| Host cell P-glycoprotein is essential for cholesterol uptake and replication of Toxoplasma gondii. | |
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MedLine Citation:
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PMID: 19389707 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Iveta Bottova; Adrian B Hehl; Sasa Stefanić; Gemma Fabriàs; Josefina Casas; Elisabeth Schraner; Jean Pieters; Sabrina Sonda |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-04-22 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 284 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-06-22 Completed Date: 2009-08-06 Revised Date: 2013-06-02 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 17438-48 Citation Subset: IM |
Affiliation:
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Institute of Parasitology, University of Zurich, Zurich, Switzerland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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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