Document Detail


Prostaglandins antagonistically control Bax activation during apoptosis.
MedLine Citation:
PMID:  20966963     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The Bax protein (Bcl-2-associated X protein) is pivotal for the apoptotic process. Bax, which resides in an inactive form in the cytosol of healthy cells, is activated during the early stages of apoptosis and becomes associated with mitochondria through poorly understood mechanisms. In this study, we show that a family of bioactive lipids, namely prostaglandins, regulates Bax-dependent apoptosis. The prostaglandin E(2) (PGE(2)) or its derivative PGA(2) binds to Bax, induces its change of conformation, and thereby triggers apoptosis. A cysteine present in the loop between the two transmembrane α-helices of Bax, Cys126 is critical for its activation. PGD(2) inhibits PGE(2) binding to Bax and PGE(2)-induced apoptosis, as well as cell death induced by staurosporine and UV-B in various cell lines. This result is consistent with the fact that apoptosis is accompanied during these treatments by an increase in PGE(2). This process is distinct, yet cooperative, from that involving the BH3-only protein Bid. Our results establish that the PGE(2)/PGD(2) balance is involved in a new early mechanism of control in the activation of Bax during apoptosis.
Authors:
L Lalier; P-F Cartron; C Olivier; C Logé; G Bougras; J-M Robert; L Oliver; F M Vallette
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-22
Journal Detail:
Title:  Cell death and differentiation     Volume:  18     ISSN:  1476-5403     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-14     Completed Date:  2011-05-31     Revised Date:  2012-03-01    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  England    
Other Details:
Languages:  eng     Pagination:  528-37     Citation Subset:  IM    
Affiliation:
INSERM U 892, Equipe Labellisée Ligue contre le Cancer, 8 Quai Moncousu, Nantes Cedex 01, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis* / drug effects
BH3 Interacting Domain Death Agonist Protein / metabolism
Cell Line, Tumor
Cell Survival / drug effects
Cysteine / metabolism
Dinoprostone / pharmacology
Humans
Models, Biological
Models, Molecular
Prostaglandin D2 / pharmacology
Prostaglandins / metabolism*
Protein Binding / drug effects
Protein Structure, Secondary
Rats
Signal Transduction / drug effects
bcl-2-Associated X Protein / chemistry,  metabolism*
Chemical
Reg. No./Substance:
0/BH3 Interacting Domain Death Agonist Protein; 0/Prostaglandins; 0/bcl-2-Associated X Protein; 363-24-6/Dinoprostone; 41598-07-6/Prostaglandin D2; 52-90-4/Cysteine

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


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