IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Mechanism of inhibition of Epigallocatechin on the Plasma Membrane Ca2+-ATPase
Autor/es:
ANA RIESCO; MARIEL MARDER; DEBORA RINALDI; MARIELA FERREIRA GOMES; JUAN PABLO ROSSI; IRENE MANGIALAVORI
Lugar:
Córdoba
Reunión:
Congreso; 243. LII Reunión de SAIB. 7 al 10 de noviembre de 2016. Universidad Nacional de Córdoba, Córdoba. Argentina.; 2016
Institución organizadora:
Sociedad Argentina de Bioquímica y Biología Molecular
Resumen:
Differential inhibition of PlasmaMembrane Ca2+-ATPase by quercetin and gossypinGentile, L.; Rinaldi, D.; Mangialavori, I.; Marder, M, Rossi,JP; Ferreira-Gomes, M.Instituto de Química y FisicoquímicaBiológicas. CONICET y Universidad de Buenos Aires.  Flavonoids are commonly found in fruit and vegetables and they are alsopart of human diet. These compoundsare also believed to have cancer chemoprotective properties by triggeringapoptosis via the Ca2+-dependent mitochondrial pathway which can be activatedthrough an increase of cytosolic [Ca2+] ([Ca2+]c)involving the inhibition of sarcoplasmic/endoplasmic reticulum Ca2+ATPase and plasma membrane calcium ATPase (PMCA). The aim of this work is tocharacterize the inhibition of PMCA by quercetin and gossypin, two flavonoidswith known anticarcinogenic activity. The differences in the mechanism ofinhibition will be analyzed considering these compound?s molecular structures,as quercetin is a flavonol aglycone and gossypin is a flavonol glycoside, andtheir possible interaction with the pump. We evaluated the [Ca2+]cin HEK293T cells and also studied the Ca2+-ATPase activity inpurified PMCA obtained from human erythrocytes. The results showed that (1)PMCA activity was inhibited by quercetin and gossypin with a K0.5 of0.34 ± 0.01 and 5.1 ± 1 mM, respectively; (2) PMCAphosphorylation showed that quercetin led to the accumulation of phosphoenzymewhile gossypin induced a decrease; (3) quercetin produced a larger calmodulinPMCA inhibition than gossypin; (4) in HEK293T cells, quercetin and gossypin loweredCa2+ removal rate compared to control. These results show thatquercetin and gossypin inhibit PMCA by different mechanisms, possibly due totheir distinct molecular structures, giving rise to the idea that PMCA could bea novel target for flavonoids. With grants of CONICET, ANPCYT and UBACYT