Document Detail


Redox cycling of the herbicide paraquat in microglial cultures.
MedLine Citation:
PMID:  15790529     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mechanisms involved in paraquat neurotoxicity that selectively target nigrostriatal dopaminergic neurons remain relatively unknown. In this study, we tested the hypotheses that paraquat exposure leads to the production of reactive oxygen species (ROS) through a process of redox cycling and that microglia represent an important site for the initiation of redox cycling reactions. Addition of paraquat to N9 microglial cultures resulted in a dose- and time-dependent release of superoxide radicals. Other agents that share with paraquat the property of redox cycling, i.e., benzyl viologen and diquat, also induced a marked production of superoxide radicals by microglia. The ability of paraquat, benzyl viologen, and diquat to induce superoxide release was correlated to their one-electron reduction potentials and thus their tendency to redox cycle. Nitric oxide synthase and NADPH oxidase were identified as enzymatic sources of electrons that triggered paraquat redox cycling by microglia. Taken together, these data provide evidence in favor of a new mechanism by which microglia could play a role in oxidative injury during neurodegenerative processes. Microglial NOS and NADPH oxidase could promote the generation of ROS via the redox cycling of paraquat-like toxicants.
Authors:
Dafna Bonneh-Barkay; Stephen H Reaney; William J Langston; Donato A Di Monte
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2005-01-06
Journal Detail:
Title:  Brain research. Molecular brain research     Volume:  134     ISSN:  0169-328X     ISO Abbreviation:  Brain Res. Mol. Brain Res.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-25     Completed Date:  2005-06-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8908640     Medline TA:  Brain Res Mol Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  52-6     Citation Subset:  IM    
Affiliation:
The Parkinson's Institute, 1170 Morse Avenue, Sunnyvale, CA 94089-1605, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetophenones / pharmacology
Animals
Benzyl Viologen / pharmacology
Cell Line
Dose-Response Relationship, Drug
Drug Interactions
Enzyme Inhibitors / pharmacology
Herbicides / pharmacology*
Mice
Microglia / drug effects*,  metabolism
Models, Biological
NG-Nitroarginine Methyl Ester / pharmacology
Nitroblue Tetrazolium / diagnostic use,  metabolism
Oxidation-Reduction / drug effects*
Paraquat / pharmacology*
Superoxides / metabolism
Time Factors
Grant Support
ID/Acronym/Agency:
ES10442/ES/NIEHS NIH HHS; ES10806/ES/NIEHS NIH HHS; ES12077/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Acetophenones; 0/Enzyme Inhibitors; 0/Herbicides; 11062-77-4/Superoxides; 13096-46-3/Benzyl Viologen; 298-83-9/Nitroblue Tetrazolium; 4685-14-7/Paraquat; 498-02-2/acetovanillone; 50903-99-6/NG-Nitroarginine Methyl Ester

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


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