Document Detail


Critical role of poly(ADP-ribose) polymerase-1 in modulating the mode of cell death caused by continuous oxidative stress.
MedLine Citation:
PMID:  19711368     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Continuously generated hydrogen peroxide (H(2)O(2)) inhibits typical apoptosis and instead initiates a caspase-independent, apoptosis-inducing factor (AIF)-mediated pyknotic cell death. This may be related to H(2)O(2)-mediated DNA damage and subsequent ATP depletion, although the exact mechanisms by which the mode of cell death is decided after H(2)O(2) exposure are still unclear. Accumulated evidence and our previous data led us to hypothesize that continuously generated H(2)O(2), not an H(2)O(2) bolus, induces severe DNA damage, signaling poly(ADP-ribose) polymerase-1 (PARP-1) activation, ATP depletion, and eventually caspase-independent cell death. Results from the present study support that H(2)O(2) generated continuously by glucose oxidase causes excessive DNA damage and PARP-1 activation. Blockage of PARP-1 by a siRNA transfection or by pharmacological inhibitor resulted in the significant inhibition of ATP depletion, loss of mitochondrial membrane potential, nuclear translocation of AIF and endonuclease G, and eventually conversion to caspase-dependent apoptosis. Overall, the current study demonstrates the different roles of PARP-1 inhibition in modulation of cell death according to the method of H(2)O(2) exposure, that is, continuous generation versus a direct addition.
Authors:
Young-Ok Son; Sung-Ho Kook; Yong-Suk Jang; Xianglin Shi; Jeong-Chae Lee
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  108     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-26     Completed Date:  2010-02-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  989-97     Citation Subset:  IM    
Copyright Information:
(c) 2009 Wiley-Liss, Inc.
Affiliation:
Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536-0001, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / chemistry
Apoptosis
Caspases / metabolism
Cell Death
Cell Line, Tumor
Comet Assay
DNA Damage
Endodeoxyribonucleases / metabolism
Gene Expression Regulation*
Glucose Oxidase / metabolism
Humans
Hydrogen Peroxide / chemistry
Mitochondria / metabolism
Oxidative Stress*
Poly(ADP-ribose) Polymerases / metabolism*
Chemical
Reg. No./Substance:
56-65-5/Adenosine Triphosphate; 7722-84-1/Hydrogen Peroxide; EC 1.1.3.4/Glucose Oxidase; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.1.-/Endodeoxyribonucleases; EC 3.1.21.-/endonuclease G; EC 3.4.22.-/Caspases

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


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