Posttranscriptional activation of BNP gene expression in response to increased left ventricular wall stress: Role of calcineurin and PKC

Olli Tenhunen, István Szokodi, Heikki Ruskoaho

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

To study the molecular mechanisms for load-induced activation of BNP gene expression, increased wall stress was imposed on isolated isovolumetrically beating adult rat hearts by distension of a fluid filled balloon within the left ventricle. The wall stress for 2 h resulted in a 1.6-fold increase in the expression of BNP gene and a 2.0-fold increase of the c-fos gene. The inhibition of transcription by actinomycin D significantly decreased the baseline BNP mRNA levels but the wall stretch-induced increase of the gene expression remained unaffected. In contrast, the protein synthesis inhibitor cycloheximide increased baseline BNP mRNA levels and abolished the load-induced activation of gene expression. Furthermore, we studied the effects of protein kinase C (PKC), calcineurin and protein phosphatase 2A (PP2A) inhibition to characterize the role of intracellular pathways in the stretch-induced gene expression in the left ventricle. The expression of BNP and c-fos genes were not influenced by calcineurin, PP2A and PKC inhibition. In conclusion, we showed that the stretch-induced activation of BNP gene expression by increased left ventricular wall stress is independent of transcriptional mechanisms and dependent on protein synthesis. Moreover, our results suggest that the load-induced activation of BNP gene expression is independent of calcineurin, PKC and PP2A.

Original languageEnglish
Pages (from-to)187-196
Number of pages10
JournalRegulatory Peptides
Volume128
Issue number3
DOIs
Publication statusPublished - Jun 30 2005

Keywords

  • Heart
  • Hypertrophy
  • Natriuretic peptides

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Clinical Biochemistry
  • Cellular and Molecular Neuroscience

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