Document Detail


The roles of poly(ADP-ribose)-metabolizing enzymes in alkylation-induced cell death.
MedLine Citation:
PMID:  18202825     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Poly(ADP-ribose) (PAR) has been identified as a DNA damage-inducible cell death signal upstream of apoptosis-inducing factor (AIF). PAR causes the translocation of AIF from mitochondria to the nucleus and triggers cell death. In living cells, PAR molecules are subject to dynamic changes pending on internal and external stress factors. Using RNA interference (RNAi), we determined the roles of poly(ADP-ribose) polymerases-1 and -2 (PARP-1, PARP-2) and poly(ADP-ribose) glycohydrolase (PARG), the key enzymes configuring PAR molecules, in cell death induced by an alkylating agent. We found that PARP-1, but not PARP-2 and PARG, contributed to alkylation-induced cell death. Likewise, AIF translocation was only affected by PARP-1. PARP-1 seems to play a major role configuring PAR as a death signal involving AIF translocation regardless of the death pathway involved.
Authors:
O Cohausz; C Blenn; M Malanga; F R Althaus
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cellular and molecular life sciences : CMLS     Volume:  65     ISSN:  1420-682X     ISO Abbreviation:  Cell. Mol. Life Sci.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-22     Completed Date:  2008-05-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9705402     Medline TA:  Cell Mol Life Sci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  644-55     Citation Subset:  IM    
Affiliation:
Institute of Pharmacology and Toxicology, University of Zurich-Vetsuisse, Winterthurerstrasse 260, 8057, Zurich, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Alkylation
Animals
Apoptosis / physiology
Cell Death / physiology*
DNA Damage
Fibroblasts / enzymology
Hela Cells
Humans
Kinetics
Mice
Poly Adenosine Diphosphate Ribose / metabolism*
Poly(ADP-ribose) Polymerases / genetics,  metabolism*
Polymerase Chain Reaction
RNA, Small Interfering / genetics
Chemical
Reg. No./Substance:
0/RNA, Small Interfering; 26656-46-2/Poly Adenosine Diphosphate Ribose; EC 2.4.2.30/Poly(ADP-ribose) Polymerases

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


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