EFFECT OF THE QUERCETIN ON THE CALCIUM TRANSPORT THROUGH BIOLOGICAL MEMBRANES

RINALDI, DEBORA E.; ESPELT, MARÍA V.; ONTIVEROS, MALLKU; ROSSI JUAN PABLO F. C.; MARDER, MARIEL; ROSSI ROLANDO C; VIGIL MAXIMILIANO ANGEL; MANGIALAVORI IRENE; FERREIRA GOMES, MARIELA

Capital Federal

Simposio; Simposio internacional Fronteras en Biociencia 3; 2018

nstituto de Investigación en Biomedicina de Buenos Aires ? CONICET ? Instituto Partner de la Sociedad Max Planck (IBioBA-CONICET-MPSP)

Recently, there has been increasing interest in the research on flavonoids from plant sources because of their beneficial properties for health. Several studies have attributed them anti-oxidative, anti-inflammatory, anti-mutagenic, and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme functions. Flavonoids exert their effect in different ways, in particular, there are flavonoids related with changes of intracellular calcium concentration suggesting that they could affect the calcium transport, including the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase and the plasma membrane Ca2+-ATPase (PMCA). However, the molecular mechanisms underlying this effect is not yet clear. This work seeks to investigate the effect of a flavonoid -quercetin- on PMCA4, a P-type ATPase essential in the control of intracellular Ca2+ in eukaryotic cells. Results show that quercetin inhibits PMCA4 with a K0.5= 0.34 ± 0.01 M, an effect that is totally dependent on Mg2+, suggesting that the inhibitor is the quercetin-Mg2+ complex. To assess whether these effects of quercetin on PMCA4 could occur in living cells, we studied: (1) the quercetin localization in HEK293T cells, and (2) the cytoplasmic [Ca2+] dynamics in HEK293T cells and Caco-2 cells. Results reveal that quercetin is incorporated into the cells and that its autofluorescence appears in the nucleus and cytoplasm. On the other hand, when HEK293T cells that overexpress PMCA4 are treated with quercetin, the cytoplasmic Ca2+ dynamics is affected probably because the PMCA activity is inhibited. Similar results were obtained in preliminary experiments in Caco-2 cells. Results indicate that PMCA is inhibited when quercetin enters the cells suggesting that it is possible a direct interaction between PMCA cytoplasmic domains and quercetin.In conclusion, our findings suggest that PMCA could be involved in the molecular mechanism underlying the quercetin effect on biological systems. Acknowledgement, with grants of CONICET, ANPCYT and UBACYT