Selectivity of plasma membrane calcium ATPase (PMCA)-mediated extrusion of toxic divalent cations in vitro and in cultured cells

FERREIRA-GOMES, MARIELA S.; MANGIALAVORI, IRENE C.; ONTIVEROS, MALLKU Q.; RINALDI, DEBORA E.; MARTIARENA, JORGE; VERSTRAETEN, SANDRA V.; ROSSI, JUAN PABLO F. C.

ARCHIVES OF TOXICOLOGY.

SPRINGER

Año: 2017

0340-5761

Abstract In the recent years, the toxicity of certain divalentcations has been associated with the alteration of intracellularCa2+homeostasis. Among other mechanisms, thesecations may affect the functionality of certain Ca2+-bindingproteins and/or Ca2+pumps. The plasma membrane calciumpump (PMCA) maintains Ca2+homeostasis in eukaryoticcells by mediating the efflux of this cation in a processcoupled to ATP hydrolysis. The aim of this work was toinvestigate both in vitro and in cultured cells if other divalentcations (Sr2+, Ba2+,Co2+,Cd2+,Pb2+or Be2+)couldbe transported by PMCA. Current results indicate that bothpurified and intact cell PMCA transported Sr2+with kineticparameters close to those of Ca2+transport. The transportof Pb2+and Co2+by purified PMCA was, respectively, 50and 75% lower than that of Ca2+,but only Co2+was extrudedby intact cells and to a very low extent. In contrast, purifiedPMCA?but not intact cell PMCA?transported Ba2+atlow rates and only when activated by limited proteolysis orby phosphatidylserine addition. Finally, purified PMCA did not transport Cd2+or Be2+,although minor Be2+transportwas measured in intact cells. Moreover, Cd2+impaired thetransport of Ca2+through various mechanisms, suggestingthat PMCA may be a potential target of Cd2+-mediated toxicity.The differential capacity of PMCA to transport thesedivalent cations may have a key role in their detoxification,limiting their noxious effects on cell homeostasis.