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Agani FH, Pichiule P, Carlos Chavez J, LaManna JC: Inhibitors of mitochondrial complex I attenuate the accumulation of hypoxia-inducible factor-1 during hypoxia in Hep3B cells. Comp Biochem Physiol A Mol Integr Physiol. 2002 May;132(1):107-9.
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-1 alpha, 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-1 alpha hypoxic response. Thus, it can be concluded that an intact, functional mitochondrial respiratory chain is required for HIF-1 alpha accumulation. |
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