1. Academic Validation
  2. Oligomycin inhibits HIF-1alpha expression in hypoxic tumor cells

Oligomycin inhibits HIF-1alpha expression in hypoxic tumor cells

  • Am J Physiol Cell Physiol. 2005 May;288(5):C1023-9. doi: 10.1152/ajpcell.00443.2004.
Yanqing Gong 1 Faton H Agani
Affiliations

Affiliation

  • 1 Dept. of Anatomy, School of Medicine, Case Western Reserve Univ., 10900 Euclid Ave., Cleveland, OH 44106, USA. fxa5@po.cwru.edu
Abstract

Hypoxia-inducible factor-1 (HIF-1) is a key regulator of cellular responses to reduced oxygen availability. The contribution of mitochondria in regulation of HIF-1alpha in hypoxic cells has received recent attention. We demonstrate that inhibition of electron transport complexes I, III, and IV diminished hypoxic HIF-1alpha accumulation in different tumor cell lines. Hypoxia-induced HIF-1alpha accumulation was not prevented by the antioxidants Trolox and N-acetyl-cysteine. Oligomycin, inhibitor of F(0)F(1)-ATPase, prevented hypoxia-induced HIF-1alpha protein accumulation and had no effect on HIF-1alpha induction by hypoxia-mimicking agents desferrioxamine or dimethyloxalylglycine. The inhibitory effect of mitochondrial respiratory chain inhibitors and oligomycin on hypoxic HIF-1alpha content was pronounced in cells exposed to hypoxia (1.5% O(2)) but decreased markedly when cells were exposed to severe oxygen deprivation (anoxia). Taken together, these results do not support the role for mitochondrial Reactive Oxygen Species in HIF-1alpha regulation, but rather suggest that inhibition of electron transport chain and impaired oxygen consumption affect HIF-1alpha accumulation in hypoxic cells indirectly via effects on prolyl hydroxylase function.

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