| The novel chromogranin A-derived serpinin and pyroglutaminated serpinin peptides are positive cardiac β-adrenergic-like inotropes. | |
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MedLine Citation:
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PMID: 22459152 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Three forms of serpinin peptides, serpinin (Ala26Leu), pyroglutaminated (pGlu)-serpinin (pGlu23Leu), and serpinin-Arg-Arg-Gly (Ala29Gly), are derived from cleavage at pairs of basic residues in the highly conserved C terminus of chromogranin A (CgA). Serpinin induces PN-1 expression in neuroendocrine cells to up-regulate granule biogenesis via a cAMP-protein kinase A-Sp1 pathway, while pGlu-serpinin inhibits cell death. The aim of this study was to test the hypothesis that serpinin peptides are produced in the heart and act as novel β-adrenergic-like cardiac modulators. We detected serpinin peptides in the rat heart by HPLC and ELISA methods. The peptides included predominantly Ala29Gly and pGlu-serpinin and a small amount of serpinin. Using the Langendorff perfused rat heart to evaluate the hemodynamic changes, we found that serpinin and pGlu-serpinin exert dose-dependent positive inotropic and lusitropic effects at 11-165 nM, within the first 5 min after administration. The pGlu-serpinin-induced contractility is more potent than that of serpinin, starting from 1 nM. Using the isolated rat papillary muscle preparation to measure contractility in terms of tension development and muscle length, we further corroborated the pGlu-serpinin-induced positive inotropism. Ala29Gly was unable to affect myocardial performance. Both pGlu-serpinin and serpinin act through a β1-adrenergic receptor/adenylate cyclase/cAMP/PKA pathway, indicating that, contrary to the β-blocking profile of the other CgA-derived cardiosuppressive peptides, vasostatin-1 and catestatin, these two C-terminal peptides act as β-adrenergic-like agonists. In cardiac tissue extracts, pGlu-serpinin increased intracellular cAMP levels and phosphorylation of phospholamban (PLN)Ser16, ERK1/2, and GSK-3β. Serpinin and pGlu-serpinin peptides emerge as novel β-adrenergic inotropic and lusitropic modulators, suggesting that CgA and the other derived cardioactive peptides can play a key role in how the myocardium orchestrates its complex response to sympathochromaffin stimulation. |
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Authors:
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Bruno Tota; Stefano Gentile; Teresa Pasqua; Eleonora Bassino; Hisatsugu Koshimizu; Niamh X Cawley; Maria C Cerra; Y Peng Loh; Tommaso Angelone |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2012-03-29 |
Journal Detail:
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Title: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 26 ISSN: 1530-6860 ISO Abbreviation: FASEB J. Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-06-29 Completed Date: 2012-09-20 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: United States |
Other Details:
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Languages: eng Pagination: 2888-98 Citation Subset: IM |
Affiliation:
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Department of Cell Biology, University of Calabria, Arcavacata di Rende, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-1 Receptor Agonists
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chemistry*,
pharmacology* Amino Acid Sequence Amino Acid Substitution Animals Cardiotonic Agents / chemistry*, pharmacology* Chromogranin A / chemistry*, genetics, pharmacology, physiology* Heart / drug effects*, physiology* Male Molecular Sequence Data Myocardial Contraction / drug effects Myocardium / chemistry Papillary Muscles / drug effects, physiology Peptide Fragments / chemistry*, genetics, pharmacology, physiology* Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-1 Receptor Agonists; 0/Cardiotonic Agents; 0/Chromogranin A; 0/Peptide Fragments |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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