An overview of the impact of natural flavonoids on P-ATPases

MALLKU ONTIVEROS; DEBORA RINALDI; MARIEL MARDER; IRENE C MANGIALAVORI; ROLANDO ROSSI; JUAN PABLO ROSSI; MARIELA FERREIRA GOMES

Congreso; L Reunión Anual de la Sociedad Argentina de Biofísica; 2022

Sociedad Argentina de Biofísica

Natural flavonoids have been the subject of research in both basic and applied science fields. The interest in said compounds is related to a wide spectrum of biological effects with the functionality to modulate the catalytic activity of a wide variety of enzymes, including P-ATPases. Our laboratory studied the effect of various flavonoids on the Ca2+-ATPase activity of plasma membrane calcium ATPase (PMCA). We showed that flavonoids such as quercetin and gossypin inhibit PMCA as a function of Mg2+ concentration, indicating that quercetin-Mg2+ or gossypin-Mg2+ are principal true inhibitors. However, it is not known whether this impact is specific to PMCA or common to all P-ATPases. The present analysis seeks to verify the impact of several natural flavonoids on different P-ATPases, such as sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) and Na+/K+-ATPase. We investigated Mg2+ concentration-dependent inhibitors that suggest the existence of Mg2+ flavonoids complexes.The results show that for SERCA and Na+/K+-ATPase the best inhibitors were the set of flavonols with 2 or 3 -OH B ring (e.g. quercetin, myricetin). For SERCA, these compounds were less effective inhibitors compared to PMCA. However, these compounds were equally effective inhibitors for Na+/K+-ATPase as for PMCA. For SERCA and Na+/K+-ATPase, gossypin had no effect or was weak inhibitor on ATPase activity opposite to the results achieved in PMCA, indicating that this inhibitor is likely candidate to be PMCA specific.Regarding Mg2+-dependent inhibition, the first results indicate that for SERCA, quercetin inhibition was not Mg2+-dependent, which indicates that the effect is not related to a flavonoid-Mg2+ complex, but to a free flavonoid effect. For Na+/K+-ATPase, quercetin inhibition was Mg2+ dependent, indicating that the effect is through a flavonoid-Mg2+ complex, as in PMCA. These results indicate that flavonoids have the ability to inhibit P-ATPases by different mechanisms.With grants of ANPCYT, CONICET and UBACYT