DIFFERENTIAL INHIBITION OF PLASMA MEMBRANE CA2+-ATPASE BY QUERCETIN AND GOSSYPIN

GENTILE, LUCILA; RINALDI, DEBORA; MANGIALAVORI IRENE; MARDER, MARIEL; ROSSI JPFC; FERREIRA GOMES, MARIELA

Cordoba

Congreso; 52 th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2016

Sociedad Argentina de Bioquimica y biología molecular

Flavonoids are commonly found in fruit and vegetables and they are also part of human diet. These compounds are also believed tohave cancer chemoprotective properties by triggering apoptosis via the Ca2+-dependent mitochondrial pathway which can be activatedthrough an increase of cytosolic [Ca2+] ([Ca2+]c). The aim of this work is to characterize the inhibition of PMCA by quercetin andgossypin, two flavonoids with known anticarcinogenic activity. The differences in the mechanism of inhibition will be analyzedconsidering these compound?s molecular structures and their possible interaction with the pump. We evaluated the [Ca2+]c inHEK293T cells and also studied the Ca2+-ATPase activity in purified PMCA obtained from human erythrocytes. The results showedthat (1) PMCA activity was inhibited by quercetin and gossypin with a K0.5 of 0.34 ± 0.01 and 5.1 ± 1 μM, respectively; (2) PMCAphosphorylation showed that quercetin led to the accumulation of phosphoenzyme while gossypin induced a decrease; (3) quercetinproduced a larger calmodulin PMCA inhibition than gossypin; (4) in HEK293T cells, quercetin and gossypin lowered Ca2+ removalrate. These results show that quercetin and gossypin inhibit PMCA by different mechanisms, possibly due to their distinct molecularstructures, giving rise to the idea that PMCA could be a novel target for flavonoids