| Prostaglandins antagonistically control Bax activation during apoptosis. | |
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MedLine Citation:
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PMID: 20966963 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-22 |
Journal Detail:
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Title: Cell death and differentiation Volume: 18 ISSN: 1476-5403 ISO Abbreviation: Cell Death Differ. Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-02-14 Completed Date: 2011-05-31 Revised Date: 2012-03-01 |
Medline Journal Info:
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Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: England |
Other Details:
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Languages: eng Pagination: 528-37 Citation Subset: IM |
Affiliation:
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INSERM U 892, Equipe Labellisée Ligue contre le Cancer, 8 Quai Moncousu, Nantes Cedex 01, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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