Extracellular signal-regulated kinase activation during cardiac hypertrophy reduces sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) transcription

Haiyan Huang, Leroy C. Joseph, Michael I. Gurin, Edward B. Thorp, John P. Morrow*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Pathologic cardiac hypertrophy can lead to heart failure, but the mechanisms involved are poorly understood. SERCA2 is critical for normal cardiac calcium handling and function and SERCA2 mRNA and protein levels are reduced by cardiac hypertrophy. We hypothesized that extracellular signal-regulated kinase (ERK) 1/2 activation during hypertrophy reduced SERCA2 transcription. Using a neonatal rat ventricular myocyte model of hypertrophy, we found that pharmacologic inhibitors of ERK activation preserve SERCA2 mRNA levels during hypertrophy. ERK activation is sufficient to reduce SERCA2 mRNA. We determined that ERK represses SERCA2 transcription via nuclear factor-kappaB (NFkB), and activation of NFkB is sufficient to reduce SERCA2 mRNA in cardiomyocytes. This work establishes novel connections between ERK, NFkB, and SERCA2 repression during cardiac hypertrophy. This mechanism may have implications for the progression of hypertrophy to heart failure.

Original languageEnglish (US)
Pages (from-to)58-63
Number of pages6
JournalJournal of Molecular and Cellular Cardiology
Volume75
DOIs
StatePublished - Oct 1 2014

Keywords

  • Cardiac hypertrophy
  • Cardiovascular disease
  • ERK
  • NF-kappaB
  • Neonatal rat ventricular myocytes
  • SERCA2

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Extracellular signal-regulated kinase activation during cardiac hypertrophy reduces sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2) transcription'. Together they form a unique fingerprint.

Cite this