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Plasmodium salvages cholesterol internalized by LDL and synthesized de novo in the liver.
MedLine Citation:
PMID:  21105984     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Our previous morphological studies illustrated the association of sterols with Plasmodium infecting hepatocytes. Because malaria parasites cannot synthesize sterols, they must scavenge these lipids from the host. In this paper, we have examined the source/s of sterols for intrahepatic Plasmodium and evaluated the importance of sterols for liver stage development. We show that Plasmodium continuously diverts cholesterol from hepatocytes until release of merozoites. Removal of plasma lipoproteins from the medium results in a 70% reduction of cholesterol content in hepatic merozoites but these parasites remain infectious in animals. Plasmodium salvages cholesterol that has been internalized by low-density lipoprotein but reduced expression of host low-density lipoprotein receptors by 70% does not influence liver stage burden. Plasmodium is also able to intercept cholesterol synthesized by hepatocytes. Pharmacological blockade of host squalene synthase or downregulation of the expression of this enzyme by 80% decreases by twofold the cholesterol content of merozoites without further impacting parasite development. These data enlighten that, on one hand, malaria parasites have moderate need of sterols for optimal development in hepatocytes and, on the other hand, they can adapt to survive in cholesterol-restrictive conditions by exploitation of accessible sterols derived from alternative sources in hepatocytes to maintain proper infectivity.
Authors:
Mehdi Labaied; Bamini Jayabalasingham; Nazneen Bano; Sung-Jae Cha; Juan Sandoval; Guimin Guan; Isabelle Coppens
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Publication Detail:
Type:  Journal Article     Date:  2010-12-28
Journal Detail:
Title:  Cellular microbiology     Volume:  13     ISSN:  1462-5822     ISO Abbreviation:  Cell. Microbiol.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883691     Medline TA:  Cell Microbiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  569-86     Citation Subset:  IM    
Copyright Information:
© 2010 Blackwell Publishing Ltd.
Affiliation:
Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health and Malaria Research Institute, Baltimore, MD 21205, USA. Department of Surgery, Uniformed Services University School of Medicine, Bethesda, MD 20814, USA.
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