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Caroline S Martinez, Franck M Peçanha, Daniela S Brum, Francielli W Santos, Jeferson L Franco, Ana Paula P Zemolin, Janete A Anselmo-Franci, Fernando B Junior, María J Alonso, Mercedes Salaices, Dalton V Vassallo, Fábio G Leivas, Giulia A Wiggers
Mercury is a ubiquitous environmental pollutant and mercury contamination and toxicity are serious hazards to human health. Some studies have shown that mercury impairs male reproductive function, but less is known about its effects following exposure at low doses and the possible mechanisms underlying its toxicity. Herein we show that exposure of rats to mercury chloride for 30 days (first dose 4.6µgkg-1, subsequent doses 0.07µgkg-1day-1) resulted in mean (±s.e.m.) blood mercury concentrations of 6.8±0...
October 19, 2016: Reproduction, Fertility, and Development
Roger A Sunde, Kevin M Thompson, Kevin L Fritsche, Jacqueline K Evenson
Second-generation selenium-deficient weanling rats fed graded levels of dietary Se were used (a) to study the impact of initial Se deficiency on dietary Se requirements; (b) to determine if further decreases in selenoperoxidase expression, especially glutathione peroxidase 4 (Gpx4), affect growth or gross disease; and (c) to examine the impact of vitamin E deficiency on biochemical and molecular biomarkers of Se status. Rats were fed a vitamin E-deficient and Se-deficient crystalline amino acid diet (3 ng Se/g diet) or that diet supplemented with 100 μg/g all-rac-α-tocopheryl acetate and/or 0, 0...
October 17, 2016: Biological Trace Element Research
Robert Janowski, Sandra Scanu, Dierk Niessing, Tobias Madl
The mammalian glutathione peroxidase (GPx) family is a key component of the cellular antioxidative defence system. Within this family, GPx4 has unique features as it accepts a large class of hydroperoxy lipid substrates and has a plethora of biological functions, including sperm maturation, regulation of apoptosis and cerebral embryogenesis. In this paper, the structure of the cytoplasmic isoform of mouse phospholipid hydroperoxide glutathione peroxidase (O70325-2 GPx4) with selenocysteine 46 mutated to cysteine is reported solved at 1...
October 1, 2016: Acta Crystallographica. Section F, Structural Biology Communications
Nicholas O Thomas, Kate P Shay, Amanda R Kelley, Judy A Butler, Tory M Hagen
Isolated hepatocytes from young (4-6mo) and old (24-26mo) F344 rats were exposed to increasing concentrations of menadione, a vitamin K derivative and redox cycling agent, to determine whether the age-related decline in Nrf2-mediated detoxification defenses resulted in heightened susceptibility to xenobiotic insult. An LC50 for each age group was established, which showed that aging resulted in a nearly 2-fold increase in susceptibility to menadione (LC50 for young: 405μM; LC50 for old: 275μM). Examination of the known Nrf2-regulated pathways associated with menadione detoxification revealed, surprisingly, that NAD(P)H: quinone oxido-reductase 1 (NQO1) protein levels and activity were induced 9-fold and 4-fold with age, respectively (p=0...
September 22, 2016: Redox Biology
Vadim N Gladyshev, Elias S Arnér, Marla J Berry, Regina Brigelius-Flohé, Elspeth A Bruford, Raymond F Burk, Bradley A Carlson, Sergi Castellano, Laurent Chavatte, Marcus Conrad, Paul R Copeland, Alan M Diamond, Donna M Driscoll, Ana Ferreiro, Leopold Flohé, Fiona R Green, Roderic Guigó, Diane E Handy, Dolph L Hatfield, John Hesketh, Peter R Hoffmann, Arne Holmgren, Robert J Hondal, Michael T Howard, Kaixun Huang, Hwa-Young Kim, Ick Young Kim, Josef Köhrle, Alain Krol, Gregory V Kryukov, Byeong Jae Lee, Byung Cheon Lee, Xin Gen Lei, Qiong Liu, Alain Lescure, Alexei V Lobanov, Joseph Loscalzo, Matilde Maiorino, Marco Mariotti, K Sandeep Prabhu, Margaret P Rayman, Sharon Rozovsky, Gustavo Salinas, Lutz Schomburg, Ulrich Schweizer, Miljan Simonović, Roger A Sunde, Petra A Tsuji, Susan Tweedie, Fulvio Ursini, Yan Zhang
The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4 and GPX6 (glutathione peroxidases), DIO1, DIO2, and DIO3 (iodothyronine deiodinases), MSRB1 (methionine-R-sulfoxide reductase 1) and SEPHS2 (selenophosphate synthetase 2)...
September 19, 2016: Journal of Biological Chemistry
Xinguo Peng, Yan Lin, Jinling Li, Mengchun Liu, Jingli Wang, Xueying Li, Jingjing Liu, Xuewen Jia, Zhongcui Jing, Zuzhou Huang, Kaiqiu Chu, Shiguo Liu
Preeclampsia (PE) is a pregnancy-specific syndrome that may be lifethreatening to pregnancies and fetus. Glutathione Peroxidase 4 (GPx4) is a powerful antioxidant enzyme that can provide protection from oxidative stress damage which plays a pivotal role in the pathology of PE. Therefore, this study aims to investigate the association between Gpx4 polymorphisms and the susceptibility to PE in Chinese Han women. TaqMan allelic discrimination real-time PCR was used to perform the genotyping of rs713041 and rs4807542 in 1008 PE patients and 1386 normotensive pregnancies...
2016: Scientific Reports
Simone Hanna Brutsch, Marlena Rademacher, Sophia Regine Roth, Karin Muller, Susanne Eder, Dagmar Viertel, Christiane Franz, Hartmut Kuhn, Astrid Borchert
Glutathione peroxidase 4 (GPX4) and arachidonic acid 15-lipoxygenase (ALOX15) are antagonizing enzymes in the metabolism of hydroperoxy lipids. In spermatoid cells and/or in the male reproductive system both enzymes are apparently expressed and GPX4 serves as anti-oxidative enzyme but also as structural protein. In this study we explored whether germ-line inactivation of the Alox15 gene might rescue male subfertility induced by heterozygous expression of catalytically silent Gpx4. To address this question we employed Gpx4 knockin mice expressing the Sec46Ala-Gpx4 mutant, in which the catalytic selenocysteine was replaced by a redox inactive alanine...
September 15, 2016: Journal of Biological Chemistry
Qingyu Wang, Jiaqiang Huang, Hao Zhang, Xingen Lei, Zhongyao Du, Chen Xiao, Silu Chen, Fazheng Ren
Selenium deficiency is the major cause of exudative diathesis in chicks. Subcutaneous hemorrhage is one of the typical symptoms of the disease. However, the reason for the occurrence of blood exudation remains unknown. In the present study, the vascular smooth muscle cells (VSMCs) were isolated from 17-day-old broiler chick embryos. Cell viability, cell apoptosis, and intracellular reactive oxygen species level under different concentrations of selenium (0-0.9 μM) were investigated. The mRNA expression levels of 25 selenoproteins and apoptosis-related genes (p53, CytC, Caspase-3, Caspase-8, Bcl-2, and Bax) were also measured...
September 13, 2016: Biological Trace Element Research
Jasmin Dächert, Hannah Schoeneberger, Katharina Rohde, Simone Fulda
Redox mechanisms play an important role in the control of various signaling pathways. Here, we report that Second mitochondrial activator of caspases (Smac) mimetic-induced cell death is regulated by redox signaling. We show that RSL3, a glutathione (GSH) peroxidase (GPX) 4 inhibitor, or Erastin, an inhibitor of the cystine/glutamate antiporter, cooperate with the Smac mimetic BV6 to induce reactive oxygen species (ROS)-dependent cell death in acute lymphoblastic leukemia (ALL) cells. Addition of the caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD...
August 29, 2016: Oncotarget
Amit Kunwar, Prachi Verma, H N Bhilwade, Michio Iwaoka, K Indira Priyadarsini
Dihydroxyselenolane (DHS), a simple water-soluble organoselenium compound, was evaluated for radioprotection in BALB/c mice after whole-body irradiation (WBI) (8Gy (60)Co, 1Gy/min), by monitoring 30-d post-irradiation survival and biochemical/histological changes in radiosensitive organs. Intraperitoneal administration of DHS at 2mg/kg for five consecutive days before irradiation and three times per week during the post-irradiation period showed maximum benefit (40% improvement in 30 d post-irradiation survival)...
September 1, 2016: Mutation Research. Genetic Toxicology and Environmental Mutagenesis
Wan Seok Yang, Katherine J Kim, Michael M Gaschler, Milesh Patel, Mikhail S Shchepinov, Brent R Stockwell
Ferroptosis is form of regulated nonapoptotic cell death that is involved in diverse disease contexts. Small molecules that inhibit glutathione peroxidase 4 (GPX4), a phospholipid peroxidase, cause lethal accumulation of lipid peroxides and induce ferroptotic cell death. Although ferroptosis has been suggested to involve accumulation of reactive oxygen species (ROS) in lipid environments, the mediators and substrates of ROS generation and the pharmacological mechanism of GPX4 inhibition that generates ROS in lipid environments are unknown...
August 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
Ya-Mei He, Hong-Hui Deng, Mei-Hong Shi, Bello Musa Bodinga, Hua-Li Chen, Zeng-Sheng Han, Zhong-Liang Jiang, Qing-Wang Li
Melatonin (N-acetyl-5-methoxytryptamine) is documented as a hormone involved in the circadian regulation of physiological and neuroendocrine function in mammals. Herein, the effects of melatonin on the functions of porcine granulosa cells in vitro were investigated. Porcine granulosa cells were cultivated with variable concentrations of melatonin (0, 0.001, 0.01, 0.1, 1.0, and 10ng/mL) for 48h. Melatonin receptor agonist (IIK7) and antagonist (Luzindole, 4P-PDOT) were used to further examine the action of melatonin...
September 2016: Animal Reproduction Science
Ulrich Schweizer, Noelia Fradejas-Villar
Selenocysteine is the 21st proteinogenic amino acid in mammals. The human genome contains 25 genes encoding selenoproteins, and their significance for human health is increasingly recognized through the identification of patients with inborn errors in selenoprotein biosynthetic factors or in individual selenoproteins. Mutations in selenoprotein N (SEPN1) lead to a spectrum of disorders collectively called SEPN1-related myopathy, and mutations in glutathione peroxidase 4 (GPX4) cause respiratory failure and bone defects, and mutations in thioredoxin reductase 2 (TXNRD2) are associated with familial glucocorticoid deficiency...
July 29, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Otgonchimeg Rentsendorj, Xiaoyuan Zhang, Matthew C Williams, Paul W Buehler, Felice D'Agnillo
Hemoglobin-based oxygen carriers (HBOCs) are being developed as oxygen and plasma volume-expanding therapeutics though their potential to promote oxidative tissue injury has raised safety concerns. Using a guinea pig exchange transfusion model, we examined the effects of polymerized bovine hemoglobin (HbG) on the transcriptional regulation, activity, and expression of the renal antioxidant enzymes; superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). HbG infusion downregulated the mRNA levels for genes encoding SOD isoforms 1-3, GPx1, GPx3, GPx4, and CAT...
2016: Toxics
Maria Carolina Rodrigues-Cunha, Lígia G Mesquita, Fabiana Bressan, Maite Del Collado, Júlio C C Balieiro, Kátia R L Schwarz, Fernanda C de Castro, Osnir Y Watanabe, Yeda F Watanabe, Lia de Alencar Coelho, Cláudia L V Leal
Melatonin may have beneficial effects when used in oocyte maturation and embryo development culture. The effect of melatonin during IVM on meiosis resumption and progression in bovine oocytes and on expression of antioxidant enzymes, nuclear fragmentation and free radicals, as well as on embryo development were assessed. Cumulus-oocyte complexes were matured in vitro with melatonin (10(-9) and 10(-6) M), FSH (positive control), or without hormones (negative control) in defined medium. Maturation rates were evaluated at 6, 12, 18, and 24 hours...
October 15, 2016: Theriogenology
Takatoshi Uchida, Osamu Sakai, Hirotaka Imai, Takashi Ueta
PURPOSE: To investigate the role of glutathione peroxidase 4 (GPx4) in corneal endothelial cells. MATERIALS AND METHODS: An immortalized human corneal endothelial cell line was used. Cells were transfected with either siRNA specifically silencing GPx4 or scrambled control siRNA. Knockdown was confirmed by Real-time RT-PCR and immunoblotting. Lipid peroxidation was evaluated by 4-hydroxy-2-nonenal immunostaining. Cytotoxicity, cell death, and cell proliferation were evaluated using a lactate dehydrogenase (LDH) activity assay, Annexin V staining, and WST-8, respectively...
July 15, 2016: Current Eye Research
Yamei He, Honghui Deng, Zhongliang Jiang, Qingwang Li, Meihong Shi, Huali Chen, Zengsheng Han
The accumulation of reactive oxygen species is detrimental to the health of the ovarian follicle. The protective, antioxidant properties of melatonin, an endogenous component of porcine follicular fluid, on apoptosis of granulosa cells were evaluated in this study. Porcine granulosa cells from medium-sized (3-5 mm), healthy follicles were cultured in serum-free conditions with melatonin (0, 0.01, 0.1, 1.0, 10, and 100 ng/mL) with or without its receptor antagonist, luzindole, followed by evaluation of apoptotic markers in the treated cells...
August 2016: Molecular Reproduction and Development
Ruifeng Fan, Haidong Yao, Xia Zhao, Changyu Cao, Tianshu Yang, Yilin Luan, Ziwei Zhang, Shiwen Xu
The aim of the present study was to clarify the effect of Selenoprotein K (Selk) silencing on the mRNA expression of 25 selenoproteins in chicken myoblasts. The specific small interfering RNA (siRNA) for Selk gene was designed and transfected into chicken myoblasts. Post-transfection mRNA expression of 25 selenoproteins was determined at various time periods i.e., 24, 48 and 72 h. Moreover, based on the results of expression of 25 selenoproteins, correlation analysis and principal component analysis (PCA) were used for further analysis...
August 2016: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
Marcus Conrad, José Pedro Friedmann Angeli
The system XC (-)/glutathione/glutathione peroxidase 4 (Gpx4) axis pivotally controls ferroptosis, a recently described form of regulated non-apoptotic cell death. Compelling evidence has established that this route of cell death is not only of high relevance for triggering cancer cell death, but also proves to be amenable for therapeutic intervention to halt ischemia/reperfusion-related diseases.
July 2015: Molecular & Cellular Oncology
Bradley A Carlson, Ryuta Tobe, Elena Yefremova, Petra A Tsuji, Victoria J Hoffmann, Ulrich Schweizer, Vadim N Gladyshev, Dolph L Hatfield, Marcus Conrad
The selenoenzyme glutathione peroxidase 4 (Gpx4) is an essential mammalian glutathione peroxidase, which protects cells against detrimental lipid peroxidation and governs a novel form of regulated necrotic cell death, called ferroptosis. To study the relevance of Gpx4 and of another vitally important selenoprotein, cytosolic thioredoxin reductase (Txnrd1), for liver function, mice with conditional deletion of Gpx4 in hepatocytes were studied, along with those lacking Txnrd1 and selenocysteine (Sec) tRNA (Trsp) in hepatocytes...
May 26, 2016: Redox Biology
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