Document Detail


Bcl-2 protects against apoptosis induced by antimycin A and bongkrekic acid without restoring cellular ATP levels.
MedLine Citation:
PMID:  12034471     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several studies indicate that mitochondrial ATP production as well as ADP/ATP exchange across mitochondrial membranes are impaired during apoptosis. We investigated whether Bcl-2 could protect against cell death under conditions in which ATP metabolism is inhibited. Inhibition of ATP production using antimycin A (AA) (complex III inhibition) combined with inhibition of ADP/ATP exchange by bongkrekic acid (BA) (adenine nucleotide translocator (ANT) inhibition) induced a sharp decrease in total cellular ATP in FL5.12 parental cells (to 35% of untreated controls after 24 h of incubation). Within 24 and 48 h, 38% and 75% of the cells had died, respectively. However, in stably transfected FL5.12 Bcl-2 subclones, no cell death occurred under these experimental conditions. Similar results were obtained with Jurkat and Bcl-2 overexpressing Jurkat cells. Total cellular ATP levels were equally affected in FL5.12 Bcl-2 overexpressing cells and FL5.12 parental cells. This indicates that Bcl-2 overexpressing cells are able to survive with very low cellular ATP content. Furthermore, Bcl-2 did not protect against cell death by restoring ATP levels. This suggests that, under these conditions, Bcl-2 acts by inhibiting the signalling cascade triggered by the inhibitors that would normally lead to apoptosis.
Authors:
Aniek O de Graaf; Jules P P Meijerink; Lambert P van den Heuvel; Ronney A DeAbreu; Theo de Witte; Joop H Jansen; Jan A M Smeitink
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1554     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-05-29     Completed Date:  2002-08-02     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  57-65     Citation Subset:  IM    
Affiliation:
Central Hematology Laboratory/Department of Hematology, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. a.degraaf@chl.azn.nl
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism*
Animals
Antimycin A / pharmacology*
Apoptosis / drug effects*
Blotting, Western
Bongkrekic Acid / pharmacology*
Cell Line
DNA Damage
Flow Cytometry
Humans
Jurkat Cells
Mice
Mitochondria / drug effects
Oxygen Consumption
Proto-Oncogene Proteins c-bcl-2 / physiology*
Chemical
Reg. No./Substance:
0/Proto-Oncogene Proteins c-bcl-2; 11076-19-0/Bongkrekic Acid; 56-65-5/Adenosine Triphosphate; 642-15-9/Antimycin A

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


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