Cardiac expressions of HIF-1 alpha and HLF/EPAS, two basic loop helix/PAS domain transcription factors involved in adaptative responses to hypoxic stresses

Abstract

Expression of many mammalian genes is regulated by oxygen tension. HIF-1 alpha and HLF/EPAS are two basic helix-loop-helix/PAS domain transcription factors that bind to hypoxia sensitive elements in the promoters /enhancers of hypoxia sensitive genes such as vascular endothelial growth factor (VEGF). This paper describes the structure of rat HIF-1 alpha and analyses expressions HIF-1 alpha and of HLF/EPAS mRNAs in lung and cardiac tissues from the rat. HLF/EPAS mRNAs appear at birth in the two tissues and are maintained at high levels throughout adult life. HIF-1 alpha mRNAs are expressed at a constant level during lung development. Their abundance increase transiently at birth in cardiac tissues. Cultured cardiomyocytes from new born rats only express HIF-1 alpha mRNAs. HIF-1 alpha mRNA expression is increased by phorbol myristate acetate but not by anoxia or cobalt. The results indicate (i) that HIF-1 alpha and HLF/EPAS are expressed in a cell specific manner and (ii) that the hypoxic induction of VEGF mRNA expression by isolated cardiomyocytes is independent of HLF/EPAS. Finally, they suggest that protein kinase C may prime hypoxia induced gene regulation by inducing expression of HIF-1 alpha mRNAs.