2. Epigallocatechin 3-gallate inhibits the plasma membrane Ca2+-ATPase:effects on calcium homeostasis

DEBORA E. RINALDI , MALLKU Q. ONTIVEROS 1, NICOLAS A. SAFFIOTI, MAXIMILIANO A. VIGIL, IRENE C. MANGIALAVORI, ROLANDO C. ROSSI, JUAN P. ROSSI, MARÍA V. ESPELT Y MARIELA S. FERREIRA-GOMES

HELIYON

CellPress

Lugar: Amsterdam; Año: 2021 vol. 7 p. 1 - 12

2405-8440

Flavonoids are natural compounds responsible for the health benefits of green tea. Some of the flavonoids presentin green tea are catechins, among which are: epigallocatechin, epicatechin-3-gallate, epicatechin, catechin andepigallocatechin-3-gallate (EGCG). The latter was found to induce apoptosis, reduce reactive oxygen species, insome conditions though in others it acts as an oxidizing agent, induce cell cycle arrest, and inhibit carcinogenesis.EGCG also was found to be involved in calcium (Ca2þ) homeostasis in excitable and in non-excitable cells. In thisstudy, we investigate the effect of catechins on plasma membrane Ca2þ-ATPase (PMCA), which is one of the mainmechanisms that extrude Ca2þ out of the cell. Our studies comprised experiments on the isolated PMCA and oncells overexpressing the pump. Among catechins that inhibited PMCA activity, the most potent inhibitor wasEGCG. EGCG inhibited PMCA activity in a reversible way favoring E1P conformation. EGCG inhibition alsooccurred in the presence of calmodulin, the main pump activator. Finally, the effect of EGCG on PMCA activitywas studied in human embryonic kidney cells (HEK293T) that transiently overexpress hPMCA4. Results show thatEGCG inhibited PMCA activity in HEK293T cells, suggesting that the effects observed on isolated PMCA occur inliving cells.