XXII. BIOCHEMICKÝ ZJAZD - Jesseniova lekárska fakulta

Lectures
DOES EXISTS ANY RELATION BETWEEN P-GLYCOPROTEIN MEDIATED
MULTIDRUG RESISTANCE AND INTraCELLULar CALCIUM HOMEOSTASIS
Zdena Sulová 1 , Mário Šereš 1 , Miroslav Barančík 2 , Lenka Gibalová 1 , Branislav Uhrík 1 ,
Lenka Poleková 1 and Albert Breier 1
1
Institute of Molecular Physiology and Genetics, Centre of Excellence of the Slovak
Research and Development Agency „BIOMEMBRANES2008”, Slovakia, 2 Institute
for Heart Research, SAV, Bratislava
Multidrug resistance (MDR) of neoplastic tissue represents real obstacle in effective
chemotherapy of cancer. Several mechanisms of MDR were identified, from which
over-expression and efflux activity of P-glycoprotein (P-gp) – plasma membrane ATPase
(ABCB1 member of ABC transporter family) – represent most common observed reason
of neoplastic diseases chemotherapy malfunction. Process of P-gp mediated MDR
seems to be related to intracellular calcium homeostasis at least indirectly because: i.
substances blocking calcium influx through L-type of calcium channels like verapamil
were often found to antagonize P-gp mediated MDR; ii. calcium signal abnormalities
were observed in cells over-expressing P-gp; iii. cells with P-gp mediated MDR were often
resistant to thapsigargin; iv. several differences in intracellular calcium localization were
observed when P-gp negative and P-gp positive cells were compared; v. differences in
contents of several proteins of endoplasmic reticulum involved in calcium homeostasis
were observed to be associated with P-gp over-expression. Current study represents an
attempt to summarize knowledge about possible relations between P-gp mediated MRD
and intracellular calcium homeostasis.
Acknowledgments: This work was supported by: APVV-0084-07, VVCE-0064-07, VEGA-
2/0123/10, VEGA-2/0155/09
XXII. Biochemistry Congress, Martin
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