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Induction of SM‐20 in PC12 cells leads to increased cytochrome c levels, accumulation of cytochrome c in the cytosol, and caspase‐dependent cell death
Author(s) -
Straub Jennifer A.,
Lipscomb Elizabeth A.,
Yoshida Eileen S.,
Freeman Robert S.
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.01688.x
Subject(s) - cytochrome c , programmed cell death , cytosol , microbiology and biotechnology , apoptosis , cytochrome , mitochondrion , nerve growth factor , biology , cell culture , caspase , apoptosome , biochemistry , enzyme , receptor , genetics
Sympathetic neurons deprived of nerve growth factor (NGF) release cytochrome c into the cytosol and undergo caspase‐dependent cell death through a process that requires de novo gene expression. Expression of the SM‐20 gene increases after NGF withdrawal, and ectopic SM‐20 expression induces cell death in NGF‐maintained neurons. To further evaluate the mechanism by which SM‐20 promotes cell death, we developed a PC12‐derived cell line in which SM‐20 expression can be induced by addition of doxycycline to the culture medium. Induction of SM‐20 in either undifferentiated or NGF‐differentiated cells resulted in cell death. Cell death was accompanied by an increase in caspase activity and was inhibited by the caspase inhibitor zVAD‐FMK. Analysis of cytochrome c in cytosolic and mitochondria‐enriched subcellular fractions revealed that induction of SM‐20 led to the accumulation of cytochrome c in the cytosol. Surprisingly, SM‐20 expression also resulted in a selective increase in the total amount of cytochrome c protein. Thus, induction of SM‐20 expression appears to affect both the amount and subcellular localization of cytochrome c in PC12 cells. These results suggest that SM‐20 promotes caspase‐dependent cell death through a mechanism involving cytochrome c .