Document Detail


Protection of dopaminergic cells by urate requires its accumulation in astrocytes.
MedLine Citation:
PMID:  22671773     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Urate is the end product of purine metabolism and a major antioxidant circulating in humans. Recent data link higher levels of urate with a reduced risk of developing Parkinson's disease and with a slower rate of its progression. In this study, we investigated the role of astrocytes in urate-induced protection of dopaminergic cells in a cellular model of Parkinson's disease. In mixed cultures of dopaminergic cells and astrocytes oxidative stress-induced cell death and protein damage were reduced by urate. By contrast, urate was not protective in pure dopaminergic cell cultures. Physical contact between dopaminergic cells and astrocytes was not required for astrocyte-dependent rescue as shown by conditioned medium experiments. Urate accumulation in dopaminergic cells and astrocytes was blocked by pharmacological inhibitors of urate transporters expressed differentially in these cells. The ability of a urate transport blocker to prevent urate accumulation into astroglial (but not dopaminergic) cells predicted its ability to prevent dopaminergic cell death. Transgenic expression of uricase reduced urate accumulation in astrocytes and attenuated the protective influence of urate on dopaminergic cells. These data indicate that urate might act within astrocytes to trigger release of molecule(s) that are protective for dopaminergic cells.
Authors:
Sara Cipriani; Cody A Desjardins; Thomas C Burdett; Yuehang Xu; Kui Xu; Michael A Schwarzschild
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-08-22
Journal Detail:
Title:  Journal of neurochemistry     Volume:  123     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-10     Completed Date:  2012-11-19     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  172-81     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.
Affiliation:
Molecular Neurobiology Laboratory, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Boston, MA 02129, USA. pattona80@hotmail.com
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Animals, Newborn
Antioxidants / metabolism*,  pharmacology*
Astrocytes / metabolism*
Cell Survival
Cells, Cultured
Chromatography, High Pressure Liquid
Coculture Techniques
Culture Media, Conditioned / pharmacology
Dopaminergic Neurons / drug effects*
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Gene Expression Regulation / drug effects,  genetics
Hydrogen Peroxide / toxicity
Mice
Mice, Inbred C57BL
Mice, Transgenic
Nitrites / metabolism
Oxidants / toxicity
Protein Carbonylation / drug effects
Reactive Oxygen Species / metabolism
Urate Oxidase / genetics
Uric Acid / metabolism*,  pharmacology*
Grant Support
ID/Acronym/Agency:
K24 NS060991/NS/NINDS NIH HHS; K24NS060991/NS/NINDS NIH HHS; R21 NS058324/NS/NINDS NIH HHS; R21NS058324/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Culture Media, Conditioned; 0/Enzyme Inhibitors; 0/Nitrites; 0/Oxidants; 0/Reactive Oxygen Species; 69-93-2/Uric Acid; 7722-84-1/Hydrogen Peroxide; EC 1.7.3.3/Urate Oxidase
Comments/Corrections

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


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