期刊
BIOCHIMIE
卷 91, 期 3, 页码 408-415出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biochi.2008.10.014
关键词
Aluminum; Succinate; alpha-Keloglutarate; Hypoxia inducible factor-1 alpha; Prolyl hydroxylase 2
资金
- Industry Canada
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 alpha-ketoglutarate (KG) mitigates the Al-mediated nuclear accumulation of hypoxia inducible factor-1 alpha (HIF-1 alpha) in cultured human hepatocytes (HepG2). The nuclear localization of HIF-1 alpha 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-1 alpha was intricately linked to the mitochondrial dysfunction observed during Al stress. BN-PAGE, immunoblot, and HPLC revealed that the loss of alpha-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-1 alpha in the nucleus. Taken together, these data indicate that the homeostasis of KG plays a pivotal role in aerobic and anaerobic respiration. (C) 2008 Elsevier Masson SAS. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据