title: Inhibiting N-cadherin-mediated adhesion affects gap junction communication in isolated rat hearts.
abstract: Cadherin-mediated adherens junctions is impaired concomitant with a decrease in connexin 43 (Cx43) in diseases or pathological processes. We have investigated the acute effects of adherens junction impairment in isolated rat hearts by introducing Ala-His-Ala-Val-Asp-NH(2) (AHAVD, a synthetic peptide) as a specific inhibitor of N-cadherin. Effect of AHAVD on N-cadherin mediated adhension was analyzed by Cardiomy-ocyte aggregation assay. Laser confocal microscopy showed disrupted cell-cell contacts in cultured neonatal cardiomyocytes co-incubated with 0.2 mM AHAVD. In isolated adult rat hearts, Cx43 was redistributed along the bilateral of cardiomyocytes from the intercalated discs and significant dephosphorylation of Cx43 on serine368 occurred concomitantly with decreased gap junction (GJ) function in dose dependent manner after 1 h perfusion with AHAVD. These results indicate that impairing cad-herin-mediated adhesion by AHAVD rapidly results in Cx43 redistribution and dephosphorylation of serine368, thereby impairing GJ communication function.
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China.
authors.forename: Hongjun
authors.initials: H
authors.lastname: Zhu
authors.forename: Hegui
authors.initials: H
authors.lastname: Wang
authors.forename: Xiwen
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Hou
authors.forename: Kejiang
authors.initials: K
authors.lastname: Cao
authors.forename: Jiangang
authors.initials: J
authors.lastname: Zou
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015820:Cadherins / Q000037:antagonists & inhibitors*; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D017629:Gap Junctions / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015820:Cadherins; D010446:Peptide Fragments