CONICET | Buscador de Institutos y Recursos Humanos

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 PATPases, 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 PATPases by different mechanisms.

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