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18β‐glycyrrhetinic acid promotes src interaction with connexin43 in rat cardiomyocytes
Author(s) -
Chung TunHui,
Wang SeuMei,
Chang YunChieh,
Chen YuhLien,
Wu JiahnChun
Publication year - 2006
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21018
Subject(s) - dephosphorylation , proto oncogene tyrosine protein kinase src , phosphorylation , tyrosine , chemistry , tyrosine kinase inhibitor , tyrosine kinase , tyrosine phosphorylation , connexin , microbiology and biotechnology , intracellular , kinase , gap junction , immunoprecipitation , phosphatase , biochemistry , biology , signal transduction , cancer , genetics , gene
The mechanism by which 18β‐glycyrrhetinic acid regulates gap junction intercellular communication (GJIC) remains poorly understood. In this study, treatment of cultured rat neonatal cardiomyocytes with 18β‐glycyrrhetinic acid resulted in dose‐dependent inhibition of GJIC as assessed by fluorescent dye transfer analysis. 18β‐Glycyrrhetinic acid induced time‐dependent serine/threonine dephosphorylation and redistribution of connexin43 (Cx43) in cardiomyocytes and the induced Cx43 dephosphorylation was prevented by the protein phosphatase inhibitor, calyculin A. However, functional analyses showed that the inhibitory effect of 18β‐glycyrrhetinic acid on dye spreading among cardiomyocytes was not blocked by calyculin A, but was blocked by the Src‐selective tyrosine kinase inhibitor, PP2. 18β‐Glycyrrhetinic acid also induced an increase in the levels of phosphorylated Src, and this effect was prevented by PP2. Immunoprecipitation using anti‐Cx43 and anti‐p‐Src antibodies showed that 18β‐glycyrrhetinic acid increased the association between p‐Src and Cx43 and induced tyrosine phosphorylation of Cx43. We conclude that the inhibitory effect of 18β‐glycyrrhetinic acid on GJIC in cardiomyocytes involves Src‐mediated tyrosine phosphorylation of Cx43. J. Cell. Biochem. 100: 653–664, 2007. © 2006 Wiley‐Liss, Inc.