Shaw Joseph R, Gabor Kristen, Hand Emily, Lankowski Alexander, Durant Lydia, Thibodeau Renee, Stanton Caitlin R, Barnaby Roxanna, Coutermarsh Bonita, Karlson Katherine H, Sato J Denry, Hamilton Joshua W, Stanton Bruce A
Department of Physiology, Dartmouth College, Dartmouth Medical School, N. College St., Hanover, NH 03755, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R1052-60. doi: 10.1152/ajpregu.00328.2006. Epub 2006 Oct 12.
Killifish are euryhaline teleosts that adapt to rapid changes in the salinity of the seawater. It is generally accepted that acclimation to seawater is mediated by cortisol activation of the glucocorticoid receptor (GR), which stimulates CFTR mRNA expression and CFTR-mediated Cl- secretion by the gill. Because there is no direct evidence in killifish that the GR stimulates CFTR gene expression, quantitative PCR studies were conducted to test the hypothesis that cortisol activation of GR upregulates CFTR mRNA expression and that this response is required for acclimation to seawater. Inhibition of the GR by RU-486 prevented killifish from acclimating to increased salinity and blocked the increase in CFTR mRNA. In contrast, inhibition of the mineralocorticoid receptor by spironolactone had no effect on acclimation to seawater. Thus acclimation to increased salinity in killifish requires signaling via the GR and includes an increase in CFTR gene expression. Because arsenic, a toxic metalloid that naturally occurs in the aquatic environment, has been shown to disrupt GR transcriptional regulation in avian and mammalian systems, studies were also conducted to determine whether arsenic disrupts cortisol-mediated activation of CFTR gene expression in this in vivo fish model and thereby blocks the ability of killifish to acclimate to increased salinity. Arsenic prevented acclimation to seawater and decreased CFTR protein abundance. However, arsenic did not disrupt the GR-induced increase in CFTR mRNA. Thus arsenic blocks acclimation to seawater in killifish by a mechanism that does not disrupt GR-mediated induction of CFTR gene expression.
鳉鱼是广盐性硬骨鱼，能够适应海水盐度的快速变化。一般认为，鳉鱼对海水的适应是由糖皮质激素受体（GR）的皮质醇激活介导的，这会刺激鳃中CFTR mRNA的表达以及CFTR介导的氯离子分泌。由于在鳉鱼中没有直接证据表明GR刺激CFTR基因表达，因此进行了定量PCR研究，以检验以下假设：GR的皮质醇激活会上调CFTR mRNA表达，并且这种反应是适应海水所必需的。RU - 486对GR的抑制作用使鳉鱼无法适应盐度增加的环境，并阻止了CFTR mRNA的增加。相反，螺内酯对盐皮质激素受体的抑制作用对适应海水没有影响。因此，鳉鱼对盐度增加的适应需要通过GR进行信号传导，并且包括CFTR基因表达的增加。由于砷是一种天然存在于水生环境中的有毒类金属，已被证明会破坏鸟类和哺乳动物系统中的GR转录调控，因此还进行了研究，以确定砷是否会破坏这种体内鱼类模型中皮质醇介导的CFTR基因表达激活，从而阻止鳉鱼适应盐度增加的能力。砷阻止了对海水的适应并降低了CFTR蛋白丰度。然而，砷并没有破坏GR诱导的CFTR mRNA增加。因此，砷通过一种不破坏GR介导的CFTR基因表达诱导的机制来阻止鳉鱼对海水的适应。
