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Bcl‐x L prevents staurosporine‐induced hepatocyte apoptosis by restoring protein kinase B/mitogen‐activated protein kinase activity and mitochondria integrity
Author(s) -
Wang Yinna,
Zhang Baochun,
Peng Ximei,
Perpetua Michele,
Harbrecht Brian G.
Publication year - 2008
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21350
Subject(s) - staurosporine , microbiology and biotechnology , protein kinase a , protein kinase c , apoptosis , caspase , mapk/erk pathway , biology , hepatocyte , programmed cell death , ly294002 , kinase , mitochondrion , protein kinase inhibitor , cytochrome c , protein kinase b , signal transduction , chemistry , biochemistry , in vitro
Our study reports that staurosporine induces apoptosis in cultured rat hepatocytes in a dose‐ and time‐dependent fashion. Staurosporine induced apparent cleavage of caspase‐8, caspase‐9, and caspase‐3. The release of cytochrome c from mitochondria, and Bid activation were also detected in staurosporine‐treated primary hepatocytes. These results suggest that mitochondria‐mediated cell death signaling may be involved in staurosporine‐induced hepatocyte apoptosis. Bcl‐x L overexpression protected from “loss of” mitochondrial transmembrane potential and prevented staurosporine‐induced caspase‐3 and caspase‐8 cleavage. Overexpression of constitutively active ERK and PKB inhibited staurosporine‐induced caspase‐3 activation and hepatocyte death. PI3K inhibitor (LY294002) and ERK inhibitor (PD98059) significantly reversed the protective effects of Bcl‐x L on staurosporine‐induced hepatocyte death. Our data suggest that Bcl‐x L prevents staurosporine‐induced hepatocyte apoptosis by modulating protein kinase B and p44/42 mitogen‐activated protein kinase activity and disrupts mitochondria death signaling. J. Cell. Physiol. 215: 676–683, 2008. © 2007 Wiley‐Liss, Inc.