Natural flavonoids inhibit the plasma membrane Ca2+-ATPase

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

BIOCHEMICAL PHARMACOLOGY

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2019

0006-2952

Research on flavonoids from plant sources has recently sparkedincreasing interest because of their beneficial health properties.Different studies have shown that flavonoids change the intracellularCa2+ homeostasis linked to alterations in the function of mitochondria,Ca2+ channels and Ca2+ pumps. These findings hint at plasma membraneCa2+-ATPase (PMCA) involvement, as it transports Ca2+ actively to theextracellular medium coupled to ATP hydrolysis, thus maintaining ioncellular homeostasis. The present study aims to investigate the effect ofseveral natural flavonoids on PMCA both in isolated protein systems andin living cells, and to establish the relationship between flavonoidstructure and inhibitory activity on PMCA.Our results show that natural flavonoids inhibited purified andmembranous PMCA with different effectiveness: quercetin and gossypin werethe most potent and their inhibition mechanisms seem to be different, asquercetin does not prevent ATP binding whereas gossypin does. Moreover,PMCA activity was inhibited in human embryonic kidney cells whichtransiently overexpress PMCA, suggesting that the effects observed onisolated systems could occur in a complex structure like a living cell.In conclusion, this work reveals a novel molecular mechanism throughwhich flavonoids inhibit PMCA, which leads to Ca2+ homeostasis andsignaling alterations in the cell.