Document Detail


Fatty acids enhance membrane permeabilization by pro-apoptotic Bax.
MedLine Citation:
PMID:  14535847     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fatty acids are known promoters of apoptosis. In the present study, the direct role of fatty acids with regard to their ability to cause membrane permeabilization by Bax was explored. Addition of fatty acids to liposomes in the presence of cations greatly enhanced the permeabilizing activity of Bax, a pro-apoptotic Bcl-2 protein. This provides a putative mechanism for the role of fatty acids in apoptosis. It is not a result of detergent-like properties of fatty acids, since a different micelle-forming amphiphile, dilysocardiolipin, was strongly inhibitory. We also demonstrate that there is a synergistic effect on Bax-induced permeabilization between Ca(2+) and Mg(2+), both on the binding of Bax to liposomes as well as on the induction of the leakage of liposomal contents. Micromolar concentrations of Ca(2+) added externally or submicromolar concentrations of free Ca(2+) present in the medium were sufficient to promote Bax-induced permeabilization synergistically with externally added Mg(2+). These results indicate that Bax can induce leakage from liposomes at ion concentrations resembling those found physiologically. The synergistic effects of Ca(2+) and Mg(2+) were observed with liposomes with different lipid compositions. Thus the action of Bax is strongly modulated by the presence of bivalent cations that can act synergistically, as well as by micelle-forming lipid components that can be either stimulatory or inhibitory.
Authors:
Raquel F Epand; Jean-Claude Martinou; Sylvie Montessuit; Richard M Epand
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  377     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-01-05     Completed Date:  2004-01-23     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  509-16     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, McMaster University Health Sciences Centre, Hamilton, ON, Canada L8N 3Z5. epand@mcmaster.ca
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MeSH Terms
Descriptor/Qualifier:
Apoptosis
Calcium / pharmacology
Cardiolipins / chemistry,  pharmacology
Cell Membrane Permeability / drug effects
Drug Synergism
Fatty Acids / chemistry,  pharmacology*,  physiology
Liposomes / chemistry,  metabolism*
Magnesium / pharmacology
Proto-Oncogene Proteins / metabolism*
Proto-Oncogene Proteins c-bcl-2*
bcl-2-Associated X Protein
Chemical
Reg. No./Substance:
0/Cardiolipins; 0/Fatty Acids; 0/Liposomes; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2-Associated X Protein; 7439-95-4/Magnesium; 7440-70-2/Calcium
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