Differential regulation of Krüppel-like factor family transcription factor expression in neonatal rat cardiac myocytes: effects of endothelin-1, oxidative stress and cytokines

Biochim Biophys Acta. 2008 Jun;1783(6):1229-36. doi: 10.1016/j.bbamcr.2008.03.007. Epub 2008 Mar 25.

Abstract

Krüppel-like transcription factors (Klfs) modulate fundamental cell processes. Cardiac myocytes are terminally-differentiated, but hypertrophy in response to stimuli such as endothelin-1. H2O2 or cytokines promote myocyte apoptosis. Microarray studies of neonatal rat myocytes identified several Klfs as endothelin-1-responsive genes. We used quantitative PCR for further analysis of Klf expression in neonatal rat myocytes. In response to endothelin-1, Klf2 mRNA expression was rapidly increased ( approximately 9-fold; 15-30 min) with later increases in expression of Klf4 and Klf6 ( approximately 5-fold; 30-60 min). All were regulated as immediate early genes (cycloheximide did not inhibit the increases in expression). Klf5 expression was increased at 1-2 h ( approximately 13-fold) as a second phase response (cycloheximide inhibited the increase). These increases were transient and attenuated by U0126. H2O2 increased expression of Klf2, Klf4 and Klf6, but interleukin-1beta or tumor necrosis factor alpha downregulated Klf2 expression with no effect on Klf4 or Klf6. Of the Klfs which repress transcription, endothelin-1 rapidly downregulated expression of Klf3, Klf11 and Klf15. The dynamic regulation of expression of multiple Klf family members in cardiac myocytes suggests that, as a family, they are actively involved in regulating phenotypic responses (hypertrophy and apoptosis) to extracellular stimuli.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Cells, Cultured
  • Endothelin-1 / pharmacology*
  • Gene Expression Regulation*
  • Hydrogen Peroxide / pharmacology
  • Interleukin-1beta / pharmacology*
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism*
  • Oxidants / pharmacology
  • Oxidative Stress*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Endothelin-1
  • Interleukin-1beta
  • Kruppel-Like Transcription Factors
  • Oxidants
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Hydrogen Peroxide