Cardiac expressions of HIF-1 alpha and HLF/EPAS, two basic loop helix/PAS domain transcription factors involved in adaptative responses to hypoxic stresses.
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.
Ladoux
A
A
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, Valbonne, France.
Frelin
C
C
D000595:Amino Acid Sequence; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors; D015152:Blotting, Northern; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006321:Heart / Q000196:embryology / Q000254:growth & development; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008168:Lung / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017422:Sequence Analysis, DNA; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; C497444:Hif1a protein, rat; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C095828:Hlf protein, rat; D013755:Tetradecanoylphorbol Acetate