Document Detail

A cytosolic factor is required for mitochondrial cytochrome c efflux during apoptosis.
MedLine Citation:
PMID:  10200498     Owner:  NLM     Status:  MEDLINE    
Treatment of HL-60 cells with staurosporine (STS) induced mitochondrial cytochrome c efflux into the cytosol, which was followed by caspase-3 activation and apoptosis. Consistent with these observations, in vitro experiments demonstrated that, except for cytochrome c, the cytosol of HL-60 cells contained sufficient amounts of all factors required for caspase-3 activation. In contrast, treatment of HCW-2 cells (an apoptotic-resistant HL-60 subclone) with STS failed to induce significant amounts of mitochondrial cytochrome c efflux, caspase-3 activation, and apoptosis. In vitro assays strongly suggested that a lack of cytochrome c in the cytosol was the primary limiting factor for caspase-3 activation in HCW-2 cells. To explore the mechanism which regulates mitochondrial cytochrome c efflux, we developed an in vitro assay which showed that cytosolic extracts from STS-treated, but not untreated, HL-60 cells contained an activity, which we designated 'CIF' (cytochrome c-efflux inducing factor), which rapidly induced cytochrome c efflux from HL-60 mitochondria. In contrast, there was no detectable CIF activity in STS-treated HCW-2 cells although the mitochondria from HCW-2 cells were responsive to the CIF activity from STS-treated HL-60 cells. These experiments have identified a novel activity, CIF, which is required for cytochrome c efflux and they indicate that the absence of CIF is the biochemical explanation for the impaired ability of HCW-2 cells to activate caspase-3 and undergo apoptosis.
Z Han; G Li; T A Bremner; T S Lange; G Zhang; R Jemmerson; J H Wyche; E A Hendrickson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cell death and differentiation     Volume:  5     ISSN:  1350-9047     ISO Abbreviation:  Cell Death Differ.     Publication Date:  1998 Jun 
Date Detail:
Created Date:  1999-04-29     Completed Date:  1999-04-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  469-79     Citation Subset:  IM    
Box G, Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island 02912, USA.
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MeSH Terms
Biological Factors / metabolism*
Caspase 3
Caspases / metabolism
Clone Cells
Cytochrome c Group / metabolism*
Cytosol / metabolism*
Deoxyadenine Nucleotides / metabolism
Enzyme Activation / drug effects
HL-60 Cells
Indoles / metabolism
Mitochondria / metabolism*
Staurosporine / pharmacology
Grant Support
Reg. No./Substance:
0/Biological Factors; 0/Cytochrome c Group; 0/Deoxyadenine Nucleotides; 0/Indoles; 1927-31-7/2'-deoxyadenosine triphosphate; 47165-04-8/DAPI; 62996-74-1/Staurosporine; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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