Inhibition of the Plasma membrane Ca2+-ATPase by Flavonoids

RINALDI, D.; MANGIALAVORI, I.; ONTIVEROS, M.; RIESCO, A.; MARDER, M.; ROSSI, J.P.; FERREIRA-GOMES, M.

Congreso; Latin American Crosstalk in Biophysics and Physiology; 2015

Flavonoids are commonly found in fruit and vegetables. Some flavonoids have been reported to reach micromolar concentration in human blood plasma [1]. These compounds would have cancer chemoprotective properties by triggering apoptosis via the Ca2+ dependent mitochondrial pathway which can be activated through an elevation of cytosolic [Ca2+].The increase of cytosolic [Ca2+] could be due to the fact that some flavonoids inhibit certain Ca2+ removing systems, as the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase and plasma membrane calcium ATPase (PMCA) [2]. The purpose of the present work was to investigate the effect of different natural flavonoids on PMCA and to establish a quantitative structure-activity correlation. The experiments were performed with inside-out vesicles and purified PMCA obtained from human erythrocytes. At 100 microM concentration, chromone, chalcone, flavanone and flavone (structural cores of some flavonoids) did not inhibit PMCA. The inhibition was enhanced when the flavonoid present: (a) a double bond between carbons 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. The presence of an OH group at the 3 position or the presence of an O-glucose at the 8 position was not essential for the inhibition. The glycosylation in the 7 or 3 position was not favorable for the inhibition.On the other hand, we investigated the mechanism of inhibition for flavonoids that inhibited PMCA in the micromolar concentration range. The compounds studied were: quercetin, epigallocatechin 3-gallate and gossypin. Our results showed that (1) flavonoids act as inhibitor in both vesicles and purified systems and (2) the inhibition is more evident in purified PMCA (