Document Detail


The protective effect of astrocyte-derived 14,15-epoxyeicosatrienoic acid on hydrogen peroxide-induced cell injury in astrocyte-dopaminergic neuronal cell line co-culture.
MedLine Citation:
PMID:  22863680     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Astrocytes perform several functions that are essential for normal neuronal activity. They play a critical role in neuronal survival during ischemia and other degenerative injuries and also modulate neuronal recovery by influencing neurite outgrowth. In this study, we investigated the neuroprotective effects of astrocyte-derived 14,15-epoxyeicosatrienoic acid (14,15-EET), metabolite of arachidonic acid by cytochrome P450 epoxygenases (CYP), against oxidative stress induced by hydrogen peroxide (H(2)O(2)). We found that dopaminergic neuronal cells (N27 cell line) stimulated with two different doses of H(2)O(2) (0.1 and 1mM) for 1h showed decreased cell viability compared to the control group, while astrocytes showed less cell death after stimulation with the same doses of H(2)O(2) for 1h. Dopaminergic neuronal cells (N27 cell line) pretreated with different doses of 14,15-EET (0.1-30 μM, 30 min) before H(2)O(2) stimulation also showed increased cell viability. Furthermore, pre-treatment of the co-cultured cells with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid, an inhibitor of the EET metabolizing enzyme, soluble epoxide hydrolase (sEH), before H(2)O(2) stimulation (1mM, for 1h) increased cell viability. It also increased the endogenous level of 14,15-EET in the media compared to control group. However, pretreatment with the CYP epoxygenase inhibitor miconazole (1-20 μM, 1h) before H(2)O(2) (1mM, 1h) stimulation showed decreased cell viability. Our data suggest that 14,15-EET which is released from astrocytes, enhances cell viability against oxidant-induced injury. Further understanding of the mechanism of 14,15-EET-mediated protection in dopaminergic neurons is imperative, as it could lead to novel therapeutic approaches for treating CNS neuropathologies, such as Parkinson's disease.
Authors:
M Terashvili; P Sarkar; M V Nostrand; J R Falck; D R Harder
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-07-31
Journal Detail:
Title:  Neuroscience     Volume:  223     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-09-24     Completed Date:  2013-05-01     Revised Date:  2014-05-09    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  68-76     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
8,11,14-Eicosatrienoic Acid / analogs & derivatives*,  chemistry,  pharmacology
Analysis of Variance
Animals
Animals, Newborn
Astrocytes / chemistry,  drug effects,  physiology*
Cell Survival / drug effects
Cells, Cultured
Chromatography, Liquid
Coculture Techniques
Dopaminergic Neurons / drug effects*,  physiology
Dose-Response Relationship, Drug
Drug Administration Schedule
Eicosanoids / metabolism
Hippocampus / cytology
Hydrogen Peroxide / toxicity
Mass Spectrometry
Membrane Potential, Mitochondrial / drug effects
Neuroprostanes / pharmacology*
Oxidants / toxicity
Rats
Rats, Sprague-Dawley
Time Factors
Grant Support
ID/Acronym/Agency:
P01 DK038226/DK/NIDDK NIH HHS; P01 HL059996/HL/NHLBI NIH HHS; P01 HL059996/HL/NHLBI NIH HHS; R01 HL033833/HL/NHLBI NIH HHS; R01 HL033833/HL/NHLBI NIH HHS; R01 HL092105/HL/NHLBI NIH HHS; R01 HL092105/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Eicosanoids; 0/Neuroprostanes; 0/Oxidants; 7324-41-6/8,11,14-Eicosatrienoic Acid; 81276-03-1/14,15-epoxy-5,8,11-eicosatrienoic acid; BBX060AN9V/Hydrogen Peroxide
Comments/Corrections

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