title: Tunicamycin depresses P-glycoprotein glycosylation without an effect on its membrane localization and drug efflux activity in L1210 cells.
abstract: P-glycoprotein (P-gp), also known as ABCB1, is a member of the ABC transporter family of proteins. P-gp is an ATP-dependent drug efflux pump that is localized to the plasma membrane of mammalian cells and confers multidrug resistance in neoplastic cells. P-gp is a 140-kDa polypeptide that is glycosylated to a final molecular weight of 170 kDa. Our experimental model used two variants of L1210 cells in which overexpression of P-gp was achieved: either by adaptation of parental cells (S) to vincristine (R) or by transfection with the human gene encoding P-gp (T). R and T cells were found to differ from S cells in transglycosylation reactions in our recent studies. The effects of tunicamycin on glycosylation, drug efflux activity and cellular localization of P-gp in R and T cells were examined in the present study. Treatment with tunicamycin caused less concentration-dependent cellular damage to R and T cells compared with S cells. Tunicamycin inhibited P-gp N-glycosylation in both of the P-gp-positive cells. However, tunicamycin treatment did not alter either the P-gp cellular localization to the plasma membrane or the P-gp transport activity. The present paper brings evidence that independently on the mode of P-gp expression (selection with drugs or transfection with a gene encoding P-gp) in L1210 cells, tunicamycin induces inhibition of N-glycosylation of this protein, without altering its function as plasma membrane drug efflux pump.
authors.affiliation: Institute of Molecular Physiology and Genetics, Centre of Excellence of the Slovak Research and Development Agency "BIOMEMBRANES2008", Slovak Academy of Sciences, Vlárska 5, Bratislava 83334, Slovakia; E-Mails:  mario.seres@savba.sk  (M.Š.);  tatiana.kurucova@savba.sk  (T.B.).
authors.forename: Mário
authors.initials: M
authors.lastname: Sereš
authors.forename: Dana
authors.initials: D
authors.lastname: Cholujová
authors.forename: Tatiana
authors.initials: T
authors.lastname: Bubenčíkova
authors.forename: Albert
authors.initials: A
authors.lastname: Breier
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Sulová
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D051379:Mice; D014415:Tunicamycin / Q000494:pharmacology*; D014750:Vincristine / Q000494:pharmacology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D014415:Tunicamycin; D014750:Vincristine