18β-Glycyrrhetinic acid promotes Src interaction with connexin43 in rat cardiomyocytes

被引：25
作者：
Chung, Tun-Hui [1 ]
Wang, Seu-Mei [1 ]
Chang, Yun-Chieh [1 ]
Chen, Yuh-Lien [1 ]
Wu, Jiahn-Chun [1 ]
机构：
[1] Natl Taiwan Univ, Dept Anat & Cell Biol, Coll Med, Taipei 10051, Taiwan
来源：
JOURNAL OF CELLULAR BIOCHEMISTRY | 2007年 / 100卷 / 03期
关键词：
gap junction; calyculin A; tyrosine phosphorylation of Cx43; Src kinase;
D O I：
10.1002/jcb.21018
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
The mechanism by which 18 beta-glycyrrhetinic acid regulates gap junction intercellular communication (GJIC) remains poorly understood. In this study, treatment of cultured rat neonatal cardiomyocytes with 18 beta-glycyrrhetinic acid resulted in dose-dependent inhibition of GJIC as assessed by fluorescent dye transfer analysis. 18 beta-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 18 beta-glycyrrhetinic acid on dye spreading among cardiomyocytes was not blocked by calyculin A, but was blocked by the Src-selective tyrosine kinase inhibitor, PP2. 18 beta-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 18 beta-glycyrrhetinic acid increased the association between p-Src and Cx43 and induced tyrosine phosphorylation of Cx43. We conclude that the inhibitory effect of 18 beta-glycyrrhetinic acid on GJIC in cardiomyocytes involves Src-mediated tyrosine phosphorylation of Cx43.
引用
收藏
页码：653 / 664
页数：12
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