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Literature summary for 1.11.1.12 extracted from

  • Kruemmel, B.; Ploetz, T.; Joerns, A.; Lenzen, S.; Mehmeti, I.
    The central role of glutathione peroxidase 4 in the regulation of ferroptosis and its implications for pro-inflammatory cytokine-mediated beta-cell death (2021), Biochim. Biophys. Acta, 1867, 166114 .
    View publication on PubMed
Search for more literature for 1.11.1.12

Cloned(Commentary)

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

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

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

Localization Comment Organism GeneOntology No. Textmining
mitochondrial inner membrane
-
 Rattus norvegicus 5743
-
mitochondrial outer membrane
-
 Rattus norvegicus 5741
-

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Rattus norvegicus P36970 male rats
-
Rattus norvegicus Lewis-1AR1 P36970 male rats
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Source Tissue

Source Tissue Comment Organism Textmining
INS-1E cell
-
 Rattus norvegicus
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liver
-
 Rattus norvegicus
-
additional information In situ RT-PCR analyses of GPx4 in rat pancreas sections, immunohistochemic analysis Rattus norvegicus
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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
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pancreatic islet cell assessment of GPx4 expression in different pancreatic islet cell types reveals a predominant expression in beta-cells Rattus norvegicus
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Substrates and Products (Substrate)

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

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 [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Rattus norvegicus

General Information

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