J. Lipid Res.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on September 1, 2005

Papers In Press, published online ahead of print July 1, 2005
J. Lipid Res., doi:10.1194/jlr.M500074-JLR200
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
M500074-JLR200v1
46/9/1923    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Androulakis, N.
Right arrow Articles by Tsoukatos, D. C
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Androulakis, N.
Right arrow Articles by Tsoukatos, D. C
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Submitted on February 23, 2005
Revised on May 31, 2005
Accepted on June 20, 2005

Molecular and mechanistic characterization of platelet-activating-factor-like bioactivity produced upon Cooper-catalyzed LDL oxidation

Nicolaos Androulakis, Herve Durand, Ewa Ninio, and Demokritos C Tsoukatos

Department of Chemistry, University of Ioannina, Ioannina, Ioannina 45110

Corresponding Author: dtsoykat{at}cc.uoi.gr

Oxidation of LDL is thought to be involved in both initiating and sustaining atherogenesis through the formation of pro-inflammatory lipids and the covalent modification of LDL particles. Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent phospholipid mediator involved in inflammation. Upon oxidation of LDL, a large amount of oxidized phospholipids with PAF-like structure, is generated by fragmentation of the polyunsaturated fatty acyl moieties esterified at sn-2 position of glycerol. Some of the oxidatively generated PAF analogs may act via the PAF receptor. We evaluated the contribution of 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16:0 PAF) as well as of other PAF analogs, on the PAF-like bioactivity formed upon Cu2+-initiated oxidation of LDL. RP-HPLC purification, and ESI-MS analyses showed that upon oxidation of LDL, with inactivated PAF-acetylhydrolase, C16:0 PAF accounted for more than 30% of PAF-like biological activity and its sn-2 boutenoyl analogue for more than 50%. However upon LDL oxidation in the presence of exogenous lyso-PAF without PAF-acetylhydrolase inactivation, C16:0 PAF formation accounted for more than 90% of the biological activity recovered. We suggest, that the C16:0 PAF, despite being a minor constituent of the LDL peroxidation products, may substantially contribute to the bioactivity formed in oxidized LDL. The higher bioactivity of C16:0 PAF, and the higher selectivity of the LDL attached lyso-PAF transacetylase towards very short acyl chains (acetate (C2) vs boutanate (C4)), may explain the above contribution.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2005 by the American Society for Biochemistry and Molecular Biology.