tailieunhanh - Báo cáo khoa học: P-Glycoprotein is localized in intermediate-density membrane microdomains distinct from classical lipid rafts and caveolar domains

P-glycoprotein (Pgp), a member of the ATP-binding cassette (ABC) super-family responsible for the ATP-driven extrusion of diverse hydrophobic molecules from cells, is a cause of multidrug resistance in human tumours. Pgp can also operate as a phospholipid and glycosphingolipid flippase, and has been functionally linked to cholesterol, suggesting that it might be associated with sphingolipid–cholesterol microdomains in cell membranes. | iFEBS Journal P-Glycoprotein is localized in intermediate-density membrane microdomains distinct from classical lipid rafts and caveolar domains Galina Radeva Jocelyne Perabo and Frances J. Sharom Department of Molecular and Cellular Biology University of Guelph Guelph Ontario Canada Key words ABC transporter caveolin-1 detergentresistant membranes lipid rafts P-glycoprotein Correspondence F. J. Sharom Department of Molecular and Cellular Biology University of Guelph Guelph Ontario Canada N1G 2W1 Fax 519 837 1802 Tel 519 824 4120 ext. 52247 E-mail fsharom@ Received 11 May 2005 revised 27 July 2005 accepted 4 August 2005 doi P-glycoprotein Pgp a member of the ATP-binding cassette ABC superfamily responsible for the ATP-driven extrusion of diverse hydrophobic molecules from cells is a cause of multidrug resistance in human tumours. Pgp can also operate as a phospholipid and glycosphingolipid flippase and has been functionally linked to cholesterol suggesting that it might be associated with sphingolipid-cholesterol microdomains in cell membranes. We have used nonionic detergent extraction and density gradient centrifugation of extracts from the multidrug-resistant Chinese hamster ovary cell line CHrB30 to address this question. Our data indicate that Pgp is localized in intermediate-density membrane microdomains different from classical lipid rafts enriched in Src-family kinases. We demonstrate that Brij-96 can selectively isolate the Pgp domains separating them from the caveolar and classical lipid rafts. Pgp was found entirely in the Brij-96-insoluble domains and only partially in the Triton X-100-insoluble membrane microdomains. We studied the sensitivity of these domains to cholesterol removal as well as their relationship to GM ganglioside- and caveolin-1-enriched caveolar domains. We found that the buoyant density of the Brij-96-based Pgp-containing microdomains was sensitive to cholesterol removal by .

• Báo cáo khoa học
• scientific reports
• Report medicine
• traditional medicine
• medical research
• hemoglobin
• medical knowledge
• medical textbooks
• medical practice
• specialized medicine
• Encyclopedia of Medical Anthropology
• medical
• health
• medical term dictionary
• y tế
• sức khỏe
• Data Mining and Medical Knowledge Management
• Premier Reference Sourse
• statements and documents scientific reports
• medical reports
• medical transfer
• the developing countries
• clinical trials
• medical management
• health care
• Healthcare knowledge management
• Knowledge identification
• Know How and Knowing That cartography
• Knowledge visualization
• Improving knowledge management
• Knowledge workers’ identities
• Evidence from the medical profession
• Knowledge workers
• Medical profession
• Organizational identification
• Knowledge Management
• Data Mining
• Text Mining
• Mapping Medical
• Bioinformatics Challenges
• Digital Libraries
• Medical Informatics
• A Handbook for Medical Teachers
• Medical Teachers
• health education
• health knowledge