The School of Public and Environmental Affairs, Indiana University, Bloomington, IN 47405, USA.
Aquat Toxicol. 2010 Jun 10;98(2):157-64. doi: 10.1016/j.aquatox.2010.02.001. Epub 2010 Feb 6.
Seawater acclimation in killifish, Fundulus heteroclitus, is mediated in part by a rapid (1h) translocation of CFTR Cl(-) channels from an intracellular pool to the plasma membrane in gill and increased CFTR-mediated Cl(-) secretion. This effect is mediated by serum and glucocorticoid-inducible kinase 1 (SGK1), which is stimulated by plasma hypertonicity rather than cortisol. Since arsenic exposure prevents acclimation to seawater by decreasing CFTR protein levels we tested the hypothesis that arsenic (as sodium arsenite) blocks acclimation to seawater by down regulating SGK1 expression. Freshwater adapted killifish were exposed to arsenic (48h) and transferred to seawater containing arsenic, and SGK and CFTR expression were measured. Arsenic reduced the seawater induced increase in SGK1 mRNA and protein abundance, and reduced both the total amount of CFTR and the amount of CFTR in the plasma membrane. The decrease in membrane CFTR reduced Cl(-) secretion. Arsenic also increased the amount of ubiquitinated CFTR and its degradation by the lysosome. Thus, we propose a model whereby arsenic reduces the ability of killifish to acclimate to seawater by blocking the seawater induced increase in SGK1, which results in increased ubiquitination and degradation of CFTR.
海水适应在食蚊鱼（Fundulus heteroclitus）中部分受到 CFTR Cl(-) 通道从细胞内池快速（1h）易位到鳃中的质膜和 CFTR 介导的 Cl(-)分泌增加的介导。这种作用由血清和糖皮质激素诱导激酶 1（SGK1）介导，其被血浆高渗而非皮质醇刺激。由于砷暴露通过降低 CFTR 蛋白水平来阻止海水适应，因此我们测试了以下假设：砷（以亚砷酸钠的形式）通过下调 SGK1 表达来阻断海水适应。将适应淡水的食蚊鱼暴露于砷（48h）并转移到含砷的海水中，并测量 SGK 和 CFTR 的表达。砷降低了海水诱导的 SGK1 mRNA 和蛋白丰度的增加，并降低了 CFTR 的总量和质膜中的 CFTR 量。质膜 CFTR 的减少降低了 Cl(-)的分泌。砷还增加了泛素化 CFTR 的量及其通过溶酶体的降解。因此，我们提出了一个模型，其中砷通过阻断海水诱导的 SGK1 增加来降低食蚊鱼适应海水的能力，从而导致 CFTR 的泛素化和降解增加。
