Journal
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR AND INTEGRATIVE PHYSIOLOGY
Volume 132, Issue 1, Pages 107-109Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S1095-6433(01)00535-9
Keywords
mitochondrial complex I; hypoxia; Hep3B cells; rotenone; MPP; oxygen sensing
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Funding
- NHLBI NIH HHS [HL 56470] Funding Source: Medline
- NINDS NIH HHS [NS 37111, NS 38632] Funding Source: Medline
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Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that regulates transcriptional activation of several genes that are responsive to oxygen lack, including erythropoietin, vascular endothelial growth factor, various glycolytic enzymes and the GLUT-1 glucose transporter. Because mitochondria have been postulated to be involved in the regulation of HIF-1, we tested the effects of mitochondrial electron transport chain complex I inhibitors, rotenone and 1-methyl-4-phenylpiridinium (MPP+), on hypoxic-induced accumulation of HIF-1alpha, the regulated component of the dimer. We found, consistent with our previous observations in Cath.a and PC12 cells, that rotenone and MPP- attenuated the HIF-1alpha hypoxic response. Thus, it can be concluded that an intact, functional mitochondrial respiratory chain is required for HIF-1alpha accumulation. (C) 2002 Elsevier Science Inc. All fights reserved.
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