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2030-01-01
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- IOC - Artigos de Periódicos [12973]
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LDL UPTAKE BY LEISHMANIA AMAZONENSIS: INVOLVEMENT OF MEMBRANE LIPID MICRODOMAINS
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Abstract
Leishmania amazonensis lacks a de novo mechanism for cholesterol synthesis and therefore must scavenge
this lipid from the host environment. In this study we show that the L. amazonensis takes up and metabolizes
human LDL1 particles in both a time and dose-dependent manner. This mechanism implies the
presence of a true LDL receptor because the uptake is blocked by both low temperature and by the excess
of non-labelled LDL. This receptor is probably associated with specific microdomains in the membrane of
the parasite, such as rafts, because this process is blocked by methyl-b-cyclodextrin (MCBD). Cholesteryl
ester fluorescently-labeled LDL (BODIPY-cholesteryl-LDL) was used to follow the intracellular distribution
of this lipid. After uptake it was localized in large compartments along the parasite body. The accumulation
of LDL was analyzed by flow cytometry using FITC-labeled LDL particles. Together these data
show for the first time that L. amazonensis is able to compensate for its lack of lipid synthesis through
the use of a lipid importing machinery largely based on the uptake of LDL particles from the host. Understanding
the details of the molecular events involved in this mechanism may lead to the identification of
novel targets to block Leishmania infection in human hosts.
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