Quercetin, a potencial inhibitor of Plasma Membrane Ca2+-ATPas

MANGIALAVORI, IC. RINALDI, D.; AMABLE, G.; REY, O.; ROSSI, JP; FERREIRA-GOMES, M1

Mar del Plata

Congreso; 239. LI Reunión Anual de la Sociedad Argentina de Investigaciones Bioquímicas; 2015

Sociedad Argentina de Investigaciones Bioquímicas

Inhibition of the Plasma membrane Ca2+-ATPaseby QuercetinMangialavori, I.1; Rinaldi, D.1; Riesco, A.1;Marder, M.1; Rossi, JP1; Ferreira-Gomes, M1. 1Instituto deQuímica y Fisicoquímica Biológicas. ?Prof. A. Paladini?. Dto de QuímicaBiológica, FFyB. UBA. irenem@qb.ffyb.uba.ar Flavonoidsare group of hydroxylated polycyclic molecules found in fruit and vegetablesand found micromolars concentrations in human blood plasma. These havebeneficial health effects, including cancer chemoprotection. One mechanismproposed to explain this is that they are able to induce apoptosis in cancercells by inhibiting of kinases and Ca2+-ATPases. Apoptosis would initiatevia a Ca2+-dependent mitochondrial pathway, which can be activatedthrough an exaggerated elevation of cytosolic [Ca2+] ([Ca2+]cyt).In this sense, the plasma membrane calcium ATPase (PMCA) plays an essentialrole in maintaining intracellular Ca2+ homeostasis.Thepurpose of this work is to investigate to quercetin as a potent flavoneinhibitor of PMCA and determine the mechanism of action.Weevaluated the effect of quercetin on the variation of [Ca2+]cytin HEK 293T cells. The results show that the rate of removal of Ca2+is less in the presence of flavonoid respect to the control suggesting that thosesystems that remove calcium would be affected, including the PMCA. In order tostudy this effect directly on the PMCA we evaluated Ca2+-ATPaseactivity using vesicles and purified PMCA obtained from human erythrocytes. Theresults show that quercetin can inhibitthe activity of PMCA in the micromolar concentration range.Theseresults suggest that PMCA could be a specific target of flavonoids contributing to elevation of [Ca2+]cyt during cancer cells apoptosis.