ABCMdb

PMID: 15256468

Trompier D, Chang XB, Barattin R, du Moulinet D'Hardemare A, Di Pietro A, Baubichon-Cortay H
Verapamil and its derivative trigger apoptosis through glutathione extrusion by multidrug resistance protein MRP1.
Cancer Res. 2004 Jul 15;64(14):4950-6., 2004-07-15 [PubMed]

Sentences

No. Mutations Sentence Comment

5 ABCC1 p.Lys1333Leu Because parental BHK cells were not, as well as cells expressing an inactive (K1333L) MRP1 mutant, this indicated that cell death involved functional MRP1 transporter. Login to comment 33 ABCC1 p.Lys1333Leu BHK-21 cells stably transfected with either wild-type or (K1333L) mutant MRP1 have been described previously (20, 21). Login to comment 108 ABCC1 p.Lys1333Leu To check whether the MRP1 transporter was directly involved in hypersensitivity, BHK-21 cells transfected with an inactive MRP1 (K1333L) mutant (20) were analyzed for their sensitivity toward verapamil and its derivative. Login to comment 127 ABCC1 p.Lys1333Leu The lactate dehydrogenase release induced by verapamil (A) or NMeOHI2 (B) on BHK-21 control cells (᭛), or BHK-21 cells transfected with either wild-type (᭜) or K1333L mutant MRP1 (E), was determined in the incubation medium after 24-h treatment with the indicated concentrations. Login to comment 130 ABCC1 p.Lys1333Leu Both verapamil (Fig. 7A) and NMeOHI2 (Fig. 7B) induced a strong and fast (in Ͻ1 h) decrease in total cellular gluthatione content, whereas no significant decrease was observed with untransfected control cells (Fig. 7) or BHK-21 cells expressing the inactive MRP1 (K1333L) mutant (data not shown). Login to comment 184 ABCC1 p.Lys1333Leu Taking into account that no cytotoxicity and no GSH decrease were observed on either control cells or cells expressing an inactive (K1333L) MRP1 mutant, the involvement of active MRP1 clearly emerged as being responsible for direct efflux of GSH leading to intracellular depletion. Login to comment