Exploring the Impact of Quercetin on Cellular Calcium Regulation: A Study on Plasma Membrane Calcium ATPase.

PAKCIARZ PABLO; ONTIVEROS, MALLKU; HOLZWARTH CELESTE; RINALDI, DEBORA; DE TEZANOS PINTO, FELICITAS; ROSSI J. P. F. C; MANGIALAVORI IRENE; FERREIRA GOMES, MARIELA

Córdoba

Congreso; LI Reunión Anual de la Sociedad Argentina de Biofisica; 2023

Sociedad Argentina de Biofisica

Recently, research on flavonoids derived from plant sources has attracted increasinginterest due to their health-promoting properties. Several studies have indicated thatflavonoids alter intracellular calcium (Ca2+) homeostasis, potentially related to their effectson Ca2+ transport systems, such as the plasma membrane Ca2+-ATPases (PMCA). PMCAactively transports Ca2+ to the extracellular medium through ATP hydrolysis, thusmaintaining cellular homeostasis, with calmodulin (CaM) as its main modulator. Ourprevious results indicate that quercetin, a flavonol aglycone, inhibits the activity ofpurified PMCA through a Mg2+ complex. The aim of this work is to characterize PMCAinhibition by quercetin, both in isolated protein systems and in living cells. First, weinvestigated the impact of the lipid environment on the PMCA inhibition by quercetin.Results indicate that the inhibition was not influenced by the lipid environment,suggesting a direct interaction between Mg-quercetin and PMCA. Furthermore, weobserved that the presence of lipids stabilized quercetin, thereby preventing its oxidation.On the other hand, our study of PMCA activation by CaM also demonstrates that quercetininhibits PMCA activity regardless of the presence of CaM, suggesting no interaction withthe CaM binding site. This is significant as CaM-activated PMCA is responsible for theexpulsion of Ca2+ during a transient increase in the concentration of this cation in thecytoplasm of living cells.Finally, studies performed on HeK293T cells treated with quercetin in the presence of thelipid DMPC indicate that quercetin enters the cells and remains in the cytoplasm.Additionally, cytoplasmic Ca2+ measurements suggest that the systems responsible forCa2+ expulsion from cytoplasmic are affected in the presence of quercetin/DMPC.In summary, this study provides evidence that can explain the molecular basis of theeffects of quercetin on Ca2+ homeostasis in cells.AcknowldegmentsThis work was supported by grants from CONICET, ANPCYT and UBACYT.