Document Detail


Oltipraz-induced phase 2 enzyme response conserved in cells lacking mitochondrial DNA.
MedLine Citation:
PMID:  16188238     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Oltipraz, a member of a class of 1,2-dithiolethiones, is a potent phase 2 enzyme inducing agent used as a cancer chemopreventive. In this study, we investigated regulation of the phase 2 enzyme response and protection against endogenous oxidative stress in lymphoblastic leukemic parental CEM cells and cells lacking mitochondrial DNA (mtDNA) (rho0) by oltipraz. Glutathione (GSH) levels (total and mitochondrial) and glutathione S-transferase (GST) activity were significantly increased after pretreatment with oltipraz in both parental (rho+) and rho0 cells, and both cell lines were resistant to mitochondrial oxidation, loss of mitochondrial membrane potential, and cell death in response to the GSH depleting agent diethylmaleate. These results show that the phase 2 enzyme response, by enhancing GSH-dependent systems involved in xenobiotic metabolism, blocks endogenous oxidative stress and cell death, and that this response is intact in cells lacking mtDNA.
Authors:
Yee Liu Chua; Dawei Zhang; Urs Boelsterli; Philip K Moore; Matthew Whiteman; Jeffrey S Armstrong
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  337     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-10-03     Completed Date:  2005-11-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  375-81     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, National University of Singapore, Singapore 117597, Singapore.
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MeSH Terms
Descriptor/Qualifier:
Anticarcinogenic Agents / pharmacology*
Cell Line, Tumor
Cell Survival / drug effects
DNA, Mitochondrial / drug effects
Glutathione / metabolism*
Glutathione Transferase / metabolism*
Humans
Leukemia, Lymphoid / enzymology,  metabolism,  pathology
Membrane Potentials / drug effects
Mitochondria / physiology,  ultrastructure
Oxidative Stress / drug effects*
Pyrazines / pharmacology*
Reactive Oxygen Species / metabolism
Chemical
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/DNA, Mitochondrial; 0/Pyrazines; 0/Reactive Oxygen Species; 64224-21-1/oltipraz; 70-18-8/Glutathione; EC 2.5.1.18/Glutathione Transferase

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


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