QUERCETIN, A POTENTIAL INHIBITOR OF THE PLASMA MEMBRANE CAATPASE

MANGIALAVORI IRENE; RINALDI, DEBORA; AMABLE, GASTON; REY, OSVALDO; ROSSI JUAN PABLO; FERREIRA GOMES, MARIELA

Mar del Plata

Congreso; SAIB 2015. 51 Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2015

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Flavonoids are commonly found in fruit and vegetables and these are also present in human plasma. Thesecompounds are also believed to have cancer chemoprotective properties by triggering apoptosis via the Ca2+-dependent mitochondrial pathway which can be activated through an elevation of cytosolic [Ca2+] ([Ca2+]c). Theincrease of [Ca2+]c could be due to the fact that some flavonoids are able to inhibit some Ca2+ removing systems, assarcoplasmic/endoplasmic reticulum Ca2+-ATPase and plasma membrane calcium ATPase (PMCA). The effect offlavonoids on PMCA is not yet clear.The purpose of the present work is to investigate the possible inhibitory effectsof a flavonoid, quercetin, on PMCA. For this, we evaluated the [Ca2+]c in HEK293T cells and also studied the Ca2+-ATPase activity in vesicles and purified PMCA both obtained from human erythrocytes. The results show that (1) therate of Ca2+ removal is lower in the presence of quercetin with respect to the control suggesting that the Ca2+removing systems could be affected, including PMCA; (2) quercetin acts as inhibitor in both vesicles and purifiedsystems in a micromolar concentration range and (3) the inhibition is noncompetitive with Ca2+. These resultssuggest that PMCA could be a specific target of flavonoids contributing to elevation of [Ca2+]c during cancer cellsapoptosis.