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KMID : 0578320100300030193
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Molecules and Cells
2010 Volume.30 No. 3 p.193 ~ p.200
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Inhibiting N-Cadherin-Mediated Adhesion Affects Gap Junction Communication in Isolated Rat Hearts
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Zhu Hong-Jun
Hegui Wang
Xiwen Zhang
Xiaofeng Hou
Kejiang Cao
Jiangang Zou
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Abstract
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Cadherin-mediated adherens junctions is impaired conco-mitant 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-NH2 (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.
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KEYWORD
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adherens junction, connexin 43, gap junction, N-cadherin, synthetic polypeptides
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