Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Facultad de Farmacia y Bioquímica, Junín 956, Ciudad Autónoma de Buenos Aires, C1113AAD, Argentina.
Arch Toxicol. 2018 Jan;92(1):273-288. doi: 10.1007/s00204-017-2031-9. Epub 2017 Jul 18.
In the recent years, the toxicity of certain divalent cations has been associated with the alteration of intracellular Ca homeostasis. Among other mechanisms, these cations may affect the functionality of certain Ca-binding proteins and/or Ca pumps. The plasma membrane calcium pump (PMCA) maintains Ca homeostasis in eukaryotic cells by mediating the efflux 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 (Sr, Ba, Co, Cd, Pb or Be) could be transported by PMCA. Current results indicate that both purified and intact cell PMCA transported Sr with kinetic parameters close to those of Ca transport. The transport of Pb and Co by purified PMCA was, respectively, 50 and 75% lower than that of Ca, but only Co was extruded by intact cells and to a very low extent. In contrast, purified PMCA-but not intact cell PMCA-transported Ba at low rates and only when activated by limited proteolysis or by phosphatidylserine addition. Finally, purified PMCA did not transport Cd or Be, although minor Be transport was measured in intact cells. Moreover, Cd impaired the transport of Ca through various mechanisms, suggesting that PMCA may be a potential target of Cd-mediated toxicity. The differential capacity of PMCA to transport these divalent cations may have a key role in their detoxification, limiting their noxious effects on cell homeostasis.
近年来，某些二价阳离子的毒性已与细胞内 Ca 稳态的改变有关。在其他机制中，这些阳离子可能会影响某些 Ca 结合蛋白和/或 Ca 泵的功能。质膜 Ca 泵（PMCA）通过介导该阳离子的外流与 ATP 水解偶联，从而维持真核细胞的 Ca 稳态。这项工作的目的是研究其他二价阳离子（Sr、Ba、Co、Cd、Pb 或 Be）是否可以通过 PMCA 在体外和培养细胞中进行转运。目前的结果表明，纯化的和完整细胞 PMCA 都以接近 Ca 转运的动力学参数转运 Sr。纯化的 PMCA 对 Pb 和 Co 的转运分别比 Ca 低 50%和 75%，但只有 Co 被完整细胞外排，而且程度非常低。相比之下，Ba 以低速率被纯化的 PMCA 转运，但只有在受到有限的蛋白水解或添加磷脂酰丝氨酸的激活时才被完整的 PMCA 转运。最后，纯化的 PMCA 不转运 Cd 或 Be，尽管在完整的细胞中测量到了少量的 Be 转运。此外，Cd 通过多种机制损害 Ca 的转运，表明 PMCA 可能是 Cd 介导的毒性的潜在靶标。PMCA 转运这些二价阳离子的不同能力可能在它们的解毒中起关键作用，限制它们对细胞内稳态的有害影响。
