Transcriptional regulation by hypoxia-inducible factor 1 - Molecular mechanisms of oxygen homeostasis

Human cells require O-2 for many metabolic processes, most notably oxidative phosphorylation, the major source of ATP generation, and hypoxia plays a significant pathophysiologic role in a variety of cardiovascular disorders. Hypoxia-inducible factor I (HIF-1) is a transcriptional activator of genes whose products, including erythropoietin, vascular endothelial growth factor, and glycolytic enzymes, are involved in systemic, local, and cellular responses to hypoxia that either increase O-2 delivery or induce alternative metabolic pathways that do not require O-2. The level of HIF-1 expression in cultured cells is proportional to the degree of hypoxia over the range of O-2 concentrations associated with physiologic and pathophysiologic conditions in vivo. Further investigation of HIF-1 function in vivo may lead to novel therapeutic approaches that modulate cellular responses to hypoxia/ischemia.