Endothelin-1-specific activation of B-type natriuretic peptide gene via p38 mitogen-activated protein kinase and nuclear ETS factors.
Terminally differentiated cardiac myocytes adapt to mechanical and neurohumoral stress via morphological changes of individual cells accompanied by reactivation of fetal pattern of gene expression. Endothelin-1, a powerful paracrine mediator of myocyte growth, induces similar changes in cultured cardiac myocytes as those seen in hypertrophied heart in vivo. By using rat B-type natriuretic peptide promoter, we identified a novel ETS binding sequence, on which nuclear protein binding is activated in endothelin-1-treated cultured cardiac myocytes. This sequence binds ETS-like gene-1 transcription factor and mediates endothelin-1-specific activation of transcription, but not responses to increased calcium signaling via l-type calcium channels, angiotensin II treatment, or mechanical stretch of myocytes. Interestingly, endothelin-1 activated signaling converges via p38 mitogen-activated protein kinase-dependent mechanism on ETS binding site, whereas this element inhibits extracellular signal-regulated kinase activated transcription. In conclusion, given the fundamental role of the interaction of mitogen-activated protein kinases and ETS factors in regulation of eukaryotic cell differentiation, growth, and oncogenesis, these results provide the unique evidence of a endothelin-1- and mitogen-activated protein kinase-regulated ETS factor pathway for cardiac myocytes.
Pikkarainen
Sampsa
S
Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, P. O. Box 5000, Finland.
Tokola
Heikki
H
Kerkelä
Risto
R
Majalahti-Palviainen
Theresa
T
Vuolteenaho
Olli
O
Ruskoaho
Heikki
H
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D019332:Endothelin-1 / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
D017931:DNA Primers; D019332:Endothelin-1; D009687:Nuclear Proteins; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases