Document Detail


Identification of a novel class of endoperoxides from arachidonate autoxidation.
MedLine Citation:
PMID:  14594817     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Free radical-initiated lipid autoxidation in low density lipoprotein (LDL) has been implicated in the pathogenesis of atherosclerosis. Oxidation of the lipid components of LDL leads to a complex mixture of hydroperoxides, bicyclic endoperoxides, monocyclic peroxides, and serial cyclic peroxides. The oxidation compounds and/or their decomposition products can modify protein components, which may lead to various diseases. A novel class of peroxides (termed dioxolane-isoprostanes) having a bicyclic endoperoxide moiety characteristic of the isoprostanes and a dioxolane peroxide functionality in the same molecule was identified in the product mixture formed from in vitro autoxidation of cholesteryl arachidonate. The same products are also detected in in vitro oxidized LDL. Various mass spectrometric techniques have been applied to characterize these new peroxides. The structure of these compounds has also been confirmed by independent synthesis. We reason, based on the free radical mechanism of the transformation, that only the 12- and 8-peroxyl radicals (those leading to 12-HPETE and 8-HPETE) of arachidonate can form these new peroxides. We also suggest that the formation of these peroxides provides a rationale to explain the fact that 5- and 15-series isoprostanes are formed in preference to 8- and 12-series. Furthermore, series of other isoprostanes, such as dioxolane A(2), D(2), E(2), etc., can be derived from the dioxolane-isoprostane peroxides. These findings offer further insights into the oxidation products of arachidonate and the opportunity to study their potential biological relevance.
Authors:
Huiyong Yin; Jason D Morrow; Ned A Porter
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2003-10-31
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  279     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-01-26     Completed Date:  2004-03-11     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3766-76     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, USA.
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MeSH Terms
Descriptor/Qualifier:
Arachidonic Acid / chemistry*
Arachidonic Acids / chemistry,  metabolism
Cholesterol Esters / chemistry,  metabolism
Chromatography, High Pressure Liquid
Chromatography, Thin Layer
Free Radicals
Gas Chromatography-Mass Spectrometry
Humans
Hydrogen Peroxide / chemistry
Isoprostanes / metabolism
Leukotrienes / chemistry
Lipid Metabolism
Lipoproteins / chemistry
Lipoproteins, LDL / metabolism
Models, Chemical
Oxygen / metabolism
Peroxidase / chemistry,  classification*
Platelet Aggregation Inhibitors / pharmacology
Silver / chemistry
Spectrometry, Mass, Electrospray Ionization
Time Factors
Ultraviolet Rays
Grant Support
ID/Acronym/Agency:
CA 77839/CA/NCI NIH HHS; CHE 9996188//PHS HHS; DK 48831/DK/NIDDK NIH HHS; GM15431/GM/NIGMS NIH HHS; HL17921/HL/NHLBI NIH HHS; P30 ES00267/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Arachidonic Acids; 0/Cholesterol Esters; 0/Free Radicals; 0/Isoprostanes; 0/Leukotrienes; 0/Lipoproteins; 0/Lipoproteins, LDL; 0/Platelet Aggregation Inhibitors; 506-32-1/Arachidonic Acid; 604-34-2/cholesteryl arachidonate; 67675-13-2/12-HPETE; 7440-22-4/Silver; 7722-84-1/Hydrogen Peroxide; 7782-44-7/Oxygen; EC 1.11.1.7/Peroxidase

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


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