IN-VIVO EXPRESSION OF MESSENGER-RNAS ENCODING HYPOXIA-INDUCIBLE FACTOR-1

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric basic helix-loop -helix transcription factor that regulates genes whose products play k ey roles in maintaining O-2 homeostasis. We have previously demonstrat ed that HIF-1 mRNA, protein, and DNA-binding activity are induced when mammalian tissue culture cells are subjected to hypoxia. In this pape r, we report our analysis of HIF-1 mRNA expression in vivo. We demonst rate expression of HIF-1 alpha and HIF-1 beta (ARNT) mRNA in all human , rat, and mouse organs assayed and show for the first time that HIF-1 mRNA expression was induced in brain, kidney, and lung when rats or m ice were exposed to reduced ambient O-2 concentrations for 30 to 60 mi n. The ubiquitous in vivo expression of HIF-1 alpha and HIF-1 beta (AR NT) mRNA is consistent with the proposed role of HIF-1 in coordinating adaptive transcriptional responses to hypoxia. (C) 1996 Academic Pres s, Inc.