TRANSCRIPTIONAL REGULATION BY HYPOXIA-INDUCIBLE FACTOR-1 - MOLECULAR MECHANISMS OF OXYGEN HOMEOSTASIS

Human cells require O-2 for many metabolic processes, most notably oxi dative phosphorylation, the major source of ATP generation, and hypoxi a plays a significant pathophysiologic role in a variety of cardiovasc ular disorders. Hypoxia-inducible factor I (HIF-1) is a transcriptiona l activator of genes whose products, including erythropoietin, vascula r endothelial growth factor, and glycolytic enzymes, are involved in s ystemic, local, and cellular responses to hypoxia that either increase O-2 delivery or induce alternative metabolic pathways that do not req uire O-2. The level of HIF-1 expression in cultured cells is proportio nal to the degree of hypoxia over the range of O-2 concentrations asso ciated with physiologic and pathophysiologic conditions in vivo. Furth er investigation of HIF-1 function in vivo may lead to novel therapeut ic approaches that modulate cellular responses to hypoxia/ischemia.