Adrenomedullin gene expression is developmentally regulated and induced by hypoxia in rat ventricular cardiac myocytes

Stephania Cormier, Son V. Nguyen, William C. Claycomb

Research output: Contribution to journalArticle

189 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)17787-17792
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number28
DOIs
StatePublished - Jul 10 1998

Fingerprint

Adrenomedullin
Cardiac Myocytes
Gene expression
Rats
Gene Expression
Hypoxia-Inducible Factor 1
Transcription
Messenger RNA
Muscle
Myocardium
Adrenomedullin Receptors
Genes
Binding Sites
Hypoxia
5' Flanking Region
Transcription Initiation Site
Polymerase chain reaction
Reverse Transcription
Transfection
Nucleotides

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Adrenomedullin gene expression is developmentally regulated and induced by hypoxia in rat ventricular cardiac myocytes. / Cormier, Stephania; Nguyen, Son V.; Claycomb, William C.

In: Journal of Biological Chemistry, Vol. 273, No. 28, 10.07.1998, p. 17787-17792.

Research output: Contribution to journalArticle

Cormier, Stephania ; Nguyen, Son V. ; Claycomb, William C. / Adrenomedullin gene expression is developmentally regulated and induced by hypoxia in rat ventricular cardiac myocytes. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 28. pp. 17787-17792.
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