| Obestatin affords cardioprotection to the ischemic-reperfused isolated rat heart and inhibits apoptosis in cultures of similarly stressed cardiomyocytes. | |
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MedLine Citation:
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PMID: 20525876 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Obestatin, a newly discovered peptide encoded by the ghrelin gene, induces the expression of genes regulating pancreatic beta-cell differentiation, insulin biosynthesis, and glucose metabolism. It also activates antiapoptotic signaling pathways such as phosphoinositide 3-kinase (PI3K) and ERK1/2 in pancreatic beta-cells and human islets. Since these kinases have been shown to protect against myocardial injury, we sought to investigate whether obestatin would exert cardioprotective effects. Both isolated perfused rat heart and cultured cardiomyocyte models of ischemia-reperfusion (I/R) were used to measure infarct size and cell apoptosis as end points of injury. The presence of specific obestatin receptors on cardiac cells as well as the signaling pathways underlying the obestatin effect were also studied. In the isolated heart, the addition of rat obestatin-(1-23) before ischemia reduced infarct size and contractile dysfunction in a concentration-dependent manner, whereas obestatin-(23-1), a synthetic analog with an inverse aminoacid sequence, was ineffective. The cardioprotective effect of obestatin-(1-23) was observed at concentrations of 10-50 nmol/l and was abolished by inhibiting PI3K or PKC by the addition of wortmannin (100 nmol/l) or chelerythrine, (5 micromol/l), respectively. In rat H9c2 cardiac cells or isolated ventricular myocytes subjected to I/R, 50 nmol/l obestatin-(1-23) reduced cardiomyocyte apoptosis and reduced caspase-3 activation; the antiapoptotic effect was blocked by the inhibition of PKC, PI3K, or ERK1/2 pathways. In keeping with these functional findings, radioreceptor binding results revealed the presence of specific high-affinity obestatin-binding sites, mainly localized on membranes of the ventricular myocardium and cardiomyocytes. Our data suggest that, by acting on specific receptors, obestatin-(1-23) activates PI3K, PKC-epsilon, PKC-delta, and ERK1/2 signaling and protects cardiac cells against myocardial injury and apoptosis induced by I/R. |
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Authors:
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Giuseppe Alloatti; Elisa Arnoletti; Eleonora Bassino; Claudia Penna; Maria Giulia Perrelli; Corrado Ghé; Giampiero Muccioli |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-04 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 299 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-30 Completed Date: 2010-08-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H470-81 Citation Subset: IM |
Affiliation:
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Dipartimento di Biologia Animale e dell'Uomo, Via Accademia Albertina, 13, Torino 10123, Italy. giuseppe.alloatti@unito.it |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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antagonists & inhibitors,
metabolism Animals Apoptosis* / drug effects Caspase 3 / metabolism Cells, Cultured Disease Models, Animal Dose-Response Relationship, Drug Male Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors, metabolism Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors, metabolism Myocardial Contraction* / drug effects Myocardial Infarction / metabolism, pathology, physiopathology, prevention & control* Myocardial Reperfusion Injury / metabolism, pathology, physiopathology, prevention & control* Myocytes, Cardiac / drug effects, metabolism*, pathology Peptide Hormones / administration & dosage, metabolism* Peptides / pharmacology Perfusion Protein Kinase C-delta / antagonists & inhibitors, metabolism Protein Kinase C-epsilon / antagonists & inhibitors, metabolism Protein Kinase Inhibitors / pharmacology Rats Receptors, Ghrelin / metabolism Signal Transduction Time Factors Ventricular Function, Left* / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Peptide Hormones; 0/Peptides; 0/Protein Kinase Inhibitors; 0/Receptors, Ghrelin; 0/obestatin, rat; EC 2.7.1.-/Prkcd protein, rat; EC 2.7.1.-/Prkce protein, rat; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.13/Protein Kinase C-delta; EC 2.7.11.13/Protein Kinase C-epsilon; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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