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

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

ARCHIVES OF TOXICOLOGY.

SPRINGER

Año: 2018 vol. 92 p. 273 - 288

0340-5761

In the recent years, the toxicity of certain divalent cations has been associated with the alteration of intracellular Ca2+ homeostasis. Among other mechanisms, these cations may afect the functionality of certain Ca2+-bindingproteins and/or Ca2+ pumps. The plasma membrane calcium pump (PMCA) maintains Ca2+ homeostasis in eukaryotic cells by mediating the efux of this cation in a process coupled to ATP hydrolysis. The aim of this work was to investigate both in vitro and in cultured cells if other divalent cations (Sr2+, Ba2+, Co2+, Cd2+, Pb2+ or Be2+) could be transported by PMCA. Current results indicate that both purifed and intact cell PMCA transported Sr2+ with kinetic parameters close to those of Ca2+ transport. The transport of Pb2+ and Co2+ by purifed PMCA was, respectively, 50 and 75% lower than that of Ca2+, but only Co2+ was extrudedby intact cells and to a very low extent. In contrast, purifed PMCA?but not intact cell PMCA?transported Ba2+ at low rates and only when activated by limited proteolysis or by phosphatidylserine addition. Finally, purifed PMCA did not transport Cd2+ or Be2+, although minor Be2+ transport was measured in intact cells. Moreover, Cd2+ impaired the transport of Ca2+ through various mechanisms, suggesting that PMCA may be a potential target of Cd2+-mediated toxicity. The diferential capacity of PMCA to transport these divalent cations may have a key role in their detoxifcation, limiting their noxious efects on cell homeostasis.