Document Detail


Host cell P-glycoprotein is essential for cholesterol uptake and replication of Toxoplasma gondii.
MedLine Citation:
PMID:  19389707     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
P-glycoprotein (P-gp) is a membrane-bound efflux pump that actively exports a wide range of compounds from the cell and is associated with the phenomenon of multidrug resistance. However, the role of P-gp in normal physiological processes remains elusive. Using P-gp-deficient fibroblasts, we showed that P-gp was critical for the replication of the intracellular parasite Toxoplasma gondii but was not involved in invasion of host cells by the parasite. Importantly, we found that the protein participated in the transport of host-derived cholesterol to the intracellular parasite. T. gondii replication in P-gp-deficient host cells not only resulted in reduced cholesterol content in the parasite but also altered its sphingolipid metabolism. In addition, we found that different levels of P-gp expression modified the cholesterol metabolism in uninfected fibroblasts. Collectively our findings reveal a key and previously undocumented role of P-gp in host-parasite interaction and suggest a physiological role for P-gp in cholesterol trafficking in mammalian cells.
Authors:
Iveta Bottova; Adrian B Hehl; Sasa Stefanić; Gemma Fabriàs; Josefina Casas; Elisabeth Schraner; Jean Pieters; Sabrina Sonda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-22
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  284     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-06-22     Completed Date:  2009-08-06     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17438-48     Citation Subset:  IM    
Affiliation:
Institute of Parasitology, University of Zurich, Zurich, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biological Transport
Blotting, Western
Cells, Cultured
Cholesterol / metabolism*
Chromatography, Liquid
Embryo, Mammalian / cytology,  metabolism
Fibroblasts / cytology,  metabolism
Fluorescent Antibody Technique
Host-Parasite Interactions
Lipids / analysis
Mass Spectrometry
Mice
Mice, Knockout
NIH 3T3 Cells / parasitology
Neospora / metabolism
P-Glycoproteins / physiology*
Toxoplasma / growth & development*,  metabolism*
Chemical
Reg. No./Substance:
0/Lipids; 0/P-Glycoproteins; 57-88-5/Cholesterol
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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