Possible mechanism of GATA4 inhibiting myocardin activity during cardiac hypertrophy

J Cell Biochem. 2019 Jun;120(6):9047-9055. doi: 10.1002/jcb.28178. Epub 2018 Dec 23.

Abstract

Myocardin is an important factor that regulates cardiac hypertrophy, and its activity can be regulated by GATA4. However, the molecular mechanism of the above process remains unclear. This paper presents three kinds of possible molecular mechanisms of GATA4 inhibiting myocardin activity in the process of cardiac hypertrophy. First, a competitive combination of GATA4 and SRF with myocardin could reduce the formation of the myocardin-SRF-CarG box complex when GATA4 was overexpressed. Second, overexpression of GATA4 could inhibit the combination of myocardin and p300 and downregulate acetylated myocardin levels. Finally, GATA4 could upregulate the phosphorylation of myocardin protein upon activation of the ERK pathway. These findings may provide insight into the function of GATA4 and myocardin in the occurrence and development of cardiac hypertrophy.

Keywords: GATA4; cardiac hypertrophy; myocardin; signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Western
  • COS Cells
  • Cardiomegaly / genetics
  • Cardiomegaly / metabolism*
  • Cells, Cultured
  • Chlorocebus aethiops
  • Flavonoids / pharmacology
  • GATA4 Transcription Factor / genetics
  • GATA4 Transcription Factor / metabolism*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Immunoprecipitation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Serum Response Factor / genetics
  • Serum Response Factor / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*

Substances

  • Flavonoids
  • GATA4 Transcription Factor
  • Gata4 protein, rat
  • Nuclear Proteins
  • Serum Response Factor
  • Trans-Activators
  • myocardin
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one