Cloned (Comment) | Organism |
---|---|
gene Gpx4, quantitative real-time PCR expression analysis and absolute quantification of GPx4, recombinant overexpression of hGPx4 in insulin-producing RINm5F cells and in INS-1E cells | Rattus norvegicus |
Protein Variants | Comment | Organism |
---|---|---|
additional information | silencing of GPx4 by RNA interference, siRNA-mediated knockdown of GPx4 in insulin-producing beta-cells. Overexpression of GPx4 in insulin-producing RINm5F cells prevents tert-BHP-induced cell death. GPx4 overexpression provides minor protection of insulin-producing RINm5F cells against pro-inflammatory cytokines | Rattus norvegicus |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(1S,3R)-RSL3 | a selective GPx4 inhibitor, causes a decrease in intracellular ATP levels after 24 h in primary pancreatic rat islets | Rattus norvegicus | |
ferrostatin-1 | along with the prevention of beta-cell death, siGPx4-mediated induction of lipid peroxidation and ATP depletion are reduced significantly in the presence of ferroptosis inhibitor ferrostatin-1 at 0.001 mM | Rattus norvegicus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
mitochondrial inner membrane | - |
Rattus norvegicus | 5743 | - |
mitochondrial outer membrane | - |
Rattus norvegicus | 5741 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
2 glutathione + a hydroperoxy-fatty-acyl-[lipid] | Rattus norvegicus | - |
glutathione disulfide + a hydroxy-fatty-acyl-[lipid] + H2O | - |
? | |
2 glutathione + a hydroperoxy-fatty-acyl-[lipid] | Rattus norvegicus Lewis-1AR1 | - |
glutathione disulfide + a hydroxy-fatty-acyl-[lipid] + H2O | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Rattus norvegicus | P36970 | male rats | - |
Rattus norvegicus Lewis-1AR1 | P36970 | male rats | - |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
INS-1E cell | - |
Rattus norvegicus | - |
liver | - |
Rattus norvegicus | - |
additional information | In situ RT-PCR analyses of GPx4 in rat pancreas sections, immunohistochemic analysis | Rattus norvegicus | - |
pancreatic beta cell | insulin-producing beta-cells and primary islets. Pancreatic beta-cells are endowed with a unique high expression level of GPx4, while GPx4 expression is significantly lower in insulin-producing RINm5F cells | Rattus norvegicus | - |
pancreatic islet cell | assessment of GPx4 expression in different pancreatic islet cell types reveals a predominant expression in beta-cells | Rattus norvegicus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
2 glutathione + a hydroperoxy-fatty-acyl-[lipid] | - |
Rattus norvegicus | glutathione disulfide + a hydroxy-fatty-acyl-[lipid] + H2O | - |
? | |
2 glutathione + a hydroperoxy-fatty-acyl-[lipid] | - |
Rattus norvegicus Lewis-1AR1 | glutathione disulfide + a hydroxy-fatty-acyl-[lipid] + H2O | - |
? | |
2 glutathione + tert-butyl hydroperoxide | - |
Rattus norvegicus | glutathione disulfide + tert-butyl hydroxide + H2O | - |
? | |
2 glutathione + tert-butyl hydroperoxide | - |
Rattus norvegicus Lewis-1AR1 | glutathione disulfide + tert-butyl hydroxide + H2O | - |
? | |
additional information | total GPx activity is determined in a photometric NADPH-coupled assay using tert-BHP as the substrate. The decrease of NADPH absorbance is monitored at 340 nm | Rattus norvegicus | ? | - |
- |
|
additional information | total GPx activity is determined in a photometric NADPH-coupled assay using tert-BHP as the substrate. The decrease of NADPH absorbance is monitored at 340 nm | Rattus norvegicus Lewis-1AR1 | ? | - |
- |
Synonyms | Comment | Organism |
---|---|---|
glutathione peroxidase 4 | - |
Rattus norvegicus |
GPx4 | - |
Rattus norvegicus |
PHGPX | UniProt | Rattus norvegicus |
phospholipid hydroperoxidase | - |
Rattus norvegicus |
phospholipid hydroperoxide glutathione peroxidase | UniProt | Rattus norvegicus |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Rattus norvegicus |
General Information | Comment | Organism |
---|---|---|
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 | Rattus norvegicus |
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 | Rattus norvegicus |
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 | Rattus norvegicus |