Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The translocation of spin-labeled analogues of phosphatidylcholine (4-doxylpentanoyl-PC, SL-PC), phosphatidylethanolamine (SL-PE), phosphatidylserine (SL-PS), and sphingomyelin (SL-SM) from the outer to the inner leaflet of the plasma membrane bilayer was investigated in dog kidney MDCK II and human colon Caco-2 cells. Disappearance from the outer leaflet was assayed using back-exchange to serum albumin. Experiments with cells in suspension as well as with polarized cells on filters were performed at reduced temperatures (10 and 20 degreesC) to suppress endocytosis and hydrolysis of spin-labeled lipids. For both epithelial cell lines, a fast ATP-dependent inward movement of the aminophospholipids SL-PS and SL-PE was found, while SL-SM was only slowly internalized without any effect of ATP depletion. The kinetics of redistribution of SL-PC were clearly different between the two cell lines. In MDCK II cells, SL-PC was rapidly internalized in an ATP-dependent and N-ethylmaleimide-sensitive manner and at a rate similar to that of the aminophospholipids. In contrast, in Caco-2 cells the inward movement of SL-PC was much slower than that of the aminophospholipids, did not depend on ATP, and was not N-ethylmaleimide-sensitive. Inhibitor studies indicated that the outward-translocating multidrug resistance P-glycoprotein present in these cells did not affect the kinetics of inward translocation. Internalization was always similar on the apical and basolateral cell surface, suggesting the presence of the same phospholipid translocator(s) on both surface domains of epithelial cells. We propose that Caco-2 cells contain the well-known aminophospholipid translocase, while MDCK II cells contain either two translocases, namely, the aminophospholipid translocase and a phosphatidylcholine-specific translocase, or one translocase of a new type, translocating aminophospholipids as well as phosphatidylcholine.
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PMID:Protein-mediated inward translocation of phospholipids occurs in both the apical and basolateral plasma membrane domains of epithelial cells. 989 Aug 92

Rhamnose-binding lectin from catfish (Silurus asotus) eggs (SAL) has the ability to induce externalization of phosphatidylserine (PS), followed by cell shrinkage in globotriaosylceramide (Gb3)-expressing Burkitt's lymphoma Raji cells. Because phospholipid scramblase and aminophospholipid translocase did not participate in SAL-induced PS externalization, we examined the relationship of ATP-binding cassette (ABC) transporters, such as multidrug resistance (MDR) 1 P-glycoprotein (MDR1 P-gp) and MDR-associated protein 1 (MRP1), for translocation of PS. Since cyclosporin A (MDR1 P-gp inhibitor) but not MK571 (MRP1 inhibitor) inhibited SAL-induced PS externalization, it was suggested that MDR1 P-gp is involved in this phenomenon. On the other hand, SAL activated both of the ABC transporters for efflux of rhodamine123 (MDR1 P-gp substrate, Rho123) and 5-carboxyfluorescein diacetate (MRP1 substrate, 5-CFDA) in Raji cells. In contrast, SAL did not activate these two transporters in Gb3-negative cell lines, such as K562 and doxorubicin-resistant K562 cells, involving not only PS externalization but also efflux of Rho123 or 5-CFDA. Since Gb3 and both transporters in Raji cells are located in the glycosphingolipid-enriched microdomain (GEM), it is suggested that the binding of SAL to Gb3 localized in the GEM specifically induces MDR1 P-gp activation in Raji cells.
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PMID:Catfish egg lectin causes rapid activation of multidrug resistance 1 P-glycoprotein as a lipid translocase. 1574 65