title: Enhanced PKCε mediated phosphorylation of connexin43 at serine 368 by a carboxyl-terminal mimetic peptide is dependent on injury.
abstract: The gap junction (GJ) protein connexin (Cx43) is important for organized action potential propagation between mammalian cardiomyocytes. Disruption of the highly ordered distribution of Cx43 GJs is characteristic of cardiac tissue after ischemic injury. We recently demonstrated that epicardial administration of a peptide mimetic of the Cx43 carboxyl-terminus reduced pathologic remodeling of Cx43 GJs and protected against induced arrhythmias following ventricular injury. Treatment of injuries with the carboxyl-terminal peptide was associated with an increase in phosphorylation at serine 368 of the Cx43 carboxyl-terminus. Here, we report that Cx43 peptide treatment of uninjured hearts does not prompt a similar increase in phosphorylation. Moreover, we show that peptide treatment of undisturbed cultured HeLa cells expressing a Cx43 construct also exhibit no changes in Cx43 phosphorylation at serine 368. However, in parallel with the results in vivo, a trend of increasing phosphorylation at serine 368 was observed in Cx43-expressing HeLa cells following scratch wounding of cultured monolayers. These results suggest that peptide-enhanced phosphorylation of the Cx43 carboxyl-terminus is dependent on injury-mediated cellular responses.
authors.affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Palatinus
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Rhett
authors.forename: Robert G
authors.initials: RG
authors.lastname: Gourdie
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism*
chemical_list: D018031:Connexin 43; C500216:GJA1 protein, human; D010455:Peptides; D051744:Protein Kinase C-epsilon