keyword
MENU ▼
Read by QxMD icon Read
search

Gpx4

keyword
https://www.readbyqxmd.com/read/27860262/ferroptosis-a-new-form-of-cell-death-and-its-relationships-with-tumourous-diseases
#1
REVIEW
Haitao Yu, Pengyi Guo, Xiaozai Xie, Yi Wang, Gang Chen
Ferroptosis is a newly discovered type of cell death that differs from traditional apoptosis and necrosis and results from iron-dependent lipid peroxide accumulation. Ferroptotic cell death is characterized by cytological changes, including cell volume shrinkage and increased mitochondrial membrane density. Ferroptosis can be induced by two classes of small-molecule substances known as class 1 (system Xc(-) inhibitors) and class 2 ferroptosis inducers [glutathione peroxidase 4 (GPx4) inhibitors]. In addition to these small-molecule substances, a number of drugs (e...
November 10, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27836545/discovery-of-gpx4-inhibitory-peptides-from-random-peptide-t7-phage-display-and-subsequent-structural-analysis
#2
Kotaro Sakamoto, Satoshi Sogabe, Yusuke Kamada, Shin-Ichi Matsumoto, Akito Kadotani, Jun-Ichi Sakamoto, Akiyoshi Tani
The phospholipid hydroperoxidase glutathione peroxidase (GPX4) is an enzyme that reduces lipid hydroperoxides in lipid membranes. Recently, GPX4 has been investigated as a target molecule that induces iron-dependent cell death (ferroptosis) selectively in cancer cells that express mutant Ras. GPX4 inhibitors have the potential to become novel anti-cancer drugs. However, there are no druggable pockets for conventional small molecules on the molecular surface of GPX4. To generate GPX4 inhibitors, we examined the use of peptides as an alternative to small molecules...
November 8, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27816518/antioxidant-responses-in-hibernating-chinese-soft-shelled-turtle-pelodiscus-sinensis-hatchlings
#3
Wen-Yi Zhang, Cui-Juan Niu, Bo-Jian Chen, Lin Yuan
The antioxidant defense system protects turtles from oxidative stress during hibernation. The present study examined changes of the antioxidant enzymes both on mRNA level and enzyme activity level during hibernation of Chinese soft-shelled turtle Pelodiscus sinensis hatchlings. The upstream regulator NF-E2 related factor 2 (Nrf2) mRNA was also measured. Samples were taken at pre-hibernation (17.0°C, Mud temperature (MT)), hibernation (5.8°C, MT) and arousal (20.1°C, MT). Nrf2 exhibited a tissue-specific pattern of expression with a decrease in the brain, slight increase in the liver and heart during hibernation, and significant increase during arousal in all the three tissues...
November 3, 2016: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/27811014/regulated-necrosis-related-molecule-mrna-expression-in-humans-mice-and-murine-acute-tissue-injury-systemic-autoimmunity-leading-to-progressive-organ-damage-and-progressive-fibrosis
#4
Mohsen Honarpisheh, Jyaysi Desai, Julian A Marschner, Marc Weidenbusch, Maciej Lech, Volker Vielhauer, Hans-Joachim Anders, Shrikant R Mulay
The species-specific, as well as organ-specific expression of regulated necrosis (RN)-related molecules, is not known. We determined the expression levels of TNFR1, RIPK1, RIPK3, MLKL, CASP8, FADD, CIAP1, CIAP2, GPX4, CYPD, CASP1, NLRP3, and PARP1 in human and mouse solid organs. We observed significant differences in expression of these molecules between human and mice. In addition, we characterized their expression profiles in acute as well as persistent tissue injury and chronic tissue remodeling using acute and chronic kidney injury models...
November 3, 2016: Bioscience Reports
https://www.readbyqxmd.com/read/27777421/glutathione-peroxidase-4-a-new-player-in-neurodegeneration
#5
B R Cardoso, D J Hare, A I Bush, B R Roberts
Glutathione peroxidase 4 (GPx4) is an antioxidant enzyme reported as an inhibitor of ferroptosis, a recently discovered non-apoptotic form of cell death. This pathway was initially described in cancer cells and has since been identified in hippocampal and renal cells. In this Perspective, we propose that inhibition of ferroptosis by GPx4 provides protective mechanisms against neurodegeneration. In addition, we suggest that selenium deficiency enhances susceptibility to ferroptotic processes, as well as other programmed cell death pathways due to a reduction in GPx4 activity...
October 25, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27773819/fancd2-protects-against-bone-marrow-injury-from-ferroptosis
#6
Xinxin Song, Yangchun Xie, Rui Kang, Wen Hou, Xiaofang Sun, Michael W Epperly, Joel S Greenberger, Daolin Tang
Bone marrow injury remains a serious concern in traditional cancer treatment. Ferroptosis is an iron- and oxidative-dependent form of regulated cell death that has become part of an emerging strategy for chemotherapy. However, the key regulator of ferroptosis in bone marrow injury remains unknown. Here, we show that Fanconi anemia complementation group D2 (FANCD2), a nuclear protein involved in DNA damage repair, protects against ferroptosis-mediated injury in bone marrow stromal cells (BMSCs). The classical ferroptosis inducer erastin remarkably increased the levels of monoubiquitinated FANCD2, which in turn limited DNA damage in BMSCs...
October 20, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27755963/reproductive-dysfunction-after-mercury-exposure-at-low-levels-evidence-for-a-role-of-glutathione-peroxidase-gpx-1-and-gpx4-in-male-rats
#7
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
https://www.readbyqxmd.com/read/27752918/minimum-selenium-requirements-increase-when-repleting-second-generation-selenium-deficient-rats-but-are-not-further-altered-by-vitamin-e-deficiency
#8
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
https://www.readbyqxmd.com/read/27710939/crystal-and-solution-structural-studies-of-mouse-phospholipid-hydroperoxide-glutathione-peroxidase-4
#9
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
https://www.readbyqxmd.com/read/27687220/glutathione-maintenance-mitigates-age-related-susceptibility-to-redox-cycling-agents
#10
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...
December 2016: Redox Biology
https://www.readbyqxmd.com/read/27645994/selenoprotein-gene-nomenclature
#11
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, Edward E Schmidt, Lutz Schomburg, Ulrich Schweizer, Miljan Simonović, Roger A Sunde, Petra A Tsuji, Susan Tweedie, Fulvio Ursini, Philip D Whanger, 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 sulfoxide reductase B1), and SEPHS2 (selenophosphate synthetase 2)...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27641822/evaluation-of-glutathione-peroxidase-4-role-in-preeclampsia
#12
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
https://www.readbyqxmd.com/read/27634046/male-subfertility-induced-by-heterozygous-expression-of-catalytically-inactive-glutathione-peroxidase-4-is-rescued-in-vivo-by-systemic-inactivation-of-the-alox15-gene
#13
Simone Hanna Brütsch, Marlena Rademacher, Sophia Regina Roth, Karin Müller, 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 a 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 knock-in mice expressing the Sec46Ala-Gpx4 mutant, in which the catalytic selenocysteine was replaced by a redox inactive alanine...
November 4, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27620890/selenium-deficiency-induced-apoptosis-of-chick-embryonic-vascular-smooth-muscle-cells-and-correlations-with-25-selenoproteins
#14
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
https://www.readbyqxmd.com/read/27588473/rsl3-and-erastin-differentially-regulate-redox-signaling-to-promote-smac-mimetic-induced-cell-death
#15
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
https://www.readbyqxmd.com/read/27542713/dihydroxyselenolane-dhs-supplementation-improves-survival-following-whole-body-irradiation-wbi-by-suppressing-tissue-specific-inflammatory-responses
#16
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
https://www.readbyqxmd.com/read/27506793/peroxidation-of-polyunsaturated-fatty-acids-by-lipoxygenases-drives-ferroptosis
#17
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
https://www.readbyqxmd.com/read/27477115/melatonin-modulates-the-functions-of-porcine-granulosa-cells-via-its-membrane-receptor-mt2-in-vitro
#18
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
https://www.readbyqxmd.com/read/27473727/why-21-the-significance-of-selenoproteins-for-human-health-revealed-by-inborn-errors-of-metabolism
#19
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
https://www.readbyqxmd.com/read/27471729/transcriptional-suppression-of-renal-antioxidant-enzyme-systems-in-guinea-pigs-exposed-to-polymerized-cell-free-hemoglobin
#20
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
keyword
keyword
110024
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"