PF2401-SF, standardized fraction of Salvia miltiorrhiza and its constituents, tanshinone I, tanshinone IIA, and cryptotanshinone, protect primary cultured rat hepatocytes from bile acid-induced apoptosis by inhibiting JNK phosphorylation

2007 ◽  
Vol 45 (10) ◽  
pp. 1891-1898 ◽  
Author(s):  
Eun-Jeon Park ◽  
Yu-Zhe Zhao ◽  
Youn-Chul Kim ◽  
Dong Hwan Sohn
Keyword(s):  
Bile Acid ◽  
Salvia Miltiorrhiza ◽  
Rat Hepatocytes ◽  
Tanshinone Iia ◽  
Tanshinone I ◽  
Primary Cultured Rat Hepatocytes ◽  
Cultured Rat Hepatocytes ◽  
Induced Apoptosis

cAMP inhibits bile acid-induced apoptosis by blocking caspase activation and cytochromecrelease

2002 ◽  
Vol 283 (3) ◽  
pp. G727-G738 ◽  
Author(s):  
Cynthia R. L. Webster ◽  
Paul Usechak ◽  
M. Sawkat Anwer
Keyword(s):  
Bile Acid ◽  
Cytochrome C ◽  
Rat Hepatocytes ◽  
Dependent Manner ◽  
Cytochrome C Release ◽  
Akt Phosphorylation ◽  
Apoptotic Effect ◽  
Cultured Rat Hepatocytes ◽  
Phosphoinositide 3 Kinase ◽  
Induced Apoptosis

We have previously shown that cAMP protects against bile acid-induced apoptosis in cultured rat hepatocytes in a phosphoinositide 3-kinase (PI3K)-dependent manner. In the present studies, we investigated the mechanisms involved in this anti-apoptotic effect. Hepatocyte apoptosis induced by glycodeoxycholate (GCDC) was associated with mitochondrial depolarization, activation of caspases, the release of cytochrome c from the mitochondria, and translocation of BAX from the cytosol to the mitochondria. cAMP inhibited GCDC-induced apoptosis, caspase 3 and caspase 9 activation, and cytochrome c release in a PI3K-dependent manner. cAMP activated PI3K in p85 immunoprecipitates and resulted in PI3K-dependent activation of the survival kinase Akt. Chemical inhibition of Akt phosphorylation with SB-203580 partially blocked the protective effect of cAMP. cAMP resulted in wortmannin-independent phosphorylation of BAD and was associated with translocation of BAD from the mitochondria to the cytosol. These results suggest that GCDC-induced apoptosis in cultured rat hepatocytes proceeds through a caspase-dependent intracellular stress pathway and that the survival effect of cAMP is mediated in part by PI3K-dependent Akt activation at the level of the mitochondria.

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