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https://www.readbyqxmd.com/read/29144989/cysteine-dioxygenase-1-mediates-erastin-induced-ferroptosis-in-human-gastric-cancer-cells
#1
Shihui Hao, Jiang Yu, Wanming He, Qiong Huang, Yang Zhao, Bishan Liang, Shuyi Zhang, Zhaowei Wen, Shumin Dong, Jinjun Rao, Wangjun Liao, Min Shi
BACKGROUND: Ferroptosis is a recently discovered form of iron-dependent nonapoptotic cell death. It is characterized by loss of the activity of the lipid repair enzyme, glutathione peroxidase 4 (GPX4), and accumulation of lethal reactive lipid oxygen species. However, we still know relatively little about ferroptosis and its molecular mechanism in gastric cancer (GC) cells. Here, we demonstrate that erastin, a classic inducer of ferroptosis, induces this form of cell death in GC cells and that cysteine dioxygenase 1 (CDO1) plays an important role in this process...
November 13, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29128369/inhibition-of-poly-adp-ribose-polymerase-1-alters-expression-of-mitochondria-related-genes-in-pc12-cells-relevance-to-mitochondrial-homeostasis-in-neurodegenerative-disorders
#2
Grzegorz A Czapski, Magdalena Cieślik, Przemysław L Wencel, Sylwia Wójtowicz, Robert P Strosznajder, Joanna B Strosznajder
Alzheimer's disease (AD) is characterized by the release of amyloid beta peptides (Aβ) in the form of monomers/oligomers which may lead to oxidative stress, mitochondria dysfunction, synaptic loss, neuroinflammation and, in consequence, to overactivation of poly(ADP-ribose) polymerase-1 (PARP-1). However, Aβ peptides are also released in the brain ischemia, traumatic injury and in inflammatory response. PARP-1 is suggested to be a promising target in therapy of neurodegenerative disorders. We investigated the impact of PARP-1 inhibition on transcription of mitochondria-related genes in PC12 cells...
November 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29127085/gpx4-inhibition-selectively-targets-drug-tolerant-persister-cells
#3
(no author information available yet)
Targeting GPX4 induces selective cell death of drug-tolerant persister tumor cells by ferroptosis.
November 10, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29122055/extruded-linseed-alone-or-in-combination-with-fish-oil-modifies-mammary-gene-expression-profiles-in-lactating-goats
#4
Y Faulconnier, L Bernard, C Boby, J Domagalski, Y Chilliard, C Leroux
Nutrition is a major factor that regulates ruminant milk components, particularly its fatty acid (FA) composition, which is an important determinant of milk nutritional quality. In the mammary gland, milk component biosynthesis involves a large number of genes under nutritional regulation that are not well understood. Thus, the objective of the present study was to evaluate the effects of extruded linseeds (EL) alone or in combination with fish oil (ELFO) on goat mammary gene expression. In total, 14 goats were fed one of the following three diets: a natural grassland hay basal diet (CTRL) alone, CTRL supplemented with 530 g/day of EL, or 340 g/day of EL plus 39 g/day of fish oil (ELFO)...
November 10, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/29118419/melatonin-promotes-triacylglycerol-accumulation-via-mt2-receptor-during-differentiation-in-bovine-intramuscular-preadipocytes
#5
Wucai Yang, Keqiong Tang, Yaning Wang, Yingying Zhang, Linsen Zan
Melatonin (N-acetyl-5-methoxytryptamine) is a derivative of tryptophan which is produced and secreted mainly by the pineal gland and regulates a variety of important central and peripheral actions. To examine the potential effects of melatonin on the proliferation and differentiation of bovine intramuscular preadipocytes (BIPs), BIPs were incubated with different concentrations of melatonin. Melatonin supplementation at 1 mM significantly increased peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer-binding protein (C/EBP) β, and C/EBPα expression and promoted the differentiation of BIPs into adipocytes with large lipid droplets and high cellular triacylglycerol (TAG) levels...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29107684/ethylene-glycol-dimethacrylate-and-diethylene-glycol-dimethacrylate-exhibits-cytotoxic-and-genotoxic-effect-on-human-gingival-fibroblasts-via-induction-of-reactive-oxygen-species
#6
Anna Bielecka-Kowalska, Piotr Czarny, Paulina Wigner, Ewelina Synowiec, Bartosz Kowalski, Marzena Szwed, Renata Krupa, Monika Toma, Malgorzata Drzewiecka, Ireneusz Majsterek, Janusz Szemraj, Tomasz Sliwinski, Michał Kowalski
Although methacrylic acid derivatives in their polymeric form are considered to be safe, insufficient polymerization and the release of monomers due to either mechanical or enzymatical factors can lead to their reaching millimolar concentrations in local tissue. The present study evaluates the effect of two methacrylate monomers - ethylene glycol dimethacrylate (EGDMA) and diethylene glycol dimethacrylate (DEGDMA) - on human gingival fibroblasts (HGFs). Both monomers were found to reduce cells viability in MTT assay, increase apoptosis and cause cell cycle arrest in G1/G0 phase...
October 28, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29053969/pebp1-wardens-ferroptosis-by-enabling-lipoxygenase-generation-of-lipid-death-signals
#7
Sally E Wenzel, Yulia Y Tyurina, Jinming Zhao, Claudette M St Croix, Haider H Dar, Gaowei Mao, Vladimir A Tyurin, Tamil S Anthonymuthu, Alexandr A Kapralov, Andrew A Amoscato, Karolina Mikulska-Ruminska, Indira H Shrivastava, Elizabeth M Kenny, Qin Yang, Joel C Rosenbaum, Louis J Sparvero, David R Emlet, Xiaoyan Wen, Yoshinori Minami, Feng Qu, Simon C Watkins, Theodore R Holman, Andrew P VanDemark, John A Kellum, Ivet Bahar, Hülya Bayır, Valerian E Kagan
Ferroptosis is a form of programmed cell death that is pathogenic to several acute and chronic diseases and executed via oxygenation of polyunsaturated phosphatidylethanolamines (PE) by 15-lipoxygenases (15-LO) that normally use free polyunsaturated fatty acids as substrates. Mechanisms of the altered 15-LO substrate specificity are enigmatic. We sought a common ferroptosis regulator for 15LO. We discovered that PEBP1, a scaffold protein inhibitor of protein kinase cascades, complexes with two 15LO isoforms, 15LO1 and 15LO2, and changes their substrate competence to generate hydroperoxy-PE...
October 19, 2017: Cell
https://www.readbyqxmd.com/read/29038744/autophagy-and-ferroptosis-what-s-the-connection
#8
Rui Kang, Daolin Tang
PURPOSE OF REVIEW: Autophagy is a conserved intracellular degradation system and plays a dual role in cell death, depending on context and phase. Ferroptosis is a new form of regulated cell death that mainly depends on iron accumulation and lipid peroxidation. In this review, we summarize the processes of autophagy and ferroptosis and discuss their crosstalk mechanisms at the molecular level. RECENT FINDINGS: The original study shows that ferroptosis is morphologically, biochemically, and genetically distinct from autophagy and other types of cell death...
June 2017: Current Pathobiology Reports
https://www.readbyqxmd.com/read/28972104/the-%C3%AE-6%C3%AE-4-integrin-promotes-resistance-to-ferroptosis
#9
Caitlin W Brown, John J Amante, Hira Lal Goel, Arthur M Mercurio
Increases in lipid peroxidation can cause ferroptosis, a form of cell death triggered by inhibition of glutathione peroxidase 4 (GPX4), which catalyzes the reduction of lipid peroxides and is a target of ferroptosis inducers, such as erastin. The α6β4 integrin protects adherent epithelial and carcinoma cells from ferroptosis induced by erastin. In addition, extracellular matrix (ECM) detachment is a physiologic trigger of ferroptosis, which is evaded by α6β4. The mechanism that enables α6β4 to evade ferroptosis involves its ability to protect changes in membrane lipids that are proferroptotic...
September 28, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28958587/investigation-of-antioxidant-systems-in-human-meibomian-gland-and-conjunctival-tissues
#10
Hachemi Nezzar, Joyce N Mbekeani, Anais Noblanc, Frédéric Chiambaretta, Joël R Drevet, Ayhan Kocer
Oxidative stress (OS) associated with direct contact with the environment and light exposure is a very potent and continuous stressor of the ocular surface and internal structures of the eye that are required to manage its effects. Constant replenishment of tears together with the superficial lipid layer produced by the meibomian glands (MG) is one protective mechanism. The lipid-rich fraction of the tears coats the deeper aqueous fraction, preventing its evaporation. However, lipids are particularly sensitive to oxidative damage that could alter tear film quality...
September 27, 2017: Experimental Eye Research
https://www.readbyqxmd.com/read/28941462/skq1-regulates-expression-of-nrf2-are-controlled-genes-encoding-antioxidant-enzymes-and-their-activity-in-cerebral-cortex-under-oxidative-stress
#11
V V Vnukov, O I Gutsenko, N P Milyutina, I V Kornienko, A A Ananyan, A A Plotnikov, S B Panina
The administration of SkQ1 to rats at the dose of 50 nmol/kg for five days significantly increased the mRNA levels of transcription factor Nrf2 and of Nrf2-controlled genes encoding antioxidant enzymes SOD1, SOD2, CAT, and GPx4, whereas changes in the level of mRNA of SOD3 in the cerebral cortex of the rat brain were not significant. This was accompanied by activation of antioxidant enzymes (SOD, CAT, GPx, and GST) and increase in reduced glutathione concentration. Under oxidative stress induced by hyperoxia (0...
August 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28917047/detection-of-selenoproteins-by-laser-ablation-inductively-coupled-plasma-mass-spectrometry-la-icp-ms-in-immobilized-ph-gradient-ipg-strips
#12
Jordan Sonet, Sandra Mounicou, Laurent Chavatte
In contrast to other trace elements that are cofactors of enzymes and removed from proteins under denaturing conditions, Se is covalently bound to proteins when incorporated into selenoproteins, since it is a component of selenocysteine aminoacid. It implies that selenoproteins can undergo several biochemical separation methods in stringent and chaotropic conditions and still maintain the presence of selenium in the primary sequence. This feature has been used to develop a method for the detection of trace levels of human selenoproteins in cell extracts without the use of radioactive isotopes...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28904321/altered-expression-of-mitochondrial-antioxidants-in-oral-squamous-cell-carcinoma
#13
Sumita Banerjee, Saikat Mukherjee, Sanjib Mitra, Pallav Singhal
Reactive oxygen species, if produced in excess by oxidative phosphorylation, contributes to mitochondrial DNA damage and progressive respiratory chain dysfunction, leading to various diseases including carcinogenesis. Mitochondria are susceptible to oxidative stress (OS) owing to lack of introns, protective histones, and DNA repair enzymes. However, mitochondria are protected from OS by numerous antioxidants such as superoxide dismutase 2 (SOD2), catalase, glutaredoxin 2 (GLRX2), reduced glutathione (GSH), glutathione peroxidase (GPX), and thioredoxin 2 (TXN2)...
2017: Journal of Oral Science
https://www.readbyqxmd.com/read/28893626/low-density-lipoprotein-docosahexaenoic-acid-nanoparticles-induce-ferroptotic-cell-death-in-hepatocellular-carcinoma
#14
Weijun Ou, Rohit S Mulik, Arnida Anwar, Jeffrey G McDonald, Xiaoshun He, Ian R Corbin
Low-density lipoprotein nanoparticles reconstituted with the natural omega-3 fatty acid, docosahexaenoic acid (LDL-DHA), have been reported to selectively kill hepatoma cells and reduce the growth of orthotopic liver tumors in the rat. To date, little is known about the cell death pathways by which LDL-DHA nanoparticles kill tumor cells. Here we show that the LDL-DHA nanoparticles are cytotoxic to both rat hepatoma and human hepatocellular carcinoma (HCC) cell lines. Following LDL-DHA treatment both rat and human HCC cells experience pronounced lipid peroxidation, depletion of glutathione and inactivation of the lipid antioxidant glutathione peroxidase-4 (GPX4) prior to cell death...
September 8, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28837769/the-potency-of-diarylamine-radical-trapping-antioxidants-as-inhibitors-of-ferroptosis-underscores-the-role-of-autoxidation-in-the-mechanism-of-cell-death
#15
Ron Shah, Kaitlyn Margison, Derek A Pratt
Two aromatic amines (ferrostatin-1 and liproxstatin-1) were recently identified from high-throughput screening efforts to uncover potent inhibitors of ferroptosis, the necrotic-like cell death induced by inhibition of glutathione peroxidase 4 (GPX4), deletion of the corresponding gpx4 gene, or starvation of GPX4 of its reducing cosubstrate, glutathione (GSH). We have since demonstrated that these two aromatic amines are highly effective radical-trapping antioxidants (RTAs) in lipid bilayers, suggesting that they subvert ferroptosis by inhibiting lipid peroxidation (autoxidation) and, thus, that this process drives the execution of ferroptosis...
September 18, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28837255/role-of-the-chalcogen-s-se-te-in-the-oxidation-mechanism-of-the-glutathione-peroxidase-active-site
#16
Marco Bortoli, Mauro Torsello, F Matthias Bickelhaupt, Laura Orian
The oxidation by H2 O2 of the human phospholipid hydroperoxide glutathione peroxidase (GPx4), used as a model peroxidase selenoenzyme, as well as that of its cysteine (Cys) and tellurocysteine (Tec) mutants, was investigated in silico through a combined classic and quantum mechanics approach to assess the role of the different chalcogens. To perform this analysis, new parameters for selenocysteine (Sec) and tellurocysteine (Tec) were accurately derived for the AMBER ff14SB force field. The oxidation represents the initial step of the antioxidant activity of GPx, which catalyzes the reduction of H2 O2 and organic hydroperoxides by glutathione (GSH)...
August 24, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/28814533/dietary-selenium-deficiency-or-excess-reduces-sperm-quality-and-testicular-mrna-abundance-of-nuclear-glutathione-peroxidase-4-in-rats
#17
Ji-Chang Zhou, Shijie Zheng, Junluan Mo, Xiongshun Liang, Yuanfei Xu, Huimin Zhang, Chunmei Gong, Xiao-Li Liu, Xin Gen Lei
Background: Glutathione peroxidase (GPX) 4 and selenoprotein P (SELENOP) are abundant, and several variants are expressed in the testis.Objective: We determined the effects of dietary selenium deficiency or excess on sperm quality and expressions of GPX4 and SELENOP variants in rat testis and liver.Methods: After weaning, male Sprague-Dawley rats were fed a Se-deficient basal diet (BD) for 5 wk until they were 9 wk old [mean ± SEM body weight (BW) = 256 ± 5 g]. They were then fed the BD diet alone (deficient) or with 0...
October 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28811867/modulation-of-glutathione-hemostasis-by-inhibition-of-12-15-lipoxygenase-prevents-ros-mediated-cell-death-after-hepatic-ischemia-and-reperfusion
#18
Moritz Drefs, Michael N Thomas, Markus Guba, Martin K Angele, Jens Werner, Marcus Conrad, Christian J Steib, Lesca M Holdt, Joachim Andrassy, Andrej Khandoga, Markus Rentsch
BACKGROUND: Reactive oxygen species- (ROS-) mediated ischemia-reperfusion injury (IRI) detrimentally impacts liver transplantation and resection. 12/15-Lipoxygenase (12/15-LOX), an antagonistic protein of the glutathione peroxidase 4 (GPX4) signaling cascade, was proven to mediate cell death in postischemic cerebral and myocardial tissue. The aim of this study was to investigate the impact of 12/15-LOX inhibition on hepatic IRI. METHODS: Livers of C57BL/6 mice were exposed to 60 minutes of partial warm ischemia and 90 minutes of reperfusion after previous Baicalein administration, an inhibitor of 12/15-LOX...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28805353/the-role-of-melatonin-receptor-mtnr1a-in-the-action-of-melatonin-on-bovine-granulosa-cells
#19
Shu-Juan Wang, Wen-Ju Liu, Li-Ke Wang, Xun-Sheng Pang, Li-Guo Yang
Granulosa cells (GCs) play an important role in ovarian follicle growth, development, and follicular atresia. In the present study, we investigated the effects of Melatonin on bovine GCs, and asked if MTNR1A was involved in their response to this indole hormone. Our results indicated that Melatonin inhibited GC apoptosis by up-regulating the expression of BCL2, BCL-XL, GPX4, and SOD1, and down-regulating the expression of BAX, CASP3, and TP53. Moreover, Melatonin modulated bovine GC function by decreasing the expression of INHA, INHBB, FSHR, and TGFBR3, and the abundance of Inhibin β and Activin B, while increasing the expression of LHR, INHBA, and secretion of progesterone by GCs...
August 14, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28783123/iron-oxidative-damage-and-ferroptosis-in-rhabdomyosarcoma
#20
REVIEW
Alessandro Fanzani, Maura Poli
Recent data have indicated a fundamental role of iron in mediating a non-apoptotic and non-necrotic oxidative form of programmed cell death termed ferroptosis that requires abundant cytosolic free labile iron to promote membrane lipid peroxidation. Different scavenger molecules and detoxifying enzymes, such as glutathione (GSH) and glutathione peroxidase 4 (GPX4), have been shown to overwhelm or exacerbate ferroptosis depending on their expression magnitude. Ferroptosis is emerging as a potential weapon against tumor growth since it has been shown to potentiate cell death in some malignancies...
August 7, 2017: International Journal of Molecular Sciences
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