title: Endothelin-1-specific activation of B-type natriuretic peptide gene via p38 mitogen-activated protein kinase and nuclear ETS factors.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, P. O. Box 5000, Finland.
authors.forename: Sampsa
authors.initials: S
authors.lastname: Pikkarainen
authors.forename: Heikki
authors.initials: H
authors.lastname: Tokola
authors.forename: Risto
authors.initials: R
authors.lastname: Kerkelä
authors.forename: Theresa
authors.initials: T
authors.lastname: Majalahti-Palviainen
authors.forename: Olli
authors.initials: O
authors.lastname: Vuolteenaho
authors.forename: Heikki
authors.initials: H
authors.lastname: Ruskoaho
mesh_terms: 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
chemical_list: 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