Hypoxic activation of the atrial natriuretic peptide gene promoter through direct and indirect actions of hypoxia-inducible factor-1

Yang Sook Chun, Ju Yeon Hyun, Yong Geun Kwak, In-San Kim, Chan Hyung Kim, Eunjoo Choi, Myung Suk Kim, Jong Wan Park

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Atrial natriuretic peptide (ANP) is a cardiac peptide, the transcription of which is up-regulated in the ischaemic ventricle. However, the molecular mechanism of ANP induction is unclear. This study demonstrated that ANP mRNA expression in rat ventricular myocardium is induced in an early phase of ischaemia, preceded by hypoxia-inducible factor-1 (HIF-1) α expression. The ANP gene was also induced by hypoxia or HIF-1 inducers such as CoCl2 and desferrioxamine in H9c2 and neonatal cardiomyocytes. The 2307 bp 5′-flanking region of the rat ANP gene was cloned and fused to the luciferase gene. Evidence of the promoter activity was only apparent in the myocytes and was induced by hypoxia and HIF-1 inducers. The overexpression of HIF-1α markedly enhanced ANP promoter activity, and a dominant-negative isoform completely suppressed it. We demonstrated that the promoter regions are essential for hypoxic ANP induction. One promoter region, containing the HIF-1-binding sequence, is regulated directly by HIF-1. The other region is also activated by HIF-1 despite having no HIF-1-binding sequence. These results suggest that HIF-1 enhances the transactivation of the ANP gene in hypoxic myocytes, implying that stimulation of the ANP promoter by HIF-1 may in fact be responsible for the induction of the ANP gene in ischaemic ventricular myocardium.

Original languageEnglish
Pages (from-to)149-157
Number of pages9
JournalBiochemical Journal
Volume370
Issue number1
DOIs
Publication statusPublished - 2003 Feb 15
Externally publishedYes

Fingerprint

Hypoxia-Inducible Factor 1
Atrial Natriuretic Factor
Genes
Chemical activation
Genetic Promoter Regions
Muscle Cells
Myocardium
Deferoxamine
5' Flanking Region
Transcription
Luciferases
Cardiac Myocytes
Transcriptional Activation
Rats
Protein Isoforms
Ischemia

Keywords

  • Atrial natriuretic peptide
  • Cardiomyocyte
  • Hypoxia-inducible factor-1
  • Ischaemia

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Hypoxic activation of the atrial natriuretic peptide gene promoter through direct and indirect actions of hypoxia-inducible factor-1. / Chun, Yang Sook; Hyun, Ju Yeon; Kwak, Yong Geun; Kim, In-San; Kim, Chan Hyung; Choi, Eunjoo; Kim, Myung Suk; Park, Jong Wan.

In: Biochemical Journal, Vol. 370, No. 1, 15.02.2003, p. 149-157.

Research output: Contribution to journalArticle

Chun, Yang Sook ; Hyun, Ju Yeon ; Kwak, Yong Geun ; Kim, In-San ; Kim, Chan Hyung ; Choi, Eunjoo ; Kim, Myung Suk ; Park, Jong Wan. / Hypoxic activation of the atrial natriuretic peptide gene promoter through direct and indirect actions of hypoxia-inducible factor-1. In: Biochemical Journal. 2003 ; Vol. 370, No. 1. pp. 149-157.
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