Angiotensin II and the ERK pathway mediate the induction of myocardin by hypoxia in cultured rat neonatal cardiomyocytes

Chiung Zuan Chiu, Bao Wei Wang, Tun Hui Chung, Kou Gi Shyu

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Hypoxic injury to cardiomyocytes is a stress that causes cardiac pathology through cardiac-restricted gene expression. SRF (serum-response factor) and myocardin are important for cardiomyocyte growth and differentiation in response to myocardial injuries. Previous studies have indicated that AngII (angiotensin II) stimulates both myocardin expression and cardiomyocyte hypertrophy. In the present study, we evaluated the expression of myocardin and AngII after hypoxia in regulating gene transcription in neonatal cardiomyocytes. Cultured rat neonatal cardiomyocytes were subjected to hypoxia, and the expression of myocardin and AngII were evaluated. Different signal transduction pathway inhibitors were used to identify the pathway(s) responsible for myocardin expression. An EMSA (electrophoretic mobility-shift assay) was used to identify myocardin/SRF binding, and a luciferase assay was used to identify transcriptional activity of myocardin/SRF in neonatal cardiomyocytes. Both myocardin and AngII expression increased after hypoxia, with AngII appearing at an earlier time point than myocardin. Myocardin expression was stimulated by AngII and ERK (extracellular-signal-regulated kinase) phosphorylation, but was suppressed by an ARB (AngII type 1 receptor blocker), an ERK pathway inhibitor and myocardin siRNA (small interfering RNA). AngII increased both myocardin expression and transcription in neonatal cardiomyocytes. Binding of myocardin/SRF was identified using an EMSA, and a luciferase assay indicated the transcription of myocardin/SRF in neonatal cardiomyocytes. Increased BNP (B-type natriuretic peptide), MHC (myosin heavy chain) and [3H]proline incorporation into cardiomyocytes was identified after hypoxia with the presence of myocardin in hypertrophic cardiomyocytes. In conclusion, hypoxia in cardiomyocytes increased myocardin expression, which is mediated by the induction of AngII and the ERK pathway, to cause cardiomyocyte hypertrophy. Myocardial hypertrophy was identified as an increase in transcriptional activities, elevated hypertrophic and cardiomyocyte phenotype markers, and morphological hypertrophic changes in cardiomyocytes.

Original languageEnglish
Pages (from-to)273-282
Number of pages10
JournalClinical Science
Volume119
Issue number7
DOIs
Publication statusPublished - Oct 2010

Fingerprint

Extracellular Signal-Regulated MAP Kinases
Cardiac Myocytes
Angiotensin II
Serum Response Factor
Hypertrophy
Hypoxia
myocardin
Electrophoretic Mobility Shift Assay
Luciferases
Angiotensin II Type 1 Receptor Blockers
Myosin Heavy Chains
Brain Natriuretic Peptide
Wounds and Injuries
Proline
Small Interfering RNA

Keywords

  • Angiotensin II
  • Cardiomyocyte hypertrophy
  • Extracellular-signal-regulated kinase (ERK)
  • Myocardin
  • Serum-response factor
  • Transcriptional activity

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Angiotensin II and the ERK pathway mediate the induction of myocardin by hypoxia in cultured rat neonatal cardiomyocytes. / Chiu, Chiung Zuan; Wang, Bao Wei; Chung, Tun Hui; Shyu, Kou Gi.

In: Clinical Science, Vol. 119, No. 7, 10.2010, p. 273-282.

Research output: Contribution to journalArticle

Chiu, Chiung Zuan ; Wang, Bao Wei ; Chung, Tun Hui ; Shyu, Kou Gi. / Angiotensin II and the ERK pathway mediate the induction of myocardin by hypoxia in cultured rat neonatal cardiomyocytes. In: Clinical Science. 2010 ; Vol. 119, No. 7. pp. 273-282.
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