nuclear power plants currently have degradation problems associated with lead-induced stress corrosion cracking in a caustic solution. Effects of an applied potential on SCC is tested for middle-annealed Alloy 600 specimens since their corrosion potential can be changed when lead oxide coexists with other oxidizing species like copper oxide in the sludge. In addition, all the steam generator tubing materials used for nuclear power plants being operated and currently under construction in Korea are tested in a caustic solution with lead oxide. (author)

  5. Calculation of a steam generating tube stressed state under temperature oscillations in burnout zone

    International Nuclear Information System (INIS)

    Vorob'ev, V.A.; Loshchinin, V.M.; Remizov, O.V.

    1982-01-01

    The technique for evaluating the steam generating tube stressed state under the wall temperature oscillations in the burnout zone is described. The technique is based on analytical solutions for transfer functions connecting the amplitude of surface temperature oscillation with the amplitude and frequency of heat transfer coefficient oscillation and amplitude of thermoelastic stress oscillation with that of temperature oscillation. The results of calculations according to considered technique are compared with that of the problem numerical solution. The conclusion is made that the technique under consideration may be applied for evaluation of steam generator evaporating tube lifetime [ru

  6. The role of 12/15-lipoxygenases in ROS-mediated neuronal cell death

    OpenAIRE

    Tobaben, Svenja

    2011-01-01

    Oxidative stress has been established as a key trigger of neuronal dysfunction and death in age-related neurodegenerative diseases and in delayed neuronal death after acute brain injury by ischemic stroke or brain trauma. Despite increasing knowledge on the toxicity of reactive oxygen species (ROS) and oxidized reaction products that may further accelerate neuronal cell death, the major sources of ROS formation and the mechanisms ...

  7. Establishing the subcellular localization of photodynamically-induced ROS using 3,3′-diaminobenzidine: A methodological proposal, with a proof-of-concept demonstration

    DEFF Research Database (Denmark)

    Stockert, Juan Carlos; Blazquez-Castro, Alfonso

    2016-01-01

    The critical involvement of reactive oxygen species (ROS) in both physiological and pathological processes in cell biology makes their detection and assessment a fundamental topic in biomedical research. Established methodologies to study ROS in cell biology take advantage of oxidation reactions...... is proved in a photodynamic model of ROS generation, the principle is applicable to many different scenarios of intracellular ROS production. As a consequence this proposed methodology should greatly complement other techniques aiming at establishing a precise subcellular localization of ROS generation....... between the ROS and a reduced probe. After reacting the probe reveals the presence of ROS either by the appearance of colour (chromogenic reaction) or fluorescence (fluorogenic reaction). However current methodologies rarely allow for a site-specific detection of ROS production. Here we propose...

  8. Beyond the polymerase-γ theory: Production of ROS as a mode of NRTI-induced mitochondrial toxicity.

    Directory of Open Access Journals (Sweden)

    Reuben L Smith

    Full Text Available Use of some HIV-1 nucleoside reverse transcriptase inhibitors (NRTI is associated with severe adverse events. However, the exact mechanisms behind their toxicity has not been fully understood. Mitochondrial dysfunction after chronic exposure to specific NRTIs has predominantly been assigned to mitochondrial polymerase-γ inhibition by NRTIs. However, an increasing amount of data suggests that this is not the sole mechanism. Many NRTI induced adverse events have been linked to the incurrence of oxidative stress, although the causality of events leading to reactive oxygen species (ROS production and their role in toxicity is unclear. In this study we show that short-term effects of first generation NRTIs, which are rarely discussed in the literature, include inhibition of oxygen consumption, decreased ATP levels and increased ROS production. Collectively these events affect fitness and longevity of C. elegans through mitohormetic signalling events. Furthermore, we demonstrate that these effects can be normalized by addition of the anti-oxidant N-acetylcysteine (NAC, which suggests that ROS likely influence the onset and severity of adverse events upon drug exposure.

  9. SERPINA3K plays antioxidant roles in cultured pterygial epithelial cells through regulating ROS system.

    Directory of Open Access Journals (Sweden)

    Chengpeng Zhu

    Full Text Available We recently demonstrated that SERPINA3K, a serine proteinase inhibitor, has antioxidant activity in the cornea. Here we investigated the antioxidant effects of SERPINA3K on the pterygial, which is partially caused by oxidative stress in pathogenesis. The head part of primary pterygial tissue was dissected and then cultured in keratinocyte serum-free defined medium (KSFM. The cultured pterygial epithelial cells (PECs were treated with SERPINA3K. The cell proliferation and migration of PECs were measured and analyzed. Western blot and quantitative real-time polymerase chain reaction (PCR assay were performed. It showed that SERPINA3K significantly suppressed the cell proliferation of PECs in a concentration-dependent manner, compared with cultured human conjunctival epithelial cells. SERPINA3K also inhibited the cell migration of PECs. Towards its underlying mechanism, SERPINA3K had antioxidant activities on the PECs by significantly inhibiting NADPH oxidase 4 (NOX4, which is an important enzyme of ROS generation, and by elevating the levels of key antioxidant factors of ROS: such as NAD(PH dehydrogenase (quinone 1 (NQO1, NF-E2-related factor-2 (NRF2 and superoxide dismutases (SOD2. Meanwhile, SERPINA3K down-regulated the key effectors of Wnt signaling pathway: β-catenin, nonphospho-β-catenin, and low-density lipoprotein receptor-related protein 6 (LRP6. We provided novel evidence that SERPINA3K had inhibitory effects on pterygium and SERPINA3K played antioxidant role via regulating the ROS system and antioxidants.

  10. Estimation of the supplementary axial wall stress generated at peak flow by an arterial stenosis

    International Nuclear Information System (INIS)

    Doriot, Pierre-Andre

    2003-01-01

    Mechanical stresses in arterial walls are known to be implicated in the development of atherosclerosis. While shear stress and circumferential stress have received a lot of attention, axial stress has not. Yet, stenoses can be intuitively expected to produce a supplementary axial stress during flow systole in the region immediately proximal to the constriction cone. In this paper, a model for the estimation of this effect is presented, and ten numerical examples are computed. These examples show that the cyclic increase in axial stress can be quite considerable in severe stenoses (typically 120% or more of the normal stress value). This result is in best agreement with the known mechanical or morphological risk factors of stenosis progression and restenosis (hypertension, elevated pulse pressure, degree of stenosis, stenosis geometry, residual stenosis, etc). The supplementary axial stress generated by a stenosis might create the damages in the endothelium and in the elastic membranes which potentiate the action of the other risk factors (hyperlipidaemia, diabetes, etc). It could thus be an important cause of stenosis progression and of restenosis

  11. Estimation of the supplementary axial wall stress generated at peak flow by an arterial stenosis

    Science.gov (United States)

    Doriot, Pierre-André

    2003-01-01

    Mechanical stresses in arterial walls are known to be implicated in the development of atherosclerosis. While shear stress and circumferential stress have received a lot of attention, axial stress has not. Yet, stenoses can be intuitively expected to produce a supplementary axial stress during flow systole in the region immediately proximal to the constriction cone. In this paper, a model for the estimation of this effect is presented, and ten numerical examples are computed. These examples show that the cyclic increase in axial stress can be quite considerable in severe stenoses (typically 120% or more of the normal stress value). This result is in best agreement with the known mechanical or morphological risk factors of stenosis progression and restenosis (hypertension, elevated pulse pressure, degree of stenosis, stenosis geometry, residual stenosis, etc). The supplementary axial stress generated by a stenosis might create the damages in the endothelium and in the elastic membranes which potentiate the action of the other risk factors (hyperlipidaemia, diabetes, etc). It could thus be an important cause of stenosis progression and of restenosis.

  12. Oxidative stress in NSC-741909-induced apoptosis of cancer cells

    Directory of Open Access Journals (Sweden)

    Huang Peng

    2010-04-01

    Full Text Available Abstract Background NSC-741909 is a novel anticancer agent that can effectively suppress the growth of several cell lines derived from lung, colon, breast, ovarian, and kidney cancers. We recently showed that NSC-741909-induced antitumor activity is associated with sustained Jun N-terminal kinase (JNK activation, resulting from suppression of JNK dephosphorylation associated with decreased protein levels of MAPK phosphatase-1. However, the mechanisms of NSC-741909-induced antitumor activity remain unclear. Because JNK is frequently activated by oxidative stress in cells, we hypothesized that reactive oxygen species (ROS may be involved in the suppression of JNK dephosphorylation and the cytotoxicity of NSC-741909. Methods The generation of ROS was measured by using the cell-permeable nonfluorescent compound H2DCF-DA and flow cytometry analysis. Cell viability was determined by sulforhodamine B assay. Western blot analysis, immunofluorescent staining and flow cytometry assays were used to determine apoptosis and molecular changes induced by NSC-741909. Results Treatment with NSC-741909 induced robust ROS generation and marked MAPK phosphatase-1 and -7 clustering in NSC-741909-sensitive, but not resistant cell lines, in a dose- and time-dependent manner. The generation of ROS was detectable as early as 30 min and ROS levels were as high as 6- to 8-fold above basal levels after treatment. Moreover, the NSC-741909-induced ROS generation could be blocked by pretreatment with antioxidants, such as nordihydroguaiaretic acid, aesculetin, baicalein, and caffeic acid, which in turn, inhibited the NSC-741909-induced JNK activation and apoptosis. Conclusion Our results demonstrate that the increased ROS production was associated with NSC-741909-induced antitumor activity and that ROS generation and subsequent JNK activation is one of the primary mechanisms of NSC-741909-mediated antitumor cell activity.

  13. ROS evaluation for a series of CNTs and their derivatives using an ESR method with DMPO

    International Nuclear Information System (INIS)

    Tsuruoka, S; Noguchi, T; Endo, M; Tristan, F; Terrones, M; Takeuchi, K; Koyama, K; Usui, Y; Matsumoto, H; Saito, N; Porter, D W; Castranova, V

    2013-01-01

    Carbon nanotubes (CNTs) are important materials in advanced industries. It is a concern that pulmonary exposure to CNTs may induce carcinogenic responses. It has been recently reported that CNTs scavenge ROS though non-carbon fibers generate ROS. A comprehensive evaluation of ROS scavenging using various kinds of CNTs has not been demonstrated well. The present work specifically investigates ROS scavenging capabilities with a series of CNTs and their derivatives that were physically treated, and with the number of commercially available CNTs. CNT concentrations were controlled at 0.2 through 0.6 wt%. The ROS scavenging rate was measured by ESR with DMPO. Interestingly, the ROS scavenging rate was not only influenced by physical treatments, but was also dependent on individual manufacturing methods. Ratio of CNTs to DMPO/ hydrogen peroxide is a key parameter to obtain appropriate ROS quenching results for comparison of CNTs. The present results suggest that dangling bonds are not a sole factor for scavenging, and electron transfer on the CNT surface is not clearly determined to be the sole mechanism to explain ROS scavenging.

  14. ROS evaluation for a series of CNTs and their derivatives using an ESR method with DMPO.

    Science.gov (United States)

    Tsuruoka, S; Takeuchi, K; Koyama, K; Noguchi, T; Endo, M; Tristan, F; Terrones, M; Matsumoto, H; Saito, N; Usui, Y; Porter, D W; Castranova, V

    Carbon nanotubes (CNTs) are important materials in advanced industries. It is a concern that pulmonary exposure to CNTs may induce carcinogenic responses. It has been recently reported that CNTs scavenge ROS though non-carbon fibers generate ROS. A comprehensive evaluation of ROS scavenging using various kinds of CNTs has not been demonstrated well. The present work specifically investigates ROS scavenging capabilities with a series of CNTs and their derivatives that were physically treated, and with the number of commercially available CNTs. CNT concentrations were controlled at 0.2 through 0.6 wt%. The ROS scavenging rate was measured by ESR with DMPO. Interestingly, the ROS scavenging rate was not only influenced by physical treatments, but was also dependent on individual manufacturing methods. Ratio of CNTs to DMPO/ hydrogen peroxide is a key parameter to obtain appropriate ROS quenching results for comparison of CNTs. The present results suggest that dangling bonds are not a sole factor for scavenging, and electron transfer on the CNT surface is not clearly determined to be the sole mechanism to explain ROS scavenging.

  15. The p66(Shc adaptor protein controls oxidative stress response in early bovine embryos.

    Directory of Open Access Journals (Sweden)

    Dean H Betts

    Full Text Available The in vitro production of mammalian embryos suffers from high frequencies of developmental failure due to excessive levels of permanent embryo arrest and apoptosis caused by oxidative stress. The p66Shc stress adaptor protein controls oxidative stress response of somatic cells by regulating intracellular ROS levels through multiple pathways, including mitochondrial ROS generation and the repression of antioxidant gene expression. We have previously demonstrated a strong relationship with elevated p66Shc levels, reduced antioxidant levels and greater intracellular ROS generation with the high incidence of permanent cell cycle arrest of 2-4 cell embryos cultured under high oxygen tensions or after oxidant treatment. The main objective of this study was to establish a functional role for p66Shc in regulating the oxidative stress response during early embryo development. Using RNA interference in bovine zygotes we show that p66Shc knockdown embryos exhibited increased MnSOD levels, reduced intracellular ROS and DNA damage that resulted in a greater propensity for development to the blastocyst stage. P66Shc knockdown embryos were stress resistant exhibiting significantly reduced intracellular ROS levels, DNA damage, permanent 2-4 cell embryo arrest and diminished apoptosis frequencies after oxidant treatment. The results of this study demonstrate that p66Shc controls the oxidative stress response in early mammalian embryos. Small molecule inhibition of p66Shc may be a viable clinical therapy to increase the developmental potential of in vitro produced mammalian embryos.

  16. Potential hepatic toxicity of buprofezin at sublethal concentrations: ROS-mediated conversion of energy metabolism.

    Science.gov (United States)

    Ji, Xiaotong; Ku, Tingting; Zhu, Na; Ning, Xia; Wei, Wei; Li, Guangke; Sang, Nan

    2016-12-15

    Buprofezin is known for its broad-spectrum action and environmental safety. The popularity of buprofezin has raised concerns about its potentially adverse effects on human health and risk to the environment. In this study, we first identified the liver as one of the major organs in which buprofezin accumulated, and we detected a severe oxidative stress response. Next, we demonstrated that sublethal concentrations of buprofezin promoted the conversion of energy metabolism from the aerobic tricarboxylic acid (TCA) cycle and oxidative phosphorylation to anaerobic glycolysis. Importantly, reactive oxygen species (ROS) generation partially accounted for the shunting of the energy metabolism through the buprofezin-mediated inhibition of cytochrome c oxidase activity. ROS directly perturbed the activities of several key TCA cycle enzymes, stimulated glycolysis, and indirectly disturbed the activity of the respiratory chain complex by altering mitochondrial DNA (mtDNA). These findings clarify the potential mechanisms of buprofezin toxicity and provide biomarkers for buprofezin-mediated hepatotoxicity at sublethal concentrations. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Literature-based discovery of diabetes- and ROS-related targets

    Directory of Open Access Journals (Sweden)

    Pande Manjusha

    2010-10-01

    Full Text Available Abstract Background Reactive oxygen species (ROS are known mediators of cellular damage in multiple diseases including diabetic complications. Despite its importance, no comprehensive database is currently available for the genes associated with ROS. Methods We present ROS- and diabetes-related targets (genes/proteins collected from the biomedical literature through a text mining technology. A web-based literature mining tool, SciMiner, was applied to 1,154 biomedical papers indexed with diabetes and ROS by PubMed to identify relevant targets. Over-represented targets in the ROS-diabetes literature were obtained through comparisons against randomly selected literature. The expression levels of nine genes, selected from the top ranked ROS-diabetes set, were measured in the dorsal root ganglia (DRG of diabetic and non-diabetic DBA/2J mice in order to evaluate the biological relevance of literature-derived targets in the pathogenesis of diabetic neuropathy. Results SciMiner identified 1,026 ROS- and diabetes-related targets from the 1,154 biomedical papers (http://jdrf.neurology.med.umich.edu/ROSDiabetes/. Fifty-three targets were significantly over-represented in the ROS-diabetes literature compared to randomly selected literature. These over-represented targets included well-known members of the oxidative stress response including catalase, the NADPH oxidase family, and the superoxide dismutase family of proteins. Eight of the nine selected genes exhibited significant differential expression between diabetic and non-diabetic mice. For six genes, the direction of expression change in diabetes paralleled enhanced oxidative stress in the DRG. Conclusions Literature mining compiled ROS-diabetes related targets from the biomedical literature and led us to evaluate the biological relevance of selected targets in the pathogenesis of diabetic neuropathy.

  18. Role of ROS in Aβ42 Mediated Activation of Cerebral Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Andrey Tsoy

    2014-12-01

    elevation. However, total expression levels of P-selectin were not changed following exposure to Aβ42. Pre-treatment with NAC attenuated Aβ42 induced P-selectin localization, while NAC alone did not significantly affect P selectin localization. As a positive control, H2O2 also increased P-selectin expression on the cell surface, which peaked after 30 minutes of H2O2 treatment. Exposure of CECs with Aβ42 promoted actin polymerization, which peaked after 10 minutes of Aβ42 treatment, while no significant increase of F-actin intensity was observed when cells were pre-treated with NAC. H2O2 was able to mimic Aβ42 induced oxidative stress, causing increased actin polymerization with similar timing.Conclusions. The results of our study have indicated that Aβ42 induced accumulation of P-selectin on the surface of bEnd3 cells and promoted actin polymerization, and all these events were correlated with ROS generation. The rapid post-translational cell signaling response mediated by ROS may well represent an important physiological trigger of the microvascular inflammatory responses in AD and requires further investigations.

  19. A kinetic model for stress generation in thin films grown from energetic vapor fluxes

    Energy Technology Data Exchange (ETDEWEB)

    Chason, E.; Karlson, M. [School of Engineering, Brown University, Providence, Rhode Island 02912 (United States); Colin, J. J.; Abadias, G. [Institut P' , Département Physique et Mécanique des Matériaux, Université de Poitiers-CNRS-ENSMA, SP2MI, Téléport 2, Bd M. et P. Curie, F-86962 Chasseneuil-Futuroscope (France); Magnfält, D.; Sarakinos, K. [Nanoscale Engineering Division, Department of Physics, Chemistry and Biology, Linköping University, SE-581 83 Linköping (Sweden)

    2016-04-14

    We have developed a kinetic model for residual stress generation in thin films grown from energetic vapor fluxes, encountered, e.g., during sputter deposition. The new analytical model considers sub-surface point defects created by atomic peening, along with processes treated in already existing stress models for non-energetic deposition, i.e., thermally activated diffusion processes at the surface and the grain boundary. According to the new model, ballistically induced sub-surface defects can get incorporated as excess atoms at the grain boundary, remain trapped in the bulk, or annihilate at the free surface, resulting in a complex dependence of the steady-state stress on the grain size, the growth rate, as well as the energetics of the incoming particle flux. We compare calculations from the model with in situ stress measurements performed on a series of Mo films sputter-deposited at different conditions and having different grain sizes. The model is able to reproduce the observed increase of compressive stress with increasing growth rate, behavior that is the opposite of what is typically seen under non-energetic growth conditions. On a grander scale, this study is a step towards obtaining a comprehensive understanding of stress generation and evolution in vapor deposited polycrystalline thin films.

  20. Transient thermal stresses in composite hollow circular cylinder due to partial heat generation

    International Nuclear Information System (INIS)

    Goshima, Takahito; Miyao, Kaju

    1979-01-01

    Clad materials are adopted for the machines and structures used in contact with high temperature, corrosive atmosphere in view of their strength and economy. Large thermal stress sometimes arises in clad cylinders due to uneaven temperature field and the difference in linear thermal expansion. Vessels are often heated uneavenly, and shearing stress occurs, which is not observed in uniform heating. In this study, infinitely long, concentric cylinders of two layers were analyzed, when the internal heat changing in stepped state is generated in cylindrical form. The unsteady thermal stress occurred was determined, using thermo-elastic potential and stress functions, and assuming the thermal properties and elastic modulus of materials as constant regardless of the temperature. Laplace transformation was used, and the basic equations for thermo-elastic displacement were employed as the basis of calculation. The analysis of the temperature distribution and stress is explained. Numerical calculation was carried out on the example of an internal cylinder of SUS 304 stainless steel and an external cylinder of mild steel. The maximum shearing stress occurred in the direction of 40 deg from the heat source, and was affected largely by the position of heat generation. The effect became remarkable as time elapsed. (Kako, I.)

  1. Thermodynamic method for generating random stress distributions on an earthquake fault

    Science.gov (United States)

    Barall, Michael; Harris, Ruth A.

    2012-01-01

    This report presents a new method for generating random stress distributions on an earthquake fault, suitable for use as initial conditions in a dynamic rupture simulation. The method employs concepts from thermodynamics and statistical mechanics. A pattern of fault slip is considered to be analogous to a micro-state of a thermodynamic system. The energy of the micro-state is taken to be the elastic energy stored in the surrounding medium. Then, the Boltzmann distribution gives the probability of a given pattern of fault slip and stress. We show how to decompose the system into independent degrees of freedom, which makes it computationally feasible to select a random state. However, due to the equipartition theorem, straightforward application of the Boltzmann distribution leads to a divergence which predicts infinite stress. To avoid equipartition, we show that the finite strength of the fault acts to restrict the possible states of the system. By analyzing a set of earthquake scaling relations, we derive a new formula for the expected power spectral density of the stress distribution, which allows us to construct a computer algorithm free of infinities. We then present a new technique for controlling the extent of the rupture by generating a random stress distribution thousands of times larger than the fault surface, and selecting a portion which, by chance, has a positive stress perturbation of the desired size. Finally, we present a new two-stage nucleation method that combines a small zone of forced rupture with a larger zone of reduced fracture energy.

  2. Oxidative stress in cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Shyamal K Goswami

    2015-01-01

    Full Text Available Oxidative stress caused by various oxygen containing free radicals and reactive species (collectively called "Reactive Oxygen Species" or ROS has long been attributed to cardiovascular diseases. In human body, major oxidizing species are super oxide, hydrogen peroxide, hydroxyl radical, peroxy nitrite etc. ROS are produced from distinct cellular sources, enzymatic and non-enzymatic; have specific physicochemical properties and often have specific cellular targets. Although early studies in nineteen sixties and seventies highlighted the deleterious effects of these species, later it was established that they also act as physiological modulators of cellular functions and diseases occur only when ROS production is deregulated. One of the major sources of cellular ROS is Nicotinamide adenine dinucleotide phosphate oxidases (Noxes that are expressed in almost all cell types. Superoxide and hydrogen peroxide generated from them under various conditions act as signal transducers. Due to their immense importance in cellular physiology, various Nox inhibitors are now being developed as therapeutics. Another free radical of importance in cardiovascular system is nitric oxide (a reactive nitrogen species generated from nitric oxide synthase(s. It plays a critical role in cardiac function and its dysregulated generation along with superoxide leads to the formation of peroxynitrite a highly deleterious agent. Despite overwhelming evidences of association between increased level of ROS and cardiovascular diseases, antioxidant therapies using vitamins and omega 3 fatty acids have largely been unsuccessful till date. Also, there are major discrepancies between studies with laboratory animals and human trials. It thus appears that the biology of ROS is far complex than anticipated before. A comprehensive understanding of the redox biology of diseases is thus needed for developing targeted therapeutics.

  3. OXIDATIVE STRESS IN MUSCLE GROWTH AND ADAPTATION TO PHYSICAL EXERCISE

    Directory of Open Access Journals (Sweden)

    Ihor Yurkevych

    2015-05-01

    Full Text Available In a few last decades oxidative stress detected in a variety of physiological processes where reactive oxygen species (ROS and reactive nitrogen species (RNS play a central role. They are directly involved in oxidation of proteins, lipids and nucleic acids. In certain concentrations they are necessary for cell division, proliferation and apoptosis. Contractile muscle tissue at aerobic conditions form high ROS flow that may modulate a variety of cell functions, for example proliferation. However, slight increase in ROS level provide hormetic effect which may participate in adaptation to heavy weight training resulted in hypertrophy and proliferation of skeletal muscle fibers. This review will discuss ROS types, sites of generation, strategies to increase force production and achieve skeletal muscle hypertrophy.

  4. Influence of early stress on social abilities and serotonergic functions across generations in mice.

    Directory of Open Access Journals (Sweden)

    Tamara B Franklin

    Full Text Available Exposure to adverse environments during early development is a known risk factor for several psychiatric conditions including antisocial behavior and personality disorders. Here, we induced social anxiety and altered social recognition memory in adult mice using unpredictable maternal separation and maternal stress during early postnatal life. We show that these social defects are not only pronounced in the animals directly subjected to stress, but are also transmitted to their offspring across two generations. The defects are associated with impaired serotonergic signaling, in particular, reduced 5HT1A receptor expression in the dorsal raphe nucleus, and increased serotonin level in a dorsal raphe projection area. These findings underscore the susceptibility of social behaviors and serotonergic pathways to early stress, and the persistence of their perturbation across generations.

  5. Effects of stress conditions on the generation of negative bias temperature instability-associated interface traps

    International Nuclear Information System (INIS)

    Zhang Yue; Pu Shi; Lei Xiao-Yi; Chen Qing; Ma Xiao-Hua; Hao Yue

    2013-01-01

    The exponent n of the generation of an interface trap (N it ), which contributes to the power-law negative bias temperature instability (NBTI) degradation, and the exponent's time evolution are investigated by simulations with varying the stress voltage V g and temperature T. It is found that the exponent n in the diffusion-limited phase of the degradation process is irrelevant to both V g and T. The time evolution of the exponent n is affected by the stress conditions, which is reflected in the shift of the onset of the diffusion-limited phase. According to the diffusion profiles, the generation of the atomic hydrogen species, which is equal to the buildup of N it , is strongly correlated with the stress conditions, whereas the diffusion of the hydrogen species shows V g -unaffected but T-affected relations through the normalized results

  6. 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.

  7. Role of oxidative stress in cadmium toxicity and carcinogenesis

    International Nuclear Information System (INIS)

    Liu Jie; Qu Wei; Kadiiska, Maria B.

    2009-01-01

    Cadmium (Cd) is a toxic metal, targeting the lung, liver, kidney, and testes following acute intoxication, and causing nephrotoxicity, immunotoxicity, osteotoxicity and tumors after prolonged exposures. Reactive oxygen species (ROS) are often implicated in Cd toxicology. This minireview focused on direct evidence for the generation of free radicals in intact animals following acute Cd overload and discussed the association of ROS in chronic Cd toxicity and carcinogenesis. Cd-generated superoxide anion, hydrogen peroxide, and hydroxyl radicals in vivo have been detected by the electron spin resonance spectra, which are often accompanied by activation of redox sensitive transcription factors (e.g., NF-κB, AP-1 and Nrf2) and alteration of ROS-related gene expression. It is generally agreed upon that oxidative stress plays important roles in acute Cd poisoning. However, following long-term Cd exposure at environmentally-relevant low levels, direct evidence for oxidative stress is often obscure. Alterations in ROS-related gene expression during chronic exposures are also less significant compared to acute Cd poisoning. This is probably due to induced adaptation mechanisms (e.g., metallothionein and glutathione) following chronic Cd exposures, which in turn diminish Cd-induced oxidative stress. In chronic Cd-transformed cells, less ROS signals are detected with fluorescence probes. Acquired apoptotic tolerance renders damaged cells to proliferate with inherent oxidative DNA lesions, potentially leading to tumorigenesis. Thus, ROS are generated following acute Cd overload and play important roles in tissue damage. Adaptation to chronic Cd exposure reduces ROS production, but acquired Cd tolerance with aberrant gene expression plays important roles in chronic Cd toxicity and carcinogenesis.

  8. Impact of oxidative stress on exercising skeletal muscle.

    Science.gov (United States)

    Steinbacher, Peter; Eckl, Peter

    2015-04-10

    It is well established that muscle contractions during exercise lead to elevated levels of reactive oxygen species (ROS) in skeletal muscle. These highly reactive molecules have many deleterious effects, such as a reduction of force generation and increased muscle atrophy. Since the discovery of exercise-induced oxidative stress several decades ago, evidence has accumulated that ROS produced during exercise also have positive effects by influencing cellular processes that lead to increased expression of antioxidants. These molecules are particularly elevated in regularly exercising muscle to prevent the negative effects of ROS by neutralizing the free radicals. In addition, ROS also seem to be involved in the exercise-induced adaptation of the muscle phenotype. This review provides an overview of the evidences to date on the effects of ROS in exercising muscle. These aspects include the sources of ROS, their positive and negative cellular effects, the role of antioxidants, and the present evidence on ROS-dependent adaptations of muscle cells in response to physical exercise.

  9. Internal stresses in steel plate generated by shape memory alloy inserts

    International Nuclear Information System (INIS)

    Malard, B.; Pilch, J.; Sittner, P.; Davydov, V.; Sedlák, P.; Konstantinidis, K.; Hughes, D.J.

    2012-01-01

    Graphical abstract: Display Omitted Highlights: ► Thermoresponsive internal stresses introduced into steel by embedding SMA inclusions. ► Neutron strain scanning on steel plate coupons with NiTi inserts at 21 °C and 130 °C. ► Internal stress field in steel evaluated directly from strains and by FE simulation. ► Internal stress generation by SMA insert resistant to thermal and mechanical fatigue. - Abstract: Neutron strain scanning was employed to investigate the internal stress fields in steel plate coupons with embedded prestrained superelastic NiTi shape memory alloy inserts. Strain fields in steel were evaluated at T = 21 °C and 130 °C on virgin coupons as well as on mechanically and thermally fatigued coupons. Internal stress fields were evaluated by direct calculation of principal stress components from the experimentally measured lattice strains as well as by employing an inverse finite element modeling approach. It is shown that if the NiTi inserts are embedded into the elastic steel matrix following a carefully designed technological procedure, the internal stress fields vary with temperature in a reproducible and predictable way. It is estimated that this mechanism of internal stress generation can be safely applied in the temperature range from −20 °C to 150 °C and is relatively resistant to thermal and mechanical fatigue. The predictability and fatigue endurance of the mechanism are of essential importance for the development of future smart metal matrix composites or smart structures with embedded shape memory alloy components.

  10. Oxidative stress generated damage to DNA by gastrointestinal exposure to insoluble particles

    DEFF Research Database (Denmark)

    Møller, Peter; Folkmann, J K; Danielsen, P H

    2012-01-01

    that gastrointestinal exposure to single-walled carbon nanotubes (SWCNT), fullerenes C60, carbon black, titanium dioxide and diesel exhaust particles generates oxidized DNA base lesions in organs such as the bone marrow, liver and lung. Oral exposure to nanosized carbon black has also been associated with increased...... level of lipid peroxidation derived exocyclic DNA adducts in the liver, suggesting multiple pathways of oxidative stress for particle-generated damage to DNA. At equal dose, diesel exhaust particles (SRM2975) generated larger levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in rat liver than carbon black...

  11. Quality of Life and Stressful Life Events in First and Second Generation Immigrant Adolescents

    Directory of Open Access Journals (Sweden)

    Ida Lemos

    2013-09-01

    Full Text Available The aim of this study was to examine differences in quality of life and stressful life events, in first and second generation immigrant adolescents living in Algarve. A total of 172 immigrant adolescents participated in the study, completing the kidscreen-52, the stressful and negative life events inventory and a socio-demographic questionnaire. Results suggest that younger immigrant adolescents report more physical well-being and a higher mood level. Concerning gender differences, girls scored higher than boys in physical well-being, mood and self-perception, but no differences were found on the other kidscreen subscales. First generation immigrants scored significantly higher than second generation ones on the general quality of life index, psychological well-being, autonomy, financial resources and school environment. However, the second-generation immigrants did not seem to be more exposed to stressful life events than the first-generation group. When selecting relevant variables for well-being promotion and for intervention, we must consider that immigrants are more exposed to economic vulnerability, may experience difficulties in adapting to a different school context, and are at higher risk of social exclusion.

  12. Regulation of ROS in transmissible gastroenteritis virus-activated apoptotic signaling

    Energy Technology Data Exchange (ETDEWEB)

    Ding, Li [College of Veterinary Medicine, Northwest A and F University, Yangling, Shaanxi 712100 (China); College of Life Sciences, Hainan Normal University, Haikou, Hainan 571158 (China); Zhao, Xiaomin; Huang, Yong; Du, Qian; Dong, Feng; Zhang, Hongling; Song, Xiangjun; Zhang, Wenlong [College of Veterinary Medicine, Northwest A and F University, Yangling, Shaanxi 712100 (China); Tong, Dewen, E-mail: dwtong@nwsuaf.edu.cn [College of Veterinary Medicine, Northwest A and F University, Yangling, Shaanxi 712100 (China)

    2013-12-06

    Highlights: •TGEV infection induced ROS accumulation. •ROS accumulation is involved in TGEV-induced mitochondrial integrity impairment. •ROS is associated with p53 activation and apoptosis occurrence in TGEV-infected cells. -- Abstract: Transmissible gastroenteritis virus (TGEV), an enteropathogenic coronavirus, causes severe lethal watery diarrhea and dehydration in piglets. Previous studies indicate that TGEV infection induces cell apoptosis in host cells. In this study, we investigated the roles and regulation of reactive oxygen species (ROS) in TGEV-activated apoptotic signaling. The results showed that TGEV infection induced ROS accumulation, whereas UV-irradiated TGEV did not promote ROS accumulation. In addition, TGEV infection lowered mitochondrial transmembrane potential in PK-15 cell line, which could be inhibited by ROS scavengers, pyrrolidinedithiocarbamic (PDTC) and N-acetyl-L-cysteine (NAC). Furthermore, the two scavengers significantly inhibited the activation of p38 MAPK and p53 and further blocked apoptosis occurrence through suppressing the TGEV-induced Bcl-2 reduction, Bax redistribution, cytochrome c release and caspase-3 activation. These results suggest that oxidative stress pathway might be a key element in TGEV-induced apoptosis and TGEV pathogenesis.

  13. Repeated short-term stress synergizes the ROS signalling through up regulation of NFkB and iNOS expression induced due to combined exposure of trichloroethylene and UVB rays.

    Science.gov (United States)

    Ali, Farrah; Sultana, Sarwat

    2012-01-01

    Restraint stress is known to catalyse the pathogenesis of the variety of chronic inflammatory disorders. The present study was designed to evaluate the effect of repeated short-term stress (RRS) on cellular transduction apart from oxidative burden and early tumour promotional biomarkers induced due to combined exposure of trichloroethylene (TCE) and Ultra-violet radiation (UVB). RRS leads to the increase in the expression of the stress responsive cellular transduction elements NFkB-p65 and activity of iNOS in the epidermal tissues of mice after toxicant exposure. RRS augments the steep depletion of the cellular antioxidant machinery which was evidenced by the marked depletion in GSH (Glutathione and GSH dependant enzymes), superoxide dismutase and catalase activity that were observed at significance level of P stressed animals and down regulation of DT-diaphorase activity (P short-term stress in the toxic response of TCE and UVB radiation.

  14. Mitigation of caustic stress corrosion cracking of steam generator tube materials by blowdown -a case study

    International Nuclear Information System (INIS)

    Dutta, Anu; Patwegar, I.A.; Chaki, S.K.; Venkat Raj, V.

    2000-01-01

    The vertical U-tube steam generators are among the most important equipment in nuclear power plants as they form the vital link between the reactor and the turbogenerator. Over ∼ 35 years of operating experience of water cooled reactor has demonstrated that steam generator tubes are susceptible to various forms of degradation. This degradation leads to failure and outages of the power plant. A majority of these failures have been attributed to concentrated alkali attacks in the low flow areas such as crevices in the tube to tube sheet joints, baffle plate location and the areas of sludge deposits. Free hydroxides can be produced by improper maintenance of phosphate chemical control in the secondary side of the steam generators and also by the thermal decomposition of impurities present in the condenser cooling water which may leak into the feed water through the condenser tubes. The free hydroxides concentrate in the low flow areas. This buildup of free hydroxide in combination with residual stress leads to caustic stress corrosion cracking. In order to mitigate caustic stress corrosion cracking of Inconel 600 tubes, the trend is to avoid phosphate dosing. Instead All Volatile Treatment (AVT) for secondary water is used backed by full flow condensate polishing. Sodium hydroxide concentration is now being considered as the basis for steam generator blowdown. A methodology has been established for determining the blowdown requirement in order to mitigate caustic stress corrosion cracking in the secondary side of the vertical U-tube natural circulation steam generator. A case study has been carried out for zero solid treatment (AVT coupled with full flow condensate polishing plant) water chemistry. Only continuous blowdown schemes have been studied based on maximum caustic concentration permissible in the secondary side of the steam generator. The methodology established can also be used for deciding concentration of any other impurities

  15. Experimental residual stress evaluation of hydraulic expansion transitions in Alloy 690 steam generator tubing

    International Nuclear Information System (INIS)

    McGregor, R.; Doherty, P.; Hornbach, D.; Abdelsalam, U.

    1995-01-01

    Nuclear Steam Generator (SG) service reliability and longevity have been seriously affected worldwide by corrosion at the tube-to-tubesheet joint expansion. Current SG designs for new facilities and replacement projects enhance corrosion resistance through the use of advanced tubing materials and improved joint design and fabrication techniques. Here, transition zones of hydraulic expansions have undergone detailed experimental evaluation to define residual stress and cold-work distribution on and below the secondary-side surface. Using X-ray diffraction techniques, with supporting finite element analysis, variations are compared in tubing metallurgical condition, tube/pitch geometry, expansion pressure, and tube-to-hole clearance. Initial measurements to characterize the unexpanded tube reveal compressive stresses associated with a thin work-hardened layer on the outer surface of the tube. The gradient of cold-work was measured as 3% to 0% within .001 inch of the surface. The levels and character of residual stresses following hydraulic expansion are primarily dependent on this work-hardened surface layer and initial stress state that is unique to each tube fabrication process. Tensile stresses following expansion are less than 25% of the local yield stress and are found on the transition in a narrow circumferential band at the immediate tube surface (< .0002 inch/0.005 mm depth). The measurements otherwise indicate a predominance of compressive stresses on and below the secondary-side surface of the transition zone. Excellent resistance to SWSCC initiation is offered by the low levels of tensile stress and cold-work. Propagation of any possible cracking would be deterred by the compressive stress field that surrounds this small volume of tensile material

  16. Friend or foe? Reactive oxygen species production, scavenging and signaling in plant response to environmental stresses.

    Science.gov (United States)

    Czarnocka, Weronika; Karpiński, Stanisław

    2018-01-10

    In the natural environment, plants are exposed to a variety of biotic and abiotic stress conditions that trigger rapid changes in the production and scavenging of reactive oxygen species (ROS). The production and scavenging of ROS is compartmentalized, which means that, depending on stimuli type, they can be generated and eliminated in different cellular compartments such as the apoplast, plasma membrane, chloroplasts, mitochondria, peroxisomes, and endoplasmic reticulum. Although the accumulation of ROS is generally harmful to cells, ROS play an important role in signaling pathways that regulate acclimatory and defense responses in plants, such as systemic acquired acclimation (SAA) and systemic acquired resistance (SAR). However, high accumulations of ROS can also trigger redox homeostasis disturbance which can lead to cell death, and in consequence, to a limitation in biomass and yield production. Different ROS have various half-lifetimes and degrees of reactivity toward molecular components such as lipids, proteins, and nucleic acids. Thus, they play different roles in intra- and extra-cellular signaling. Despite their possible damaging effect, ROS should mainly be considered as signaling molecules that regulate local and systemic acclimatory and defense responses. Over the past two decades it has been proven that ROS together with non-photochemical quenching (NPQ), hormones, Ca 2+ waves, and electrical signals are the main players in SAA and SAR, two physiological processes essential for plant survival and productivity in unfavorable conditions. Copyright © 2018. Published by Elsevier Inc.

  17. Stress generation in a developmental context: the role of youth depressive symptoms, maternal depression, the parent-child relationship, and family stress.

    Science.gov (United States)

    Chan, Priscilla T; Doan, Stacey N; Tompson, Martha C

    2014-02-01

    The present study examined stress generation in a developmental and family context among 171 mothers and their preadolescent children, ages 8-12 years, at baseline (Time 1) and 1-year follow-up (Time 2). In the current study, we examined the bidirectional relationship between children's depressive symptoms and dependent family stress. Results suggest that children's baseline level of depressive symptoms predicted the generation of dependent family stress 1 year later. However, baseline dependent family stress did not predict an increase in children's depressive symptoms 1 year later. In addition, we examined whether a larger context of both child chronic strain (indicated by academic, behavioral, and peer stress) and family factors, including socioeconomic status and parent-child relationship quality, would influence the stress generation process. Although both chronic strain and socioeconomic status were not associated with dependent family stress at Time 2, poorer parent-child relationship quality significantly predicted greater dependent family stress at Time 2. Child chronic strain, but neither socioeconomic status nor parent-child relationship quality, predicted children's depression symptoms at Time 2. Finally, gender, maternal depression history, and current maternal depressive symptoms did not moderate the relationship between level of dependent family stress and depressive symptoms. Overall, findings provide partial support for a developmental stress generation model operating in the preadolescent period.

  18. Endothelial cell oxidative stress and signal transduction

    Directory of Open Access Journals (Sweden)

    ROCIO FONCEA

    2000-01-01

    Full Text Available Endothelial dysfunction (ED is an early event in atherosclerotic disease, preceding clinical manifestations and complications. Increased reactive oxygen species (ROS have been implicated as important mechanisms that contribute to ED, and ROS’s may function as intracellular messengers that modulate signaling pathways. Several intracellular signal events stimulated by ROS have been defined, including the identification of two members of the mitogen activated protein kinase family (ERK1/2 and big MAP kinase, BMK1, tyrosine kinases (Src and Syk and different isoenzymes of PKC as redox-sensitive kinases. ROS regulation of signal transduction components include the modification in the activity of transcriptional factors such as NFkB and others that result in changes in gene expression and modifications in cellular responses. In order to understand the intracellular mechanisms induced by ROS in endothelial cells (EC, we are studying the response of human umbilical cord vein endothelial cells to increased ROS generation by different pro-atherogenic stimuli. Our results show that Homocysteine (Hcy and oxidized LDL (oxLDL enhance the activity and expression of oxidative stress markers, such as NFkB and heme oxygenase 1. These results suggest that these pro-atherogenic stimuli increase oxidative stress in EC, and thus explain the loss of endothelial function associated with the atherogenic process

  19. ROS-activated calcium signaling mechanisms regulating endothelial barrier function.

    Science.gov (United States)

    Di, Anke; Mehta, Dolly; Malik, Asrar B

    2016-09-01

    Increased vascular permeability is a common pathogenic feature in many inflammatory diseases. For example in acute lung injury (ALI) and its most severe form, the acute respiratory distress syndrome (ARDS), lung microvessel endothelia lose their junctional integrity resulting in leakiness of the endothelial barrier and accumulation of protein rich edema. Increased reactive oxygen species (ROS) generated by neutrophils (PMNs) and other inflammatory cells play an important role in increasing endothelial permeability. In essence, multiple inflammatory syndromes are caused by dysfunction and compromise of the barrier properties of the endothelium as a consequence of unregulated acute inflammatory response. This review focuses on the role of ROS signaling in controlling endothelial permeability with particular focus on ALI. We summarize below recent progress in defining signaling events leading to increased endothelial permeability and ALI. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Perceived family stress, parenting efficacy, and child externalizing behaviors in second-generation immigrant mothers.

    Science.gov (United States)

    Yaman, Ayşe; Mesman, Judi; van Ijzendoorn, Marinus H; Bakermans-Kranenburg, Marian J

    2010-04-01

    Examining family stress and parenting efficacy in relation to child externalizing problems in immigrant families. In this study, we compared the levels of family stress, parenting efficacy, and toddler externalizing behaviors in Dutch (n = 175) and second-generation Turkish immigrant families (n = 175) living in the Netherlands. In addition, the influence of Turkish mothers' acculturation on toddler externalizing behaviors and its association with perceived stress and efficacy were examined. Turkish mothers reported higher levels of daily stress and marital discord than Dutch mothers, but did not differ in perceptions of parenting efficacy and children's externalizing behaviors. The associations between child and family variables were similar in the Dutch and the Turkish groups, as more family stress was related to more externalizing behaviors in toddlers. Low parenting efficacy was the most important predictor of child externalizing behaviors in both groups. Acculturation of Turkish mothers was not associated with family and child variables, and did not moderate the association between family variables and child externalizing behaviors. However, emotional connectedness to the Turkish culture was related to less daily stress and fewer marital problems. The results support the no-group differences hypothesis and also imply that cultural maintenance may be adaptive for parental well-being.

  1. The influence of lead on stress corrosion cracking of steam generator tubing

    International Nuclear Information System (INIS)

    Ryan Curtis Wolfe

    2015-01-01

    Lead (Pb) is present at low concentrations on the secondary side of steam generators, but is known to accumulate in steam generator sludge and become concentrated in crevices and cracks. Pb is known to have played a role in the degradation of Alloy 600MA tubing, necessitating the replacement of those steam generators. There is new evidence which indicates that Pb has also played a role in the stress corrosion cracking (SCC) of Alloy 600TT. Furthermore. laboratory testing indicates that advanced tubing alloys such as Alloy 690TT and Alloy 800NG area also susceptible to this attack. In response to these vulnerabilities, utilities are attempting to manufacture tubing using processes which will impart optimal corrosion resistance, fabricate and operate SG's to minimize stress in the tubing, undertake efforts to identify and remove the sources of Pb, reduce the existing inventory of Pb using chemical or mechanical cleaning processes, and maintain rigorous chemistry controls. Research is warranted to qualify chemical methods to mitigate PbSCC that may be observed in service. This presentation will review work performed through the Electric Power Research Institute (EPRI) to address the issue of Pb-assisted stress corrosion cracking of steam generator tubing. (author)

  2. Influence of treatment by vibration in residual stress generated in the laser welding of HSLA and IF steels

    International Nuclear Information System (INIS)

    Chuvas, T.C.; Fonseca, M.P. Cindra; Castello, D.A.

    2010-01-01

    The stress relieving treatment by vibration is a new technology under development, which has many advantages over thermal methods. In this work was analyzed the surface residual stress generated in the laser welding of biphasic HSLA and IF steels, both used in the automotive industry. Residual stresses were measured by X-ray diffraction, by the sen 2 Ψ method. Residual stresses generated in the welding of the samples were tensile at all points measured. After welding, the samples were submitted to the mechanical vibration treatment. Some samples presented a significant reduction in the stress values. The welded joints were also characterized by optical microscopy. (author)

  3. Cisplatin Induces a Mitochondrial-ROS Response That Contributes to Cytotoxicity Depending on Mitochondrial Redox Status and Bioenergetic Functions

    Science.gov (United States)

    Marullo, Rossella; Werner, Erica; Degtyareva, Natalya; Moore, Bryn; Altavilla, Giuseppe; Ramalingam, Suresh S.; Doetsch, Paul W.

    2013-01-01

    Cisplatin is one of the most effective and widely used anticancer agents for the treatment of several types of tumors. The cytotoxic effect of cisplatin is thought to be mediated primarily by the generation of nuclear DNA adducts, which, if not repaired, cause cell death as a consequence of DNA replication and transcription blockage. However, the ability of cisplatin to induce nuclear DNA (nDNA) damage per se is not sufficient to explain its high degree of effectiveness nor the toxic effects exerted on normal, post-mitotic tissues. Oxidative damage has been observed in vivo following exposure to cisplatin in several tissues, suggesting a role for oxidative stress in the pathogenesis of cisplatin-induced dose-limiting toxicities. However, the mechanism of cisplatin-induced generation of ROS and their contribution to cisplatin cytotoxicity in normal and cancer cells is still poorly understood. By employing a panel of normal and cancer cell lines and the budding yeast Saccharomyces cerevisiae as model system, we show that exposure to cisplatin induces a mitochondrial-dependent ROS response that significantly enhances the cytotoxic effect caused by nDNA damage. ROS generation is independent of the amount of cisplatin-induced nDNA damage and occurs in mitochondria as a consequence of protein synthesis impairment. The contribution of cisplatin-induced mitochondrial dysfunction in determining its cytotoxic effect varies among cells and depends on mitochondrial redox status, mitochondrial DNA integrity and bioenergetic function. Thus, by manipulating these cellular parameters, we were able to enhance cisplatin cytotoxicity in cancer cells. This study provides a new mechanistic insight into cisplatin-induced cell killing and may lead to the design of novel therapeutic strategies to improve anticancer drug efficacy. PMID:24260552

  4. Understanding the impact of prior depression on stress generation: examining the roles of current depressive symptoms and interpersonal behaviours.

    Science.gov (United States)

    Shih, Josephine H; Eberhart, Nicole K

    2008-08-01

    Stress generation is a process in which individuals contribute to stressful life events. While research has supported an association between current depression and stress generation, it has been noted that individuals with prior depression tend to contribute to stressors even when they are no longer experiencing a depressive episode. The aim of the study is to elucidate the pathways through which prior major depression predicts interpersonal stress generation in women. Specifically, we examined current subsyndromal depressive symptoms and problematic interpersonal behaviours as potential mediators. Fifty-one college women were followed prospectively for 6 weeks. Participants were interviewed to assess current and past depression as well as stressful life events they experienced over the 6-week period. The findings suggest that prior major depression continues to have an impact even after the episode has ended, as the disorder continues to contribute to stress generation through residual depressive symptoms.

  5. Northeast storms ranked by wind stress and wave-generated bottom stress observed in Massachusetts Bay, 1990-2006

    Science.gov (United States)

    Butman, B.; Sherwood, C.R.; Dalyander, P.S.

    2008-01-01

    Along the coast of the northeastern United States, strong winds blowing from the northeast are often associated with storms called northeasters, coastal storms that strongly influence weather. In addition to effects caused by wind stress, the sea floor is affected by bottom stress associated with these storms. Bottom stress caused by orbital velocities associated with surface waves integrated over the duration of a storm is a metric of storm strength at the sea floor. Near-bottom wave-orbital velocities calculated by using measurements of significant wave height and dominant wave period and the parametric spectral method described in Wiberg and Sherwood [Wiberg, P.L., Sherwood, C.R. Calculating wave-generated bottom orbital velocities from surface wave parameters. Computers in Geosciences, in press] compared well with observations in Massachusetts Bay. Integrated bottom-wave stress (called IWAVES), calculated at 30 m water depth, and a companion storm-strength metric, integrated surface wind stress at 10 m (called IWINDS), are used to provide an overview of the strength, frequency, and timing of large storms in Massachusetts Bay over a 17-year period from January 1990 through December 2006. These new metrics reflect both storm duration and intensity. Northeast storms were the major cause of large waves in Massachusetts Bay because of the long fetch to the east: of the strongest 10% of storms (n=38) ranked by IWAVES, 22 had vector-averaged wind stress from the northeast quadrant. The Blizzard of December 1992, the Perfect Storm of October 1991, and a December 2003 storm were the strongest three storms ranked by IWAVES and IWINDS, and all were northeasters. IWAVES integrated over the winter season (defined as October-May) ranged by about a factor of 11; the winters with the highest integrated IWAVES were 1992-1993 and 2004-2005 and the winter with the lowest integrated IWAVES was 2001-2002. May 2005 was the only month in the 17-year record that two of the nine

  6. Shear flow generation by Reynolds stress and suppression of resistive g-modes

    International Nuclear Information System (INIS)

    Sugama, H.; Horton, W.

    1993-08-01

    Suppression of resistive g-mode turbulence by background shear flow generated from a small external flow source and amplified by the fluctuation-induced Reynolds stress is demonstrated and analyzed. The model leads to a paradigm for the low-to-high (L-H) confinement mode transition. To demonstrate the L-H transition model, single-helicity nonlinear fluid simulations using the vorticity equation for the electrostatic potential, the pressure fluctuation equation and the background poloidal flow equation are used in the sheared slab configuration. The relative efficiency of the external flow and the Reynolds stress for producing shear flow depends on the poloidal flow damping parameter ν which is given by neoclassical theory. For large ν, the external flow is a dominant contribution to the total background poloidal shear flow and its strength predicted by the neoclassical theory is not enough to suppress the turbulence significantly. In contrast, for small ν, we show that the fluctuations drive a Reynolds stress that becomes large and suddenly, at some critical point in time, shear flow much larger than the external flow is generated and leads to an abrupt, order unity reduction of the turbulent transport just like that of the L-H transition in tokamak experiments. It is also found that, even in the case of no external flow, the shear flow generation due to the Reynolds stress occurs through the nonlinear interaction of the resistive g-modes and reduces the transport. To supplement the numerical solutions we derive the Landau equation for the mode amplitude of the resistive g-mode taking into account the fluctuation-induced shear flow and analyze the opposite action of the Reynolds stress in the resistive g turbulence compared with the classical shear flow Kelvin-Helmholtz (K-H) driven turbulence

  7. Transient porosity pulses and microfracturing during a stress-generating retrograde metamorphic reaction

    Science.gov (United States)

    Renard, F.; Zheng, X.; Cordonnier, B.; Zhu, W.; Jamtveit, B.

    2017-12-01

    Several geological processes involve mineral transformations where nominally dry rocks transform into hydrated ones when left in contact with water (i.e. eclogitization, serpentinization). In these systems, the transformation induces stress if the rock is confined, and the new minerals create a so-called force of crystallization. Here, we study a model retrograde metamorphic reaction, the hydration of periclase, MgO, into brucite, Mg(OH)2, to quantify the coupling between reaction, stress generation, porosity evolution and fracturing. This hydration reaction generates a volume increase of 110%, and a density decrease of 33.8% of the solid. Samples of a microporous MgO ceramics were reacted at 170-211°C, 5-80 MPa confining pressure, 6-95 MPa differential stress and 5 MPa pore fluid pressure. They were installed into an X-ray transparent triaxial deformation rig, called Hades, and mounted on a synchrotron microtomography stage. Each experiment lasted between 2 and 5 hours, during which between 35 and 130 three-dimensional images were acquired, allowing to follow the chemical transformation and the deformation of the sample. Below 30 MPa mean pressure, the hydration reaction was coupled to fracturing of the MgO ceramics, and the transformation rate followed a sigmoidal kinetics curve with a slow initiation, a fast reaction coupled to fracturing and the generation of a transient porosity pulse, and a slow-down until an almost complete transformation of periclase into brucite.. Conversely, above 30 MPa, the reaction kinetics was very slow, without fracturing over the time scale of the experiment. When considering the driving force of the hydration reaction, stress generation should be several hundreds MPa, whereas the present experiments show that fracturing occurred only below 30 MPa. This indicates that the potential energy due to phase transformation generates much lower stress than what is estimated from non-equilibrium thermodynamics. A possible interpretation of

  8. Climate change and the vulnerability of electricity generation to water stress in the European Union

    Science.gov (United States)

    Behrens, Paul; van Vliet, Michelle T. H.; Nanninga, Tijmen; Walsh, Brid; Rodrigues, João F. D.

    2017-08-01

    Thermoelectric generation requires large amounts of water for cooling. Recent warm periods have led to curtailments in generation, highlighting concerns about security of supply. Here we assess EU-wide climate impacts for 1,326 individual thermoelectric plants and 818 water basins in 2020 and 2030. We show that, despite policy goals and a decrease in electricity-related water withdrawal, the number of regions experiencing some reduction in power availability due to water stress rises from 47 basins to 54 basins between 2014 and 2030, with further plants planned for construction in stressed basins. We examine the reasons for these pressures by including water demand for other uses. The majority of vulnerable basins lie in the Mediterranean region, with further basins in France, Germany and Poland. We investigate four adaptations, finding that increased future seawater cooling eases some pressures. This highlights the need for an integrated, basin-level approach in energy and water policy.

  9. Role of S100A1 in hypoxia-induced inflammatory response in cardiomyocytes via TLR4/ROS/NF-κB pathway.

    Science.gov (United States)

    Yu, Jiangkun; Lu, Yanyu; Li, Yapeng; Xiao, Lili; Xing, Yu; Li, Yanshen; Wu, Leiming

    2015-09-01

    S100A1 plays a crucial role in hypoxia-induced inflammatory response in cardiomyocytes. However, the role of S100A1 in hypoxia-induced inflammatory response in cardiomyocytes is still unknown. enzyme-linked immunosorbent assay (ELISA) was performed for the determination of inflammatory cytokines. Immunocytochemistry and immunofluorescence, Western blot analysis and Real-time polymerase chain reaction (RT-PCR) were conducted to assess protein or mRNA expressions. Fluorogenic probe dihydroethidium (DHE) was used to evaluate the generation of reactive oxygen species (ROS) while Hoechst 33342 staining for apoptosis. Small interfering RNA (siRNA) for S100A1 was used to evaluate the role of S100A1. The levels of ROS and inflammatory cytokine including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-8 in H9c2 cells were increased remarkably by hypoxia. However, IL-37 protein or mRNA levels were decreased significantly. Both Toll-like receptor 4 (TLR4) inhibitor Ethyl (6R)-6-[N-(2-Chloro-4fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate (TAK-242) treatment or siRNA S100A1 downregulated TLR4 expression and inflammatory cytokine level and mRNA in H9c2 cells, as well as weakening ROS and phospho-p65 Nuclear factor (NF)-κB levels. Further, S100A1 treatment significantly reduced TNF-α protein or mRNA level whereas enhanced IL-37 protein or mRNA level, and could attenuate ROS and phospho-p65 NF-κB levels. Our results demonstrate that S100A1 can regulate the inflammatory response and oxidative stress in H9C2 cells via TLR4/ROS/NF-κB pathway. These findings provide an interesting strategy for protecting cardiomyocytes from hypoxia-induced inflammatory response. © 2015 Royal Pharmaceutical Society.

  10. A study on the Stress Corrosion Cracking reduction method of Steam Generator secondary side of KSNP

    International Nuclear Information System (INIS)

    Kim, June Hoon; Lee, Goune Jin

    2014-01-01

    In order to avoid sludge accumulation affecting the life of the steam generator, the best way is to prevent the sludge inflow in advance by optimization of water quality management through chemical concentration and pH control etc. However it is very difficult to prevent sludge accumulation under the weak condition of corrosion, such as condensation, boiling and high temperature of feed-water in NPPs. Particularly stress corrosion cracking occurs in a top-of-tube sheet area of steam generator with an increase in number of operation years of Korea Standard Nuclear Plant(KSNP)... The purpose of this study is to improve suppression of stress corrosion cracking and life extension for steam generator and improve plant efficiency by performing full length bulk high chemical cleaning in order to remove iron oxide of steam generator secondary side in KSNP Hanbit Unit 6. This study analyzed the Free EDTA and Fe concentrations and sludge removal after performed full length bulk high temperature chemical cleaning for removing the iron oxide of steam generator secondary side, which of Hanbit unit 6 of KSNP. 1) It showed a typical pattern that Fe concentration increased in accordance with to decrease Free EDTA(Ethylene Diamine Tetea acetic Acid) concentration. 2) Sludge removal based on iron oxide after performing the full length bulk high temperature chemical cleaning was 3001kg and sludge removal by lancing additionally was 200.1kg

  11. Nanomedicine in the ROS-mediated pathophysiology: Applications and clinical advances.

    Science.gov (United States)

    Nash, Kevin M; Ahmed, Salahuddin

    2015-11-01

    Reactive oxygen species (ROS) are important in regulating normal cell physiological functions, but when produced in excess lead to the augmented pathogenesis of various diseases. Among these, ischemia reperfusion injury, Alzheimer's disease and rheumatoid arthritis are particularly important. Since ROS can be counteracted by a variety of antioxidants, natural and synthetic antioxidants have been developed. However, due to the ubiquitous production of ROS in living systems, poor in vivo efficiency of these agents and lack of target specificity, the current clinical modalities to treat oxidative stress damage are limited. Advances in the developing field of nanomedicine have yielded nanoparticles that can prolong antioxidant activity, and target specificity of these agents. This article reviews recent advances in antioxidant nanoparticles and their applications to manage oxidative stress-mediated diseases. Production of reactive oxygen species (ROS) is a purely physiological process in many disease conditions. However, excessive and uncontrolled production will lead to oxidative stress and further tissue damage. Advances in nanomedicine have provided many novel strategies to try to combat and counteract ROS. In this review article, the authors comprehensively highlighted the current status and future developments in using nanotechnology for providing novel therapeutic options in this field. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Artifacts Generated During Azoalkane Peroxy Radical Oxidative Stress Testing of Pharmaceuticals Containing Primary and Secondary Amines.

    Science.gov (United States)

    Nefliu, Marcela; Zelesky, Todd; Jansen, Patrick; Sluggett, Gregory W; Foti, Christopher; Baertschi, Steven W; Harmon, Paul A

    2015-12-01

    We report artifactual degradation of pharmaceutical compounds containing primary and secondary amines during peroxy radical-mediated oxidative stress carried out using azoalkane initiators. Two degradation products were detected when model drug compounds dissolved in methanol/water were heated to 40°C with radical initiators such as 2,2'-azobis(2-methylpropionitrile) (AIBN). The primary artifact was identified as an α-aminonitrile generated from the reaction of the amine group of the model drug with formaldehyde and hydrogen cyanide, generated as byproducts of the stress reaction. A minor artifact was generated from the reaction between the amine group and isocyanic acid, also a byproduct of the stress reaction. We report the effects of pH, initiator/drug molar ratio, and type of azoalkane initiator on the formation of these artifacts. Mass spectrometry and nuclear magnetic resonance were used for structure elucidation, whereas mechanistic studies, including stable isotope labeling experiments, cyanide analysis, and experiments exploring the effects of butylated hydroxyanisole addition, were employed to support the degradation pathways. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  13. Inverse method for stress monitoring in pressure components of steam generators

    International Nuclear Information System (INIS)

    Duda, P.

    2003-01-01

    The purpose of this work is to formulate a space marching method, which can be used to solve inverse multidimensional heat conduction problems. The method is designed to reconstruct the transient temperature distribution in a whole construction element based on measured temperatures taken at selected points inside or on the outer surface of the construction element. Next, the Finite Element Method is used to calculate thermal stresses and stresses caused by other loads such as, for instance, internal pressure. The developed method for solving temperature and total stress distribution will be tested using the measured temperatures generated from a direct solution. Transient temperature and total stress distribution obtained from method presented below will be compared with the values obtained from the direct solution. Finally, the presented method will be applied in order to monitor temperature and stress distribution in an outlet header using the real measured temperature values at seven points on the header's outer surface during the power boiler's shut down operation. The presented method allows to optimize the power block's start-up and shut-down operations, contributes to the reduction of heat loss during these operations and to the extension of power block's life. The fatigue and creep usage factor can be computed in an on-line mode. The presented method herein can be applied to monitoring systems that work in conventional as well as in nuclear power plants. (author)

  14. Influence of flow stress choice on the plastic collapse estimation of axially cracked steam generator tubes

    International Nuclear Information System (INIS)

    Tonkovic, Zdenko; Skozrit, Ivica; Alfirevic, Ivo

    2008-01-01

    The influence of the choice of flow stress on the plastic collapse estimation of axially cracked steam generator (SG) tubes is considered. The plastic limit and collapse loads of thick-walled tubes with external axial semi-elliptical surface cracks are investigated by three-dimensional non-linear finite element (FE) analyses. The limit pressure solution as a function of the crack depth, length and tube geometry has been developed on the basis of extensive FE limit load analyses employing the elastic-perfectly plastic material behaviour and small strain theory. Unlike the existing solutions, the newly developed analytical approximation of the plastic limit pressure for thick-walled tubes is applicable to a wide range of crack dimensions. Further, the plastic collapse analysis with a real strain-hardening material model and a large deformation theory is performed and an analytical approximation for the estimation of the flow stress is proposed. Numerical results show that the flow stress, defined by some failure assessment diagram (FAD) methods, depends not only on the tube material, but also on the crack geometry. It is shown that the plastic collapse pressure results, in the case of deeper cracks obtained by using the flow stress as the average of the yield stress and the ultimate tensile strength, can become unsafe

  15. NUMERICAL SIMULATION OF RESIDUAL STRESSES GENERATED IN THE WIRE DRAWING PROCESS FOR DIFFERENT PROCESS PARAMETERS

    Directory of Open Access Journals (Sweden)

    Juliana Zottis

    2014-03-01

    Full Text Available The drawing process of steel bars is usually used to check better dimensional accuracy and mechanical properties to the material. In the other hand, the major concern found in manufacturing axes through this process is the appearance of distortion of shape. Such distortions are directly linked to the accumulation of residual stresses generated during the processes. As a result, this paper aims to study the influence of process parameters such as shape of puller, speed and lubrication used in wire drawing analyzing the accumulation of residual stress after the process. The stress analysis was performed by FEM being used two simulation software: Simufact.formingGP and DeformTM. Through these analyzes, it was found that the shape of how the bar is pulled causes a reduction of up to 100 MPa in residual stresses in the center of the bar, which represents an important factor in the study of the possible causes of the distortion. As well as factors speed and homogeneity of lubrication significantly altered the profile of residual stresses in the bar.

  16. ROS Mediates Radiation-Induced Differentiation in Human Lung Fibroblast

    International Nuclear Information System (INIS)

    Park, Sa Rah; Ahn, Ji Yeon; Kim, Mi Hyeung; Lim, Min Jin; Yun, Yeon Sook; Song, Jie Young

    2009-01-01

    One of the most common tumors worldwide is lung cancer and the number of patients with lung cancer received radiotherapy is increasing rapidly. Although radiotherapy may have lots of advantages, it can also induce serious adverse effects such as acute radiation pneumonitis and pulmonary fibrosis. Pulmonary fibrosis is characterized by excessive production of smooth muscle actin-alpha (a-SMA) and accumulation of extracellular matrix (ECM) such as collagen and fibronectin. There has been a great amount of research about fibrosis but the exact mechanism causing the reaction is not elucidated especially in radiation-induced fibrosis. Until now it has been known that several factors such as transforming growth factor (TGF-b), tumor necrosis factor (TNF), IL-6, platelet-derived growth factor (PDGF) and reactive oxygen species are related to fibrosis. It is also reported that reactive oxygen species (ROS) can be induced by radiation and can act as a second messenger in various signaling pathways. Therefore we focused on the role of ROS in radiation induced fibrosis. Here, we suggest that irradiation generate ROS mainly through NOX4, result in differentiation of lung fibroblast into myofibroblast

  17. Increased expression of native cytosolic Cu/Zn superoxide dismutase and ascorbate peroxidase improves tolerance to oxidative and chilling stresses in cassava (Manihot esculenta Crantz)

    OpenAIRE

    Xu, Jia; Yang, Jun; Duan, Xiaoguang; Jiang, Yueming; Zhang, Peng

    2014-01-01

    Background Cassava (Manihot esculenta Crantz) is a tropical root crop, and is therefore, extremely sensitive to low temperature; its antioxidative response is pivotal for its survival under stress. Timely turnover of reactive oxygen species (ROS) in plant cells generated by chilling-induced oxidative damages, and scavenging can be achieved by non-enzymatic and enzymatic reactions in order to maintain ROS homeostasis. Results Transgenic cassava plants that co-express cytosolic superoxide dismu...

  18. Residual stress control and design of next-generation ultra-hard gear steels

    Science.gov (United States)

    Qian, Yana

    In high power density transmission systems, Ni-Co secondary hardening steels have shown great potential for next-generation gear applications due to their excellent strength, toughness and superior fatigue performance. Study of residual stress generation and evolution in Ferrium C61 and C67 gear steels revealed that shot peening and laser peening processes effectively produce desired beneficial residual stress in the steels for enhanced fatigue performance. Surface residual stress levels of -1.4GPa and -1.5GPa were achieved in shot peened C61 and laser peened C67, respectively, without introducing large surface roughness or defects. Higher compressive residual stress is expected in C67 according to a demonstrated correlation between attainable residual stress and material hardness. Due to the lack of appropriate shot media, dual laser peening is proposed for future peening optimization in C67. A novel non-destructive synchrotron radiation technique was implemented and applied for the first time for residual stress distribution analysis in gear steels with large composition and property gradients. Observed substantial residual stress redistribution and material microstructure change during the rolling contact fatigue screening test with extremely high 5.4GPa load indicates the unsuitability of the test as a fatigue life predictor. To exploit benefits of higher case hardness and associated residual stress, a new material and process (CryoForm70) aiming at 70Rc surface hardness was designed utilizing the systems approach based on thermodynamics and secondary hardening mechanisms. The composition design was first validated by the excellent agreement between experimental and theoretical core martensite start temperature in the prototype. A novel cryogenic deformation process was concurrently designed to increase the case martensite volume fraction from 76% to 92% for enhanced strengthening efficiency and surface hardness. High temperature vacuum carburizing was

  19. Mechanisms of nanotoxicity: Generation of reactive oxygen species

    Directory of Open Access Journals (Sweden)

    Peter P. Fu

    2014-03-01

    Full Text Available Nanotechnology is a rapidly developing field in the 21st century, and the commercial use of nanomaterials for novel applications is increasing exponentially. To date, the scientific basis for the cytotoxicity and genotoxicity of most manufactured nanomaterials are not understood. The mechanisms underlying the toxicity of nanomaterials have recently been studied intensively. An important mechanism of nanotoxicity is the generation of reactive oxygen species (ROS. Overproduction of ROS can induce oxidative stress, resulting in cells failing to maintain normal physiological redox-regulated functions. This in turn leads to DNA damage, unregulated cell signaling, change in cell motility, cytotoxicity, apoptosis, and cancer initiation. There are critical determinants that can affect the generation of ROS. These critical determinants, discussed briefly here, include: size, shape, particle surface, surface positive charges, surface-containing groups, particle dissolution, metal ion release from nanometals and nanometal oxides, UV light activation, aggregation, mode of interaction with cells, inflammation, and pH of the medium.

  20. Assessment of a Standardized ROS Production Profile in Humans by Electron Paramagnetic Resonance

    Directory of Open Access Journals (Sweden)

    Simona Mrakic-Sposta

    2012-01-01

    Full Text Available Despite the growing interest in the role of reactive oxygen species (ROS in health and disease, reliable quantitative noninvasive methods for the assessment of oxidative stress in humans are still lacking. EPR technique, coupled to a specific spin probe (CMH: 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine is here presented as the method of choice to gain a direct measurement of ROS in biological fluids and tissues. The study aimed at demonstrating that, differently from currently available “a posteriori” assays of ROS-induced damage by means of biomolecules (e.g., proteins and lipids spin-trapping EPR provides direct evidence of the “instantaneous” presence of radical species in the sample and, as signal areas are proportional to the number of excited electron spins, lead to absolute concentration levels. Using a recently developed bench top continuous wave system (e-scan EPR scanner, Bruker dealing with very low ROS concentration levels in small (50 μL samples, we successfully monitored rapid ROS production changes in peripheral blood of athletes after controlled exercise and sedentary subjects after antioxidant supplementation. The correlation between EPR results and data obtained by various enzymatic assays (e.g., protein carbonyls and thiobarbituric acid reactive substances was determined too. Synthetically, our method allows reliable, quick, noninvasive quantitative determination of ROS in human peripheral blood.

  1. Antioxidant potential of CORM-A1 and resveratrol during TNF-α/cycloheximide-induced oxidative stress and apoptosis in murine intestinal epithelial MODE-K cells

    International Nuclear Information System (INIS)

    Babu, Dinesh; Leclercq, Georges; Goossens, Vera; Remijsen, Quinten; Vandenabeele, Peter; Motterlini, Roberto; Lefebvre, Romain A.

    2015-01-01

    Targeting excessive production of reactive oxygen species (ROS) could be an effective therapeutic strategy to prevent oxidative stress-associated gastrointestinal inflammation. NADPH oxidase (NOX) and mitochondrial complexes (I and II) are the major sources of ROS production contributing to TNF-α/cycloheximide (CHX)-induced apoptosis in the mouse intestinal epithelial cell line, MODE-K. In the current study, the influence of a polyphenolic compound (resveratrol) and a water-soluble carbon monoxide (CO)-releasing molecule (CORM-A1) on the different sources of TNF-α/CHX-induced ROS production in MODE-K cells was assessed. This was compared with H 2 O 2 -, rotenone- or antimycin-A-induced ROS-generating systems. Intracellular total ROS, mitochondrial-derived ROS and mitochondrial superoxide anion (O 2 · − ) production levels were assessed. Additionally, the influence on TNF-α/CHX-induced changes in mitochondrial membrane potential (Ψ m ) and mitochondrial function was studied. In basal conditions, CORM-A1 did not affect intracellular total or mitochondrial ROS levels, while resveratrol increased intracellular total ROS but reduced mitochondrial ROS production. TNF-α/CHX- and H 2 O 2 -mediated increase in intracellular total ROS production was reduced by both resveratrol and CORM-A1, whereas only resveratrol attenuated the increase in mitochondrial ROS triggered by TNF-α/CHX. CORM-A1 decreased antimycin-A-induced mitochondrial O 2 · − production without any influence on TNF-α/CHX- and rotenone-induced mitochondrial O 2 · − levels, while resveratrol abolished all three effects. Finally, resveratrol greatly reduced and abolished TNF-α/CHX-induced mitochondrial depolarization and mitochondrial dysfunction, while CORM-A1 only mildly affected these parameters. These data indicate that the cytoprotective effect of resveratrol is predominantly due to mitigation of mitochondrial ROS, while CORM-A1 acts solely on NOX-derived ROS to protect MODE-K cells from TNF

  2. Towards Interactive, Incremental Programming of ROS Nodes

    DEFF Research Database (Denmark)

    Adam, Marian Sorin; Schultz, Ulrik Pagh

    Writing software for controlling robots is a complex task, usually demanding command of many programming languages and requiring significant experimentation. We believe that a bottom-up development process that complements traditional component- and MDSD-based approaches can facilitate...... experimentation. We propose the use of an internal DSL providing both a tool to interactively create ROS nodes and a behaviour-replacement mechanism to interactively reshape existing ROS nodes by wrapping the external interfaces (the publish/subscribe topics), dynamically controlled using the Python command line...

  3. Monitoring of facial stress during space flight: Optical computer recognition combining discriminative and generative methods

    Science.gov (United States)

    Dinges, David F.; Venkataraman, Sundara; McGlinchey, Eleanor L.; Metaxas, Dimitris N.

    2007-02-01

    Astronauts are required to perform mission-critical tasks at a high level of functional capability throughout spaceflight. Stressors can compromise their ability to do so, making early objective detection of neurobehavioral problems in spaceflight a priority. Computer optical approaches offer a completely unobtrusive way to detect distress during critical operations in space flight. A methodology was developed and a study completed to determine whether optical computer recognition algorithms could be used to discriminate facial expressions during stress induced by performance demands. Stress recognition from a facial image sequence is a subject that has not received much attention although it is an important problem for many applications beyond space flight (security, human-computer interaction, etc.). This paper proposes a comprehensive method to detect stress from facial image sequences by using a model-based tracker. The image sequences were captured as subjects underwent a battery of psychological tests under high- and low-stress conditions. A cue integration-based tracking system accurately captured the rigid and non-rigid parameters of different parts of the face (eyebrows, lips). The labeled sequences were used to train the recognition system, which consisted of generative (hidden Markov model) and discriminative (support vector machine) parts that yield results superior to using either approach individually. The current optical algorithm methods performed at a 68% accuracy rate in an experimental study of 60 healthy adults undergoing periods of high-stress versus low-stress performance demands. Accuracy and practical feasibility of the technique is being improved further with automatic multi-resolution selection for the discretization of the mask, and automated face detection and mask initialization algorithms.

  4. The effect of restraints type on the generated stresses in gantry crane beam

    Directory of Open Access Journals (Sweden)

    Sowa Leszek

    2018-01-01

    Full Text Available This paper includes an analysis of the mechanical phenomena in the gantry crane beam, because the cranes are currently one of the most common devices for the transporting loads. Designing modern mechanical structures is a complex task that requires the use of appropriate tools. Such a modern tool is the numerical simulation, which uses different numerical methods. One of the best known methods is the finite element method, also used here. Simulations are limited to analysis of the strength of the gantry crane beam that was the loaded of the force load movement along its length. The numerical analysis was made to the gantry crane beam which cross-section was an I-beam and ends were fixed in different ways. As the result of numerical calculations, the stresses and displacements of the structure of gantry were obtained. The influence of the restraints type and changing the loading force position on generate the Huber-Misses stress in the gantry crane beam was estimated. The aim was to ensure that the maximum equivalent stress generated in the gantry crane beam was less than the strength of material, because then the construction is safe.

  5. Residual stresses associated with the hydraulic expansion of steam generator tubing into tubesheets

    International Nuclear Information System (INIS)

    Middlebrooks, W.B.; Harrod, D.L.; Gold, R.E.

    1991-01-01

    Westinghouse has used three different processes for the full depth expansion of tubes into the tube sheets of recirculating nuclear steam generators: mechanical rolling, explosive expansion and hydraulic expansion. Each process aims at expanding tubes tightly to tube sheets, leaving the smallest possible secondary side crevice depth, and minimizing the residual stress in the expanded tubes, all for the purpose of mitigating the effect of corrosion phenomena. The hydraulic expansion process was qualified and has been implemented since 1978, and more than 1.1 million tube ends have been hydraulically expanded into production units. In this paper, the results of the recent analytical studies related to the residual stress in the expanded tubes are summarized. The method of hydraulic expansion is explained, and some important parameters are given. Finite element method, theoretical incremental analysis, tube sheet yielding and residual stress, contact pressure, sensitivity analysis and temperature effect in the central region of tube sheets, and the residual stress in the transition zone are described. (K.I.)

  6. Dehydrins Impart Protection against Oxidative Stress in Transgenic Tobacco Plants.

    Science.gov (United States)

    Halder, Tanmoy; Upadhyaya, Gouranga; Basak, Chandra; Das, Arup; Chakraborty, Chandrima; Ray, Sudipta

    2018-01-01

    Environmental stresses generate reactive oxygen species (ROS) which might be detrimental to the plants when produced in an uncontrolled way. However, the plants ameliorate such stresses by synthesizing antioxidants and enzymes responsible for the dismutation of ROS. Additionally, the dehydrins were also able to protect the inactivation of the enzyme lactate dehydrogenase against hydroxyl radicals (OH ⋅ ) generated during Fenton's reaction. SbDhn1 and SbDhn2 overexpressing transgenic tobacco plants were able to protect against oxidative damage. Transgenic tobacco lines showed better photosynthetic efficiency along with high chlorophyll content, soluble sugar and proline. However, the malonyl dialdehyde (MDA) content was significantly lower in transgenic lines. Experimental evidence demonstrates the protective effect of dehydrins on electron transport chain in isolated chloroplast upon methyl viologen (MV) treatment. The transgenic tobacco plants showed significantly lower superoxide radical generation () upon MV treatment. The accumulation of the H 2 O 2 was also lower in the transgenic plants. Furthermore, in the transgenic plants the expression of ROS scavenging enzymes was higher compared to non-transformed (NT) or vector transformed (VT) plants. Taken together these data, during oxidative stress dehydrins function by scavenging the () directly and also by rendering protection to the enzymes responsible for the dismutation of () thereby significantly reducing the amount of hydrogen peroxides formed. Increase in proline content along with other antioxidants might also play a significant role in stress amelioration. Dehydrins thus function co-operatively with other protective mechanisms under oxidative stress conditions rendering protection in stress environment.

  7. Aluminium-induced excessive ROS causes cellular damage and metabolic shifts in black gram Vigna mungo (L.) Hepper.

    Science.gov (United States)

    Chowra, Umakanta; Yanase, Emiko; Koyama, Hiroyuki; Panda, Sanjib Kumar

    2017-01-01

    Aluminium-induced oxidative damage caused by excessive ROS production was evaluated in black gram pulse crop. Black gram plants were treated with different aluminium (Al 3+ ) concentrations (10, 50 and 100 μM with pH 4.7) and further the effects of Al 3+ were characterised by means of root growth inhibition, histochemical assay, ROS content analysis, protein carbonylation quantification and 1 H-NMR analysis. The results showed that aluminium induces excessive ROS production which leads to cellular damage, root injury, stunt root growth and other metabolic shifts. In black gram, Al 3+ induces cellular damage at the earliest stage of stress which was characterised from histochemical analysis. From this study, it was observed that prolonged stress can activate certain aluminium detoxification defence mechanism. Probably excessive ROS triggers such defence mechanism in black gram. Al 3+ can induce excessive ROS initially in the root region then transported to other parts of the plant. As much as the Al 3+ concentration increases, the rate of cellular injury and ROS production also increases. But after 72 h of stress, plants showed a lowered ROS level and cellular damage which indicates the upregulation of defensive mechanisms. Metabolic shift analysis also showed that the black gram plant under stress has less metabolic content after 24 h of treatment, but gradually, it was increased after 72 h of treatment. It was assumed that ROS played the most important role as a signalling molecule for aluminium stress in black gram.

  8. Finite element simulations of internal stresses generated during the ferroelastic deformation of NiTi bodies

    International Nuclear Information System (INIS)

    Manach, P.Y.; Favier, D.; Rio, G.

    1996-01-01

    The aim of this paper is to analyse the generation of internal stresses during the predeformation of NiTi shape memory alloys in the martensitic state. This allows to determine the initial stress state in which the material will transform during the shape memory effect due to heating consecutively to this prestrain. In that way a three-dimensional finite element model of the deformation of shape memory alloys has been developed, the constitutive law being defined using an elastohysteresis tensor model. The influence of behavioural and geometrical factors are illustrated considering the numerical simulation of different cases of practical importance for industrial applications : the study of the bending behaviour of a NiTi cantilever beam as well as the study of the swelling of a pipe connection under both uniform and non uniform internal displacement fields. (orig.)

  9. New process for the relief of mechanically induced stresses in steam generator tubes

    International Nuclear Information System (INIS)

    Joyeux, J.P.

    1980-01-01

    Heat exchangers include very generally a set of tubes assembled in 'U-type' exchangers or in 'pass-through' exchangers. The tubes are introduced in holes drilled in the tube sheet plate, welded at their extremity and expanded to insure the necessary tightness. The steam generators built by FRAMATOME belong to the U-type and include, depending upon the nominal power of the plant, about three or five thousand inconel tubes. This material has been selected for its resistance to corrosion action at high temperatures. But one drawback of inconel is that residual stress lowers considerably this resistance to corrosion; so it is very important to apply manufacturing processes involving a residual stress level as low as possible. A new process, which involves 'kiss' rolling, is described. (author)

  10. Laboratory results of stress corrosion cracking of steam generator tubes in a complex environment - An update

    Energy Technology Data Exchange (ETDEWEB)

    Horner, Olivier; Pavageau, Ellen-Mary; Vaillant, Francois [EDF R and D, Materials and Mechanics of Components Department, 77818 Moret-sur-Loing (France); Bouvier, Odile de [EDF Nuclear Engineering Division, Centre d' Expertise et d' Inspection dans les Domaines de la Realisation et de l' Exploitation, 93206 Saint Denis (France)

    2004-07-01

    Stress corrosion cracking occurs in the flow-restricted areas on the secondary side of steam generator tubes of Pressured Water Reactors (PWR), where water pollutants are likely to concentrate. Chemical analyses carried out during the shutdowns gave some insight into the chemical composition of these areas, which has evolved during these last years (i.e. less sodium as pollutants). It has been modeled in laboratory by tests in two different typical environments: the sodium hydroxide and the sulfate environments. These models satisfactorily describe the secondary side corrosion of steam generator tubes for old plant units. Furthermore, a third typical environment - the complex environment - which corresponds to an All Volatile Treatment (AVT) environment containing alumina, silica, phosphate and acetic acid has been recently studied. This particular environment satisfactorily reproduces the composition of the deposits observed on the surface of the steam generator tubes as well as the degradation of the tubes. A review of the recent laboratory results obtained by considering the complex environment are presented here. Several tests have been carried out in order to study initiation and propagation of secondary side corrosion cracking for some selected materials in such an environment. 600 Thermally Treated (TT) alloy reveals to be less sensitive to secondary side corrosion cracking than 600 Mill Annealed (MA) alloy. Finally, the influence of some related factors like stress, temperature and environmental factors are discussed. (authors)

  11. Laboratory results of stress corrosion cracking of steam generator tubes in a complex environment - An update

    International Nuclear Information System (INIS)

    Horner, Olivier; Pavageau, Ellen-Mary; Vaillant, Francois; Bouvier, Odile de

    2004-01-01

    Stress corrosion cracking occurs in the flow-restricted areas on the secondary side of steam generator tubes of Pressured Water Reactors (PWR), where water pollutants are likely to concentrate. Chemical analyses carried out during the shutdowns gave some insight into the chemical composition of these areas, which has evolved during these last years (i.e. less sodium as pollutants). It has been modeled in laboratory by tests in two different typical environments: the sodium hydroxide and the sulfate environments. These models satisfactorily describe the secondary side corrosion of steam generator tubes for old plant units. Furthermore, a third typical environment - the complex environment - which corresponds to an All Volatile Treatment (AVT) environment containing alumina, silica, phosphate and acetic acid has been recently studied. This particular environment satisfactorily reproduces the composition of the deposits observed on the surface of the steam generator tubes as well as the degradation of the tubes. A review of the recent laboratory results obtained by considering the complex environment are presented here. Several tests have been carried out in order to study initiation and propagation of secondary side corrosion cracking for some selected materials in such an environment. 600 Thermally Treated (TT) alloy reveals to be less sensitive to secondary side corrosion cracking than 600 Mill Annealed (MA) alloy. Finally, the influence of some related factors like stress, temperature and environmental factors are discussed. (authors)

  12. Life prediction of steam generator tubing due to stress corrosion crack using Monte Carlo Simulation

    International Nuclear Information System (INIS)

    Hu Jun; Liu Fei; Cheng Guangxu; Zhang Zaoxiao

    2011-01-01

    Highlights: → A life prediction model for SG tubing was proposed. → The initial crack length for SCC was determined. → Two failure modes called rupture mode and leak mode were considered. → A probabilistic life prediction code based on Monte Carlo method was developed. - Abstract: The failure of steam generator tubing is one of the main accidents that seriously affects the availability and safety of a nuclear power plant. In order to estimate the probability of the failure, a probabilistic model was established to predict the whole life-span and residual life of steam generator (SG) tubing. The failure investigated was stress corrosion cracking (SCC) after the generation of one through-wall axial crack. Two failure modes called rupture mode and leak mode based on probabilistic fracture mechanics were considered in this proposed model. It took into account the variance in tube geometry and material properties, and the variance in residual stresses and operating conditions, all of which govern the propagations of cracks. The proposed model was numerically calculated by using Monte Carlo Simulation (MCS). The plugging criteria were first verified and then the whole life-span and residual life of the SG tubing were obtained. Finally, important sensitivity analysis was also carried out to identify the most important parameters affecting the life of SG tubing. The results will be useful in developing optimum strategies for life-cycle management of the feedwater system in nuclear power plants.

  13. European contribution to the study of ROS

    DEFF Research Database (Denmark)

    Egea, Javier; Fabregat, Isabel; Frapart, Yves M

    2017-01-01

    The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better u...

  14. UPP mediated Diabetic Retinopathy via ROS/PARP and NF-κB inflammatory factor pathways.

    Science.gov (United States)

    Luo, D-W; Zheng, Z; Wang, H; Fan, Y; Chen, F; Sun, Y; Wang, W-J; Sun, T; Xu, X

    2015-01-01

    Diabetic retinopathy (DR) is a leading cause of blindness in adults at working age. Human diabetic retinopathy is characterized by the basement membrane thick, pericytes loss, microaneurysms formation, retina neovascularization and vitreous hemorrhage. To investigate whether UPP activated ROS/PARP and NF-κB inflammatory factor pathways in Diabetic Retinopathy, human retinal endothelial cells (HRECs) and rats with streptozotocin-induced diabetes were used to determine the effect of UPP on ROS generation, cell apoptosis, mitochondrial membrane potential (ΔΨm) and inflammatory factor protein expression, through flow cytometry assay, immunohistochemistry, Real-time PCR, Western blot analysis and ELISA. The levels of ROS and apoptosis and the expressions of UPP (Ub and E3) and inflammatory factor protein were increased in high glucose-induced HRECs and retina of diabetic rats, while ΔΨm was decreased. The UPP inhibitor and UbshRNA could attenuate these effects through inhibiting the pathway of ROS/PARP and the expression of NF-κB inflammatory factors, and the increased UPP was a result of high glucose-induced increase of ROS generation and NF-κBp65 expression, accompanied with the decrease of ΔΨm. Clinical study showed the overexpression of UPP and detachment of epiretinal membranes in proliferative DR (PDR) patients. It has been indicated that the pathogenic effect of UPP on DR was involved in the increase of ROS generation and NF-κB expression, which associated with the ROS/PARP and NF-κB inflammatory factor pathways. Our study supports a new insight for further application of UPP inhibitor in DR treatment.

  15. Curcumin-induced inhibition of cellular reactive oxygen species generation: novel therapeutic implications.

    Science.gov (United States)

    Balasubramanyam, M; Koteswari, A Adaikala; Kumar, R Sampath; Monickaraj, S Finny; Maheswari, J Uma; Mohan, V

    2003-12-01

    There is evidence for increased levels of circulating reactive oxygen species (ROS) in diabetics, as indirectly inferred by the findings of increased lipid peroxidation and decreased antioxidant status. Direct measurements of intracellular generation of ROS using fluorescent dyes also demonstrate an association of oxidative stress with diabetes. Although phenolic compounds attenuate oxidative stress-related tissue damage, there are concerns over toxicity of synthetic phenolic antioxidants and this has considerably stimulated interest in investigating the role of natural phenolics in medicinal applications. Curcumin (the primary active principle in turmeric, Curcuma longa Linn.) has been claimed to represent a potential antioxidant and antiinflammatory agent with phytonutrient and bioprotective properties. However there are lack of molecular studies to demonstrate its cellular action and potential molecular targets. In this study the antioxidant effect of curcumin as a function of changes in cellular ROS generation was tested. Our results clearly demonstrate that curcumin abolished both phorbol-12 myristate-13 acetate (PMA) and thapsigargin-induced ROS generation in cells from control and diabetic subjects. The pattern of these ROS inhibitory effects as a function of dose-dependency suggests that curcumin mechanistically interferes with protein kinase C (PKC) and calcium regulation. Simultaneous measurements of ROS and Ca2+ influx suggest that a rise in cytosolic Ca2+ may be a trigger for increased ROS generation. We suggest that the antioxidant and antiangeogenic actions of curcumin, as a mechanism of inhibition of Ca2+ entry and PKC activity, should be further exploited to develop suitable and novel drugs for the treatment of diabetic retinopathy and other diabetic complications.

  16. Relational Security Moderates the Effect of Serotonin Transporter Gene Polymorphism (5-HTTLPR) on Stress Generation and Depression among Adolescents

    Science.gov (United States)

    Starr, Lisa R.; Hammen, Constance; Brennan, Patricia A.; Najman, Jake M.

    2013-01-01

    Previous research demonstrates that carriers of the short allele of the serotonin transporter gene (5-HTTLPR) show both greater susceptibility to depression in response to stressful life events and higher rates of generation of stressful events in response to depression. The current study examines relational security (i.e., self-reported beliefs…

  17. Factors associated with involvement in nonmetropolitan LGBTQ organizations: Proximity? Generativity? Minority stress? Social location?

    Science.gov (United States)

    Paceley, Megan S; Oswald, Ramona Faith; Hardesty, Jennifer L

    2014-01-01

    Little is known about involvement in LGBTQ organizations. Factors associated with involvement in nonmetropolitan LGBTQ organizations were examined using logistic regression and survey data from 426 LGBTQ individuals residing in a nonmetropolitan region. Involvement was examined in five types of organizations (professional, social/recreational, religious, political, and community center/charity). The same model testing proximity, generativity, minority stress, and social location hypotheses was repeated for each organization type. Results demonstrate that the generativity hypothesis is most strongly supported. Indeed, emotional attachment to the LGBTQ community significantly increased the odds of involvement in every type of organization. However, the factors associated with involvement otherwise differed by organization type. Implications for organizational leaders are discussed.

  18. Stress corrosion cracking of steam generator tube and primary pipe in PWR type nuclear power plants

    International Nuclear Information System (INIS)

    Zhang Weiguo; Gao Fengqin; Zhou Hongyi

    1993-01-01

    The behavior of stress corrosion cracking (SCC) is studied by slow strain rate test (SSRT), constant load test (CLT) and low frequency cyclic loading test (LFCLT). The purpose of these tests is to get the test data for evaluating the integrity of pressurized boundary of pipes in Qinshan and Guangdong nuclear power plants. Tested materials are 316 nuclear grade stainless steel (SS) for primary pipes in welded heat affected zone (WHAZ) and steam generator tubes, such as Incoloy-800, Inconel-600, Inconel-690 and 321 SS which are used for steam generator in PWR. The effects of material metallurgy, shot-peening treatment, tensile load, strain rate, cyclic load and water chemistry on the behavior of SCC are investigated

  19. Autophagy inhibitor chloroquine increases sensitivity to cisplatin in QBC939 cholangiocarcinoma cells by mitochondrial ROS.

    Directory of Open Access Journals (Sweden)

    Xianzhi Qu

    Full Text Available The tumor cells have some metabolic characteristics of the original tissues, and the metabolism of the tumor cells is closely related to autophagy. However, the mechanism of autophagy and metabolism in chemotherapeutic drug resistance is still poorly understood. In this study, we investigated the role and mechanism of autophagy and glucose metabolism in chemotherapeutic drug resistance by using cholangiocarcinoma QBC939 cells with primary cisplatin resistance and hepatocellular carcinoma HepG2 cells. We found that QBC939 cells with cisplatin resistance had a higher capacity for glucose uptake, consumption, and lactic acid generation, and higher activity of the pentose phosphate pathway compared with HepG2 cells, and the activity of PPP was further increased after cisplatin treatment in QBC939 cells. It is suggested that there are some differences in the metabolism of glucose in hepatocellular carcinoma and cholangiocarcinoma cells, and the activation of PPP pathway may be related to the drug resistance. Through the detection of autophagy substrates p62 and LC3, found that QBC939 cells have a higher flow of autophagy, autophagy inhibitor chloroquine can significantly increase the sensitivity of cisplatin in cholangiocarcinoma cells compared with hepatocellular carcinoma HepG2 cells. The mechanism may be related to the inhibition of QBC939 cells with higher activity of the PPP, the key enzyme G6PDH, which reduces the antioxidant capacity of cells and increases intracellular ROS, especially mitochondrial ROS. Therefore, we hypothesized that autophagy and the oxidative stress resistance mediated by glucose metabolism may be one of the causes of cisplatin resistance in cholangiocarcinoma cells. It is suggested that according to the metabolism characteristics of tumor cells, inhibition of autophagy lysosome pathway with chloroquine may be a new route for therapeutic agents against cholangiocarcinoma.

  20. Pomegranate protects against arsenic-induced p53-dependent ROS-mediated inflammation and apoptosis in liver cells.

    Science.gov (United States)

    Choudhury, Sreetama; Ghosh, Sayan; Mukherjee, Sudeshna; Gupta, Payal; Bhattacharya, Saurav; Adhikary, Arghya; Chattopadhyay, Sreya

    2016-12-01

    Molecular mechanisms involved in arsenic-induced toxicity are complex and elusive. Liver is one of the most favored organs for arsenic toxicity as methylation of arsenic occurs mostly in the liver. In this study, we have selected a range of environmentally relevant doses of arsenic to examine the basis of arsenic toxicity and the role of pomegranate fruit extract (PFE) in combating it. Male Swiss albino mice exposed to different doses of arsenic presented marked hepatic injury as evident from histological and electron microscopic studies. Increased activities of enzymes alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatase corroborated extensive liver damage. It was further noted that arsenic exposure initiated reactive oxygen species (ROS)-dependent apoptosis in the hepatocytes involving loss of mitochondrial membrane potential. Arsenic significantly increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB), coupled with increase in phosphorylated Iκ-B, possibly as adaptive cellular survival strategies. Arsenic-induced oxidative DNA damage to liver cells culminated in p53 activation and increased expression of p53 targets like miR-34a and Bax. Pomegranate polyphenols are known to possess remarkable antioxidant properties and are capable of protecting normal cells from various stimuli-induced oxidative stress and toxicities. We explored the protective role of PFE in ameliorating arsenic-induced hepatic damage. PFE was shown to reduce ROS generation in hepatocytes, thereby reducing arsenic-induced Nrf2 activation. PFE also inhibited arsenic-induced NF-κB-inflammatory pathway. Data revealed that PFE reversed arsenic-induced hepatotoxicity and apoptosis by modulating the ROS/Nrf2/p53-miR-34a axis. For the first time, we have mapped the possible signaling pathways associated with arsenic-induced hepatotoxicity and its rescue by pomegranate polyphenols. Copyright

  1. Stress generation in adolescence: Contributions from five-factor model (FFM) personality traits and childhood maltreatment.

    Science.gov (United States)

    Kushner, Shauna C; Bagby, R Michael; Harkness, Kate L

    2017-04-01

    Youth with depression are theorized to generate stress in their lives because of a complex interaction between their personal characteristics and their chronic environmental context. Using a moderated regression approach, we provided a novel test of this hypothesis by examining whether adolescent 5-factor model personality traits moderate the associations between early emotional, physical, and sexual maltreatment and life events experienced in the past 6 months. Participants in this cross-sectional study were 110 adolescents (M = 16.24, SD = 1.53, age range = 13-17, 74.5% female) with major depressive disorder. The relation of physical maltreatment to dependent interpersonal life events was moderated by extraversion. Among physically maltreated youth, dependent interpersonal events were positively associated with extraversion. Further, the relation of sexual maltreatment to independent events were moderated by extraversion and agreeableness. Among sexually maltreated youth, independent events were negatively associated with extraversion and positively associated with agreeableness. The observed vulnerability-risk interactions are discussed in terms of their implications for understanding the role of stress generation mechanisms in an integrated model of depression. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  2. Low level genome mistranslations deregulate the transcriptome and translatome and generate proteotoxic stress in yeast

    Directory of Open Access Journals (Sweden)

    Paredes João A

    2012-06-01

    Full Text Available Abstract Background Organisms use highly accurate molecular processes to transcribe their genes and a variety of mRNA quality control and ribosome proofreading mechanisms to maintain intact the fidelity of genetic information flow. Despite this, low level gene translational errors induced by mutations and environmental factors cause neurodegeneration and premature death in mice and mitochondrial disorders in humans. Paradoxically, such errors can generate advantageous phenotypic diversity in fungi and bacteria through poorly understood molecular processes. Results In order to clarify the biological relevance of gene translational errors we have engineered codon misreading in yeast and used profiling of total and polysome-associated mRNAs, molecular and biochemical tools to characterize the recombinant cells. We demonstrate here that gene translational errors, which have negligible impact on yeast growth rate down-regulate protein synthesis, activate the unfolded protein response and environmental stress response pathways, and down-regulate chaperones linked to ribosomes. Conclusions We provide the first global view of transcriptional and post-transcriptional responses to global gene translational errors and we postulate that they cause gradual cell degeneration through synergistic effects of overloading protein quality control systems and deregulation of protein synthesis, but generate adaptive phenotypes in unicellular organisms through activation of stress cross-protection. We conclude that these genome wide gene translational infidelities can be degenerative or adaptive depending on cellular context and physiological condition.

  3. Real-time investigation of antibiotics-induced oxidative stress and superoxide release in bacteria using an electrochemical biosensor.

    Science.gov (United States)

    Liu, Xiaobo; Marrakchi, Mouna; Jahne, Michael; Rogers, Shane; Andreescu, Silvana

    2016-02-01

    The involvement of oxidative stress in the mechanism of antibiotics-meditated cell death is unclear and subject to debate. The kinetic profile and a quantitative relationship between the release of reactive oxygen species (ROS), bacteria and antibiotic type remain elusive. Here we report direct measurements and analytical quantification of the release of superoxide radicals (O2(·-)), a major contributor to ROS, in antibiotics-treated bacterial cultures using a cytochrome c electrochemical biosensor. The specificity of electrochemical measurements was established by the addition of superoxide dismutase (SOD) which decreased the O2(·-) signal. Measurements using a general ROS-specific fluorescence dye and colony forming units (CFU) assays were performed side-by-side to determine the total ROS and establish the relationship between ROS and the degree of lethality. Exposure of Escherichia coli and Listeria monocytogenes cultures to antibiotics increased the release of O2(·-) radicals in a dose-dependent manner, suggesting that the transmembrane generation of ROS may occur as part of the antibiotic action. The study provides a quantitative methodology and fundamental knowledge to further explore the role of oxidative stress in antibiotics-meditated bacterial death and to assess physiological changes associated with the complex metabolic events related to oxidative stress and bacterial resistance. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Central roles of iron in the regulation of oxidative stress in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Matsuo, Ryo; Mizobuchi, Shogo; Nakashima, Maya; Miki, Kensuke; Ayusawa, Dai; Fujii, Michihiko

    2017-10-01

    Oxygen is essential for aerobic organisms but causes cytotoxicity probably through the generation of reactive oxygen species (ROS). In this study, we screened for the genes that regulate oxidative stress in the yeast Saccharomyces cerevisiae, and found that expression of CTH2/TIS11 caused an increased resistance to ROS. CTH2 is up-regulated upon iron starvation and functions to remodel metabolism to adapt to iron starvation. We showed here that increased resistance to ROS by CTH2 would likely be caused by the decreased ROS production due to the decreased activity of mitochondrial respiration, which observation is consistent with the fact that CTH2 down-regulates the mitochondrial respiratory proteins. We also found that expression of CTH1, a paralog of CTH2, also caused an increased resistance to ROS. This finding supported the above view, because mitochondrial respiratory proteins are the common targets of CTH1 and CTH2. We further showed that supplementation of iron in medium augmented the growth of S. cerevisiae under oxidative stress, and expression of CTH2 and supplementation of iron collectively enhanced its growth under oxidative stress. Since CTH2 is regulated by iron, these findings suggested that iron played crucial roles in the regulation of oxidative stress in S. cerevisiae.

  5. High hydrostatic pressure leads to free radicals accumulation in yeast cells triggering oxidative stress.

    Science.gov (United States)

    Bravim, Fernanda; Mota, Mainã M; Fernandes, A Alberto R; Fernandes, Patricia M B

    2016-08-01

    Saccharomyces cerevisiae is a unicellular organism that during the fermentative process is exposed to a variable environment; hence, resistance to multiple stress conditions is a desirable trait. The stress caused by high hydrostatic pressure (HHP) in S. cerevisiae resembles the injuries generated by other industrial stresses. In this study, it was confirmed that gene expression pattern in response to HHP displays an oxidative stress response profile which is expanded upon hydrostatic pressure release. Actually, reactive oxygen species (ROS) concentration level increased in yeast cells exposed to HHP treatment and an incubation period at room pressure led to a decrease in intracellular ROS concentration. On the other hand, ethylic, thermic and osmotic stresses did not result in any ROS accumulation in yeast cells. Microarray analysis revealed an upregulation of genes related to methionine metabolism, appearing to be a specific cellular response to HHP, and not related to other stresses, such as heat and osmotic stresses. Next, we investigated whether enhanced oxidative stress tolerance leads to enhanced tolerance to HHP stress. Overexpression of STF2 is known to enhance tolerance to oxidative stress and we show that it also leads to enhanced tolerance to HHP stress. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. A Fundamental study of remedial technology development to prevent stress corrosion cracking of steam generator tubing

    Energy Technology Data Exchange (ETDEWEB)

    Park, In Gyu; Lee, Chang Soon [Sunmoon University, Asan (Korea)

    1998-04-01

    Most of the PWR Steam generators with tubes in Alloy 600 alloy are affected by Stress Corrosion Cracking, such as PWSCC(Primary Water Stress Corrosion Cracking) and ODSCC(Outside Diameter Stress Corrosion Cracking). This study was undertaken to establish the background for remedial technology development to prevent SCC. in the report are included the following topics: (1) General: (i) water chemistry related factors, (ii) Pourbaix(Potential-pH) Diagram, (iii) polarization plot, (iv) corrosion mode of Alloy 600, 690, and 800, (v) IGA/SCC growth rate, (vi) material suspetibility of IGA/SCC, (vii) carbon solubility of Alloy 600 (2) Microstructures of Alloy 600 MA, Alloy 600 TT, Alloy 600 SEN Alloy 690 TT(Optical, SEM, and TEM) (3) Influencing factors for PWSCC initiation rate of Alloy 600: (i) microstructure, (ii) water chemistry(B, Li), (iii) temperature, (iv) plastic deformation, (v) stress relief annealing (4) Influencing factors for PWSCC growth rate of Alloy 600: (i) water chemistry(B, Li), (ii) Scott Model, (iii) intergranular carbide, (iv) temperature, (v) hold time (5) Laboratory conditions for ODSCC initiation rate: 1% NaOH, 316 deg C; 1% NaOH, 343 deg C; 50% NaOH, 288 deg C; 10% NaOH, 302 deg C; 10% NaOH, 316 deg C; 50% NaOH, 343 deg C (6) Sludge effects for ODSCC initiation rate: CuO, Cr{sub 2}O{sub 3}, Fe{sub 3}O{sub 4} (7) Influencing factors for PWSCC growth rate of Alloy 600: (i) Caustic concentration effect, (ii) carbonate addition effect (8) Sulfate corrosion: (i) sulfate ratio and pH effect, (ii) wastage rate of Alloy 600 and Alloy 690 (9) Crevice corrosion: (i) experimental setup for crevice corrosion, (ii) organic effect, (iii) (Na{sub 2}SO{sub 4} + NaOH) effect (10) Remedial measures for SCC: (i) Inhibitors, (ii) ZnO effect. (author). 30 refs., 174 figs., 51 tabs.

  7. Shear flow generation by Reynolds stress and suppression of resistive g modes

    International Nuclear Information System (INIS)

    Sugama, H.; Horton, W.

    1993-01-01

    The authors have investigated suppression of the resistive g mode turbulence by background shear flow produced by the external source and by the fluctuation-induced Reynolds stress. For that purpose, the authors used the model consisting of the equations describing the electrostatic potential φ≡(φ 0 +φ) and the pressure fluctuation p of the resistive g mode, and the equation for the background poloidal flow. They have done the single-helicity nonlinear simulations using the model equations in the sheared slab configuration. They find that, in the nonlinear turbulent regime, significant suppression of the turbulent transport is realized only when the shear flow v' E exceeds that which makes the fastest-growing linear modes marginally stable. With the shear flow which decreases the fastest linear growth rates by about a half, the turbulent transport in the saturated state is about the same as in the case of no shear flow. As seen from the equation for the background flow v E , the relative efficiency of the external flow and the Reynolds stress for producing shear flow depends on the parameter ν. For large ν, the external flow is a dominant contribution to the total background poloidal shear flow although its strength predicted by the neoclassical theory is not enough to suppress the turbulence significantly. On the other hand, for small ν, they observe that, as the fluctuations grow, the Reynolds stress becomes large and suddenly at some critical point in time shear flow much larger than the external one is generated and leads to the significant reduction of the turbulent transport just like that of the L-H transition in tokamak experiments. It is remarkable that the Reynolds stress due to the resistive g mode fluctuations works not as a conventional viscosity term weakening the shear flow but as a negative viscosity term enhancing it

  8. Hydroxychavicol, a betel leaf component, inhibits prostate cancer through ROS-driven DNA damage and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Gundala, Sushma Reddy; Yang, Chunhua [Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Mukkavilli, Rao [Advinus Therapeutics, Karnataka (India); Paranjpe, Rutugandha; Brahmbhatt, Meera; Pannu, Vaishali; Cheng, Alice [Department of Biology, Georgia State University, Atlanta, GA 30303 (United States); Reid, Michelle D. [Department of Pathology, Emory University School of Medicine, Atlanta, GA (United States); Aneja, Ritu, E-mail: raneja@gsu.edu [Department of Biology, Georgia State University, Atlanta, GA 30303 (United States)

    2014-10-01

    Dietary phytochemicals are excellent ROS-modulating agents and have been shown to effectively enhance ROS levels beyond toxic threshold in cancer cells to ensure their selective killing while leaving normal cells unscathed. Here we demonstrate that hydroxychavicol (HC), extracted and purified from Piper betel leaves, significantly inhibits growth and proliferation via ROS generation in human prostate cancer, PC-3 cells. HC perturbed cell-cycle kinetics and progression, reduced clonogenicity and mediated cytotoxicity by ROS-induced DNA damage leading to activation of several pro-apoptotic molecules. In addition, HC treatment elicited a novel autophagic response as evidenced by the appearance of acidic vesicular organelles and increased expression of autophagic markers, LC3-IIb and beclin-1. Interestingly, quenching of ROS with tiron, an antioxidant, offered significant protection against HC-induced inhibition of cell growth and down regulation of caspase-3, suggesting the crucial role of ROS in mediating cell death. The collapse of mitochondrial transmembrane potential by HC further revealed the link between ROS generation and induction of caspase-mediated apoptosis in PC-3 cells. Our data showed remarkable inhibition of prostate tumor xenografts by ∼ 72% upon daily oral administration of 150 mg/kg bw HC by quantitative tumor volume measurements and non-invasive real-time bioluminescent imaging. HC was well-tolerated at this dosing level without any observable toxicity. This is the first report to demonstrate the anti-prostate cancer efficacy of HC in vitro and in vivo, which is perhaps attributable to its selective prooxidant activity to eliminate cancer cells thus providing compelling grounds for future preclinical studies to validate its potential usefulness for prostate cancer management. - Highlights: • HC perturbs cell-cycle progression by induction of reactive oxygen species (ROS). • HC mediated cytotoxicity by ROS-induced DNA damage leading to

  9. Hydroxychavicol, a betel leaf component, inhibits prostate cancer through ROS-driven DNA damage and apoptosis

    International Nuclear Information System (INIS)

    Gundala, Sushma Reddy; Yang, Chunhua; Mukkavilli, Rao; Paranjpe, Rutugandha; Brahmbhatt, Meera; Pannu, Vaishali; Cheng, Alice; Reid, Michelle D.; Aneja, Ritu

    2014-01-01

    Dietary phytochemicals are excellent ROS-modulating agents and have been shown to effectively enhance ROS levels beyond toxic threshold in cancer cells to ensure their selective killing while leaving normal cells unscathed. Here we demonstrate that hydroxychavicol (HC), extracted and purified from Piper betel leaves, significantly inhibits growth and proliferation via ROS generation in human prostate cancer, PC-3 cells. HC perturbed cell-cycle kinetics and progression, reduced clonogenicity and mediated cytotoxicity by ROS-induced DNA damage leading to activation of several pro-apoptotic molecules. In addition, HC treatment elicited a novel autophagic response as evidenced by the appearance of acidic vesicular organelles and increased expression of autophagic markers, LC3-IIb and beclin-1. Interestingly, quenching of ROS with tiron, an antioxidant, offered significant protection against HC-induced inhibition of cell growth and down regulation of caspase-3, suggesting the crucial role of ROS in mediating cell death. The collapse of mitochondrial transmembrane potential by HC further revealed the link between ROS generation and induction of caspase-mediated apoptosis in PC-3 cells. Our data showed remarkable inhibition of prostate tumor xenografts by ∼ 72% upon daily oral administration of 150 mg/kg bw HC by quantitative tumor volume measurements and non-invasive real-time bioluminescent imaging. HC was well-tolerated at this dosing level without any observable toxicity. This is the first report to demonstrate the anti-prostate cancer efficacy of HC in vitro and in vivo, which is perhaps attributable to its selective prooxidant activity to eliminate cancer cells thus providing compelling grounds for future preclinical studies to validate its potential usefulness for prostate cancer management. - Highlights: • HC perturbs cell-cycle progression by induction of reactive oxygen species (ROS). • HC mediated cytotoxicity by ROS-induced DNA damage leading to

  10. Controlled intracellular generation of reactive oxygen species in human mesenchymal stem cells using porphyrin conjugated nanoparticles.

    Science.gov (United States)

    Lavado, Andrea S; Chauhan, Veeren M; Zen, Amer Alhaj; Giuntini, Francesca; Jones, D Rhodri E; Boyle, Ross W; Beeby, Andrew; Chan, Weng C; Aylott, Jonathan W

    2015-09-14

    Nanoparticles capable of generating controlled amounts of intracellular reactive oxygen species (ROS), that advance the study of oxidative stress and cellular communication, were synthesized by functionalizing polyacrylamide nanoparticles with zinc(II) porphyrin photosensitisers. Controlled ROS production was demonstrated in human mesenchymal stem cells (hMSCs) through (1) production of nanoparticles functionalized with varying percentages of Zn(II) porphyrin and (2) modulating the number of doses of excitation light to internalized nanoparticles. hMSCs challenged with nanoparticles functionalized with increasing percentages of Zn(II) porphyrin and high numbers of irradiations of excitation light were found to generate greater amounts of ROS. A novel dye, which is transformed into fluorescent 7-hydroxy-4-trifluoromethyl-coumarin in the presence of hydrogen peroxide, provided an indirect indicator for cumulative ROS production. The mitochondrial membrane potential was monitored to investigate the destructive effect of increased intracellular ROS production. Flow cytometric analysis of nanoparticle treated hMSCs suggested irradiation with excitation light signalled controlled apoptotic cell death, rather than uncontrolled necrotic cell death. Increased intracellular ROS production did not induce phenotypic changes in hMSC subcultures.

  11. Hydroxychavicol, a betel leaf component, inhibits prostate cancer through ROS-driven DNA damage and apoptosis

    Science.gov (United States)

    Gundala, Sushma Reddy; Yang, Chunhua; Mukkavilli, Rao; Paranjpe, Rutugandha; Brahmbhatt, Meera; Pannu, Vaishali; Cheng, Alice; Reid, Michelle D.; Aneja, Ritu

    2015-01-01

    Dietary phytochemicals are excellent ROS-modulating agents and have been shown to effectively enhance ROS levels beyond toxic threshold in cancer cells to ensure their selective killing while leaving normal cells unscathed. Here we demonstrate that hydroxychavicol (HC), extracted and purified from Piper betel leaves, significantly inhibits growth and proliferation via ROS generation in human prostate cancer, PC-3 cells. HC perturbed cell-cycle kinetics and progression, reduced clonogenicity and mediated cytotoxicity by ROS-induced DNA damage leading to activation of several pro-apoptotic molecules. In addition, HC treatment elicited a novel autophagic response as evidenced by the appearance of acidic vesicular organelles and increased expression of autophagic markers, LC3-IIb and beclin-1. Interestingly, quenching of ROS with tiron, an antioxidant, offered significant protection against HC-induced inhibition of cell growth and down regulation of caspase-3, suggesting the crucial role of ROS in mediating cell death. The collapse of mitochondrial transmembrane potential by HC further revealed the link between ROS generation and induction of caspase-mediated apoptosis in PC-3 cells. Our data showed remarkable inhibition of prostate tumor xenografts by ~72% upon daily oral administration of 150 mg/kg bw HC by quantitative tumor volume measurements and non-invasive real-time bioluminescent imaging. HC was well-tolerated at this dosing level without any observable toxicity. This is the first report to demonstrate the anti-prostate efficacy of HC in vitro and in vivo, which is perhaps attributable to its selective prooxidant activity to eliminate cancer cells thus providing compelling grounds for future preclinical studies to validate its potential usefulness for prostate cancer management. PMID:25064160

  12. Hydroxychavicol, a betel leaf component, inhibits prostate cancer through ROS-driven DNA damage and apoptosis.

    Science.gov (United States)

    Gundala, Sushma Reddy; Yang, Chunhua; Mukkavilli, Rao; Paranjpe, Rutugandha; Brahmbhatt, Meera; Pannu, Vaishali; Cheng, Alice; Reid, Michelle D; Aneja, Ritu

    2014-10-01

    Dietary phytochemicals are excellent ROS-modulating agents and have been shown to effectively enhance ROS levels beyond toxic threshold in cancer cells to ensure their selective killing while leaving normal cells unscathed. Here we demonstrate that hydroxychavicol (HC), extracted and purified from Piper betel leaves, significantly inhibits growth and proliferation via ROS generation in human prostate cancer, PC-3 cells. HC perturbed cell-cycle kinetics and progression, reduced clonogenicity and mediated cytotoxicity by ROS-induced DNA damage leading to activation of several pro-apoptotic molecules. In addition, HC treatment elicited a novel autophagic response as evidenced by the appearance of acidic vesicular organelles and increased expression of autophagic markers, LC3-IIb and beclin-1. Interestingly, quenching of ROS with tiron, an antioxidant, offered significant protection against HC-induced inhibition of cell growth and down regulation of caspase-3, suggesting the crucial role of ROS in mediating cell death. The collapse of mitochondrial transmembrane potential by HC further revealed the link between ROS generation and induction of caspase-mediated apoptosis in PC-3 cells. Our data showed remarkable inhibition of prostate tumor xenografts by ~72% upon daily oral administration of 150mg/kg bw HC by quantitative tumor volume measurements and non-invasive real-time bioluminescent imaging. HC was well-tolerated at this dosing level without any observable toxicity. This is the first report to demonstrate the anti-prostate cancer efficacy of HC in vitro and in vivo, which is perhaps attributable to its selective prooxidant activity to eliminate cancer cells thus providing compelling grounds for future preclinical studies to validate its potential usefulness for prostate cancer management. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Sensitivity of the green algae Chlamydomonas reinhardtii to gamma radiation: Photosynthetic performance and ROS formation

    Energy Technology Data Exchange (ETDEWEB)

    Gomes, Tânia, E-mail: tania.gomes@niva.no [Norwegian Institute for Water Research (NIVA), Section of Ecotoxicology and Risk Assessment, Gaustadalléen 21, N-0349, Oslo (Norway); Centre for Environmental Radioactivity, Norwegian University of Life Sciences (NMBU), Post Box 5003, N-1432 Ås (Norway); Xie, Li [Norwegian Institute for Water Research (NIVA), Section of Ecotoxicology and Risk Assessment, Gaustadalléen 21, N-0349, Oslo (Norway); Centre for Environmental Radioactivity, Norwegian University of Life Sciences (NMBU), Post Box 5003, N-1432 Ås (Norway); Brede, Dag; Lind, Ole-Christian [Centre for Environmental Radioactivity, Norwegian University of Life Sciences (NMBU), Post Box 5003, N-1432 Ås (Norway); Department for Environmental Sciences, Faculty of Environmental Science & Technology, Norwegian University of Life Sciences (NMBU), Post Box 5003, N-1432, Ås (Norway); Solhaug, Knut Asbjørn [Centre for Environmental Radioactivity, Norwegian University of Life Sciences (NMBU), Post Box 5003, N-1432 Ås (Norway); Department of Ecology and Natural Resource Management, Norwegian University of Life Sciences (NMBU), Postbox 5003, N-1432, Ås (Norway); Salbu, Brit [Centre for Environmental Radioactivity, Norwegian University of Life Sciences (NMBU), Post Box 5003, N-1432 Ås (Norway); Department for Environmental Sciences, Faculty of Environmental Science & Technology, Norwegian University of Life Sciences (NMBU), Post Box 5003, N-1432, Ås (Norway); and others

    2017-02-15

    Highlights: • Chlorophyll fluorescence parameters affected at higher dose rates. • Changes in PSII associated with electron transport and energy dissipation pathways. • Dose-dependent ROS production in algae exposed to gamma radiation. • Decrease in photosynthetic efficiency connected to ROS formation. - Abstract: The aquatic environment is continuously exposed to ionizing radiation from both natural and anthropogenic sources, making the characterization of ecological and health risks associated with radiation of large importance. Microalgae represent the main source of biomass production in the aquatic ecosystem, thus becoming a highly relevant biological model to assess the impacts of gamma radiation. However, little information is available on the effects of gamma radiation on microalgal species, making environmental radioprotection of this group of species challenging. In this context, the present study aimed to improve the understanding of the effects and toxic mechanisms of gamma radiation in the unicellular green algae Chlamydomonas reinhardtii focusing on the activity of the photosynthetic apparatus and ROS formation. Algal cells were exposed to gamma radiation (0.49–1677 mGy/h) for 6 h and chlorophyll fluorescence parameters obtained by PAM fluorometry, while two fluorescent probes carboxy-H{sub 2}DFFDA and DHR 123 were used for the quantification of ROS. The alterations seen in functional parameters of C. reinhardtii PSII after 6 h of exposure to gamma radiation showed modifications of PSII energy transfer associated with electron transport and energy dissipation pathways, especially at the higher dose rates used. Results also showed that gamma radiation induced ROS in a dose-dependent manner under both light and dark conditions. The observed decrease in photosynthetic efficiency seems to be connected to the formation of ROS and can potentially lead to oxidative stress and cellular damage in chloroplasts. To our knowledge, this is the first

  14. Sensitivity of the green algae Chlamydomonas reinhardtii to gamma radiation: Photosynthetic performance and ROS formation

    International Nuclear Information System (INIS)

    Gomes, Tânia; Xie, Li; Brede, Dag; Lind, Ole-Christian; Solhaug, Knut Asbjørn; Salbu, Brit

    2017-01-01

    Highlights: • Chlorophyll fluorescence parameters affected at higher dose rates. • Changes in PSII associated with electron transport and energy dissipation pathways. • Dose-dependent ROS production in algae exposed to gamma radiation. • Decrease in photosynthetic efficiency connected to ROS formation. - Abstract: The aquatic environment is continuously exposed to ionizing radiation from both natural and anthropogenic sources, making the characterization of ecological and health risks associated with radiation of large importance. Microalgae represent the main source of biomass production in the aquatic ecosystem, thus becoming a highly relevant biological model to assess the impacts of gamma radiation. However, little information is available on the effects of gamma radiation on microalgal species, making environmental radioprotection of this group of species challenging. In this context, the present study aimed to improve the understanding of the effects and toxic mechanisms of gamma radiation in the unicellular green algae Chlamydomonas reinhardtii focusing on the activity of the photosynthetic apparatus and ROS formation. Algal cells were exposed to gamma radiation (0.49–1677 mGy/h) for 6 h and chlorophyll fluorescence parameters obtained by PAM fluorometry, while two fluorescent probes carboxy-H 2 DFFDA and DHR 123 were used for the quantification of ROS. The alterations seen in functional parameters of C. reinhardtii PSII after 6 h of exposure to gamma radiation showed modifications of PSII energy transfer associated with electron transport and energy dissipation pathways, especially at the higher dose rates used. Results also showed that gamma radiation induced ROS in a dose-dependent manner under both light and dark conditions. The observed decrease in photosynthetic efficiency seems to be connected to the formation of ROS and can potentially lead to oxidative stress and cellular damage in chloroplasts. To our knowledge, this is the first report

  15. Examining coping style and the relationship between stress and subjective well-being in Australia's 'sandwich generation'.

    Science.gov (United States)

    Gillett, Jade E; Crisp, Dimity A

    2017-09-01

    The sandwich generation represents adults, often in midlife, who care for both children and ageing parents/relatives. While the stress they experience has received some attention, little research has investigated the subjective well-being (SWB) of this population. This study examined the relationship between perceived stress and SWB and the moderating effect of coping style. Ninety-three participants (80 women), aged 23-63 years, completed an online survey measuring perceived stress, coping strategies, life satisfaction and positive and negative affect. Stress was negatively associated with SWB. While emotion- and problem-focused coping were directly associated with SWB outcomes, the only moderating effect found was for avoidance-focused coping (AFC). Specifically, AFC was associated with higher positive affect for those reporting lower stress. This study highlights the need to recognise the distinct circumstances that exist for the sandwich generation. Limitations and suggestions for future research are discussed. © 2017 AJA Inc.

  16. Oxidative stress drivers and modulators in obesity and cardiovascular disease: from biomarkers to therapeutic approach.

    Science.gov (United States)

    Santilli, F; Guagnano, M T; Vazzana, N; La Barba, S; Davi, G

    2015-01-01

    This review article is intended to describe how oxidative stress regulates cardiovascular disease development and progression. Epigenetic mechanisms related to oxidative stress, as well as more reliable biomarkers of oxidative stress, are emerging over the last years as potentially useful tools to design therapeutic approaches aimed at modulating enhanced oxidative stress "in vivo", thereby mitigating the consequent atherosclerotic burden. As a paradigm, we describe the case of obesity, in which the intertwining among oxidative stress, due to caloric overload, chronic low-grade inflammation induced by adipose tissue dysfunction, and platelet activation represents a vicious cycle favoring the progression of atherothrombosis. Oxidative stress is a major player in the pathobiology of cardiovascular disease (CVD). Reactive oxygen species (ROS)- dependent signaling pathways prompt transcriptional and epigenetic dysregulation, inducing chronic low-grade inflammation, platelet activation and endothelial dysfunction. In addition, several oxidative biomarkers have been proposed with the potential to improve current understanding of the mechanisms underlying CVD. These include ROS-generating and/or quenching molecules, and ROS-modified compounds, such as F2-isoprostanes. There is also increasing evidence that noncoding micro- RNA (mi-RNA) are critically involved in post- transcriptional regulation of cell functions, including ROS generation, inflammation, regulation of cell proliferation, adipocyte differentiation, angiogenesis and apoptosis. These molecules have promising translational potential as both markers of disease and site of targeted interventions. Finally, oxidative stress is a critical target of several cardioprotective drugs and nutraceuticals, including antidiabetic agents, statins, renin-angiotensin system blockers, polyphenols and other antioxidants. Further understanding of ROS-generating mechanisms, their biological role as well as potential therapeutic

  17. Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1.

    Science.gov (United States)

    Sada, Kiminori; Nishikawa, Takeshi; Kukidome, Daisuke; Yoshinaga, Tomoaki; Kajihara, Nobuhiro; Sonoda, Kazuhiro; Senokuchi, Takafumi; Motoshima, Hiroyuki; Matsumura, Takeshi; Araki, Eiichi

    2016-01-01

    We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD) overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner.

  18. Stress corrosion cracking susceptibility of steam generator tube materials in AVT (all volatile treatment) chemistry contaminated with lead

    International Nuclear Information System (INIS)

    Gomez Briceno, D.; Castano, M.L.; Garcia, M.S.

    1996-01-01

    Alloy 600 steam generator tubing has shown a high susceptibility to stress corrosion degradation at the operation conditions of pressurized water reactors. Several contaminants, such as lead, have been postulated as being responsible for producing the secondary side stress corrosion cracking that has occurred mainly at the location where these contaminants can concentrate. An extensive experimental work has been carried out in order to better understand the effects of lead on the stress corrosion cracking susceptibility of steam generator tube materials, namely Alloys 600, 690 and 800. This paper presents the experimental work conducted with a view to determining the influence of lead oxide concentration in AVT (all volatile treatment) conditions on the stress corrosion resistance of nickel alloys used in the fabrication of steam generator tubing. (orig.)

  19. Resveratrol protects vascular endothelial cells from high glucose-induced apoptosis through inhibition of NADPH oxidase activation-driven oxidative stress.

    Science.gov (United States)

    Chen, Feng; Qian, Li-Hua; Deng, Bo; Liu, Zhi-Min; Zhao, Ying; Le, Ying-Ying

    2013-09-01

    Hyperglycemia-induced oxidative stress has been implicated in diabetic vascular complications in which NADPH oxidase is a major source of reactive oxygen species (ROS) generation. Resveratrol is a naturally occurring polyphenol, which has vasoprotective effects in diabetic animal models and inhibits high glucose (HG)-induced oxidative stress in endothelial cells. We aimed to examine whether HG-induced NADPH oxidase activation and ROS production contribute to glucotoxicity to endothelial cells and the effect of resveratrol on glucotoxicity. Using a murine brain microvascular endothelial cell line bEnd3, we found that NADPH oxidase inhibitor (apocynin) and resveratrol both inhibited HG-induced endothelial cell apoptosis. HG-induced elevation of NADPH oxidase activity and production of ROS were inhibited by apocynin, suggesting that HG induces endothelial cell apoptosis through NADPH oxidase-mediated ROS production. Mechanistic studies revealed that HG upregulated NADPH oxidase subunit Nox1 but not Nox2, Nox4, and p22(phox) expression through NF-κB activation, which resulted in elevation of NADPH oxidase activity and consequent ROS production. Resveratrol prevented HG-induced endothelial cell apoptosis through inhibiting HG-induced NF-κB activation, NADPH oxidase activity elevation, and ROS production. HG induces endothelial cell apoptosis through NF-κB/NADPH oxidase/ROS pathway, which was inhibited by resveratrol. Our findings provide new potential therapeutic targets against brain vascular complications of diabetes. © 2013 John Wiley & Sons Ltd.

  20. MAP17, a ROS-dependent oncogene

    International Nuclear Information System (INIS)

    Carnero, Amancio

    2012-01-01

    MAP17 is a small 17 kDa non-glycosylated membrane protein previously identified as being overexpressed in carcinomas. Breast tumor cells that overexpress MAP17 show an increased tumoral phenotype with enhanced proliferative capabilities both in the presence or the absence of contact inhibition, decreased apoptotic sensitivity, and increased migration. MAP17-expressing clones also grow better in nude mice. The increased malignant cell behavior induced by MAP17 is associated with an increase in reactive oxygen species (ROS) production, and the treatment of MAP17-expressing cells with antioxidants results in a reduction in the tumorigenic properties of these cells. The MAP17-dependent increase in ROS and tumorigenesis relies on its PDZ-binding domain because disruption of this sequence by point mutations abolishes the ability of MAP17 to enhance ROS production and tumorigenesis. MAP17 is overexpressed in a great variety of human carcinomas, including breast tumors. Immunohistochemical analysis of MAP17 during cancer progression demonstrates that overexpression of the protein strongly correlates with tumoral progression. Generalized MAP17 overexpression in human carcinomas indicates that MAP17 can be a good marker for tumorigenesis and, especially, for malignant progression.

  1. Durum wheat dehydrin (DHN-5) confers salinity tolerance to transgenic Arabidopsis plants through the regulation of proline metabolism and ROS scavenging system.

    Science.gov (United States)

    Saibi, Walid; Feki, Kaouthar; Ben Mahmoud, Rihem; Brini, Faiçal

    2015-11-01

    The wheat dehydrin (DHN-5) gives birth to salinity tolerance to transgenic Arabidopsis plants by the regulation of proline metabolism and the ROS scavenging system. Dehydrins (DHNs) are involved in plant abiotic stress tolerance. In this study, we reported that salt tolerance of transgenic Arabidopsis plants overexpressing durum wheat dehydrin (DHN-5) was closely related to the activation of the proline metabolism enzyme (P5CS) and some antioxidant biocatalysts. Indeed, DHN-5 improved P5CS activity in the transgenic plants generating a significant proline accumulation. Moreover, salt tolerance of Arabidopsis transgenic plants was accompanied by an excellent activation of antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and peroxide dismutase (POD) and generation of a lower level of hydrogen peroxide (H2O2) in leaves compared to the wild-type plants. The enzyme activities were enhanced in these transgenic plants in the presence of exogenous proline. Nevertheless, proline accumulation was slightly reduced in transgenic plants promoting chlorophyll levels. All these results suggest the crucial role of DHN-5 in response to salt stress through the activation of enzymes implicated in proline metabolism and in ROS scavenging enzymes.

  2. Effects of exposure to high glucose on primary cultured hippocampal neurons: involvement of intracellular ROS accumulation.

    Science.gov (United States)

    Liu, Di; Zhang, Hong; Gu, Wenjuan; Zhang, Mengren

    2014-06-01

    Recent studies showed that hyperglycemia is the main trigger of diabetic cognitive impairment and can cause hippocampus abnormalities. The goal of this study is to explore the effects of different concentrations of high glucose for different exposure time on cell viability as well as intracellular reactive oxygen species (ROS) generation of primary cultured hippocampal neurons. Hippocampal neurons were exposed to different concentrations of high glucose (50, 75, 100, 125, and 150 mM) for 24, 48, 72 and 96 h. Cell viability and nuclear morphology were evaluated by MTT and Hoechst assays, respectively. Intracellular ROS were monitored using the fluorescent probe DCFH-DA. The results showed that, compared with control group, the cell viability of all high glucose-treated groups decreased significantly after 72 h and there also was a significant increase of apoptotic nuclei in high glucose-treated groups from 72 to 96 h. Furthermore, 50 mM glucose induced a peak rise in ROS generation at 24 h and the intracellular ROS levels of 50 mM glucose group were significantly higher than the corresponding control group from 6 to 72 h. These results suggest that hippocampal neurons could be injured by high glucose exposure and the neuronal injury induced by high glucose is potentially mediated through intracellular ROS accumulation.

  3. X-ray evaluation of residual stress distributions within surface machined layer generated by surface machining and sequential welding

    International Nuclear Information System (INIS)

    Taniguchi, Yuu; Okano, Shigetaka; Mochizuki, Masahito

    2017-01-01

    The excessive tensile residual stress generated by welding after surface machining may be an important factor to cause stress corrosion cracking (SCC) in nuclear power plants. Therefore we need to understand and control the residual stress distribution appropriately. In this study, residual stress distributions within surface machined layer generated by surface machining and sequential welding were evaluated by X-ray diffraction method. Depth directional distributions were also investigated by electrolytic polishing. In addition, to consider the effect of work hardened layer on the residual stress distributions, we also measured full width at half maximum (FWHM) obtained from X-ray diffraction. Testing material was a low-carbon austenitic stainless steel type SUS316L. Test specimens were prepared by surface machining with different cutting conditions. Then, bead-on-plate welding under the same welding condition was carried out on the test specimens with different surface machined layer. As a result, the tensile residual stress generated by surface machining increased with increasing cutting speed and showed nearly uniform distributions on the surface. Furthermore, the tensile residual stress drastically decreased with increasing measurement depth within surface machined layer. Then, the residual stress approached 0 MPa after the compressive value showed. FWHM also decreased drastically with increasing measurement depth and almost constant value from a certain depth, which was almost equal regardless of the machining condition, within surface machined layer in all specimens. After welding, the transverse distribution of the longitudinal residual stress varied in the area apart from the weld center according to machining conditions and had a maximum value in heat affected zone. The magnitude of the maximum residual stress was almost equal regardless of the machining condition and decreased with increasing measurement depth within surface machined layer. Finally, the

  4. ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Pierpaola Davalli

    2016-01-01

    Full Text Available The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS and/or Reactive Nitrosative Species (RNS. Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging.

  5. Bartter/Gitelman syndromes as a model to study systemic oxidative stress in humans.

    Science.gov (United States)

    Maiolino, Giuseppe; Azzolini, Matteo; Rossi, Gian Paolo; Davis, Paul A; Calò, Lorenzo A

    2015-11-01

    Reactive oxygen species (ROS) are intermediates in reduction-oxidation reactions that begin with the addition of one electron to molecular oxygen, generating the primary ROS superoxide, which in turn interacts with other molecules to produce secondary ROS, such as hydrogen peroxide, hydroxyl radical, and peroxynitrite. ROS are continuously produced during metabolic processes and are deemed to play an important role in cardiovascular diseases, namely, myocardial hypertrophy and fibrosis and atherosclerosis, via oxidative damage of lipids, proteins, and deoxyribonucleic acid. Angiotensin II (Ang II) is a potent vasoactive agent that also exerts mitogenic, proinflammatory, and profibrotic effects through several signaling pathways, in part involving ROS, particularly superoxide and hydrogen peroxide. Moreover, Ang II stimulates NADPH oxidases, leading to higher ROS generation and oxidative stress. Bartter/Gitelman syndrome patients, despite elevated plasma renin activity, Ang II, and aldosterone levels, exhibit reduced peripheral resistance, normal/low blood pressure, and blunted pressor effect of vasoconstrictors. In addition, notwithstanding the activation of the renin-angiotensin system and the increased plasma levels of Ang II, these patients display decreased production of ROS, reduced oxidative stress, and increased antioxidant defenses. In fact, Bartter/Gitelman syndrome patients are characterized by reduced levels of p22(phox) gene expression and undetectable plasma peroxynitrite levels, while showing increased plasma antioxidant power and expression of antioxidant enzymes, such as heme oxygenase-1. In conclusion, multifarious data suggest that Bartter and Gitelman syndrome patients are a model of low oxidative stress and high antioxidant defenses. The contribution offered by the study of these syndromes in elucidating the molecular mechanisms underlying this favorable status could offer chances for new therapeutic targets in disease characterized by high

  6. Uric Acid Induces Hepatic Steatosis by Generation of Mitochondrial Oxidative Stress

    Science.gov (United States)

    Lanaspa, Miguel A.; Sanchez-Lozada, Laura G.; Choi, Yea-Jin; Cicerchi, Christina; Kanbay, Mehmet; Roncal-Jimenez, Carlos A.; Ishimoto, Takuji; Li, Nanxing; Marek, George; Duranay, Murat; Schreiner, George; Rodriguez-Iturbe, Bernardo; Nakagawa, Takahiko; Kang, Duk-Hee; Sautin, Yuri Y.; Johnson, Richard J.

    2012-01-01

    Metabolic syndrome represents a collection of abnormalities that includes fatty liver, and it currently affects one-third of the United States population and has become a major health concern worldwide. Fructose intake, primarily from added sugars in soft drinks, can induce fatty liver in animals and is epidemiologically associated with nonalcoholic fatty liver disease in humans. Fructose is considered lipogenic due to its ability to generate triglycerides as a direct consequence of the metabolism of the fructose molecule. Here, we show that fructose also stimulates triglyceride synthesis via a purine-degrading pathway that is triggered from the rapid phosphorylation of fructose by fructokinase. Generated AMP enters into the purine degradation pathway through the activation of AMP deaminase resulting in uric acid production and the generation of mitochondrial oxidants. Mitochondrial oxidative stress results in the inhibition of aconitase in the Krebs cycle, resulting in the accumulation of citrate and the stimulation of ATP citrate lyase and fatty-acid synthase leading to de novo lipogeneis. These studies provide new insights into the pathogenesis of hepatic fat accumulation under normal and diseased states. PMID:23035112

  7. Diagnosis of 3-dimensional geometry and stress corrosion cracking in steam generator tubes

    International Nuclear Information System (INIS)

    Lee, D.H.; Choi, M.S.; Hur, D.H.; Kim, K.M.; Han, J.H.; Song, M.H.

    2015-01-01

    Most of the corrosive degradations in steam generator tubes of nuclear power plants are closely related to the residual stress existing in the local region of a geometric change, that is, an expansion transition, u-bend, dent, bulge, etc. Therefore, accurate information on a geometric anomaly (precursor of degradation) in a tube is a prerequisite to the activity of pre- and in-service non destructive inspection for a precise and earlier detection of a defect in order to prevent a failure during an operation, and also for a root cause analysis of a failure. In this paper, a new diagnostic eddy current probe technology which has simultaneous dual function of a 3-dimensional geometry measurement and defect detection in steam generator tube is introduced. The D-Probe is a rotary type eddy current coil probe equipped with 3 different eddy current coil units (surface riding type plus-point and pancake coils for defect detection, and non-surface riding type shielded high frequency pancake coil for tube profile measurement). A specific data analysis software has been developed. By comparing the eddy current data from the defect with those from the geometric changes, the relationship between the degradation and geometric changes can be revealed. Also, it supplies information on tube location at which defect is most probable and thus, a more efficient detection of earlier degradation. The use of D-probe and analysis software has been demonstrated for steam generator tubes with various geometric anomalies in manufacturing and operating nuclear power plants

  8. Cobalt iron oxide nanoparticles induce cytotoxicity and regulate the apoptotic genes through ROS in human liver cells (HepG2).

    Science.gov (United States)

    Ahamed, Maqusood; Akhtar, Mohd Javed; Khan, M A Majeed; Alhadlaq, Hisham A; Alshamsan, Aws

    2016-12-01

    Cobalt iron oxide (CoFe 2 O 4 ) nanoparticles (CIO NPs) have been one of the most widely explored magnetic NPs because of their excellent chemical stability, mechanical hardness and heat generating potential. However, there is limited information concerning the interaction of CIO NPs with biological systems. In this study, we investigated the reactive oxygen species (ROS) mediated cytotoxicity and apoptotic response of CIO NPs in human liver cells (HepG2). Diameter of crystalline CIO NPs was found to be 23nm with a band gap of 1.97eV. CIO NPs induced cell viability reduction and membrane damage, and degree of induction was dose- and time-dependent. CIO NPs were also found to induce oxidative stress revealed by induction of ROS, depletion of glutathione and lower activity of superoxide dismutase enzyme. Real-time PCR data has shown that mRNA level of tumor suppressor gene p53 and apoptotic genes (bax, CASP3 and CASP9) were higher, while the expression level of anti-apoptotic gene bcl-2 was lower in cells following exposure to CIO NPs. Activity of caspase-3 and caspase-9 enzymes was also higher in CIO NPs exposed cells. Furthermore, co-exposure of N-acetyl-cysteine (ROS scavenger) efficiently abrogated the modulation of apoptotic genes along with the prevention of cytotoxicity caused by CIO NPs. Overall, we observed that CIO NPs induced cytotoxicity and apoptosis in HepG2 cells through ROS via p53 pathway. This study suggests that toxicity mechanisms of CIO NPs should be further investigated in animal models. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Similar stress responses are elicited by copper and ultraviolet radiation in the aquatic plant Lemna gibba: Implication of reactive oxygen species as common signals

    International Nuclear Information System (INIS)

    Babu, T.S.; Akhtar, T.A.; Lampi, M.A.; Tripuranthakam, S.; Dixon, D.G.; Greenberg, B.M.

    2003-01-01

    Metals and ultraviolet (UV) radiation are two environmental stressors that can cause damage to plants. These two types of stressors often impact simultaneously on plants and both are known to promote reactive oxygen species (ROS) production. However, little information is available on the potential parallel stress responses elicited by metals and UV radiation. Using the aquatic plant Lemna gibba, we found that copper and simulated solar radiation (SSR, a light source containing photosynthetically active radiation (PAR) and UV radiation) induced similar responses in the plants. Both copper and SSR caused ROS formation. The ROS levels were higher when copper was combined with SSR than when applied with PAR. Higher concentrations of copper plus PAR caused toxicity as monitored by diminished growth and chlorophyll content. This toxicity was more pronounced when copper was combined with SSR. Because the generation of ROS was also higher when copper was combined with SSR, we attributed this enhanced toxicity to elevated levels of ROS. In comparison to PAR-grown plants, SSR treated plants exhibited elevated levels of superoxide dismutase (SOD) and glutathione reductase (GR). These enzyme levels were further elevated under both PAR and SSR when copper was added at concentrations that generated ROS. Interestingly, copper treatment in the absence of SSR (i.e. copper plus PAR) induced synthesis of the same flavonoids as those observed in SSR without copper. Finally, addition of either dimethyl thiourea or GSH (two common ROS scavengers) lowered in vivo ROS production, alleviated toxicity and diminished induction of GR as well as accumulation of UV absorbing compounds. Thus, the potential of ROS being a common signal for acclimation to stress by both copper and UV can be considered. (author)

  10. Stress

    Science.gov (United States)

    ... can be life-saving. But chronic stress can cause both physical and mental harm. There are at least three different types of stress: Routine stress related to the pressures of work, family, and other daily responsibilities Stress brought about ...

  11. Periodontitis and increase in circulating oxidative stress

    OpenAIRE

    Takaaki Tomofuji; Koichiro Irie; Toshihiro Sanbe; Tetsuji Azuma; Daisuke Ekuni; Naofumi Tamaki; Tatsuo Yamamoto; Manabu Morita

    2009-01-01

    Reactive oxygen species (ROS) are products of normal cellular metabolism. However, excessive production of ROS oxidizes DNA, lipids and proteins, inducing tissue damage. Studies have shown that periodontitis induces excessive ROS production in periodontal tissue. When periodontitis develops, ROS produced in the periodontal lesion diffuse into the blood stream, resulting in the oxidation of blood molecules (circulating oxidative stress). Such oxidation may be detrimental to systemic health. Fo...

  12. Stress corrosion cracking of steam generator tube and primary pipe in PWR type nuclear power plants

    International Nuclear Information System (INIS)

    Zhang Weiguo; Gao Fengqin; Zhou Hongyi

    1992-03-01

    The behavior of stress corrosion cracking (SCC) was studied by slow strain rate test (SSRT), constant load test (CLT) and low frequency cyclic loading test (LFCLT). The purpose of these tests is to get the test data for evaluating the integrity of pressurized boundary of pipes in Qinshan and Guangdong nuclear power plants (NPPs). Tested materials are 316 nuclear grade stainless steel (SS) for primary pipes in welded heat affected zone (WHAZ) and tubes of heat transfer, such as Incoloy-800, Inconel-600 and 321 SS which are used for steam generator in PWR NPPs. The effects of material metallurgy, shot peening treatment, tensile load, strain rate, cyclic load and water chemistry on the behavior of SCC were considered

  13. Observations and insights into Pb-assisted stress corrosion cracking of alloy 600 steam generator tubes

    International Nuclear Information System (INIS)

    Thomas, L.; Bruemmer, Stephen M.

    2005-01-01

    Pb-assisted stress-corrosion cracking (PbSCC) of Alloy 600 steam-generator tubing in high-temperature-water service and laboratory tests were studied by analytical transmission electron microscopy of cross-sectioned samples. Examinations of pulled tubes from many pressurized water reactors revealed lead in cracks from 11 of 17 samples. Comparisons of the degraded intergranular structures with ones produced in simple laboratory tests with PbO in near-neutral AVT water showed that the PbSCC characteristics in service tubing could be reproduced without complex chemistries and heat-flow conditions that can occur during plant operation. Observations of intergranular and transgranular cracks promoted by Pb in the test samples also provided new insights into the mechanisms of PbSCC in mill-annealed and thermally treated Alloy 600

  14. Stresses generated by two zygomatic implant placement techniques associated with conventional inclined anterior implants

    Directory of Open Access Journals (Sweden)

    Paulo H.T. Almeida

    2018-06-01

    Full Text Available Purpose: To make a comparative evaluation, by means of the finite element method, of the stress generated on supporting tissues and prosthetic system components, using zygomatic implants with the exteriorized and extramaxillary techniques, and different placement positions, associated either with inclined anterior implants, or those without inclination. Materials and methods: Eight (8 tridimensional models were created to represent the clinical situations being researched, using the dataset of scanned images of an edentulous model. The implants and prosthetic components were photographed on millimeter paper and inserted into Rhinoceros 3D modeling computer software. From the measurements made on the image, the virtual models were made. The application force was distributed on the occlusal surface of the working side of the left maxillary first molar, first and second premolars, and incisal regions of the central incisor, simulating the occlusal load during mastication, in a total of 150 N. Results: The extramaxillary technique presented considerable variation in increased tension on the prosthesis screws and bone tissue. In the exteriorized technique, the highest tension values occurred in the region of the ridge, and the lowest, on the zygomatic process; the absence of cantilever reduced the stress on bone tissue in almost all regions. Conclusion: The exteriorized technique was shown to be more favorable to the distribution of stresses on the micro-unit screws and bone tissue, with the model with zygomatic implant placed in the region of the first molar and inclined anterior implant presenting the best results. Keywords: Zygomatic implants, Atrophic maxilla, Finite element analysis, Cantilever, Inclined implant

  15. Curcumin Generates Oxidative Stress and Induces Apoptosis in Adult Schistosoma mansoni Worms.

    Directory of Open Access Journals (Sweden)

    Daniela de Paula Aguiar

    Full Text Available Inducing apoptosis is an interesting therapeutic approach to develop drugs that act against helminthic parasites. Researchers have investigated how curcumin (CUR, a biologically active compound extracted from rhizomes of Curcuma longa, affects Schistosoma mansoni and several cancer cell lines. This study evaluates how CUR influences the induction of apoptosis and oxidative stress in couples of adult S. mansoni worms. CUR decreased the viability of adult worms and killed them. The tegument of the parasite suffered morphological changes, the mitochondria underwent alterations, and chromatin condensed. Different apoptotic parameters were determined in an attempt to understand how CUR affected adult S. mansoni worms. CUR induced DNA damage and fragmentation and increased the expression of SmCASP3/7 transcripts and the activity of Caspase 3 in female and male worms. However, CUR did not intensify the activity of Caspase 8 in female or male worms. Evaluation of the superoxide anion and different antioxidant enzymes helped to explore the mechanism of parasite death further. The level of superoxide anion and the activity of Superoxide Dismutase (SOD increased, whereas the activity of Glutathione-S-Transferase (GST, Glutathione reductase (GR, and Glutathione peroxidase (GPX decreased, which culminated in the oxidation of proteins in adult female and male worms incubated with CUR. In conclusion, CUR generated oxidative stress followed by apoptotic-like-events in both adult female and male S. mansoni worms, ultimately killing them.

  16. Critical role of mitochondrial ROS is dependent on their site of production on the electron transport chain in ischemic heart.

    Science.gov (United States)

    Madungwe, Ngonidzashe B; Zilberstein, Netanel F; Feng, Yansheng; Bopassa, Jean C

    2016-01-01

    Reactive oxygen species (ROS) generation has been implicated in many pathologies including ischemia/reperfusion (I/R) injury. This led to multiple studies on antioxidant therapies to treat cardiovascular diseases but paradoxically, results have so far been mixed as ROS production can be beneficial as a signaling mechanism and in cardiac protection via preconditioning interventions. We investigated whether the differential impact of increased ROS in injury as well as in protection could be explained by their site of production on the mitochondrial electron transport chain. Using amplex red to measure ROS production, we found that mitochondria isolated from hearts after I/R produced more ROS than non-ischemic when complex I substrate (glutamate/malate) was used. Interestingly, the substrates of complex II (succinate) and ubiquinone (sn-glycerol 3-phosphate, G3P) produced less ROS in mitochondria from I/R hearts compared to normal healthy hearts. The inhibitors of complex I (rotenone) and complex III (antimycin A) increased ROS production when glutamate/malate and G3P were used; in contrast, they reduced ROS production when the complex II substrate was used. Mitochondrial calcium retention capacity required to induce mitochondrial permeability transition pore (mPTP) opening was measured using calcium green fluorescence and was found to be higher when mitochondria were treated with G3P and succinate compared to glutamate/malate. Furthermore, Langendorff hearts treated with glutamate/malate exhibited reduced cardiac functional recovery and increased myocardial infarct size compared to hearts treated with G3P. Thus, ROS production by the stimulated respiratory chain complexes I and III has opposite roles: cardio-deleterious when produced in complex I and cardio-protective when produced in complex III. The mechanism of these ROS involves the inhibition of the mPTP opening, a key event in cell death following ischemia/reperfusion injury.

  17. Inhibition of macrophage oxidative stress prevents the reduction of ABCA-1 transporter induced by advanced glycated albumin.

    Science.gov (United States)

    de Souza Pinto, Raphael; Castilho, Gabriela; Paim, Bruno Alves; Machado-Lima, Adriana; Inada, Natalia M; Nakandakare, Edna Regina; Vercesi, Aníbal Eugênio; Passarelli, Marisa

    2012-05-01

    We investigated the role of aminoguanidine and benfotiamine on the inhibition of reactive oxygen species (ROS) generation in macrophages induced by advanced glycated albumin (AGE-albumin) and its relationship with cell cholesterol homeostasis, emphasizing the expression of the ATP binding cassette transporter A-1 (ABCA-1). AGE-albumin was made by incubating fatty acid-free albumin with 10 mM glycolaldehyde. ROS production and ABCA-1 protein level were determined by flow cytometry in J774 macrophages treated along time with control (C) or AGE-albumin alone or in the presence of aminoguanidine or benfotiamine. Mitochondrial function was evaluated by oxygraphy. Compared to C-albumin, AGE-albumin increased ROS production in macrophages, which was ascribed to the activities of NADPH oxidase and of the mitochondrial system. Mitochondrial respiratory chain activity was reduced in cells incubated with AGE-albumin. ROS generation along time was associated with the reduction in macrophage ABCA-1 protein level. Aminoguanidine prevented ROS elevation and restored the ABCA-1 content in macrophages; on the other hand, benfotiamine that promoted a lesser reduction in ROS generation was not able to restore ABCA-1 levels. Inhibition of oxidative stress induced by AGE-albumin prevents disturbances in reverse cholesterol transport by curbing the reduction of ABCA-1 elicited by advanced glycation in macrophages and therefore may contribute to the prevention of atherosclerosis in diabetes mellitus.

  18. Coordinated Actions of Glyoxalase and Antioxidant Defense Systems in Conferring Abiotic Stress Tolerance in Plants

    Directory of Open Access Journals (Sweden)

    Mirza Hasanuzzaman

    2017-01-01

    Full Text Available Being sessile organisms, plants are frequently exposed to various environmental stresses that cause several physiological disorders and even death. Oxidative stress is one of the common consequences of abiotic stress in plants, which is caused by excess generation of reactive oxygen species (ROS. Sometimes ROS production exceeds the capacity of antioxidant defense systems, which leads to oxidative stress. In line with ROS, plants also produce a high amount of methylglyoxal (MG, which is an α-oxoaldehyde compound, highly reactive, cytotoxic, and produced via different enzymatic and non-enzymatic reactions. This MG can impair cells or cell components and can even destroy DNA or cause mutation. Under stress conditions, MG concentration in plants can be increased 2- to 6-fold compared with normal conditions depending on the plant species. However, plants have a system developed to detoxify this MG consisting of two major enzymes: glyoxalase I (Gly I and glyoxalase II (Gly II, and hence known as the glyoxalase system. Recently, a novel glyoxalase enzyme, named glyoxalase III (Gly III, has been detected in plants, providing a shorter pathway for MG detoxification, which is also a signpost in the research of abiotic stress tolerance. Glutathione (GSH acts as a co-factor for this system. Therefore, this system not only detoxifies MG but also plays a role in maintaining GSH homeostasis and subsequent ROS detoxification. Upregulation of both Gly I and Gly II as well as their overexpression in plant species showed enhanced tolerance to various abiotic stresses including salinity, drought, metal toxicity, and extreme temperature. In the past few decades, a considerable amount of reports have indicated that both antioxidant defense and glyoxalase systems have strong interactions in conferring abiotic stress tolerance in plants through the detoxification of ROS and MG. In this review, we will focus on the mechanisms of these interactions and the coordinated

  19. Coordinated Actions of Glyoxalase and Antioxidant Defense Systems in Conferring Abiotic Stress Tolerance in Plants

    Science.gov (United States)

    Hasanuzzaman, Mirza; Nahar, Kamrun; Hossain, Md. Shahadat; Mahmud, Jubayer Al; Rahman, Anisur; Inafuku, Masashi; Oku, Hirosuke; Fujita, Masayuki

    2017-01-01

    Being sessile organisms, plants are frequently exposed to various environmental stresses that cause several physiological disorders and even death. Oxidative stress is one of the common consequences of abiotic stress in plants, which is caused by excess generation of reactive oxygen species (ROS). Sometimes ROS production exceeds the capacity of antioxidant defense systems, which leads to oxidative stress. In line with ROS, plants also produce a high amount of methylglyoxal (MG), which is an α-oxoaldehyde compound, highly reactive, cytotoxic, and produced via different enzymatic and non-enzymatic reactions. This MG can impair cells or cell components and can even destroy DNA or cause mutation. Under stress conditions, MG concentration in plants can be increased 2- to 6-fold compared with normal conditions depending on the plant species. However, plants have a system developed to detoxify this MG consisting of two major enzymes: glyoxalase I (Gly I) and glyoxalase II (Gly II), and hence known as the glyoxalase system. Recently, a novel glyoxalase enzyme, named glyoxalase III (Gly III), has been detected in plants, providing a shorter pathway for MG detoxification, which is also a signpost in the research of abiotic stress tolerance. Glutathione (GSH) acts as a co-factor for this system. Therefore, this system not only detoxifies MG but also plays a role in maintaining GSH homeostasis and subsequent ROS detoxification. Upregulation of both Gly I and Gly II as well as their overexpression in plant species showed enhanced tolerance to various abiotic stresses including salinity, drought, metal toxicity, and extreme temperature. In the past few decades, a considerable amount of reports have indicated that both antioxidant defense and glyoxalase systems have strong interactions in conferring abiotic stress tolerance in plants through the detoxification of ROS and MG. In this review, we will focus on the mechanisms of these interactions and the coordinated action of

  20. Oxidative Stress Facilitates IFN-γ-Induced Mimic Extracellular Trap Cell Death in A549 Lung Epithelial Cancer Cells.

    Science.gov (United States)

    Lin, Chiou-Feng; Chen, Chia-Ling; Chien, Shun-Yi; Tseng, Po-Chun; Wang, Yu-Chih; Tsai, Tsung-Ting

    2016-01-01

    We previously demonstrated that IFN-γ induces an autophagy-regulated mimic extracellular trap cell death (ETosis) in A549 human lung cancer cells. Regarding reactive oxygen species (ROS) are involved in ETosis, this study investigated the role of oxidative stress. After IFN-γ stimulation, a necrosis-like cell death mimic ETosis occurred accompanied by the inhibition of cell growth, aberrant nuclear staining, and nucleosome release. ROS were generated in a time-dependent manner with an increase in NADPH oxidase component protein expression. STAT1-mediated IFN regulatory factor-1 activation was essential for upregulating ROS production. By genetically silencing p47phox, IFN-γ-induced ROS and mimic ETosis were significantly attenuated. This mechanistic study indicated that ROS may mediate DNA damage followed by histone H3 citrullination. Furthermore, ROS promoted IFN-γ-induced mimic ETosis in cooperation with autophagy. These findings further demonstrate that ROS regulates IFN-γ-induced mimic ETosis in lung epithelial malignancy.

  1. Interpretation of metabolic memory phenomenon using a physiological systems model: What drives oxidative stress following glucose normalization?

    Science.gov (United States)

    Voronova, Veronika; Zhudenkov, Kirill; Helmlinger, Gabriel; Peskov, Kirill

    2017-01-01

    Hyperglycemia is generally associated with oxidative stress, which plays a key role in diabetes-related complications. A complex, quantitative relationship has been established between glucose levels and oxidative stress, both in vitro and in vivo. For example, oxidative stress is known to persist after glucose normalization, a phenomenon described as metabolic memory. Also, uncontrolled glucose levels appear to be more detrimental to patients with diabetes (non-constant glucose levels) vs. patients with high, constant glucose levels. The objective of the current study was to delineate the mechanisms underlying such behaviors, using a mechanistic physiological systems modeling approach that captures and integrates essential underlying pathophysiological processes. The proposed model was based on a system of ordinary differential equations. It describes the interplay between reactive oxygen species production potential (ROS), ROS-induced cell alterations, and subsequent adaptation mechanisms. Model parameters were calibrated using different sources of experimental information, including ROS production in cell cultures exposed to various concentration profiles of constant and oscillating glucose levels. The model adequately reproduced the ROS excess generation after glucose normalization. Such behavior appeared to be driven by positive feedback regulations between ROS and ROS-induced cell alterations. The further oxidative stress-related detrimental effect as induced by unstable glucose levels can be explained by inability of cells to adapt to dynamic environment. Cell adaptation to instable high glucose declines during glucose normalization phases, and further glucose increase promotes similar or higher oxidative stress. In contrast, gradual ROS production potential decrease, driven by adaptation, is observed in cells exposed to constant high glucose.

  2. The Fumarate Reductase of Bacteroides thetaiotaomicron, unlike That of Escherichia coli, Is Configured so that It Does Not Generate Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Zheng Lu

    2017-01-01

    Full Text Available The impact of oxidative stress upon organismal fitness is most apparent in the phenomenon of obligate anaerobiosis. The root cause may be multifaceted, but the intracellular generation of reactive oxygen species (ROS likely plays a key role. ROS are formed when redox enzymes accidentally transfer electrons to oxygen rather than to their physiological substrates. In this study, we confirm that the predominant intestinal anaerobe Bacteroides thetaiotaomicron generates intracellular ROS at a very high rate when it is aerated. Fumarate reductase (Frd is a prominent enzyme in the anaerobic metabolism of many bacteria, including B. thetaiotaomicron, and prior studies of Escherichia coli Frd showed that the enzyme is unusually prone to ROS generation. Surprisingly, in this study biochemical analysis demonstrated that the B. thetaiotaomicron Frd does not react with oxygen at all: neither superoxide nor hydrogen peroxide is formed. Subunit-swapping experiments indicated that this difference does not derive from the flavoprotein subunit at which ROS normally arise. Experiments with the related enzyme succinate dehydrogenase discouraged the hypothesis that heme moieties are responsible. Thus, resistance to oxidation may reflect a shift of electron density away from the flavin moiety toward the iron-sulfur clusters. This study shows that the autoxidizability of a redox enzyme can be suppressed by subtle modifications that do not compromise its physiological function. One implication is that selective pressures might enhance the oxygen tolerance of an organism by manipulating the electronic properties of its redox enzymes so they do not generate ROS.

  3. Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system

    International Nuclear Information System (INIS)

    Lu, Changfang; Zou, Yu; Liu, Yuzhang; Niu, Yingcai

    2017-01-01

    Recently, oxidative stress is involved in hepatofibrogenesis. Matrix metalloproteinase-2 (MMP-2) is required for activation of hepatic stellate cells (HSCs) in response to reactive oxygen species (ROS). This study was designed to explore the hypothesis that the inhibitory effect of rosmarinic acid (RA) on HSCs activation might mainly result from its antioxidant capability by increasing the synthesis of glutathione (GSH) involved in nuclear factor kappa B (NF-κB)-dependent inhibition of MMP-2 activity. Here, we demonstrate that RA reverses activated HSCs to quiescent cells. Concomitantly, RA inhibits MMP-2 activity. RNA interference-imposed knockdown of NF-κB abolished down-regulation of MMP-2 by RA. RA-mediated inactivation of NF-κB could be blocked by the diphenyleneiodonium chloride (DPI; a ROS inhibitor). Conversely, transfection of dominant-negative (DN) mutant of extracellular signal-regulated kinases 2 (ERK2), c-Jun N-terminal kinase 1 (JNK1), or p38α kinase had no such effect. Simultaneously, RA suppresses ROS generation and lipid peroxidation (LPO) whereas increases cellular GSH in HSC-T6 cells. Furthermore, RA significantly increased antioxidant response element (ARE)-mediated luciferase activity, nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and catalytic subunits from glutamate cysteine ligase (GCLc) expression, but not modulatory subunits from GCL (GCLm). RA-mediated up-regulation of GClc is inhibited by the shRNA-induced Nrf2 knockdown. The knocking down of Nrf2 or buthionine sulfoximine (a GCL inhibitor) abolished RA-mediated inhibition of ROS. Collectively, these results provide novel insights into the mechanisms of RA as an antifibrogenic candidate in the prevention and treatment of liver fibrosis. - Highlights: • RA reverses activated HSCs to quiescent cells. • RA suppresses MMP-2 activity through a NF-κB-dependent pathway. • Inhibition of oxidative stress by RA is dependent on nuclear translocation of Nrf2

  4. Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Changfang; Zou, Yu; Liu, Yuzhang; Niu, Yingcai, E-mail: nyc1968@126.com

    2017-03-01

    Recently, oxidative stress is involved in hepatofibrogenesis. Matrix metalloproteinase-2 (MMP-2) is required for activation of hepatic stellate cells (HSCs) in response to reactive oxygen species (ROS). This study was designed to explore the hypothesis that the inhibitory effect of rosmarinic acid (RA) on HSCs activation might mainly result from its antioxidant capability by increasing the synthesis of glutathione (GSH) involved in nuclear factor kappa B (NF-κB)-dependent inhibition of MMP-2 activity. Here, we demonstrate that RA reverses activated HSCs to quiescent cells. Concomitantly, RA inhibits MMP-2 activity. RNA interference-imposed knockdown of NF-κB abolished down-regulation of MMP-2 by RA. RA-mediated inactivation of NF-κB could be blocked by the diphenyleneiodonium chloride (DPI; a ROS inhibitor). Conversely, transfection of dominant-negative (DN) mutant of extracellular signal-regulated kinases 2 (ERK2), c-Jun N-terminal kinase 1 (JNK1), or p38α kinase had no such effect. Simultaneously, RA suppresses ROS generation and lipid peroxidation (LPO) whereas increases cellular GSH in HSC-T6 cells. Furthermore, RA significantly increased antioxidant response element (ARE)-mediated luciferase activity, nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and catalytic subunits from glutamate cysteine ligase (GCLc) expression, but not modulatory subunits from GCL (GCLm). RA-mediated up-regulation of GClc is inhibited by the shRNA-induced Nrf2 knockdown. The knocking down of Nrf2 or buthionine sulfoximine (a GCL inhibitor) abolished RA-mediated inhibition of ROS. Collectively, these results provide novel insights into the mechanisms of RA as an antifibrogenic candidate in the prevention and treatment of liver fibrosis. - Highlights: • RA reverses activated HSCs to quiescent cells. • RA suppresses MMP-2 activity through a NF-κB-dependent pathway. • Inhibition of oxidative stress by RA is dependent on nuclear translocation of Nrf2

  5. Effects of Mountain Ultra-Marathon Running on ROS Production and Oxidative Damage by Micro-Invasive Analytic Techniques.

    Directory of Open Access Journals (Sweden)

    Simona Mrakic-Sposta

    . Considered altogether the investigated variables showed up that exhaustive and prolonged exercise not only promotes the generation of ROS but also induces oxidative stress, transient renal impairment and inflammation.

  6. Piper nigrum ethanolic extract rich in piperamides causes ROS overproduction, oxidative damage in DNA leading to cell cycle arrest and apoptosis in cancer cells.

    Science.gov (United States)

    de Souza Grinevicius, Valdelúcia Maria Alves; Kviecinski, Maicon Roberto; Santos Mota, Nádia Sandrini Ramos; Ourique, Fabiana; Porfirio Will Castro, Luiza Sheyla Evenni; Andreguetti, Rafaela Rafognato; Gomes Correia, João Francisco; Filho, Danilo Wilhem; Pich, Claus Tröger; Pedrosa, Rozangela Curi

    2016-08-02

    Ayurvedic and Chinese traditional medicine and tribal people use herbal preparations containing Piper nigrum fruits for the treatment of many health disorders like inflammation, fever, asthma and cancer. In Brazil, traditional maroon culture associates the spice Piper nigrum to health recovery and inflammation attenuation. The aim of the current work was to evaluate the relationship between reactive oxygen species (ROS) overproduction, DNA fragmentation, cell cycle arrest and apoptosis induced by Piper nigrum ethanolic extract and its antitumor activity. The plant was macerated in ethanol. Extract constitution was assessed by TLC, UV-vis and ESI-IT-MS/MS spectrometry. The cytotoxicity, proliferation and intracellular ROS generation was evaluated in MCF-7 cells. DNA damage effects were evaluated through intercalation into CT-DNA, plasmid DNA cleavage and oxidative damage in CT-DNA. Tumor growth inhibition, survival time increase, apoptosis, cell cycle arrest and oxidative stress were assessed in Ehrlich ascites carcinoma-bearing mice. Extraction yielded 64mg/g (36% piperine and 4.2% piperyline). Treatments caused DNA damage and reduced cell viability (EC50=27.1±2.0 and 80.5±6.6µg/ml in MCF-7 and HT-29 cells, respectively), inhibiting cell proliferation by 57% and increased ROS generation in MCF-7 cells (65%). Ehrlich carcinoma was inhibited by the extract, which caused reduction of tumor growth (60%), elevated survival time (76%), cell cycle arrest and induced apoptosis. The treatment with extract increased Bax and p53 and inhibited Bcl-xL and cyclin A expression. It also induced an oxidative stress in vivo verified as enhanced lipid peroxidation and carbonyl proteins content and increased activities of glutathione reductase, superoxide dismutase and catalase. GSH concentration was decreased in tumor tissue from mice. The ethanolic extract has cytotoxic and antiproliferative effect on MCF-7 cells and antitumor effect in vivo probably due to ROS overproduction

  7. Photocatalytic ROS production and phototoxicity of titanium dioxide nanoparticles is dependent on solar UV radiation spectrum

    Science.gov (United States)

    Generation of reactive oxygen species (ROS) by titanium dioxide nanoparticles (nano-TiO2) and its consequent phototoxicity to Daphnia magna were measured under different solar UV radiation spectrum by applying a series of optical filters in a solar simulator. Removing UVB (280-32...

  8. Arabidopsis GRI is involved in the regulation of cell death induced by extracellular ROS.

    Science.gov (United States)

    Wrzaczek, Michael; Brosché, Mikael; Kollist, Hannes; Kangasjärvi, Jaakko

    2009-03-31

    Reactive oxygen species (ROS) have important functions in plant stress responses and development. In plants, ozone and pathogen infection induce an extracellular oxidative burst that is involved in the regulation of cell death. However, very little is known about how plants can perceive ROS and regulate the initiation and the containment of cell death. We have identified an Arabidopsis thaliana protein, GRIM REAPER (GRI), that is involved in the regulation of cell death induced by extracellular ROS. Plants with an insertion in GRI display an ozone-sensitive phenotype. GRI is an Arabidopsis ortholog of the tobacco flower-specific Stig1 gene. The GRI protein appears to be processed in leaves with a release of an N-terminal fragment of the protein. Infiltration of the N-terminal fragment of the GRI protein into leaves caused cell death in a superoxide- and salicylic acid-dependent manner. Analysis of the extracellular GRI protein yields information on how plants can initiate ROS-induced cell death during stress response and development.

  9. ROS and RNS Signaling in Heart Disorders: Could Antioxidant Treatment Be Successful?

    Directory of Open Access Journals (Sweden)

    Igor Afanas'ev

    2011-01-01

    Full Text Available There is not too much success in the antioxidant treatment of heart deceases in humans. However a new approach is now developed that suggests that depending on their structures and concentrations antioxidants can exhibit much more complicated functions in many pathological disorders. It is now well established that physiological free radicals superoxide and nitric oxide together with their derivatives hydrogen peroxide and peroxynitrite (all are named reactive oxygen species (ROS and reactive nitrogen species (RNS play a more important role in heart diseases through their signaling functions. Correspondingly this work is dedicated to the consideration of damaging signaling by ROS and RNS in various heart and vascular disorders: heart failure (congestive heart failure or CHF, left ventricular hypertrophy (LVH, coronary heart disease, cardiac arrhythmias, and so forth. It will be demonstrated that ROS overproduction (oxidative stress is a main origin of the transformation of normal physiological signaling processes into the damaging ones. Furthermore the favorable effects of low/moderate oxidative stress through preconditioning mechanisms in ischemia/reperfusion will be considered. And in the last part we will discuss the possibility of efficient application of antioxidants and enzyme/gene inhibitors for the regulation of damaging ROS signaling in heart disorders.

  10. Stress analysis of pressurized water reactor steam generator tube denting phenomena. Interim report

    International Nuclear Information System (INIS)

    Thomas, J.M.; Cipolla, R.C.; Ranjan, G.V.; Derbalian, G.

    1978-07-01

    In some Pressurized Water Reactor (PWR) steam generators, a corrosion product has formed on the carbon steel support plate in the crevice between the tube and support plate. The corrosion product occupies more volume than the original metal; the tube-to-support plate crevice volume is thus consumed with corrosion product, and further corrosive action results in a radially inward force on the tube and a radially outward force on the corroding support plate. This has resulted in indentation (''denting'') of the tube, accompanied by occasional cracking. Large in-plane deformation and cracking of support plates has also been observed in the most severely affected plants along with some serious side effects, such as deformation and cracking of inner row tube U-bends caused by support plate movement. Mechanical aspects of the tube denting phenomena have been studied using analytical models. The models used ranged from closed form analytical solutions to state-of-the-art numerical elastic-plastic computer program for moderate strains. It was found that tube dents, such as those observed in operating steam generators, are associated with yielding of both the tubes and support plates. Also studied were the stresses in tube U-bends caused by support plate flow slot deformation

  11. The Eastern Renewable Generation Integration Study: Insights on System Stress: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Bloom, Aaron; Novacheck, Josh

    2017-04-12

    The Eastern Renewable Generation Integration Study (ERGIS) explores the operational impacts of the wide spread adoption of wind and solar photovoltaics (PV) resources in North America's Eastern and Quebec Interconnections. We explore the impact of large scale adoption of wind and solar generation on the unit commitment and economic dispatch of the largest coordinated power system in the world by simulating hourly and five-minute operations. Using NREL's high-performance computing capabilities and new methodologies to model operations, we found that the modeled system, as simulated with evolutionary change in 2026, could balance the variability and uncertainty of wind and solar PV at a five-minute level under a variety of conditions. Our simulations achieve instantaneous penetrations that exceed 50% of load while meeting an annual penetration of 30% on an energy basis. The system meets balanced load and supply in all intervals, with modest curtailment, using technologies and practices that are widely available today. However, a variety of the conditions present in these simulations deviate substantially from historical practice. In this work, we analyze potentially stressful system conditions that occur in the simulations and identify opportunities for innovation, regulatory reform, and changes in operating practices that require further analysis to enable the transition to a system with more wind and solar PV.

  12. JNK and NADPH Oxidase Involved in Fluoride-Induced Oxidative Stress in BV-2 Microglia Cells

    Directory of Open Access Journals (Sweden)

    Ling Yan

    2013-01-01

    Full Text Available Excessive fluoride may cause central nervous system (CNS dysfunction, and oxidative stress is a recognized mode of action of fluoride toxicity. In CNS, activated microglial cells can release more reactive oxygen species (ROS, and NADPH oxidase (NOX is the major enzyme for the production of extracellular superoxide in microglia. ROS have been characterized as an important secondary messenger and modulator for various mammalian intracellular signaling pathways, including the MAPK pathways. In this study we examined ROS production and TNF-α, IL-1β inflammatory cytokines releasing, and the expression of MAPKs in BV-2 microglia cells treated with fluoride. We found that fluoride increased JNK phosphorylation level of BV-2 cells and pretreatment with JNK inhibitor SP600125 markedly reduced the levels of intracellular and NO. NOX inhibitor apocynin and iNOS inhibitor SMT dramatically decreased NaF-induced ROS and NO generations, respectively. Antioxidant melatonin (MEL resulted in a reduction in JNK phosphorylation in fluoride-stimulated BV-2 microglia. The results confirmed that NOX and iNOS played an important role in fluoride inducing oxidative stress and NO production and JNK took part in the oxidative stress induced by fluoride and meanwhile also could be activated by ROS in fluoride-treated BV-2 cells.

  13. JNK and NADPH Oxidase Involved in Fluoride-Induced Oxidative Stress in BV-2 Microglia Cells

    Science.gov (United States)

    Yan, Ling; Liu, Shengnan; Wang, Chen; Wang, Fei; Song, Yingli; Yan, Nan; Xi, Shuhua; Liu, Ziyou; Sun, Guifan

    2013-01-01

    Excessive fluoride may cause central nervous system (CNS) dysfunction, and oxidative stress is a recognized mode of action of fluoride toxicity. In CNS, activated microglial cells can release more reactive oxygen species (ROS), and NADPH oxidase (NOX) is the major enzyme for the production of extracellular superoxide in microglia. ROS have been characterized as an important secondary messenger and modulator for various mammalian intracellular signaling pathways, including the MAPK pathways. In this study we examined ROS production and TNF-α, IL-1β inflammatory cytokines releasing, and the expression of MAPKs in BV-2 microglia cells treated with fluoride. We found that fluoride increased JNK phosphorylation level of BV-2 cells and pretreatment with JNK inhibitor SP600125 markedly reduced the levels of intracellular O2 ·− and NO. NOX inhibitor apocynin and iNOS inhibitor SMT dramatically decreased NaF-induced ROS and NO generations, respectively. Antioxidant melatonin (MEL) resulted in a reduction in JNK phosphorylation in fluoride-stimulated BV-2 microglia. The results confirmed that NOX and iNOS played an important role in fluoride inducing oxidative stress and NO production and JNK took part in the oxidative stress induced by fluoride and meanwhile also could be activated by ROS in fluoride-treated BV-2 cells. PMID:24072958

  14. Genome-wide association for sensitivity to chronic oxidative stress in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Katherine W Jordan

    Full Text Available Reactive oxygen species (ROS are a common byproduct of mitochondrial energy metabolism, and can also be induced by exogenous sources, including UV light, radiation, and environmental toxins. ROS generation is essential for maintaining homeostasis by triggering cellular signaling pathways and host defense mechanisms. However, an imbalance of ROS induces oxidative stress and cellular death and is associated with human disease, including age-related locomotor impairment. To identify genes affecting sensitivity and resistance to ROS-induced locomotor decline, we assessed locomotion of aged flies of the sequenced, wild-derived lines from the Drosophila melanogaster Genetics Reference Panel on standard medium and following chronic exposure to medium supplemented with 3 mM menadione sodium bisulfite (MSB. We found substantial genetic variation in sensitivity to oxidative stress with respect to locomotor phenotypes. We performed genome-wide association analyses to identify candidate genes associated with variation in sensitivity to ROS-induced decline in locomotor performance, and confirmed the effects for 13 of 16 mutations tested in these candidate genes. Candidate genes associated with variation in sensitivity to MSB-induced oxidative stress form networks of genes involved in neural development, immunity, and signal transduction. Many of these genes have human orthologs, highlighting the utility of genome-wide association in Drosophila for studying complex human disease.

  15. TNF-α mediates choroidal neovascularization by upregulating VEGF expression in RPE through ROS-dependent β-catenin activation.

    Science.gov (United States)

    Wang, Haibo; Han, Xiaokun; Wittchen, Erika S; Hartnett, M Elizabeth

    2016-01-01

    Inflammation, oxidative stress, and angiogenesis have been proposed to interact in age-related macular degeneration. It has been postulated that external stimuli that cause oxidative stress can increase production of vascular endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells. In this study, we tested the hypothesis that the inflammatory cytokine, tumor necrosis factor alpha (TNF-α), contributed to choroidal neovascularization (CNV) by upregulating VEGF in RPE through intracellular reactive oxygen species (ROS)-dependent signaling and sought to understand the mechanisms involved. In a murine laser-induced CNV model, 7 days after laser treatment and intravitreal neutralizing mouse TNF-α antibody or isotype immunoglobulin G (IgG) control, the following measurements were made: 1) TNF-α protein and VEGF protein in RPE/choroids with western blot, 2) CNV volume in RPE/choroidal flatmounts, and 3) semiquantification of oxidized phospholipids stained with E06 antibody within CNV with immunohistochemistry (IHC). In cultured human RPE cells treated with TNF-α or PBS control, 1) ROS generation was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence assay, and 2) NOX4 protein and VEGF protein or mRNA were measured with western blot or quantitative real-time PCR in cells pretreated with apocynin or nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) inhibitor, VAS 2870, or transfected with p22phox siRNA, and each was compared to its appropriate control. Western blots of phosphorylated p65 (p-p65), total p65 and β-actin, and quantitative real-time PCR of VEGF mRNA were measured in human RPE cells treated with TNF-α and pretreatment with the nuclear factor kappa B inhibitor, Bay 11-7082 or control. Western blots of β-catenin, VEGF, and p22phox and coimmunoprecipitation of β-catenin and T-cell transcriptional factor were performed in human RPE cells treated with TNF-α following pretreatment with

  16. Carvedilol, a third-generation β-blocker prevents oxidative stress-induced neuronal death and activates Nrf2/ARE pathway in HT22 cells

    Energy Technology Data Exchange (ETDEWEB)

    Ouyang, Ying [Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Chen, Ziwei [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Tan, Min [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Department of Traditional Chinese Medicine Chemistry, College of Chinese Materia Madica, Guangzhou University of Chinese Medicine, Guangzhou 510006 (China); Liu, Anmin [Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Chen, Meihui [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Liu, Jun [Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China); Pi, Rongbiao, E-mail: pirb@mail.sysu.edu.cn [Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou (China); Fang, Jianpei, E-mail: jpf2005@163.com [Department of Pediatrics, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou (China)

    2013-11-29

    Highlights: •Carvedilol significantly prevented oxidative stress-induced cell death. •Carvedilol significantly decreased the production of ROS. •Carvedilol activated Nrf2/ARE pathway. •Carvedilol increased the protein levels of HO-1 and NQO-1. -- Abstract: Carvedilol, a nonselective β-adrenoreceptor blocker with pleiotropic activities has been shown to exert neuroprotective effect due to its antioxidant property. However, the neuroprotective mechanism of carvedilol is still not fully uncovered. Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. Here we investigated the effect of carvedilol on oxidative stress-induced cell death (glutamate 2 mM and H{sub 2}O{sub 2} 600 μM) and the activity of Nrf2/ARE pathway in HT22 hippocampal cells. Carvedilol significantly increased cell viability and decreased ROS in HT22 cells exposed to glutamate or H{sub 2}O{sub 2}. Furthermore, carvedilol activated the Nrf2/ARE pathway in a concentration-dependent manner, and increased the protein levels of heme oxygenase-1(HO-1) and NAD(P)H quinone oxidoreductase-1(NQO-1), two downstream factors of the Nrf2/ARE pathway. Collectively, our results indicate that carvedilol protects neuronal cell against glutamate- and H{sub 2}O{sub 2}-induced neurotoxicity possibly through activating the Nrf2/ARE signaling pathway.

  17. Stress relieving procedure and facility by shot-peening the inside surface of NPP steam generators tubes

    International Nuclear Information System (INIS)

    Banica, I.; Maioru, H.

    1994-01-01

    Residual stress relieving of the transition zones between the deformed part and the non deformed part of the heat exchanger tubes expanded in tube sheets of the NPP equipment, is a technological problem attacked on international level as well as on national level through the continuing programme initiated by ICEMENERG. The most recent statistical data point out that over 75% of tube failures are taking place in the tube-to-tubesheet connection zone, a great number of them being produced in this area by intergranular attack and stress corrosion cracking. The increased occurrence of these incidents is explained first by the existence of residual stresses inside tube surfaces, induced by expanding the tubes. Relieving these residual stresses is the purpose of the outlined procedure and it is achieved by overlapping effects (compression stresses added over tensile stresses). In this paper aspects of the procedure are presented and also a facility is described for stress relieving by introducing compressive stresses from uniform and generalized collisions of the inside surface with micro balls of great kinetic energy carried by a pressurized gas. The stress relieving facility can be acted by remote control, the whole process being completely automatic. The procedure aims to the operation maintenance of the NPP steam generators. (Author)

  18. The hormesis effect of plasma-elevated intracellular ROS on HaCaT cells

    Science.gov (United States)

    Szili, Endre J.; Harding, Frances J.; Hong, Sung-Ha; Herrmann, Franziska; Voelcker, Nicolas H.; Short, Robert D.

    2015-12-01

    We have examined the link between ionized-gas plasma delivery of reactive oxygen species (ROS) to immortalized keratinocyte (HaCaT) cells and cell fate, defined in terms of cell viability versus death. Phospholipid vesicles were used as cell mimics to measure the possible intracellular ROS concentration, [ROSi], delivered by various plasma treatments. Cells were exposed to a helium cold atmospheric plasma (CAP) jet for different plasma exposure times (5-60 s) and gas flow rates (50-1000 ml min-1). Based upon the [ROSi] data we argue that plasma-generated ROS in the cell culture medium can readily diffuse into real cells. Plasma exposure that equated to an [ROSi] in the range of 3.81  ×  10-10-9.47  ×  10-8 M, measured at 1 h after the plasma exposure, resulted in increased cell viability at 72 h; whereas a higher [ROSi] at 1 h decreased cell viability after 72 h of culture. This may be because of the manner in which the ROS are delivered by the plasma: HaCaT cells better tolerate a low ROS flux over an extended plasma exposure period of 1 min, compared to a high flux delivered in a few seconds, although the final [ROSi] may be the same. Our results suggest that plasma stimulation of HaCaT cells follows the principle of hormesis.

  19. Rhizobium leguminosarum bv. trifolii rosR is required for interaction with clover, biofilm formation and adaptation to the environment

    Directory of Open Access Journals (Sweden)

    Piersiak Tomasz

    2010-11-01

    Full Text Available Abstract Background Rhizobium leguminosarum bv. trifolii is a symbiotic nitrogen-fixing bacterium that elicits nodules on roots of host plants Trifolium spp. Bacterial surface polysaccharides are crucial for establishment of a successful symbiosis with legumes that form indeterminate-type nodules, such as Trifolium, Pisum, Vicia, and Medicago spp. and aid the bacterium in withstanding osmotic and other environmental stresses. Recently, the R. leguminosarum bv. trifolii RosR regulatory protein which controls exopolysaccharide production has been identified and characterized. Results In this work, we extend our earlier studies to the characterization of rosR mutants which exhibit pleiotropic phenotypes. The mutants produce three times less exopolysaccharide than the wild type, and the low-molecular-weight fraction in that polymer is greatly reduced. Mutation in rosR also results in quantitative alterations in the polysaccharide constituent of lipopolysaccharide. The rosR mutants are more sensitive to surface-active detergents, antibiotics of the beta-lactam group and some osmolytes, indicating changes in the bacterial membranes. In addition, the rosR mutants exhibit significant decrease in motility and form a biofilm on plastic surfaces, which differs significantly in depth, architecture, and bacterial viability from that of the wild type. The most striking effect of rosR mutation is the considerably decreased attachment and colonization of root hairs, indicating that the mutation affects the first stage of the invasion process. Infection threads initiate at a drastically reduced rate and frequently abort before they reach the base of root hairs. Although these mutants form nodules on clover, they are unable to fix nitrogen and are outcompeted by the wild type in mixed inoculations, demonstrating that functional rosR is important for competitive nodulation. Conclusions This report demonstrates the significant role RosR regulatory protein plays in

  20. Quantification of particle-induced inflammatory stress response: a novel approach for toxicity testing of earth materials

    Directory of Open Access Journals (Sweden)

    Harrington Andrea D

    2012-04-01

    Full Text Available Abstract Background Reactive oxygen species (ROS are vital regulators of many cellular functions in the body. The intracellular ROS concentration is highly regulated by a balance between pro-oxidants and anti-oxidants. A chronic excess of pro-oxidants leads to elevated ROS concentrations and inflammation, possibly initiating or enhancing disease onset. Mineral-induced generation of ROS, the role of minerals in upregulating cellular ROS, and their role in the development of several occupational diseases are now widely recognized. However, there is no standard protocol to determine changes in ROS production in cells after exposure to mineral dust or earth materials in general. In this study, a new method for determining the degree of cellular toxicity (i.e., cytotoxicity of particles is described that will help bridge the gap in knowledge. Results By measuring the production of ROS and the viability of cells, an inflammatory stress response (ISR indicator is defined. This approach normalizes the ROS upregulation with respect to the number of viable cells at the time of measurement. We conducted experiments on a series of minerals and soils that represent materials that are inert (i.e., glass beads, anatase, and a soil with low trace element content, moderately reactive (i.e., soil with high trace element content, and highly reactive (i.e., pyrite. Inert materials generated the lowest ISR, averaging 350% compared to the control. Acid washed pyrite produced the highest ISR (1,100 fold higher than the control. The measurements conducted as a function of time showed a complex response. Most materials showed an increase in ISR with particle loading. Conclusions The amount of cellularly generated ROS and cell viability combined provide a better understanding of particle-induced oxidative stress. The results indicate that some earth materials may solicit an initial burst of ROS, followed by a second phase in which cell viability decreases and ROS

  1. The cathepsin B inhibitor z-FA-CMK induces cell death in leukemic T cells via oxidative stress.

    Science.gov (United States)

    Liow, K Y; Chow, Sek C

    2018-01-01

    The cathepsin B inhibitor benzyloxycarbonyl-phenylalanine-alanine-chloromethyl ketone (z-FA-CMK) was recently found to induce apoptosis at low concentrations in Jurkat T cells, while at higher concentrations, the cells die of necrosis. In the present study, we showed that z-FA-CMK readily depletes intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) generation. The toxicity of z-FA-CMK in Jurkat T cells was completely abrogated by N-acetylcysteine (NAC), suggesting that the toxicity mediated by z-FA-CMK is due to oxidative stress. We found that L-buthionine sulfoximine (BSO) which depletes intracellular GSH through the inhibition of GSH biosynthesis in Jurkat T cells did not promote ROS increase or induce cell death. However, NAC was still able to block z-FA-CMK toxicity in Jurkat T cells in the presence of BSO, indicating that the protective effect of NAC does not involve GSH biosynthesis. This is further corroborated by the protective effect of the non-metabolically active D-cysteine on z-FA-CMK toxicity. Furthermore, in BSO-treated cells, z-FA-CMK-induced ROS increased which remains unchanged, suggesting that the depletion of GSH and increase in ROS generation mediated by z-FA-CMK may be two separate events. Collectively, our results demonstrated that z-FA-CMK toxicity is mediated by oxidative stress through the increase in ROS generation.

  2. Adaptive stress response to menadione-induced oxidative stress in Saccharomyces cerevisiae KNU5377.

    Science.gov (United States)

    Kim, Il-Sup; Sohn, Ho-Yong; Jin, Ingnyol

    2011-10-01

    The molecular mechanisms involved in the ability of yeast cells to adapt and respond to oxidative stress are of great interest to the pharmaceutical, medical, food, and fermentation industries. In this study, we investigated the time-dependent, cellular redox homeostasis ability to adapt to menadione-induced oxidative stress, using biochemical and proteomic approaches in Saccharomyces cerevisiae KNU5377. Time-dependent cell viability was inversely proportional to endogenous amounts of ROS measured by a fluorescence assay with 2',7'-dichlorofluorescin diacetate (DCFHDA), and was hypersensitive when cells were exposed to the compound for 60 min. Morphological changes, protein oxidation and lipid peroxidation were also observed. To overcome the unfavorable conditions due to the presence of menadione, yeast cells activated a variety of cell rescue proteins including antioxidant enzymes, molecular chaperones, energy-generating metabolic enzymes, and antioxidant molecules such as trehalose. Thus, these results show that menadione causes ROS generation and high accumulation of cellular ROS levels, which affects cell viability and cell morphology and there is a correlation between resistance to menadione and the high induction of cell rescue proteins after cells enter into this physiological state, which provides a clue about the complex and dynamic stress response in yeast cells.

  3. Trans-generational effects of mild heat stress on the life history traits of an aphid parasitoid.

    Science.gov (United States)

    Ismaeil, Ibrahim; Doury, Géraldine; Desouhant, Emmanuel; Dubois, Françoise; Prevost, Geneviève; Couty, Aude

    2013-01-01

    Temperature changes are common in nature and insects are particularly exposed and sensitive to such variations which can be potential stresses, ultimately affecting life history traits and overall fitness. Braconids have been widely used to study the effects of temperature on host-parasitoid interactions and the present work focused on the solitary endoparasitoid Aphidius ervi Haliday (Hymenoptera: Braconidae Aphidiidae), an efficient biological control agent commercially used against aphids such as the potato aphid Macrosiphum euphorbiae Thomas (Sternorrhyncha: Aphididae). Contrary to previous studies using heat shocks at extreme temperatures, we evaluated the effects of mild heat stresses by transferring young parasitoid adults from the constant temperature of 20°C to either a warm (25°C) or hot (28°C) temperature, for either 1 h or 48 h. Such treatments are consistent with situations commonly experienced by parasitoids when moved from their rearing conditions to greenhouses or field conditions. The effects were evaluated both on the heat stressed A. ervi adults (G0) (immediate effects) and on their first generation (G1) progeny (trans-generational effects). G0 wasps' mortality was significantly affected by the temperature in interaction with the duration of the stress. Longevity of G0 wasps surviving the heat stress was negatively affected by the temperature and females lived longer than males. Heat stress applied to A. ervi parents also had consequences on their G1 progeny whose developmental time, rates of mummification and percentage of parasitoid completing total development were negatively affected. Surprisingly, the egg load at emergence of the G1 female progeny was increased when their mothers had been submitted to a mild heat stress of 25°C or 28°C. These results clearly demonstrate trans-generational phenotypic plasticity, showing that adaptation to thermal stresses may be achieved via maternal effects. This study also sheds light on the complexity

  4. Trans-generational effects of mild heat stress on the life history traits of an aphid parasitoid.

    Directory of Open Access Journals (Sweden)

    Ibrahim Ismaeil

    Full Text Available Temperature changes are common in nature and insects are particularly exposed and sensitive to such variations which can be potential stresses, ultimately affecting life history traits and overall fitness. Braconids have been widely used to study the effects of temperature on host-parasitoid interactions and the present work focused on the solitary endoparasitoid Aphidius ervi Haliday (Hymenoptera: Braconidae Aphidiidae, an efficient biological control agent commercially used against aphids such as the potato aphid Macrosiphum euphorbiae Thomas (Sternorrhyncha: Aphididae. Contrary to previous studies using heat shocks at extreme temperatures, we evaluated the effects of mild heat stresses by transferring young parasitoid adults from the constant temperature of 20°C to either a warm (25°C or hot (28°C temperature, for either 1 h or 48 h. Such treatments are consistent with situations commonly experienced by parasitoids when moved from their rearing conditions to greenhouses or field conditions. The effects were evaluated both on the heat stressed A. ervi adults (G0 (immediate effects and on their first generation (G1 progeny (trans-generational effects. G0 wasps' mortality was significantly affected by the temperature in interaction with the duration of the stress. Longevity of G0 wasps surviving the heat stress was negatively affected by the temperature and females lived longer than males. Heat stress applied to A. ervi parents also had consequences on their G1 progeny whose developmental time, rates of mummification and percentage of parasitoid completing total development were negatively affected. Surprisingly, the egg load at emergence of the G1 female progeny was increased when their mothers had been submitted to a mild heat stress of 25°C or 28°C. These results clearly demonstrate trans-generational phenotypic plasticity, showing that adaptation to thermal stresses may be achieved via maternal effects. This study also sheds light on

  5. Structural integrity assessment of steam generator tubes deteriorated through primary water stress corrosion cracking in transition region of tube expansion

    International Nuclear Information System (INIS)

    Silveira, Helvecio Carlos Klinke da

    2002-01-01

    In PWR plants, steam generator tube degradation has been one of the most important economical concerns, besides causing operational safety problems. In this work, a survey of steam generator tube degradation modes is done. Degradation mechanisms and influence factors are introduced and discussed. The importance of stress corrosion cracking, especially in transition region of tube expansion zone, is underlined. The actual steam generator tube plugging criteria are conservative. Proposed alternative criteria are introduced and discussed. Distinction is done to structural integrity assessment of defective tubes. Real data of tube defect indications of axial cracks in expansion transition zone due to primary water stress corrosion cracking are used in analysis. Results allow discussing application aspects of deterministic and probabilistic criteria on structural integrity assessment of tubes with defect indications. Applied models are specifics, but the application of concept may be extended to other steam generator tube degradation modes. (author)

  6. Study by X-ray diffraction and mechanical analysis of the residual stress generation during thermal spraying

    International Nuclear Information System (INIS)

    Pina, J.; Dias, A.; Lebrun, J.L.

    2003-01-01

    Thermally sprayed coatings are formed by the deposition of molten or partially molten particles, propelled onto a substrate where they impact, spread and solidify rapidly. Residual stresses are expected within the sprayed deposit as a consequence of the release of thermal and kinetic energies. A wide range of materials and two spraying techniques are considered in this study, namely atmospheric plasma spraying (APS) and high-velocity oxygen fuel. Stresses were determined by the X-ray diffraction (XRD) method. The results were compared with those calculated by mechanical analysis of stress relief in coatings detached from the substrate. Comparison of the results for adherent and free-standing coatings shows that the residual stress state can be resolved in terms of the components suggested by models that propose two stages of stress generation: quenching stresses and secondary-cooling stresses. The in-depth distribution of residual stresses, through the coating thickness, is discussed in terms of the nature of the coating system

  7. Generation of spectra and stress histories for fatigue and damage tolerance analysis of fuselage repairs

    Science.gov (United States)

    1991-10-01

    This report describes a simplified procedure for the development of stress histories : for use in the analysis of aircraft repairs.- Although repairs of all components of : the airframe are of interest, this report concentrates on stress histories fo...

  8. Effect of heat treatment and composition on stress corrosion cracking of steam generation tubing materials

    International Nuclear Information System (INIS)

    Kim, H. P.; Hwang, S. S.; Kuk, I. H.; Kim, J. S.; Oh, C. Y.

    1998-01-01

    Effects of heat treatment and alloy composition on stress corrosion cracking (SCC) of steam generator tubing materials have been studied in 40% NaOH at 315.deg.C at potential of +200mV above corrosion potential using C-ring specimen and reverse U bend specimen. The tubing materials used were commercial Alloy 600, Alloy 690 and laboratory alloys, Ni-χCr-10Fe. Commercial Alloy 600, Alloy 690 were mill annealed or thermally treated.Laboratory alloy Ni-χCr-10Fe, and some of Alloy 600 and Alloy 690 were solution annealed. Polarization curves were measured to find out any relationship between SCC susceptibility and electrochemical behaviour. The variation in thermal treatment of Alloy 600 and Alloy 690 had no effect on polarization behaviour probably due to small area fraction of carbide and Cr depletion zone near grain boundary. In anodic polarization curves, the first and second anodic peaks at about 170mV and about at 260mV, respectively, above corrosion potential were independent of Cr content, whereas the third peak at 750mV above corrosion potential and passive current density in-creased with Cr content. SCC susceptibility decreased with Cr content and thermal treatment producing semicontinuous grain boundary decoration. Examination of cross sectional area of C-ring specimen showed deep SCC cracks for the alloys with less than 17%Cr and many shallow attacks for alloy 690. The role of Cr content in steam generator tubing materials and grain boundary carbide on SCC were discussed

  9. Ion Transport and Precipitation Kinetics as Key Aspects of Stress Generation on Pore Walls Induced by Salt Crystallization

    Science.gov (United States)

    Naillon, A.; Joseph, P.; Prat, M.

    2018-01-01

    The stress generation on pore walls due to the growth of a sodium chloride crystal in a confined aqueous solution is studied from evaporation experiments in microfluidic channels in conjunction with numerical computations of crystal growth. The study indicates that the stress buildup on the pore walls is a highly transient process taking place over a very short period of time (in less than 1 s in our experiments). The analysis makes clear that what matters for the stress generation is not the maximum supersaturation at the onset of the crystal growth but the supersaturation at the interface between the solution and the crystal when the latter is about to be confined between the pore walls. The stress generation is summarized in a simple stress diagram involving the pore aspect ratio and the Damkhöler number characterizing the competition between the precipitation reaction kinetics and the ion transport towards the growing crystal. This opens up the route for a better understanding of the damage of porous materials induced by salt crystallization, an important issue in Earth sciences, reservoir engineering, and civil engineering.

  10. Role of Mitochondrial Oxidative Stress in Spaceflight-Induced Tissue Degeneration

    Science.gov (United States)

    Torres, Samantha M.; Schreurs, Ann-Sofie; Truong, Tiffany A.; Tahimic, Candice; Globus, Ruth

    2017-01-01

    Microgravity and ionizing radiation in the spaceflight environment poses multiple challenges to homeostasis and may contribute to cellular stress. Effects may include increased generation of reactive oxygen species (ROS), DNA damage and repair error, cell cycle arrest, cell senescence or death. Our central hypothesis is that prolonged exposure to the spaceflight environment leads to the excess production of ROS and oxidative damage, culminating in accelerated tissue degeneration. The main goal of this project is to determine the importance of cellular redox defense for physiological adaptations and tissue degeneration in the space environment.

  11. Stress corrosion cracking of steam generator tubing materials in lead containing solution

    International Nuclear Information System (INIS)

    Kim, H.P.; Hwang, S.S.; Kim, J.S.; Hong, J.H.

    2007-01-01

    Stress corrosion cracking (SCC) in lead (Pb) containing environments has been one of key issues in the nuclear power industry since Pb had been identified as a cause of the SCC of steam generator (SG) tubing materials in some power plants. To mitigate or prevent degradation of SG tubing materials, a mechanistic understanding of SCC in Pb containing environment is needed, along with an understanding of the source and transport behaviors of Pb species in the secondary circuit. In this work, SCC behaviors of Alloy 600 in Pb containing environments were studied. Influences of microstructures of Alloy 600 and the inhibitive additives were investigated using the C-ring and the slow strain rate tests in caustic solution and demineralized water at 315 o C. Microstructures of Alloy 600 were varied by heat treatment at different temperatures. The additives examined were nickel boride (NiB) and cerium boride (CeB 6 ). The surface films were analyzed using Auger Electron Spectroscopy (AES) and Energy Dispersive X-ray Spectroscopy (EDS). The SCC mode varied with microstructure. Effectiveness of the additives in Pb containing environments is discussed. (author)

  12. A New View of the Dynamics of Reynolds Stress Generation in Turbulent Boundary Layers

    Science.gov (United States)

    Cantwell, Brian J.; Chacin, Juan M.

    1998-01-01

    The structure of a numerically simulated turbulent boundary layer over a flat plate at Re(theta) = 670 was studied using the invariants of the velocity gradient tensor (Q and R) and a related scalar quantity, the cubic discriminant (D = 27R(exp 2)/4 + Q(exp 3)). These invariants have previously been used to study the properties of the small-scale motions responsible for the dissipation of turbulent kinetic energy. In addition, these scalar quantities allow the local flow patterns to be unambiguously classified according to the terminology proposed by Chong et al. The use of the discriminant as a marker of coherent motions reveals complex, large-scale flow structures that are shown to be associated with the generation of Reynolds shear stress -u'v'(bar). These motions are characterized by high spatial gradients of the discriminant and are believed to be an important part of the mechanism that sustains turbulence in the near-wall region.

  13. Live longer on MARS: a yeast paradigm of mitochondrial adaptive ROS signaling in aging

    Directory of Open Access Journals (Sweden)

    Gerald S. Shadel

    2014-04-01

    Full Text Available Adaptive responses to stress, including hormesis, have been implicated in longevity, but their mechanisms and out comes are not fully understood. Here, I briefly summarize a longevity mechanism elucidated in the budding yeast chronological lifespan model by which Mitochondrial Adaptive ROS Signaling (MARS promotes beneficial epigenetic and metabolic remodeling. The potential relevance of MARS to the human disease Ataxia-Telangiectasia and as a potential anti-aging target is discussed.

  14. Phenethyl isothiocyanate inhibits growth of human chronic myeloid leukemia K562 cells via reactive oxygen species generation and caspases.

    Science.gov (United States)

    Wang, Yating; Wei, Sixi; Wang, Jishi; Fang, Qin; Chai, Qixiang

    2014-07-01

    Phenethyl isothiocyanate (PEITC), a potential cancer chemopreventive constituent of cruciferous vegetables, including watercress, has been reported to inhibit cancer cell growth by arresting the cell cycle and inducing apoptosis in various human cancer cell models. However, the role of PEITC in the inhibition of human chronic myeloid leukemia (CML) K562 cell growth and its underlying mechanisms have yet to be elucidated. In the present study, PEITC was found to induce cell death through the induction of reactive oxygen species (ROS) stress and oxidative damage. Heme oxygenase‑1 (HO‑1), which participates in the development of numerous tumors and the sensitivity of these tumors to chemotherapeutic drugs, plays a protective role by modulating oxidative injury. Therefore, the present study assessed the inhibitory effect of PEITC on K562 cells and whether HO‑1 facilitated cell apoptosis and ROS generation. PEITC was found to suppress cell growth and cause apoptosis by promoting Fas and Fas ligand expression, increasing ROS generation and by the successive release of cytochrome c as well as the activation of caspase‑9 and caspase‑3. PEITC was also combined with the HO‑1 inhibitor zinc protoporphyrin IX and the inducer hemin to assess whether HO‑1 determines cell survival and ROS generation. The results of the present study suggest that PEITC may be a potential anti‑tumor compound for CML therapy, and that HO‑1 has a critical function in PEITC‑induced apoptosis and ROS generation.

  15. Artemisinin induces ROS-mediated caspase3 activation in ASTC-a-1 cells

    Science.gov (United States)

    Xiao, Feng-Lian; Chen, Tong-Sheng; Qu, Jun-Le; Liu, Cheng-Yi

    2010-02-01

    Artemisinin (ART), an antimalarial phytochemical from the sweet wormwood plant or a naturally occurring component of Artemisia annua, has been shown a potential anticancer activity by apoptotic pathways. In our report, cell counting kit (CCK-8) assay showed that treatment of human lung adenocarcinoma (ASTC-a-1) cells with ART effectively increase cell death by inducing apoptosis in a time- and dose-dependent fashion. Hoechst 33258 staining was used to detect apoptosis as well. Reactive oxygen species (ROS) generation was observed in cells exposed to ART at concentrations of 400 μM for 48 h. N-acetyl-L-cysteine (NAC), an oxygen radical scavenger, suppressed the rate of ROS generation and inhibited the ART-induced apoptosis. Moreover, AFC assay (Fluorometric assay for Caspase3 activity) showed that ROS was involved in ART-induced caspase3 acitvation. Taken together, our data indicate that ART induces ROS-mediated caspase3 activation in a time-and dose-dependent way in ASCT-a-1 cells.

  16. Transient thermal stresses in a transversely isotropic finite hollow circular cylinder due to arbitrary surface heat generations

    International Nuclear Information System (INIS)

    Sugano, Yoshihiro; Nakanishi, Takanori.

    1980-01-01

    The materials macroscopically regarded as anisotropic materials such as fiber-reinforced composite materials have become to be used for the structural elements at elevated temperature, and the studies on the problem of thermal stress in anisotropic bodies are carried out actively. The unsteady thermal stress in anisotropic finite circular cylinders has not been analyzed so far. In this study, the problem of unsteady thermal stress in an anisotropic finite circular cylinder having arbitrary surface heat generation in axial direction on the internal and external surfaces, and emitting heat from both ends and the internal and external surfaces, was analyzed. For the analysis of temperature distribution, generalized finite Fourier transformation and finite Hankel transformation were used, and thermal stress and thermal displacement were analyzed by the use of the stress function of Singh. By adopting the function used for the transformation nucleus in generalized finite Fourier transformation as the stress function, the analysis was made without separating symmetric and opposite symmetric problems. Numerical calculation was carried out on the basis of the analytical results, and the effects of the anisotropy in thermal conductivity, Young's modulus and linear expansion on unsteady temperature distribution, thermal stress and thermal displacement were quantitatively examined. (Kako, I.)

  17. ROS - Robotiikan tutkimustyökalusta kohti kaupallista menestystarinaa

    OpenAIRE

    Ahonen, Mika

    2017-01-01

    Avoimen lähdekoodin ROS-käyttöjärjestelmä on yleisesti tutkimushankkeissa käytetty robotiikan kehitysalusta. Tutkielman tavoitteena on ollut arvioida onko ROS järjestelmä, joka tulee yleistymään myös robotiikan kaupallisissa ratkaisuissa. ROS-pohjaisia kaupallisia tuotteita on jo olemassa ja sen käyttöä on pilotoitu runsaasti erilaisilla sovellusalueilla. Erityisesti palvelu- ja pilvirobotiikan alueilla ROSilla on kasvavaa potentiaalia. ROS on vielä kehittyvä järjestelmä ja ei nykyisellään...

  18. Exercise Training Attenuates the Dysregulated Expression of Adipokines and Oxidative Stress in White Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Takuya Sakurai

    2017-01-01

    Full Text Available Obesity-induced inflammatory changes in white adipose tissue (WAT, which caused dysregulated expression of inflammation-related adipokines involving tumor necrosis factor-α and monocyte chemoattractant protein-1, contribute to the development of insulin resistance. Moreover, current literature reports state that WAT generates reactive oxygen species (ROS, and the enhanced production of ROS in obese WAT has been closely associated with the dysregulated expression of adipokines in WAT. Therefore, the reduction in excess WAT and oxidative stress that results from obesity is thought to be one of the important strategies in preventing and improving lifestyle-related diseases. Exercise training (TR not only brings about a decrease in WAT mass but also attenuates obesity-induced dysregulated expression of the adipokines in WAT. Furthermore, some reports indicate that TR affects the generation of oxidative stress in WAT. This review outlines the impact of TR on the expression of inflammation-related adipokines and oxidative stress in WAT.

  19. The Role of Na/K-ATPase Signaling in Oxidative Stress Related to Obesity and Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Krithika Srikanthan

    2016-09-01

    Full Text Available Na/K-ATPase has been extensively studied for its ion pumping function, but, in the past several decades, has been identified as a scaffolding and signaling protein. Initially it was found that cardiotonic steroids (CTS mediate signal transduction through the Na/K-ATPase and result in the generation of reactive oxygen species (ROS, which are also capable of initiating the signal cascade. However, in recent years, this Na/K-ATPase/ROS amplification loop has demonstrated significance in oxidative stress related disease states, including obesity, atherosclerosis, heart failure, uremic cardiomyopathy, and hypertension. The discovery of this novel oxidative stress signaling pathway, holds significant therapeutic potential for the aforementioned conditions and others that are rooted in ROS.

  20. Different roles of ROS and Nrf2 in Cr(VI)-induced inflammatory responses in normal and Cr(VI)-transformed cells

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Ram Vinod; Pratheeshkumar, Poyil; Son, Yong-Ok; Wang, Lei [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Hitron, John Andrew [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Divya, Sasidharan Padmaja; Zhang, Zhuo [Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Center for Research on Environmental Disease, University of Kentucky, 1095 VA Drive, Lexington, KY 40536 (United States)

    2016-09-15

    Hexavalent chromium (Cr(VI)) is classified as a human carcinogen. Cr(VI) has been associated with adenocarcinomas and squamous cell carcinoma of the lung. The present study shows that acute Cr(VI) treatment in human bronchial epithelial cells (BEAS-2B) increased inflammatory responses (TNF-α, COX-2, and NF-кB/p65) and expression of Nrf2. Cr(VI)-induced generation of reactive oxygen species (ROS) are responsible for increased inflammation. Despite the fact that Nrf2 is a master regulator of response to oxidative stress, silencing of Nrf2 in the acute Cr(VI) treatment had no effect on Cr(VI)-induced inflammation. In contrast, in Cr(VI)-transformed (CrT) cells, Nrf2 is constitutively activated. Knock-down of this protein resulted in decreased inflammation, while silencing of SOD2 and CAT had no effect in the expression of these inflammatory proteins. Results obtained from the knock-down of Nrf2 in CrT cells are very different from the results obtained in the acute Cr(VI) treatment. In BEAS-2B cells, knock-down of Nrf2 had no effect in the inflammation levels, while in CrT cells a decrease in the expression of inflammation markers was observed. These results indicate that before transformation, ROS plays a critical role while Nrf2 not in Cr(VI)-induced inflammation, whereas after transformation (CrT cells), Nrf2 is constitutively activated and this protein maintains inflammation while ROS not. Constitutively high levels of Nrf2 in CrT binds to the promoter regions of COX-2 and TNF-α, leading to increased inflammation. Collectively, our results demonstrate that before cell transformation ROS are important in Cr(VI)-induced inflammation and after transformation a constitutively high level of Nrf2 is important. - Highlights: • Cr(VI)-induced ROS increased inflammation, while Nrf2 had no effect. • In the CrT cells knock-down of Nrf2 resulted in decreased inflammation. • Mechanistic differences in regulating Cr(VI)-induced inflammation.

  1. Comparative evaluation of preventive measures against primary side stress corrosion cracking of mill annealed Inconel 600 steam generator tubes

    International Nuclear Information System (INIS)

    Frederick, G.; Hernalsteen, P.

    1986-01-01

    Significant amounts of primary side cracking have been reported in the mechanically expanded area of the tubes of PWR steam generators in Europe, in Japan and to a lesser extent in the USA. The Belgian utilities are faced with the same problem. At Doel 2, where the tubes are rolled for only a part of the tubesheet, primary side cracking appeared in the roll transition. The Doel 3 and Tihange 2 steam generators, whose tubes are expanded for the full depth of the tube sheet, have experienced cracking after about 10 000 h of operation not only in the roll transition but also at roll overlaps. While some leaks and eddy current indications are associated with tubesheet or rolling anomalies, many of them are found on normal tubes. A programme was launched by the Belgian utilities and was further co-sponsored by the Electric Power Research Institute (EPRI) to develop preventive actions applicable not only to hot steam generators but also to cold steam generators already installed on site. These preventive measures include stress relaxation and metallurgical improvement of the material by an in situ heat treatment of the whole tube sheet (a steam generator model was used to evaluate the feasibility of this treatment), and the introduction of residual compressive stresses on ID by rotopeening or shotpeening without inducing unacceptable tensile stresses on OD. A comparative evaluation of these measures was established on the basis of tests performed on representative mock-ups and specimens. (author)

  2. Palmitate induces VSMC apoptosis via toll like receptor (TLR)4/ROS/p53 pathway.

    Science.gov (United States)

    Zhang, Yuanjun; Xia, Guanghao; Zhang, Yaqiong; Liu, Juxiang; Liu, Xiaowei; Li, Weihua; Lv, Yaya; Wei, Suhong; Liu, Jing; Quan, Jinxing

    2017-08-01

    Toll-like receptor 4 (TLR4) has been implicated in vascular inflammation, as well as in the pathogenesis of atherosclerosis and diabetes. Vascular smooth muscle cell (VSMC) apoptosis has been shown to induce plaque vulnerability in atherosclerosis. Previous studies reported that palmitate induced apoptosis in VSMCs; however, the role of TLR4 in palmitate-induced apoptosis in VSMCs has not yet been defined. In this study, we investigated whether or not palmitate-induced apoptosis depended on the activation of the TLR4 pathway. VSMCs were treated with or without palmitate, CRISPR/Cas9z-mediated genome editing methods were used to deplete TLR4 expression, while NADPH oxidase inhibitors were used to inhibit reactive oxygen species (ROS) generation. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, ROS was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) method, the mRNA and protein expression levels of caspase 3, caspase 9, BCL-2 and p53 were studied by real-time polymerase chain reaction (RT-PCR) and ELISA. Palmitate significantly promotes VSMC apoptosis, ROS generation, and expression of caspase 3, caspase 9 and p53; while NADPH oxidase inhibitor pretreatment markedly attenuated these effects. Moreover, knockdown of TLR4 significantly blocked palmitate-induced ROS generation and VSMC apoptosis accompanied by inhibition of caspase 3, caspase 9, p53 expression and restoration of BCL-2 expression. Our results suggest that palmitate-induced apoptosis depends on the activation of the TLR4/ROS/p53 signaling pathway, and that TLR4 may be a potential therapeutic target for the prevention and treatment of atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Cardiac Light Chain Amyloidosis: The Role of Metal Ions in Oxidative Stress and Mitochondrial Damage.

    Science.gov (United States)

    Diomede, Luisa; Romeo, Margherita; Rognoni, Paola; Beeg, Marten; Foray, Claudia; Ghibaudi, Elena; Palladini, Giovanni; Cherny, Robert A; Verga, Laura; Capello, Gian Luca; Perfetti, Vittorio; Fiordaliso, Fabio; Merlini, Giampaolo; Salmona, Mario

    2017-09-20

    The knowledge of the mechanism underlying the cardiac damage in immunoglobulin light chain (LC) amyloidosis (AL) is essential to develop novel therapies and improve patients' outcome. Although an active role of reactive oxygen species (ROS) in LC-induced cardiotoxicity has already been envisaged, the actual mechanisms behind their generation remain elusive. This study was aimed at further dissecting the action of ROS generated by cardiotoxic LC in vivo and investigating whether transition metal ions are involved in this process. In the absence of reliable vertebrate model of AL, we used the nematode Caenorhabditis elegans, whose pharynx is an "ancestral heart." LC purified from patients with severe cardiac involvement intrinsically generated high levels of ROS and when administered to C. elegans induced ROS production, activation of the DAF-16/forkhead transcription factor (FOXO) pathway, and expression of proteins involved in stress resistance and survival. Profound functional and structural ROS-mediated mitochondrial damage, similar to that observed in amyloid-affected hearts from AL patients, was observed. All these effects were entirely dependent on the presence of metal ions since addition of metal chelator or metal-binding 8-hydroxyquinoline compounds (chelex, PBT2, and clioquinol) permanently blocked the ROS production and prevented the cardiotoxic effects of amyloid LC. Innovation and Conclusion: Our findings identify the key role of metal ions in driving the ROS-mediated toxic effects of LC. This is a novel conceptual advance that paves the way for new pharmacological strategies aimed at not only counteracting but also totally inhibiting the vicious cycle of redox damage. Antioxid. Redox Signal. 27, 567-582.

  4. Oxidative stress and CCN1 protein in human skin connective tissue aging

    Directory of Open Access Journals (Sweden)

    Zhaoping Qin

    2016-06-01

    Full Text Available Reactive oxygen species (ROS is an important pathogenic factor involved in human aging. Human skin is a primary target of oxidative stress from ROS generated from both extrinsic and intrinsic sources, like ultraviolet irradiation (UV and endogenous oxidative metabolism. Oxidative stress causes the alterations of collagen-rich extracellular matrix (ECM, the hallmark of skin connective tissue aging. Age-related alteration of dermal collagenous ECM impairs skin structural integrity and creates a tissue microenvironment that promotes age-related skin diseases, such as poor wound healing and skin cancer. Here, we review recent advances in our understanding of oxidative stress and CCN1 protein (first member of CCN family proteins, a critical mediator of oxidative stress-induced skin connective tissue aging.

  5. Job Stress Risk Factors Among Power Generation and Machine Production Employees: A Case Study-2010

    OpenAIRE

    Z. Naghavi; M.R. Hajgholami; Y. Shokoohi; F. Zayeri

    2013-01-01

    Background and Objective: Job stress has been adverse effects on performance, quality of work, absents, unsafe behaviors and occupational accidents and also health problems. Risk factors of job stress can be different in various workplaces. Risk factors determination is the first step of job stress management. Identifying these risk factors among workers of Power production & Machine production industries was the aim of this study. Methods: First parts of Osipow questionnaire was used for ...

  6. Mixed convection flow of couple stress nanofluid over oscillatory stretching sheet with heat absorption/generation effects

    Directory of Open Access Journals (Sweden)

    Sami Ullah Khan

    2018-03-01

    Full Text Available The aim of this article is to highlight the unsteady mixed convective couple stress nanoliquid flow passed through stretching surface. The flow is generated due to periodic oscillations of sheet. An appropriate set of dimensionless variables are used to reduce the independent variables in governing equations arising from mathematical modeling. An analytical solution has been computed by employing the technique of homotopy method. The outcomes of various sundry parameters like couple stress parameter, the ratio of angular velocity to stretching rate, thermophoresis parameter, Hartmann number, Prandtl number, heat source/sink parameter, Schmidt number described graphically and in tabular form. It is observed that the velocity profile increases by increasing mixed convection parameter and concentration buoyancy parameter. The temperature enhances for larger values of Hartmann number and Brownian. The concentration profile increases by increasing thermophoresis parameter. Results show that wall shear stress increases by increasing couple stress parameter and ratio of oscillating frequency to stretching rate. Keywords: Oscillatory surface, Couple stress fluid, Nanoparticles, Heat absorption/generation

  7. HCV Core Protein Uses Multiple Mechanisms to Induce Oxidative Stress in Human Hepatoma Huh7 Cells

    Science.gov (United States)

    Ivanov, Alexander V.; Smirnova, Olga A.; Petrushanko, Irina Y.; Ivanova, Olga N.; Karpenko, Inna L.; Alekseeva, Ekaterina; Sominskaya, Irina; Makarov, Alexander A.; Bartosch, Birke; Kochetkov, Sergey N.; Isaguliants, Maria G.

    2015-01-01

    Hepatitis C virus (HCV) infection is accompanied by the induction of oxidative stress, mediated by several virus proteins, the most prominent being the nucleocapsid protein (HCV core). Here, using the truncated forms of HCV core, we have delineated several mechanisms by which it induces the oxidative stress. The N-terminal 36 amino acids of HCV core induced TGFβ1-dependent expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases 1 and 4, both of which independently contributed to the production of reactive oxygen species (ROS). The same fragment also induced the expression of cyclo-oxygenase 2, which, however, made no input into ROS production. Amino acids 37–191 of HCV core up-regulated the transcription of a ROS generating enzyme cytochrome P450 2E1. Furthermore, the same fragment induced the expression of endoplasmic reticulum oxidoreductin 1α. The latter triggered efflux of Ca2+ from ER to mitochondria via mitochondrial Ca2+ uniporter, leading to generation of superoxide anions, and possibly also H2O2. Suppression of any of these pathways in cells expressing the full-length core protein led to a partial inhibition of ROS production. Thus, HCV core causes oxidative stress via several independent pathways, each mediated by a distinct region of the protein. PMID:26035647

  8. Roles of Oxidative Stress, Apoptosis, PGC-1α and Mitochondrial Biogenesis in Cerebral Ischemia

    Directory of Open Access Journals (Sweden)

    Ding-I Yang

    2011-10-01

    Full Text Available The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-γ (PPARγ co-activator 1α (PGC1-α. PGC1-α is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-α is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis.

  9. Superoxide dismutases: Dual roles in controlling ROS damage and regulating ROS signaling.

    Science.gov (United States)

    Wang, Ying; Branicky, Robyn; Noë, Alycia; Hekimi, Siegfried

    2018-04-18

    Superoxide dismutases (SODs) are universal enzymes of organisms that live in the presence of oxygen. They catalyze the conversion of superoxide into oxygen and hydrogen peroxide. Superoxide anions are the intended product of dedicated signaling enzymes as well as the byproduct of several metabolic processes including mitochondrial respiration. Through their activity, SOD enzymes control the levels of a variety of reactive oxygen species (ROS) and reactive nitrogen species, thus both limiting the potential toxicity of these molecules and controlling broad aspects of cellular life that are regulated by their signaling functions. All aerobic organisms have multiple SOD proteins targeted to different cellular and subcellular locations, reflecting the slow diffusion and multiple sources of their substrate superoxide. This compartmentalization also points to the need for fine local control of ROS signaling and to the possibility for ROS to signal between compartments. In this review, we discuss studies in model organisms and humans, which reveal the dual roles of SOD enzymes in controlling damage and regulating signaling. © 2018 Wang et al.

  10. Male Infertility: The Effect of Natural Antioxidants and Phytocompounds on Seminal Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Malik Adewoyin

    2017-03-01

    Full Text Available Defective sperm function has been identified as the most common cause of infertility. The objective of this study was to review recent findings on the effects of various antioxidants on male fertility. High amounts of poly unsaturated fatty acid are found in the mammalian spermatozoa membranes, thereby making them susceptible to lipid peroxidation. Although, free radicals and reactive oxygen species (ROS play major roles in reproduction, they are strongly associated with oxidative stress. Furthermore, factors such as obesity, inflammation, pollutants and cigarette smoking are negatively correlated with spermatogenesis. Endogenous antioxidants system exists to mediate these damages. In a normal physiological state, the seminal plasma contains antioxidant enzyme mechanism that is capable of quenching these ROS as well as protecting the spermatozoa against any likely damage. However, high level of ROS triggered by inflammatory cells and oxidation of fatty acid in obese subjects may down play antioxidant mechanism resulting in oxidative stress. Evaluation of such oxidative stress is the first step in the treatment of male infertility through administration of suitable antioxidant. Notably, antioxidant such as vitamin E and C, carotenoids and carnitine have been found beneficial in restoring a balance between ROS generation and scavenging activities. There are emerging evidences that herbal products can also boost male reproductive functions. Nonetheless, a good lifestyle, regular exercise, avoidance of stress and observing safety rules at work are habits that can reverse male infertility.

  11. Stress

    Science.gov (United States)

    ... taking care of an aging parent. With mental stress, the body pumps out hormones to no avail. Neither fighting ... with type 1 diabetes. This difference makes sense. Stress blocks the body from releasing insulin in people with type 2 ...

  12. Parental Family Stress during Pregnancy and Cognitive Functioning in Early Childhood: The Generation R Study

    Science.gov (United States)

    Henrichs, Jens; Schenk, Jacqueline J.; Kok, Rianne; Ftitache, Bouchra; Schmidt, Henk G.; Hofman, Albert; Jaddoe, Vincent W. V.; Verhulst, Frank C.; Tiemeier, Henning

    2011-01-01

    We investigated whether parental family stress during pregnancy is associated with cognitive functioning in early childhood in a population-based cohort (n = 3139). Family stress was assessed using the Family Assessment Device at the 20th week of pregnancy and was reported by mothers and fathers. Mothers completed the MacArthur Communicative…

  13. NUMERICAL AND EXPERIMENTAL ANALYSIS OF RESIDUAL STRESSES GENERATED DURING HARDENING OFAISI 4140 BAR

    Directory of Open Access Journals (Sweden)

    Edwan Anderson Ariza Echeverri

    2012-09-01

    Full Text Available The aim of this work is to analyze the distribution of residual stresses resulting from the combination of volumetric changes due to heat gradients and phase changes occurring during the quenching process of an AISI/SAE 4140 steel cylinder. The mathematical model used for this objective is the AC3 modeling software of thermal treatments (transformation curves, cooling curves and microstructure, whose results were input in an finite element model, considering thermalmechanical coupling and non-linear elastic-plastic behavior, aiming the assessment of residual stresses in quenched 4140 steel cylinders. The observed microstructure confirms quantitatively and qualitatively the previsions of the AC3 Software. The results of the modeling are compared with the residual stresses measurements made using X-Ray diffraction techniques. The finite element numerical simulation shows the existence of 350 MPa compressive residual stresses in the surface region and indicates that the most significant stresses are tangential.

  14. Hyperoxia activates ATM independent from mitochondrial ROS and dysfunction.

    Science.gov (United States)

    Resseguie, Emily A; Staversky, Rhonda J; Brookes, Paul S; O'Reilly, Michael A

    2015-08-01

    High levels of oxygen (hyperoxia) are often used to treat individuals with respiratory distress, yet prolonged hyperoxia causes mitochondrial dysfunction and excessive reactive oxygen species (ROS) that can damage molecules such as DNA. Ataxia telangiectasia mutated (ATM) kinase is activated by nuclear DNA double strand breaks and delays hyperoxia-induced cell death through downstream targets p53 and p21. Evidence for its role in regulating mitochondrial function is emerging, yet it has not been determined if mitochondrial dysfunction or ROS activates ATM. Because ATM maintains mitochondrial homeostasis, we hypothesized that hyperoxia induces both mitochondrial dysfunction and ROS that activate ATM. In A549 lung epithelial cells, hyperoxia decreased mitochondrial respiratory reserve capacity at 12h and basal respiration by 48 h. ROS were significantly increased at 24h, yet mitochondrial DNA double strand breaks were not detected. ATM was not required for activating p53 when mitochondrial respiration was inhibited by chronic exposure to antimycin A. Also, ATM was not further activated by mitochondrial ROS, which were enhanced by depleting manganese superoxide dismutase (SOD2). In contrast, ATM dampened the accumulation of mitochondrial ROS during exposure to hyperoxia. Our findings suggest that hyperoxia-induced mitochondrial dysfunction and ROS do not activate ATM. ATM more likely carries out its canonical response to nuclear DNA damage and may function to attenuate mitochondrial ROS that contribute to oxygen toxicity. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Benzoquinone activates the ERK/MAPK signaling pathway via ROS production in HL-60 cells

    International Nuclear Information System (INIS)

    Ruiz-Ramos, Ruben; Cebrian, Mariano E.; Garrido, Efrain

    2005-01-01

    Benzene (BZ) is a class I carcinogen and its oxidation to reactive intermediates is a prerequisite of hematoxicity and myelotoxicity. The generated metabolites include hydroquinone, which is further oxidized to the highly reactive 1,4-benzoquinone (BQ) in bone marrow. Therefore, we explored the mechanisms underlying BQ-induced HL-60 cell proliferation by studying the role of BQ-induced reactive oxygen species (ROS) in the activation of the ERK-MAPK signaling pathway. BQ treatment (0.01-30 μM) showed that doses below 10 μM did not significantly reduce viability. ROS production after 3 μM BQ treatment increased threefold; however, catalase addition reduced ROS generation to basal levels. FACS analysis showed that BQ induced a fivefold increase in the proportion of cells in S-phase. We also observed a high proportion of Bromodeoxyuridine (BrdU) stained cells, indicating a higher DNA synthesis rate. BQ also produced rapid and prolonged phosphorylation of ERK1/2 proteins. Simultaneous treatment with catalase or PD98059, a potent MEK protein inhibitor, reduced cell recruitment into the S-phase and also abolished the ERK1/2 protein phosphorylation induced by BQ, suggesting that MEK/ERK is an important pathway involved in BQ-induced ROS mediated proliferation. The prolonged activation of ERK1/2 contributes to explain the increased S-phase cell recruitment and to understand the leukemogenic processes associated with exposure to benzene metabolites. Thus, the possible mechanism by which BQ induce HL-60 cells to enter the cell cycle and proliferate is linked to ROS production and its growth promoting effects by specific activation of regulating genes known to be activated by redox mechanisms

  16. Sensitivity of the green algae Chlamydomonas reinhardtii to gamma radiation: Photosynthetic performance and ROS formation.

    Science.gov (United States)

    Gomes, Tânia; Xie, Li; Brede, Dag; Lind, Ole-Christian; Solhaug, Knut Asbjørn; Salbu, Brit; Tollefsen, Knut Erik

    2017-02-01

    The aquatic environment is continuously exposed to ionizing radiation from both natural and anthropogenic sources, making the characterization of ecological and health risks associated with radiation of large importance. Microalgae represent the main source of biomass production in the aquatic ecosystem, thus becoming a highly relevant biological model to assess the impacts of gamma radiation. However, little information is available on the effects of gamma radiation on microalgal species, making environmental radioprotection of this group of species challenging. In this context, the present study aimed to improve the understanding of the effects and toxic mechanisms of gamma radiation in the unicellular green algae Chlamydomonas reinhardtii focusing on the activity of the photosynthetic apparatus and ROS formation. Algal cells were exposed to gamma radiation (0.49-1677mGy/h) for 6h and chlorophyll fluorescence parameters obtained by PAM fluorometry, while two fluorescent probes carboxy-H 2 DFFDA and DHR 123 were used for the quantification of ROS. The alterations seen in functional parameters of C. reinhardtii PSII after 6h of exposure to gamma radiation showed modifications of PSII energy transfer associated with electron transport and energy dissipation pathways, especially at the higher dose rates used. Results also showed that gamma radiation induced ROS in a dose-dependent manner under both light and dark conditions. The observed decrease in photosynthetic efficiency seems to be connected to the formation of ROS and can potentially lead to oxidative stress and cellular damage in chloroplasts. To our knowledge, this is the first report on changes in several chlorophyll fluorescence parameters associated with photosynthetic performance and ROS formation in microalgae after exposure to gamma radiation. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Is There Still Any Role for Oxidative Stress in Mitochondrial DNA-Dependent Aging?

    Directory of Open Access Journals (Sweden)

    Gábor Zsurka

    2018-03-01

    Full Text Available Recent deep sequencing data has provided compelling evidence that the spectrum of somatic point mutations in mitochondrial DNA (mtDNA in aging tissues lacks G > T transversion mutations. This fact cannot, however, be used as an argument for the missing contribution of reactive oxygen species (ROS to mitochondria-related aging because it is probably caused by the nucleotide selectivity of mitochondrial DNA polymerase γ (POLG. In contrast to point mutations, the age-dependent accumulation of mitochondrial DNA deletions is, in light of recent experimental data, still explainable by the segregation of mutant molecules generated by the direct mutagenic effects of ROS (in particular, of HO· radicals formed from H2O2 by a Fenton reaction. The source of ROS remains controversial, because the mitochondrial contribution to tissue ROS production is probably lower than previously thought. Importantly, in the discussion about the potential role of oxidative stress in mitochondria-dependent aging, ROS generated by inflammation-linked processes and the distribution of free iron also require careful consideration.

  18. Expression of a finger millet transcription factor, EcNAC1, in tobacco confers abiotic stress-tolerance.

    Directory of Open Access Journals (Sweden)

    Venkategowda Ramegowda

    Full Text Available NAC (NAM, ATAF1-2, and CUC2 proteins constitute one of the largest families of plant-specific transcription factors and have been shown to be involved in diverse plant processes including plant growth, development, and stress-tolerance. In this study, a stress-responsive NAC gene, EcNAC1, was isolated from the subtracted stress cDNA library generated from a drought adapted crop, finger millet, and characterized for its role in stress-tolerance. The expression analysis showed that EcNAC1 was highly induced during water-deficit and salt stress. EcNAC1 shares high amino acid similarity with rice genes that have been phylogenetically classified into stress-related NAC genes. Our results demonstrated that tobacco transgenic plants expressing EcNAC1 exhibit tolerance to various abiotic stresses like simulated osmotic stress, by polyethylene glycol (PEG and mannitol, and salinity stress. The transgenic plants also showed enhanced tolerance to methyl-viologen (MV induced oxidative stress. Reduced levels of reactive oxygen species (ROS and ROS-induced damage were noticed in pot grown transgenic lines under water-deficit and natural high light conditions. Root growth under stress and recovery growth after stress alleviation was more in transgenic plants. Many stress-responsive genes were found to be up-regulated in transgenic lines expressing EcNAC1. Our results suggest that EcNAC1 overexpression confers tolerance against abiotic stress in susceptible species, tobacco.

  19. TMEPAI regulates EMT in lung cancer cells by modulating the ROS and IRS-1 signaling pathways.

    Science.gov (United States)

    Hu, Ying; He, Kai; Wang, Dongmei; Yuan, Xinwang; Liu, Yi; Ji, Hongbin; Song, Jianguo

    2013-08-01

    The epithelial-mesenchymal transition (EMT) has been implicated in various pathophysiological processes, including cancer cell migration and distal metastasis. Reactive oxygen species (ROS) and insulin receptor substrate-1 (IRS-1) are important in cancer progression and regulation of EMT. To explore the biological significance and regulatory mechanism of EMT, we determined the expression, the biological function and the signaling pathway of prostate transmembrane protein, androgen induced-1 (TMEPAI), during the induction of EMT and cell migration. Transforming growth factor (TGF)-β1 significantly upregulated the expression of TMEPAI during EMT in human lung adenocarcinoma. Depletion of TMEPAI abolished TGF-β1-induced downregulation of ferritin heavy chain and the subsequent generation of ROS, thus suppressing TGF-β1-induced EMT and cell migration. In addition, increased ROS production and overexpression of TMEPAI downregulated the level of IRS-1. Both the addition of H2O2 and IRS-1 small interfering RNA rescued the ability of TGF-β1 to induce EMT in TMEPAI-depleted cells. Remarkably, the levels of TMEPAI in lung tumor tissues are very high, whereas its expression in normal lung epithelium is very low. Moreover, TMEPAI expression was positively correlated with the cell mesenchymal phenotype and migration potential. Our work reveals that TMEPAI contributes to TGF-β1-induced EMT through ROS production and IRS-1 downregulation in lung cancer cells.

  20. Studies on antibacterial activity of ZnO nanoparticles by ROS induced lipid peroxidation.

    Science.gov (United States)

    Dutta, R K; Nenavathu, Bhavani P; Gangishetty, Mahesh K; Reddy, A V R

    2012-06-01

    Recent studies indicated the role of ROS toward antibacterial activity. In our study we report ROS mediated membrane lipid oxidation of Escherichia coli treated with ZnO nanoparticles (NPs) as supported by detection and spectrophotometric measurement of malondialdehyde (MDA) by TBARS (thiobarbituric acid-reactive species) assay. The antibacterial effects of ZnO NPs were studied by measuring the growth curve of E. coli, which showed concentration dependent bacteriostatic and bacteriocidal effects of ZnO NPs. The antibacterial effects were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Further, antibacterial effect of ZnO NPs was found to decrease by introducing histidine to the culture medium treated with ZnO NPs. The ROS scavenging action of histidine was confirmed by treating histidine to the batch of Escherichia coli+ZnO NPs at the end of the lag phase of the growth curve (Set-I) and during inoculation (Set-II). A moderate bacteriostatic effect (lag in the E. coli growth) was observed in Set-II batch while Set-I showed no bacteriostatic effect. From these evidences we confirmed that the antibacterial effect of bare as well as TG capped ZnO NPs were due to membrane lipid peroxidation caused by the ROS generated during ZnO NPs interaction in culture medium. Copyright © 2012 Elsevier B.V. All rights reserved.