VEGA 2/0123/10

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Effect of overexpression of P-glycoprotein and development of multidrug resistance on some aspects of metabolism       

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Principal investigator: Zdena Sulová

Duration: January 2010 – December 2012
Coordinating institution: Institute of Molecular Physiology and Genetics, SAS, Bratislava

Annotation:

Expression of P-glycoprotein (P-gp) confers multidrug resistance of neoplastic cells. P-gp represents transport ATPase of plasma membrane that secures elimination of  substances from intracellular space. Several studies documented that overexpression of P-gp in cells is associated with the changes in cell morphology, in composition of cell surface saccharides that induced alteration in binding of lectins on cell surface. We have described the overexpression of P-gp is associated with changes in expression of several endoplasmic reticulum proteins involved in calcium homeostasis. This was accompanied with increased sensitivity of cells to elevation in extracellular calcium concentration and depression of cell sensitivity to thapsigargin (inhibitor of endoplasmic reticulum calcium pump). The current project will be focused on the study of phenomena that are associated with P-gp overexpression in leukemia cells using biochemical methods combined with cytochemical methods using electron and confocal microscopy.

Publications:
pdf Sulova Z, Brtko J, Macejová D, Breier A: Are Nuclear Receptors for Retinoids Involved in the Control of the Expression and Activity of P-Glycoprotein? In Retinoic Acid: Structure, Mechanisms and Roles in Disease (Cheng, L.H., It, Y. eds.) NOVA Publisher, 2012 pp. 29-52.
Breier A, Gibalova L, Seres M, Barancik M, Sulova Z: P-glycoprotein mediated multidrug resistance of cancer tissue: Implication for cancer chemotherapy. ISBN 978-80-89233-55-7, PETRUS Publisher, 2012
PubMed Breier A, Gibalova L, Seres M, Barancik M, Sulova Z. New insight into p-glycoprotein as a drug target. Anti-cancer Agents Med Chem. 13 (2013) 159-70. (IF2012=2.610)
PubMed Barancik M, Bohacova V, Gibalova L, Sedlak J, Sulova Z, Breier A. Potentiation of Anticancer Drugs: Effects of Pentoxifylline on Neoplastic Cells. Int. J. Mol. Sci. 13 (2012) 369-382
 
PubMed Bubencíkova T, Cholujová D, Messingerová L, Mislovicova D, Seres M, Breier A, Sulova Z. Detection of glycomic alterations induced by overexpression of p-glycoprotein on the surfaces of l1210 cells using sialic Acid binding lectins. Int J Mol Sci. 13, (2012) 15177-15192
 
PubMed Gibalová L, Sereš M, Rusnák A, Ditte P, Labudová M, Uhrík B, Pastorek J, Sedlák J, Breier A, Sulová Z. P-glycoprotein depresses cisplatin sensitivity in L1210 cells by inhibiting cisplatin-induced caspase-3 activation. Toxicol In Vitro. 26 (2012) 435-444. (IF2012=2.650)
PubMed Šereš M, Cholujová D, Bubenčíkova T, Breier A, Sulová Z. Tunicamycin depresses p-glycoprotein glycosylation without an effect on its membrane localization and drug efflux activity in l1210 cells. Int J Mol Sci. 12 (2011) 7772-7784. (IF2012=2.464)