HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: M600111-JLR200v1 47/7/1493    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Guillaume, C. Articles by Deregnaucourt, C. Search for Related Content PubMed PubMed Citation Articles by Guillaume, C. Articles by Deregnaucourt, C. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 47, 1493-1506, July 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Interplay between lipoproteins and bee venom phospholipase A₂ in relation to their anti-plasmodium toxicity

Carole Guillaume^*, Catherine Calzada, Michel Lagarde, Joseph Schrével^* and Christiane Deregnaucourt^1,*

^* USM 0504, Biologie Fonctionnelle des Protozoaires, Muséum National d'Histoire Naturelle, Paris, France
INSERM UMR 585, INSA-Lyon, Physiopathologie des Lipides et Membranes, Villeurbanne, France

Published, JLR Papers in Press, April 10, 2006.

¹ To whom correspondence should be addressed. e-mail: deregnau{at}mnhn.fr

We previously showed that the in vitro intraerythrocytic development of the malarial agent Plasmodium falciparum is strongly inhibited by secreted phospholipases A₂ (sPLA₂s) from animal venoms. Inhibition is dependent on enzymatic activity and requires the presence of serum lipoproteins in the parasite culture medium. To evaluate the potential involvement of host lipoproteins and sPLA₂s in malaria, we investigated the interactions between bee venom phospholipase A₂ (bvPLA₂), human triglyceride-rich lipoproteins, and infected erythrocytes. Even at high enzyme concentration (100x IC₅₀), bvPLA₂ binding to Plasmodium-infected or normal erythrocytes was not detected. On the contrary, tight association with lipoproteins was observed through the formation of buoyant bvPLA₂/lipoprotein complexes. Direct involvement of the hydrolysis lipid products in toxicity was demonstrated. Arachidonic acid (C20:4), linoleic acid (C18:2), and, to a lesser extent, docosahexaenoic acid (C22:6) appeared as the main actors in toxicity. Minimal oxidation of lipoproteins enhanced toxicity of the lipolyzed particles and induced their interaction with infected or normal erythrocytes. Fresh or oxidized lipolyzed lipoproteins induced the parasite degeneration without host cell membrane disruption, ruling out a possible membranolytic action of fatty acids or peroxidation products in the death process. In conclusion, our data enlighten on the capability of secreted PLA₂s to exert cytotoxicity via the extracellular generation of toxic lipids, and raise the question of whether such mechanisms could be at play in pathophysiological situations such as malaria.

Supplementary key words secreted phospholipase A₂ • malaria • unsaturated fatty acids • oxidation

Abbreviations: AA, arachidonic acid; BHT, butylated hydroxytoluene; bvPLA₂, bee venom phospholipase A₂; chyl, chylomicron; DHA, docosahexaenoic acid; FA, fatty acid; F-chyl/VLDL, freshly prepared chyl/VLDL; GC, gas chromatography; LA, linoleic acid; lysoPC, lysophosphatidylcholine; lysoPE, lysophosphatidylethanolamine; lysoPL, lysophospholipid; Ox-chyl/VLDL, oxidized chyl/VLDL; Ox-LDL, oxidized LDL; PC, phosphatidylcholine; PS, phosphatidylserine; RBC, red blood cell; sPLA₂, secreted phospholipase A₂; TBARS, thiobarbituric acid-reactive substances

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