Document Detail


18beta-glycyrrhetinic acid promotes src interaction with connexin43 in rat cardiomyocytes.
MedLine Citation:
PMID:  16983688     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The mechanism by which 18beta-glycyrrhetinic acid regulates gap junction intercellular communication (GJIC) remains poorly understood. In this study, treatment of cultured rat neonatal cardiomyocytes with 18beta-glycyrrhetinic acid resulted in dose-dependent inhibition of GJIC as assessed by fluorescent dye transfer analysis. 18beta-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 18beta-glycyrrhetinic acid on dye spreading among cardiomyocytes was not blocked by calyculin A, but was blocked by the Src-selective tyrosine kinase inhibitor, PP2. 18beta-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 18beta-glycyrrhetinic acid increased the association between p-Src and Cx43 and induced tyrosine phosphorylation of Cx43. We conclude that the inhibitory effect of 18beta-glycyrrhetinic acid on GJIC in cardiomyocytes involves Src-mediated tyrosine phosphorylation of Cx43.
Authors:
Tun-Hui Chung; Seu-Mei Wang; Yun-Chieh Chang; Yuh-Lien Chen; Jiahn-Chun Wu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  100     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-01-29     Completed Date:  2007-03-20     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  653-64     Citation Subset:  IM    
Affiliation:
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Communication / drug effects
Cells, Cultured
Connexin 43 / metabolism*
Dose-Response Relationship, Drug
Gap Junctions / drug effects
Glycyrrhetinic Acid / pharmacology*
Myocardium / metabolism*
Phosphorylation
Protein Binding
Proto-Oncogene Proteins pp60(c-src) / metabolism*
Rats
Rats, Wistar
Chemical
Reg. No./Substance:
0/Connexin 43; 471-53-4/Glycyrrhetinic Acid; EC 2.7.10.2/Proto-Oncogene Proteins pp60(c-src)

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