title: Neuronostatin, a novel peptide encoded by somatostatin gene, regulates cardiac contractile function and cardiomyocyte survival.
abstract: Neuronostatin, a recently discovered peptide encoded by somatostatin gene, is involved in regulation of neuronal function, blood pressure, food intake, and drinking behavior. However, the biological effects of neuronostatin on cardiac myocytes are not known, and the intracellular signaling mechanisms induced by neuronostatin remain unidentified. We analyzed the effect of neuronostatin in isolated perfused rat hearts and in cultured primary cardiomyocytes. Neuronostatin infusion alone had no effect on left ventricular (LV) contractile function or on isoprenaline- or preload-induced increase in cardiac contractility. However, infusion of neuronostatin significantly decreased the positive inotropic response to endothelin-1 (ET-1). This was associated with an increase in phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase (JNK). Treatment of both neonatal and adult cardiomyocytes with neuronostatin resulted in reduced cardiomyocyte viability. Inhibition of JNK further increased the neuronostatin-induced cell death. We conclude that neuronostatin regulates cardiac contractile function and cardiomyocyte survival. Receptors for neuronostatin need to be identified to further characterize the biological functions of the peptide.
authors.affiliation: Dept. of Pharmacology and Toxicology, Institute of Biomedicine, University of Oulu, P.O. Box 5000, FIN-90014 Oulu, Finland.
authors.forename: Laura
authors.initials: L
authors.lastname: Vainio
authors.forename: Abel
authors.initials: A
authors.lastname: Perjes
authors.forename: Niilo
authors.initials: N
authors.lastname: Ryti
authors.forename: Johanna
authors.initials: J
authors.lastname: Magga
authors.forename: Tarja
authors.initials: T
authors.lastname: Alakoski
authors.forename: Raisa
authors.initials: R
authors.lastname: Serpi
authors.forename: Leena
authors.initials: L
authors.lastname: Kaikkonen
authors.forename: Jarkko
authors.initials: J
authors.lastname: Piuhola
authors.forename: Istvan
authors.initials: I
authors.lastname: Szokodi
authors.forename: Heikki
authors.initials: H
authors.lastname: Ruskoaho
authors.forename: Risto
authors.initials: R
authors.lastname: Kerkelä
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013004:Somatostatin / Q000378:metabolism* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D010446:Peptide Fragments; C554543:neuronostatin protein, rat; D013004:Somatostatin; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4