title: Opioid peptide gene expression in the primary hereditary cardiomyopathy of the Syrian hamster. II. Role of intracellular calcium loading.
abstract: We have previously shown that prodynorphin gene expression was markedly increased in adult myocytes of BIO 14.6 cardiomyopathic hamsters and that nuclear protein kinase C (PKC) may be involved in the induction of this opioid gene. Here we report that the cytosolic Ca2+ concentration was significantly increased in resting and in KCl-depolarized cardiomyopathic myocytes compared with normal cells. In normal and in cardiomyopathic cells, KCl significantly increased prodynorphin mRNA levels and prodynorphin gene transcription. These effects were abolished by the Ca2+ channel blocker verapamil. In control myocytes, the KCl-induced increase in prodynorphin mRNA expression was in part attenuated by chelerythrine or calphostin C, two selective PKC inhibitors. In these cells, KCl induced the translocation of PKC-alpha into the nucleus, increasing nuclear PKC activity. In resting cardiomyopathic myocytes, the increase in prodynorphin mRNA levels and gene transcription were significantly attenuated by the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetraacetoxy-methylester being completely abolished when the chelating agent was administered in the presence of PKC inhibitors. KCl and the PKC activator 1,2-dioctanoyl-sn-glycerol additively stimulated prodynorphin gene expression both in normal and in cardiomyopathic cells. Therefore, we conclude that PKC activation and intracellular Ca2+ overload may represent the two major signaling mechanisms involved in the induction of the prodynorphin gene in cardiomyopathic cells.
authors.affiliation: Institute of Biological Chemistry "A. Bonsignore," School of Medicine, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ventura
authors.forename: G
authors.initials: G
authors.lastname: Pintus
authors.forename: B
authors.initials: B
authors.lastname: Tadolini
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D002451:Cell Compartmentation / Q000187:drug effects; D002467:Cell Nucleus / Q000201:enzymology / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D006224:Cricetinae; D004075:Diglycerides / Q000494:pharmacology; D004745:Enkephalins / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D002614:Chelating Agents; D004075:Diglycerides; D004745:Enkephalins; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D011498:Protein Precursors; D011189:Potassium Chloride; C033660:preproenkephalin; D011493:Protein Kinase C; D002118:Calcium