p42/p44 mitogen-activated protein kinases inhibit atrial natriuretic peptide mRNA transcription in gp130-mediated hypertrophic ventricular myocytes

Asian Pac J Trop Med. 2014 Mar;7(3):216-20. doi: 10.1016/S1995-7645(14)60024-9.

Abstract

Objective: To understand the role of ANP mRNA transcription regulation in gp130-mediated cardiomyocyte hypertrophy, and the involved mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK, also called p42/p44 MAPK) signaling pathway.

Methods: Isolated neonatal ventricular myocytes were treated with different concentrations of CT-1 (10(-9), 10(-8)and 10(-7)mol/L). MTT was used to analyze the viability and RT-PCR was used to detect ANP mRNA levels in cardiomyocyte. To inhibit p42/p44 MAPK activity in hypertrophic cardiomyocytes, the cells were pretreated with a specific MEK1 inhibitor.

Results: CT-1 significantly induced ANP mRNA expression and the viability of cardiomyocytes in a dose- and time-dependent manner. Furthermore, blocking p42/p44 MAPK activity by the special MEK1 inhibitor upregulated the ANP mRNA.

Conclusions: p42/p44 MAPK have an important role in suppressing ANP mRNA transcription and cell activity in gp130-mediated hypertrophic ventricular myocytes.

Keywords: Atrial natriuretic peptide; Cardiomyocytes; Hypertrophy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / biosynthesis
  • Atrial Natriuretic Factor / genetics*
  • Atrial Natriuretic Factor / metabolism
  • Cardiomegaly / enzymology
  • Cardiomegaly / genetics
  • Cardiomegaly / metabolism*
  • Cytokine Receptor gp130 / metabolism*
  • Cytokines / metabolism
  • Cytokines / pharmacology*
  • Heart Ventricles / cytology
  • MAP Kinase Signaling System / drug effects
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / enzymology
  • Myocytes, Cardiac / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Transcription, Genetic

Substances

  • Cytokines
  • RNA, Messenger
  • Cytokine Receptor gp130
  • Atrial Natriuretic Factor
  • cardiotrophin 1
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3