Document Detail

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.
MedLine Citation:
PMID:  12675908     Owner:  NLM     Status:  MEDLINE    
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.
Jennifer A Straub; Elizabeth A Lipscomb; Eileen S Yoshida; Robert S Freeman
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  85     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-04     Completed Date:  2003-05-14     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  318-28     Citation Subset:  IM    
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MeSH Terms
Caspases / metabolism*
Cell Count
Cell Differentiation / drug effects
Cell Survival / drug effects,  genetics
Cytochrome c Group / metabolism*
Cytosol / metabolism*
DNA-Binding Proteins*
Doxycycline / pharmacology
Enzyme Inhibitors / pharmacology
Gene Expression Regulation* / drug effects
Hypoxia-Inducible Factor-Proline Dioxygenases
Immediate-Early Proteins / genetics,  metabolism*
Nerve Growth Factor / pharmacology
PC12 Cells
Transduction, Genetic
Grant Support
Reg. No./Substance:
0/Cytochrome c Group; 0/DNA-Binding Proteins; 0/Enzyme Inhibitors; 0/Immediate-Early Proteins; 9061-61-4/Nerve Growth Factor; EC protein, rat; EC Factor-Proline Dioxygenases; EC 3.4.22.-/Caspases; N12000U13O/Doxycycline

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