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Destruction of Leishmania mexicana amazonensis amastigotes by leucine methyl ester: protection by other amino acid esters

Published online by Cambridge University Press:  06 April 2009

Silvia C. Alfieri ,
V. Zilberfarb  and
M. Rabinovitch
Silvia C. Alfieri
Affiliation:
Unite d'immunophysiologie Cellulaire, Institut Pasteur and Centre National de la Recherche Scientifique (UA 04 1113), 25 Rue du Docteur Roux, 75724 Paris Cedex, France
V. Zilberfarb
Affiliation:
Unite d'immunophysiologie Cellulaire, Institut Pasteur and Centre National de la Recherche Scientifique (UA 04 1113), 25 Rue du Docteur Roux, 75724 Paris Cedex, France
M. Rabinovitch
Affiliation:
Unite d'immunophysiologie Cellulaire, Institut Pasteur and Centre National de la Recherche Scientifique (UA 04 1113), 25 Rue du Docteur Roux, 75724 Paris Cedex, France
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Summary

l-Amino acid esters, such as leucine methyl ester (Leu-OMe) can destroy intracellular as well as isolated amastigotes of Leishmania mexicana amazonensis by a mechanism which may involve ester hydrolysis by parasite enzymes. We show here that several other esters prevented the killing of the amastigotes by Leu-OMe. Destruction of Leishmania within macrophages in culture was assessed microscopically and viability of isolated parasites was monitored by reduction of the tetrazolium MTT. The main features of the protective effect were similar for intracellular and for isolated amastigotes. Thus, (i) effective prevention of parasite killing required that the protective ester be present in the medium prior to and during exposure of infected cells or parasites to Leu-OMe; (ii) the same esters protected intracellular and isolated Leishmania against damage by Leu-OMe. Ranks of protective activity, as determined on isolated amastigotes were: Gly-OBz > Tyr-OMe > Ile-OMe > Met-OMe > Val-OMe > Ala-OMe > Gly-OMe > D-Leu-OMe; (iii) several esters were inactive in both systems (Leu-OBz, Trp-OMe and Phe-OMe). Protective activity was associated with leishmanicidal (e.g. Gly-OBz, Tyr-OMe) as well as with non-leishmanicidal (e.g. Ile-OMe, Val-OMe) esters. The results are compatible with the hypothesis that protective esters inhibit the activity of parasite enzyme(s) which hydrolyse Leu-OMe.

Type
Research Article
Information
Parasitology , Volume 95 , Issue 1 , August 1987 , pp. 31 - 41
Copyright
Copyright © Cambridge University Press 1987

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