| 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 |
Related Documents
:
|
19872533 - The non-logarithmic order of death of some bacteria. 11756663 - Arabidopsis gp91phox homologues atrbohd and atrbohf are required for accumulation of re... 11342443 - Red blood cells inhibit activation-induced cell death and oxidative stress in human per... |
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: 2013-04-16 |
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 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Prospective Analysis of Factors Related to Migraine Aura - The PAMINA Study.
Next Document: A novel HLA-B*54 allele, B*54:25, identified by sequence-based typing.