title: Chromofungin, CgA47-66-derived peptide, produces basal cardiac effects and postconditioning cardioprotective action during ischemia/reperfusion injury.
abstract: Endogenous chromogranin A (CgA)-derived peptides are secreted by nervous, endocrine and immune cells. Chromofungin (Chr: CgA47-66) is one of these peptides that display antimicrobial activities and activate neutrophils, with important implications in inflammation and innate immunity. The aim of the present study is to examine the effects of Chr on isolated and Langendorff perfused rat hearts. The study was performed by using the isolated and Langendorff perfused rat hearts, Elisa assay and real-time PCR. We found that, under basal conditions, increasing doses (11-165nM) of Chr induced negative inotropic effects without changing coronary pressure. This action was mediated by the AKT/eNOS/cGMP/PKG pathway. We also found that Chr acted as a postconditioning (PostC) agent against ischemia/reperfusion (I/R) damages, reducing infarct size and LDH level. Cardioprotection involved PI3K, RISK pathway, MitoKATP and miRNA-21. We suggest that Chr directly affects heart performance, protects against I/R myocardial injuries through the activation of prosurvival kinases. Results may propose Chr as a new physiological neuroendocrine modulator able to prevent heart dysfunctions, also encouraging the clarification of its clinical potential.
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Filice
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pasqua
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Quintieri
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Cantafio
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Scavello
authors.affiliation: Department of Experimental and Clinical Medicine, University of Catanzaro Magna Græcia, Catanzaro, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Amodio
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy; National Institute of Cardiovascular Research, Italy.
authors.forename: Maria Carmela
authors.initials: MC
authors.lastname: Cerra
authors.affiliation: University of Strasbourg, Biomatériaux et Ingénierie Tissulaire, Inserm U977, Strasbourg, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Marban
authors.affiliation: University of Strasbourg, Biomatériaux et Ingénierie Tissulaire, Inserm U977, Strasbourg, France.
authors.forename: Francis
authors.initials: F
authors.lastname: Schneider
authors.affiliation: University of Strasbourg, Biomatériaux et Ingénierie Tissulaire, Inserm U977, Strasbourg, France.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Metz-Boutigue
authors.affiliation: Department of Biology, Ecology and Earth Sciences, University of Calabria, 87036 Arcavacata di Rende, CS, Italy; National Institute of Cardiovascular Research, Italy. Electronic address: tommaso.angelone@unical.it.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Angelone
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053379:Chromogranin A / Q000494:pharmacology*; D009124:Muscle Proteins / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D053379:Chromogranin A; D009124:Muscle Proteins; D010446:Peptide Fragments; C437333:chromofungin
keywords: Cardioprotection; Chromofungin; Chromogranins; Intracellular pathways; Nitric oxide