Phosphoinositide 3-kinase, but not mitogen-activated protein kinase, pathway is involved in hepatocyte growth factor-mediated protection against bile acid-induced apoptosis in cultured rat hepatocytes

Hepatology ◽  
2001 ◽  
Vol 33 (3) ◽  
pp. 608-615 ◽  
Author(s):  
C Webster
2002 ◽  
Vol 283 (3) ◽  
pp. G727-G738 ◽  
Author(s):  
Cynthia R. L. Webster ◽  
Paul Usechak ◽  
M. Sawkat Anwer

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.


APOPTOSIS ◽  
2011 ◽  
Vol 16 (6) ◽  
pp. 581-593 ◽  
Author(s):  
Youhua Huang ◽  
Xiaohong Huang ◽  
Jia Cai ◽  
Fuzhou Ye ◽  
Qiwei Qin

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