EC Number   |
General Information |
Reference |
|---|
   1.11.1.12 | malfunction |
decrease of GPX4 expression potentially plays an important role in ferroptosis during early brain injury after SAH. Overexpression of GPX4 significantly reduces lipid peroxidation and cell death in the experimental SAH models both in vivo. Overexpression of GPX4 has a neuroprotective effect after SAH. Overexpression of GPX4 ameliorates brain edema and neurological deficits at 24 h after SAH |
-, 765297 |
| 1.11.1.12 | malfunction |
ferroptosis is an oxidative form of regulated necrotic cell death featuring glutathione (GSH) depletion, disrupted glutathione peroxidase-4 (GPX4) redox defense and detrimental lipid reactive oxygen species (ROS) formation. Mitochondrial damage in models of oxidative glutamate toxicity, glutathione peroxidase depletion, and ferroptosis. (1S,3R)-RSL3, a selective GPx4 inhibitor, mediates concentration-dependent inhibition of GPX4, lipid peroxidation, enhanced mitochondrial fragmentation, loss of mitochondrial membrane potential, and reduced mitochondrial respiration. Ferroptosis inhibitors, such as deferoxamine, ferrostatin-1 and liproxstatin-1, but also CRISPR/Cas9 Bid knockout and the BID inhibitor BI-6c9 protect against RSL3 toxicity. The mitochondria-targeted ROS scavenger mitoquinone (MitoQ) preserves mitochondrial integrity and function, and cell viability despite significant loss of GPX4 expression and associated increases in general lipid peroxidation after exposure to RSL3. BID inhibitor BI-6c9 and ferroptosis inhibitors abrogate 1S, 3R-RSL3 induced cell death, phenotypes, overview |
764701 |
| 1.11.1.12 | malfunction |
silencing of GPx4 by RNA interference and exposure to tert-butyl hydroperoxide (tert-BHP) causes ferroptosis in rat pancreatic beta-cells as evidenced by non-apoptotic cell death in association with increased lipid peroxidation, disturbs ATP synthesis, and reduces GSH content and GPx4 degradation. GPx4 overexpression as well as the ferroptosis inhibitor ferrostatin-1 effectively attenuate beta-cell death induced by tert-BHP. siGPx4- transfected INS-1E cells start to die 96 h post-transfection due to GPx4 deficiency, overview. Overexpression of GPx4 in insulin-producing RINm5F cells prevents tert-BHP-induced cell death |
-, 764207 |
| 1.11.1.12 | metabolism |
beta-cell toxic cytokines did not induce ferroptosis although beta-cells underwent cell death. Inhibition of iNOS by Nomega-nitro-L-arginine however led to a massive lipid peroxidation upon exposure to pro-inflammatory cytokines. Hence, nitric oxide produced during pro-inflammatory cytokine action prevents the induction of ferroptosis, thereby favouring apoptosis as a primary cell death mechanism. The extraordinarily high abundance of the phospholipid hydroperoxidase GPx4 in beta-cells in contrast to the very low expression in other islet cell types points to a susceptibility of beta-cells to the accumulation of toxic lipid peroxides. No involvement of ferroptosis as an alternative beta-cell death mode under pro-inflammatory cytokine attack |
-, 764207 |
| 1.11.1.12 | metabolism |
glutathione (GSH) is the most abundant intracellular antioxidant, with millimolar concentrations present in the cytosol of most cell types. The ratio of oxidized (GSSG) to reduced glutathione, which defines the glutathione redox potential (EGSH) in the Nernst equation, is an important indicator of overall cellular oxidative state. Under homeostatic conditions, the EGSH reflects a ratio of GSH:GSSG of 100:1. roGFP is a genetically encoded fluorogenic sensor that has been used in a variety of cell types for real-time assessments of the EGSH. roGFP has been shown to equilibrate with EGSH through a redox relay that is initiated by hydrogen peroxide (H2O2) and involves the participation of the enzymes GPx, glutaredoxin (Grx), and glutathione reductase (GR) |
764204 |
| 1.11.1.12 | metabolism |
mitochondrial rescue prevents glutathione peroxidase-dependent ferroptosis |
764701 |
| 1.11.1.12 | physiological function |
central role of antioxidative enzyme glutathione peroxidase 4 in the regulation of ferroptosis and its implications for pro-inflammatory cytokine-mediated beta-cell death. GPx4 is indispensable for beta-cell function under physiological conditions |
-, 764207 |
| 1.11.1.12 | physiological function |
early brain injury is an essential pathological process after subarachnoid hemorrhage (SAH), with many cell death modalities. Ferroptosis is a regulated cell death caused by the iron-dependent accumulation of lipid peroxidation, which can be prevented by glutathione peroxidase 4 (GPX4), role of GPX4 in neuronal cell death, overview. Among the various mechanisms of early brain injury, lipid peroxidation is an important mechanism and is closely related to a poor clinical outcome. The generation of oxidized phospholipid (oxPL) species plays a crucial role in ferroptosis13. Glutathione peroxidase 4 (GPX4) inhibits ferroptosis by acting as the sole enzyme to convert hydroperoxides into nontoxic lipid alcohols |
-, 765297 |
| 1.11.1.12 | physiological function |
glutathione peroxidases (GPXs) catalyzes the conversion of H2O2 or hydroperoxide to water or ethanol, and are generally considered to be the principal antioxidant enzymes for hydrogen peroxide (H2O2) detoxification. GPXs are ROS scavengers, the gene expression and enzyme activities of GPX in plant are often induced by abiotic stresses such as H2O2 and salinity treatment |
765762 |
| 1.11.1.12 | physiological function |
linoleic acid is present in the surfactant lining the airway epithelium, where it is a target of lipid peroxidation by oxidizing air pollutants such as ozone. 9-hydroperoxy-10E,12Z-octadecadienoic acid (9-HpODE) is a product of linoleic acid peroxidation that can be generated enzymatically or via radical or non-radical mediated oxidation. Exposure of human airway epithelial cells (HAEC) to 9-HpODE results in an alteration of intracellular EGSH. Enzyme glutathione peroxidase 4, GPx4, is involved in the initiation of GSH oxidation in human aortic endothelial cells (HAEC) by 9-hydroperoxy-10E,12Z-octadecadienoic acid (9-HpODE), but not in GSH oxidation induction by H2O2 or the low molecular weight alkyl tert-butyl hydroperoxide (TBH). 9-Hydroperoxy-10E,12Z-octadecadienoic acid (9-HpODE) is a product of linoleic acid peroxidation that can be generated enzymatically or via radical or non-radical mediated oxidation. Long chain lipid hydroperoxides can directly alter cytosolic EGSH independent of secondary lipid oxidation products or H2O2 production. NADPH has a protective role against 9-HpODE induced EGSH changes. GPx4 is involved specifically in the reduction of long-chain lipid hydroperoxides, leading to GSH oxidation. The same concentration of 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), the reduced product of 9-HpODE, does not result in GSH oxidation, as reported by roGFP, over the same period. Exposure to 9-HpODE causes a dose-dependent increase in GSH oxidation in HAEC that is independent of intracellular or extracellular H2O2 production and is exacerbated by NADPH depletion |
764204 |
