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• W2074651845 startingPage "511" @default.
• W2074651845 abstract "Aim Pathological release of excess zinc ions has been implicated in ischemic brain cell death. However, the underlying mechanisms remain to be elucidated. In stroke, ischemia-induced zinc release and hypoxia-inducible factor-1 (HIF-1) accumulation concurrently occur in the ischemic tissue. The present study tests the hypothesis that the presence of high intracellular zinc concentration is a major cause of modifications to PARP-1 and HIF-1α during hypoxia, which significantly contributes to cell death during ischemia. Methods Primary cortical astrocytes and C8-D1A cells were exposed to different concentrations of zinc chloride. Cell death rate and protein expression of HIF-1 and Poly(ADP-ribose) polymerase (PARP)-1 were examined after 3-h hypoxic treatment. Results Although 3-h hypoxia or 100 μM of zinc alone did not induce noticeable cytotoxicity, their combination led to a dramatic increase in astrocytic cell death in a zinc-concentration-dependent manner. Exposure of astrocytes to hypoxia for 3 h remarkably increased the levels of intracellular zinc and HIF-1α protein, which was further augmented by added exogenous zinc. Notably, HIF-1α knockdown blocked zinc-induced astrocyte death. Moreover, knockdown of PARP-1, another important protein in the response of hypoxia, attenuated the overexpression of HIF-1α and reduced the cell death rate. Conclusions Our studies show that zinc promotes hypoxic cell death through overexpression of the hypoxia response factor HIF-1α via the cell fate determine factor PARP-1 modification, which provides a novel mechanism for zinc-mediated ischemic brain injury." @default.
• W2074651845 created "2016-06-24" @default.
• W2074651845 creator A5000827632 @default.
• W2074651845 creator A5032459548 @default.
• W2074651845 creator A5063253432 @default.
• W2074651845 creator A5075012459 @default.
• W2074651845 date "2013-04-13" @default.
• W2074651845 modified "2023-10-10" @default.
• W2074651845 title "Zinc Promotes the Death of Hypoxic Astrocytes by Upregulating Hypoxia-Induced Hypoxia-Inducible Factor-1alpha Expression via Poly(ADP-ribose) Polymerase-1" @default.
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• W2074651845 doi "https://doi.org/10.1111/cns.12098" @default.
• W2074651845 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3681853" @default.
• W2074651845 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23582235" @default.
• W2074651845 hasPublicationYear "2013" @default.
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