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• W2080451545 abstract "Aluminum (Al), a known environmental pollutant, has been linked to numerous pathologies such as Alzheimer's disease and anaemia. In this study, we show that α-ketoglutarate (KG) mitigates the Al-mediated nuclear accumulation of hypoxia inducible factor-1α (HIF-1α) in cultured human hepatocytes (HepG2). The nuclear localization of HIF-1α appeared to be triggered by the Al-induced perturbation of prolyl hydroxylase 2 (PHD2). This enzyme was markedly diminished in the Al-challenged hepatocytes. The fate of PHD2 and HIF-1α was intricately linked to the mitochondrial dysfunction observed during Al stress. BN-PAGE, immunoblot, and HPLC revealed that the loss of α-ketoglutarate dehydrogenase (KGDH) and succinate dehydrogenase (SDH) activities were coupled to the accumulation of succinate. However, the treatment of the Al-stressed cells with KG recovered the activity and expression of KGDH, SDH, and PHD2 with a concomitant decrease in the levels of HIF-1α in the nucleus. Taken together, these data indicate that the homeostasis of KG plays a pivotal role in aerobic and anaerobic respiration." @default.
• W2080451545 created "2016-06-24" @default.
• W2080451545 creator A5043222849 @default.
• W2080451545 creator A5061668188 @default.
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• W2080451545 date "2009-03-01" @default.
• W2080451545 modified "2023-09-23" @default.
• W2080451545 title "α-Ketoglutarate abrogates the nuclear localization of HIF-1α in aluminum-exposed hepatocytes" @default.
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• W2080451545 doi "https://doi.org/10.1016/j.biochi.2008.10.014" @default.
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• W2080451545 hasPublicationYear "2009" @default.
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