Document Detail


Oxygen radicals induce poly(ADP-ribose) polymerase-dependent cell death in cytotoxic lymphocytes.
MedLine Citation:
PMID:  16751373     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cytotoxic T cells and NK cells will acquire features of apoptosis when exposed to oxygen radicals, but the molecular mechanisms underlying this phenomenon are incompletely understood. We have investigated the role of two enzyme systems responsible for execution of cell death, caspases and the poly(ADP-ribose) polymerase (PARP). We report that although human cytotoxic lymphocytes were only marginally protected by caspase inhibitors, PARP inhibitors completely protected lymphocytes from radical-induced apoptosis and restored their cytotoxic function. The radical-induced, PARP-dependent cell death was accompanied by nuclear accumulation of apoptosis-inducing factor and a characteristic pattern of large-fragment DNA degradation. It is concluded that the PARP/apoptosis-inducing factor axis is critically involved in oxygen radical-induced apoptosis in cytotoxic lymphocytes.
Authors:
Fredrik B Thorén; Ana I Romero; Kristoffer Hellstrand
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  176     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-05     Completed Date:  2006-07-13     Revised Date:  2008-06-05    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7301-7     Citation Subset:  AIM; IM    
Affiliation:
Department of Virology, Sahlgrenska Academy, Göteborg University, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis Inducing Factor / metabolism
Cell Death / drug effects,  immunology
Cell Nucleus / metabolism
Free Radicals / metabolism
Humans
Hydrogen Peroxide / pharmacology
Killer Cells, Natural / cytology*,  enzymology*,  immunology,  metabolism
Macrophages / enzymology,  metabolism
Phenanthrenes / pharmacology
Poly(ADP-ribose) Polymerases / antagonists & inhibitors,  physiology*
Reactive Oxygen Species / metabolism*
T-Lymphocytes, Cytotoxic / cytology*,  enzymology*,  immunology,  metabolism
Chemical
Reg. No./Substance:
0/Apoptosis Inducing Factor; 0/Free Radicals; 0/N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; 0/Phenanthrenes; 0/Reactive Oxygen Species; 7722-84-1/Hydrogen Peroxide; 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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