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Tine Iskov Kopp, Malene Outzen, Anja Olsen, Ulla Vogel, Gitte Ravn-Haren
Background: Selenium is an essential trace element and is suggested to play a role in the etiology of a number of chronic diseases. Genetic variation in genes encoding selenoproteins, such as selenoprotein P and the glutathione peroxidases, may affect selenium status and, thus, individual susceptibility to some chronic diseases. In the present study, we aimed to (1) investigate the effect of mussel and fish intake on glutathione peroxidase enzyme activity and (2) examine whether single nucleotide polymorphisms in the GPX1 , GPX4 , and SELENOP genes modify the effect of mussel and fish intake for 26 weeks on whole blood selenium, plasma selenoprotein P concentrations, and erythrocyte GPX enzyme activity in a randomized intervention trial in Denmark...
2018: Genes & Nutrition
Jiayong Tang, Aihua He, Hui Yan, Gang Jia, Guangmang Liu, Xiaoling Chen, Jingyi Cai, Gang Tian, Haiying Shang, Hua Zhao
This study was conducted to profile the selenoprotein encoding genes or proteins in mouse C2C12 cells and integrate their roles in the skeletal cell damage induced by heat stress (HS). Cells were cultured at 37.0 °C or 41.5 °C for 4, 6 or 8 days. The mRNA expression of 24 selenoprotein encoding genes and abundance of 5 selenoproteins were investigated. HS suppressed myogenic differentiation and impaired the development of muscle myotubes. HS down-regulated (P < 0.01) mRNA abundance of MYOD and MYOGENIN, and decreased (P < 0...
July 13, 2018: Scientific Reports
Ashley J Russo, Vijay A K Rathinam
Glutathione peroxidase 4 (GPX4) is an antioxidant enzyme that protects cells from lipid peroxidation. In this issue of Cell Host & Microbe, Kang et al. (2018) report that GPX4 is a negative regulator of the pyroptotic cell death pathway and plays an important role in inhibiting lethal inflammation associated with sepsis.
July 11, 2018: Cell Host & Microbe
Shahnawaz Kumbhar, Alam Z Khan, Fahmida Parveen, Zaheer A Nizamani, Farman A Siyal, Mohamed E Abd El-Hack, Fang Gan, Yunhuan Liu, Muhammad Hamid, Sonia A Nido, Kehe Huang
The study was carried out to investigate the effect of dietary selenium (Se) and vitamin E (VE) supplementation on mRNA level of heat shock proteins, selenoproteins, and antioxidant enzyme activities in the breast meat of broilers under summer heat stress conditions. A total of 200 male broilers (Ross 308) of 1 day age were randomly separated into 4 groups in a complete randomized design and were given a basal diet (Control, 0.08 mg Se/kg diet) or basal diet supplemented with VE (250 mg/kg VE), sodium selenite (0...
July 10, 2018: AMB Express
Yun Sun, Yingfeng Zheng, Chunxiao Wang, Yizhi Liu
Glutathione (GSH) protects against oxidative damage in many tissues, including retinal pigment epithelium (RPE). Oxidative stress-mediated senescence and death of RPE and subsequent death of photoreceptors have been observed in age-related macular degeneration (AMD). Although the consequences of GSH depletion have been described previously, questions remain regarding the molecular mechanisms. We herein examined the downstream effects of GSH depletion on stress-induced premature senescence (SIPS) and cell death in human RPE cells...
July 9, 2018: Cell Death & Disease
Silvia Codenotti, Maura Poli, Michela Asperti, Daniela Zizioli, Francesco Marampon, Alessandro Fanzani
PURPOSE: Ferroptosis is a programmed form of iron-dependent cell death caused by lipid hydroperoxide accumulation, which can be prevented by glutathione peroxidase 4 (GPx4) activity. Here we investigated the effects of ferroptosis inducers called erastin and RSL3, which act by glutathione depletion and GPx4 inactivation, respectively, on muscle-derived cell lines of embryonal and alveolar rhabdomyosarcoma (RMS), and mouse normal skeletal C2C12 myoblasts. METHODS: Myogenic lines were exposed to stepwise increasing concentrations of ferroptosis inducers either alone or in combination with iron supplementation, iron chelating agents (bathophenanthrolinedisulfonic acid, BPS), antioxidant molecules (glutathione, N-acetylcysteine), lipid peroxidation inhibitors (ferrostatin-1), and chemotherapeutic agents (doxorubicin and actinomycin D)...
July 3, 2018: Journal of Cancer Research and Clinical Oncology
Rui Kang, Ling Zeng, Shan Zhu, Yangchun Xie, Jiao Liu, Qirong Wen, Lizhi Cao, Min Xie, Qitao Ran, Guido Kroemer, Haichao Wang, Timothy R Billiar, Jianxin Jiang, Daolin Tang
Sepsis is a life-threatening condition caused by pathogen infection and associated with pyroptosis. Pyroptosis occurs upon activation of proinflammatory caspases and their subsequent cleavage of gasdermin D (GSDMD), resulting in GSDMD N-terminal fragments that form membrane pores to induce cell lysis. Here, we show that antioxidant defense enzyme glutathione peroxidase 4 (GPX4) and its ability to decrease lipid peroxidation, negatively regulate macrophage pyroptosis, and septic lethality in mice. Conditional Gpx4 knockout in myeloid lineage cells increases lipid peroxidation-dependent caspase-11 activation and GSDMD cleavage...
June 5, 2018: Cell Host & Microbe
Caitlin W Brown, John J Amante, Arthur M Mercurio
Ferroptosis is an iron-dependent form of programmed cell death characterized by the accumulation of lipid-targeting reactive oxygen species that kill cells by damaging their plasma membrane. The lipid-repair enzyme glutathione peroxidase 4 (GPX4) protects against this oxidative damage and enables cells to resist ferroptosis. Recent work has revealed that matrix-detached carcinoma cells can be susceptible to ferroptosis and that they can evade this fate through the signaling properties of the α6β4 integrin, which sustains GPX4 expression...
June 22, 2018: Journal of Biological Chemistry
Hui Zhao, Flora S Kalish, Ronald J Wong, David K Stevenson
PROBLEM: Uterine and placental macrophages play critical roles in maintaining a normal pregnancy. The majority of these macrophages are believed to be alternatively activated macrophages (M2). METHOD OF STUDY: Mouse bone marrow cells were differentiated into macrophages and polarized to M2 in vitro by treatment with IL-4 [M2a] or IL-10 [M2c] and M1 with LPS/IFN-γ as controls. Macrophage subtypes were confirmed by surface markers and characterized by gene expression profiles...
June 22, 2018: American Journal of Reproductive Immunology: AJRI
Adauto Tsutomu Ikejiri, Frederico Somaio Neto, Paulo Roberto Bertoletto, José Carlos Chaves, Alexandre Key WakateTeruya, Cândida Aparecida Leite Kassuya, Murched Omar Taha, Djalma José Fagundes
PURPOSE: To evaluate the effect of hyperbaric oxygenation (HBO) on the expression of the genes antioxidant glutathione peroxidase 4 (Gpx4) and lactoperoxidase (Lpo) in the lung of mice subjected to intestinal ischemia and reperfusion (IIR). METHODS: Control group (CG) in which were subjected to anesthesia, laparotomy and observation for 120 minutes; an ischemia and reperfusion group (IRG) subjected to anesthesia, laparotomy, small bowel ischemia for 60 minutes and reperfusion for 60 minutes; and three groups treated with HBO during ischemia (HBOG + I), during reperfusion (HBOG + R) and during ischemia and reperfusion (HBOG + IR)...
May 2018: Acta Cirúrgica Brasileira
Michael John Kerins, John Milligan, James Akira Wohlschlegel, Aikseng Ooi
Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary cancer syndrome characterized by inactivation of the Krebs cycle enzyme fumarate hydratase (FH). HLRCC patients are at a high risk of developing kidney cancer of type 2 papillary morphology that is refractory to current radio-, immuno-, and chemo- therapies. Hence, an effective therapy for this deadly form of cancer is urgently needed. Here we show that FH inactivation (FH-/- ) proves synthetic lethal with inducers of ferroptosis, an iron-dependent and nonapoptotic form of cell death...
June 19, 2018: Cancer Science
Jin Wang, Qi-Fan Zeng, Hui Wang, Wei Chen, Yong-Qing Zeng
Ultimate pH (pHu ) is a major determinant factor of meat quality. In this study, we investigated the effects of pHu on the muscle antioxidant capacity, and the relationship between pHu and muscle antioxidant capacity of pigs. A total of 137 pigs from three pig breeds with the same feeding condition were slaughtered and used to measure the pHu , superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), total antioxidant capacity (T-AOC), and malondialdehyde (MDA) content, and gene expression of SOD1 and GPX4...
June 13, 2018: Animal Science Journal, Nihon Chikusan Gakkaihō
Astrid Borchert, Jacqueline Kalms, Sophia R Roth, Marlena Rademacher, Andrea Schmidt, Hermann-Georg Holzhutter, Hartmut Kuhn, Patrick Scheerer
Glutathione peroxidases (GPX) are anti-oxidative enzymes that reduce organic and inorganic hydroperoxides to the corresponding alcohols at the expense of reduced glutathione. The human genome involves eight GPX genes and five of them encode for selenocysteine-containing enzymes. Among the human GPX-isoforms, GPX4 is unique since it is capable of reducing complex hydroperoxy ester lipids such as hydroperoxy phospholipids and hydroperoxy cholesterolesters. Using a number of genetically modified mouse strains the biological role of GPX4 has comprehensively characterized but the molecular enzymology is less well explored...
June 5, 2018: Biochimica et Biophysica Acta
Hsiu-Chuan Yen, Chih-Lung Lin, Bing-Shian Chen, Chih-Wei Chen, Kuo-Chen Wei, Mei-Lin Yang, Jee-Ching Hsu, Yung-Hsing Hsu
Malignant astrocytoma is the most commonly occurring brain tumor in humans. Oxidative stress is implicated in the development of cancers. Superoxide dismutase 2 (SOD2) was found to exert tumor suppressive effect in basic research, but increased SOD2 protein level was associated with higher aggressiveness of human astrocytomas. However, studies reporting alterations of antioxidant enzymes in human astrocytomas often employed less accurate methods or included different types of tumors. Here we analyzed the mRNA levels, activities, and protein levels of primary antioxidant enzymes in control brain tissues and various grades of astrocytomas obtained from 40 patients...
June 3, 2018: Free Radical Research
Jack L Arbiser, Michael Y Bonner, Nicole Ward, Justin Elsey, Shikha Rao
BACKGROUND: A link between selenium deficiency and inflammatory skin diseases have been noted by many, but this link is still not well understood. We have previously studied the efficacy of ceramide analogs, based on the fire ant venom Solenopsin A, against our psoriasis animal model. Treatment of animals with solenopsin analogs resulted in significantly improved skin as well as in a coordinate downregulation of selenoproteins, namely Glutathione Peroxidase 4 (GPX4). We thus hypothesize that ferroptosis may be a physiologic process that may protect the skin from both inflammatory and neoplastic processes...
May 28, 2018: Biochimica et Biophysica Acta
Marcus Conrad, Valerian E Kagan, Hülya Bayir, Gabriela C Pagnussat, Brian Head, Maret G Traber, Brent R Stockwell
Lipid peroxidation is the process by which oxygen combines with lipids to generate lipid hydroperoxides via intermediate formation of peroxyl radicals. Vitamin E and coenzyme Q10 react with peroxyl radicals to yield peroxides, and then these oxidized lipid species can be detoxified by glutathione and glutathione peroxidase 4 (GPX4) and other components of the cellular antioxidant defense network. Ferroptosis is a form of regulated nonapoptotic cell death involving overwhelming iron-dependent lipid peroxidation...
May 1, 2018: Genes & Development
Huizhong Feng, Brent R Stockwell
Ferroptosis is a cell death process driven by damage to cell membranes and linked to numerous human diseases. Ferroptosis is caused by loss of activity of the key enzyme that is tasked with repairing oxidative damage to cell membranes-glutathione peroxidase 4 (GPX4). GPX4 normally removes the dangerous products of iron-dependent lipid peroxidation, protecting cell membranes from this type of damage; when GPX4 fails, ferroptosis ensues. Ferroptosis is distinct from apoptosis, necroptosis, necrosis, and other modes of cell death...
May 2018: PLoS Biology
Antonio Bruni, Andrew R Pepper, Rena L Pawlick, Boris Gala-Lopez, Anissa F Gamble, Tatsuya Kin, Karen Seeberger, Gregory S Korbutt, Stefan R Bornstein, Andreas Linkermann, A M James Shapiro
Human islet transplantation has been hampered by donor cell death associated with the islet preparation procedure before transplantation. Regulated necrosis pathways are biochemically and morphologically distinct from apoptosis. Recently, ferroptosis was identified as a non-apoptotic form of iron-dependent regulated necrosis implicated in various pathological conditions. Mediators of islet oxidative stress, including glutathione peroxidase-4 (GPX4), have been identified as inhibitors of ferroptosis, and mechanisms that affect GPX4 function can impact islet function and viability...
May 22, 2018: Cell Death & Disease
Mei-Ju Liu, Ai-Gang Sun, Shi-Gang Zhao, Hui Liu, Shui-Ying Ma, Mei Li, Ying-Xue Huai, Han Zhao, Hong-Bin Liu
OBJECTIVE: To evaluate the effects of resveratrol on oocyte maturation in aged mice and humans. DESIGN: Experimental laboratory study. SETTING: University-based reproductive medicine center. PATIENT(S): A total of 64 women 38-45 years of age undergoing intracytoplasmic sperm injection (ICSI) and 48-52-week-old female C57BL/6J mice. INTERVENTION(S): In vitro culture in the presence of three different concentrations of resveratrol (0...
May 2018: Fertility and Sterility
Qingwei Meng, Tao Guo, Gaoqiang Li, Shishuai Sun, Shiqi He, Baojing Cheng, Baoming Shi, Anshan Shan
Background: Resveratrol, a plant phenol, affords protection against inflammation and oxidative stress. The objective of this study was to investigate the effects of dietary resveratrol supplementation during pregnancy and lactation on the antioxidant status of sows and piglets and on antioxidant gene expression and pathway in placenta. Methods: Forty sows were allotted to 2 dietary treatments 20 d after breeding. Sows were fed a control diet and a control diet with 300 mg/kg resveratrol...
2018: Journal of Animal Science and Biotechnology
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