Document Detail


Alterations in phospholipid and fatty acid lipid profiles in primary neocortical cells during oxidant-induced cell injury.
MedLine Citation:
PMID:  18602625     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Specific phospholipids and fatty acids altered during oxidant-induced neuronal cell injury were determined using electrospray ionization mass spectrometry (ESI-MS) and ion trapping. The oxidants hydrogen peroxide (H(2)O(2), 0-1000 microM) and tert-butylhydroperoxide (TBHP, 0-400 microM) induced time- and concentration-dependent increases in reactive oxygen species in primary cultures of mouse neocortical cells as determined by 2',7'-dichlorofluorescein diacetate staining and thiobarbituric acid formation. ESI-MS analysis of 26 m/z values, representing 42 different phospholipids, demonstrated that H(2)O(2) and TBHP increased the abundance of phospholipids containing polyunsaturated fatty acids, but had minimal affect on those containing mono- or di-unsaturated fatty acids. These increases correlated to time-dependent increase in 16:1-20:4, 16:0-20:4, 18:1-20:4 and 18:0-20:4 phosphatidylcholine. Oxidant exposure also increased mystric (14:0), palmitic (16:0), and stearic (18:0) acid twofold, oleic acid (18:1) two- to threefold, and arachidonic acid (20:4) fourfold, compared to controls. Increases in arachidonic acid levels occurred prior to increases in the phospholipids, but after increases in ROS, and correlated to increases in oxidized arachidonic acid species, specifically [20:4-OOH]-H(2)O-, 20:4-OH-, and Tri-OH-20:4-arachidonic acid. Treatment of cells with methyl arachidonyl flourophosphonate an inhibitor of Group IV and VI PLA(2), decreased oxidant-induced arachidonic acid release, while bromoenol lactone, an inhibitor of Group VI PLA(2), did not. Collectively, these data identify phospholipids and fatty acids altered during oxidant treatment of neurons and suggest differential roles for Group IV and VI PLA(2) in oxidant-induced neural cell injury.
Authors:
Brianna Peterson; Kyndra Stovall; Prashant Monian; James L Franklin; Brian S Cummings
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-05-29
Journal Detail:
Title:  Chemico-biological interactions     Volume:  174     ISSN:  0009-2797     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-11     Completed Date:  2008-09-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  163-76     Citation Subset:  IM    
Affiliation:
Department of Pharmaceutical and Biomedical Sciences, The University of Georgia, Athens, GA 30602-2352, United States.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arachidonic Acid / metabolism
Arachidonic Acids / pharmacology
Cell Death / drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Fatty Acids, Unsaturated / chemistry,  metabolism*
Hydrogen Peroxide / toxicity*
Mice
Naphthalenes / pharmacology
Neocortex / drug effects,  metabolism*,  pathology
Neurons / drug effects,  metabolism*,  pathology
Oxidants / toxicity*
Phosphodiesterase Inhibitors / pharmacology
Phospholipases A / antagonists & inhibitors
Phospholipids / chemistry,  metabolism*
Phosphonic Acids / pharmacology
Pyrones / pharmacology
Reactive Oxygen Species
Spectrometry, Mass, Electrospray Ionization
Thiobarbituric Acid Reactive Substances / metabolism
tert-Butylhydroperoxide / toxicity*
Grant Support
ID/Acronym/Agency:
NIHR01NS37110/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Arachidonic Acids; 0/Enzyme Inhibitors; 0/Fatty Acids, Unsaturated; 0/Naphthalenes; 0/Oxidants; 0/Phosphodiesterase Inhibitors; 0/Phospholipids; 0/Phosphonic Acids; 0/Pyrones; 0/Reactive Oxygen Species; 0/Thiobarbituric Acid Reactive Substances; 0/methyl arachidonylfluorophosphonate; 506-32-1/Arachidonic Acid; 75-91-2/tert-Butylhydroperoxide; 7722-84-1/Hydrogen Peroxide; 88070-98-8/6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; EC 3.1.1.-/Phospholipases A

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


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