Document Detail


A cytosolic factor is required for mitochondrial cytochrome c efflux during apoptosis.
MedLine Citation:
PMID:  10200498     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Z Han; G Li; T A Bremner; T S Lange; G Zhang; R Jemmerson; J H Wyche; E A Hendrickson
Related Documents :
1574738 - Recovery of the missing tumorigenicity in mitochondrial dna-less hela cells by introduc...
18605728 - A targetable fluorescent probe for imaging hydrogen peroxide in the mitochondria of liv...
3090018 - Respiratory systems of the bacillus cereus mother cell and forespore.
7161938 - Different sensitivities to external atp in passive permeability of transformed mouse ce...
18550808 - The cyclin-dependent kinase inhibitor p57kip2 is a negative regulator of schwann cell d...
6333268 - Diverse deoxyribonucleotide profiles in cultured human cells with differential sensitiv...
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    
Affiliation:
Box G, Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island 02912, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Apoptosis*
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
Humans
Indoles / metabolism
Kinetics
Mitochondria / metabolism*
Staurosporine / pharmacology
Grant Support
ID/Acronym/Agency:
AI 35763/AI/NIAID NIH HHS
Chemical
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Aspects of the involvement of interleukin-1 and nitric oxide in the pathogenesis of insulin-dependen...
Next Document:  Cancer cell sensitization to fas-mediated apoptosis by sodium butyrate.