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Differential regulation of Krüppel-like factor family transcription factor expression in neonatal rat cardiac myocytes: effects of endothelin-1, oxidative stress and cytokines.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2008 Jun; Vol. 1783 (6), pp. 1229-36. Date of Electronic Publication: 2008 Mar 25. - Publication Year :
- 2008
-
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.
- Subjects :
- Animals
Animals, Newborn
Blotting, Western
Cells, Cultured
Hydrogen Peroxide pharmacology
Kruppel-Like Factor 4
Kruppel-Like Transcription Factors genetics
Myocytes, Cardiac cytology
Oxidants pharmacology
RNA, Messenger genetics
RNA, Messenger metabolism
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Transcription, Genetic
Endothelin-1 pharmacology
Gene Expression Regulation
Interleukin-1beta pharmacology
Kruppel-Like Transcription Factors metabolism
Myocytes, Cardiac drug effects
Myocytes, Cardiac metabolism
Oxidative Stress
Tumor Necrosis Factor-alpha pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1783
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 18406357
- Full Text :
- https://doi.org/10.1016/j.bbamcr.2008.03.007