Tunicamycin Depresses P-Glycoprotein Glycosylation Without an Effect on Its Membrane Localization and Drug Efflux Activity in L1210 Cells

International Journal of Molecular Sciences

Mário ᘎreš²  Dana Cholujová¹  Tatiana Bubenčíkova²  Albert Breier² 

[1] Cancer Research Institute, Slovak Academy of Sciences, Vlárska 7, Bratislava 83391, Slovakia; E-Mail:;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:

关键词: P-gp (MDR1);    tunicamycin;    N-glycosylation;    L1210;   

DOI  :  10.3390/ijms12117772

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2011 by the authors; licensee MDPI, Basel, Switzerland.