PMID- 9651380 OWN - NLM STAT- MEDLINE DCOM- 19980806 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 273 IP - 28 DP - 1998 Jul 10 TI - Adrenomedullin gene expression is developmentally regulated and induced by hypoxia in rat ventricular cardiac myocytes. PG - 17787-92 AB - Adrenomedullin is a recently discovered hypotensive peptide that is expressed in a variety of cell and tissue types. Using the technique of differential display, the adrenomedullin gene was observed to be differentially expressed in developing rat heart. Reverse transcription-polymerase chain reaction analysis revealed that the level of adrenomedullin mRNA was significantly higher in adult ventricular cardiac muscle as compared with embryonic day 17 ventricular cardiac muscle. Adrenomedullin receptor mRNA was constitutively expressed throughout development of the ventricular heart. Two potential hypoxia-inducible factor-1 (HIF-1) consensus binding sites were identified in the mouse adrenomedullin promoter at -1095 and -770 nucleotides from the transcription start site. Exposure of cultured adult rat ventricular cardiac myocytes to hypoxia (1% O2) resulted in a significant, time-dependent increase in adrenomedullin mRNA levels. Transfection studies revealed that the 5'-flanking sequence of adrenomedullin was capable of mediating a hypoxia-inducible increase in transcription. Mutation of the putative HIF-1 consensus binding sites revealed that the major regulatory sequence that mediates the hypoxia-inducible transcriptional response is located at -1095. These data demonstrate that the adrenomedullin gene is developmentally regulated in ventricular cardiomyocytes, that adrenomedullin transcription can be induced by hypoxia, and that this response is primarily mediated by HIF-1 consensus sites in the adrenomedullin promoter. FAU - Cormier-Regard, S AU - Cormier-Regard S AD - Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans, Louisiana 70112, USA. FAU - Nguyen, S V AU - Nguyen SV FAU - Claycomb, W C AU - Claycomb WC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (DNA Primers) RN - 0 (Peptides) RN - 0 (RNA, Messenger) RN - 148498-78-6 (Adrenomedullin) SB - IM MH - Adrenomedullin MH - Animals MH - Base Sequence MH - Cell Hypoxia/*genetics MH - Cells, Cultured MH - DNA Primers MH - *Gene Expression Regulation, Developmental MH - Heart Ventricles/cytology/*metabolism MH - Mice MH - Mutagenesis, Site-Directed MH - Peptides/*genetics MH - Promoter Regions, Genetic MH - RNA, Messenger/genetics MH - Rats MH - Transcription, Genetic EDAT- 1998/07/04 00:00 MHDA- 1998/07/04 00:01 CRDT- 1998/07/04 00:00 PHST- 1998/07/04 00:00 [pubmed] PHST- 1998/07/04 00:01 [medline] PHST- 1998/07/04 00:00 [entrez] AID - S0021-9258(18)80556-7 [pii] AID - 10.1074/jbc.273.28.17787 [doi] PST - ppublish SO - J Biol Chem. 1998 Jul 10;273(28):17787-92. doi: 10.1074/jbc.273.28.17787.