Inhibition of the Plasma membrane -ATPase by Flavonoids Ca2+

RINALDI, DEBORA; MANGIALAVORI IRENE; ONTIVEROS, MALLKU; RIESCO, ANA; MARDER, MARIEL; ROSSI, JPFC; FERREIRA GOMES, MARIELA

Salto

Congreso; Latin American Crosstalk In Biophysics And Physiology; 2015

Flavonoids are commonly found in fruit and vegetables. Some flavonoidshave been reported to reach micromolar concentration in human bloodplasma [1]. These compounds would have cancer chemoprotectiveproperties by triggering apoptosis via the Ca2+pathway which can be activated through an elevation of cytosolic[Ca2+].The increase of cytosolic [Ca2+] could be due to the fact that someflavonoids inhibit certain Ca2+ removing systems, as thesarcoplasmic/endoplasmic reticulum Ca2+ ATPase and plasma membranecalcium ATPase (PMCA) [2].The purpose of the present work was to investigate the effect of differentnatural flavonoids on PMCA and to establish a quantitative structure-activity correlation. The experiments were performed with inside-outvesicles and purified PMCA obtained from human erythrocytes.At 100 μM concentration, chromone, chalcone, flavanone and flavone(structural cores of some flavonoids) did not inhibit PMCA. The inhibitionwas enhanced when the flavonoid present: (a) a double bond betweencarbons 2-3; (b) when the flavone nucleus is substituted with OH groups;(c) In the presence of an OH group in the 4´ position or in 3 ́ position. Thepresence of an OH group at the 3 position or the presence of an O-glucoseat the 8 position was not essential for the inhibition. The glycosylation inthe 7 or 3 position was not favorable for the inhibition.On the other hand, we investigated the mechanism of inhibition forflavonoids that inhibited PMCA in the micromolar concentration range. Thecompounds studied were: quercetin, epigallocatechin 3-gallate andgossypin. Our results showed that (1) flavonoids act as inhibitor in bothvesicles and purified systems and (2) the inhibition is more evident inpurified PMCA (