Publication Date:
1997-02-21
Description:
In a cell-free apoptosis system, mitochondria spontaneously released cytochrome c, which activated DEVD-specific caspases, leading to fodrin cleavage and apoptotic nuclear morphology. Bcl-2 acted in situ on mitochondria to prevent the release of cytochrome c and thus caspase activation. During apoptosis in intact cells, cytochrome c translocation was similarly blocked by Bcl-2 but not by a caspase inhibitor, zVAD-fmk. In vitro, exogenous cytochrome c bypassed the inhibitory effect of Bcl-2. Cytochrome c release was unaccompanied by changes in mitochondrial membrane potential. Thus, Bcl-2 acts to inhibit cytochrome c translocation, thereby blocking caspase activation and the apoptotic process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kluck, R M -- Bossy-Wetzel, E -- Green, D R -- Newmeyer, D D -- CA69381/CA/NCI NIH HHS/ -- GM50284/GM/NIGMS NIH HHS/ -- GM52735/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 1997 Feb 21;275(5303):1132-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9027315" target="_blank"〉PubMed〈/a〉
Keywords:
Amino Acid Chloromethyl Ketones/pharmacology
;
Animals
;
*Apoptosis
;
Carrier Proteins/metabolism
;
Cell Extracts
;
Cell-Free System
;
Cysteine Endopeptidases/metabolism
;
Cysteine Proteinase Inhibitors/pharmacology
;
Cytochrome c Group/*metabolism
;
Cytosol/metabolism
;
Membrane Potentials
;
Microfilament Proteins/metabolism
;
Mitochondria/*metabolism
;
Ovum
;
Proto-Oncogene Proteins c-bcl-2/*metabolism/pharmacology
;
Recombinant Proteins
;
Xenopus
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
