Inositol metabolism in euryhaline teleosts: roles in osmoregulation and disruption by organic pesticides

水生生物在许多不同的淡水(FW)和海水(SW)生境中的进化成功和生存是由于复杂的相互关联的离子和水运输系统的发展，这些系统允许动植物在极端低渗和高渗环境中渗透调节和生存。研究得很好的例子是欧洲鳗鱼和大西洋鲑鱼等泛盐生硬骨鱼，它们表现出遗传可塑性，能够在FW和SW中生存，而它们的体液渗透压和离子组成只有很小的变化。为了实现这一目标，真盐生硬骨鱼已经进化出能力来调整它们的渗透调节策略，允许从缺乏离子的FW栖息地排泄多余的水和清除盐分，同时在进入西南时逆转这些功能。最近的证据表明，简单的有机酒精肌醇是鳗鱼适应西南环境能力的核心。这种多元醇在鳃、皮肤和鳍等各种组织中合成和积累，在许多激素信号通路中发挥作用，也是一种有机渗透调节剂，防止水分的渗透损失和随后鱼类在西南方向时的干燥。鱼体表面上皮细胞积累肌醇，然后在鱼类的低渗透内部环境和高渗透外部环境之间起到屏障作用。本项目将研究参与肌醇生产和分布的基因在鳗鱼和鲑鱼两个模式物种中的表达和功能，以确定这种渗透调节物质在FW和SW适应的硬骨鱼中的作用。虽然鳗鱼和鲑鱼都能在淡水和西南之间移动，但盐度适应的生理模式略有不同。尽管性未成熟的黄鳗可以成功地适应急性转移到西南部，但性未成熟的三文鱼必须首先经历内分泌诱导的成熟过程，称为嗅觉，然后鱼才能在西南部存活。将研究鳗鱼和鲑鱼成熟和未成熟生命阶段调节肌醇生产以应对环境盐度增加的能力，以及皮质醇的影响，皮质醇是一种已知与鱼类的性成熟和盐度适应有关的激素。此外，我们最近发现，负责细胞产生肌醇的一种关键酶--肌醇单磷酸酶(IMPA)可以被FW中已知的一系列有机毒素的低浓度抑制或在某些情况下被刺激。任何环境毒素对这一关键酶活性的任何干扰都可能对鱼类随后的渗透调节能力产生深远影响。最近的证据表明，IMPA的酶活性受到细胞骨架中一种未知的蛋白质成分(S)的抑制，并且至少有一些刺激性毒素似乎扰乱了这一正常的调控系统。毒素对渗透调节和激素信号的潜在有害影响可能与鱼在FW时对酶的过度刺激和/或在鱼迁徙到西南后对酶的抑制有关。这种扰动肯定会损害鱼类的渗透调节能力，这很可能对鱼类迁徙和该物种的总体繁殖力产生严重影响。在过去的30年里，鲑鱼和鳗鱼的数量都急剧下降。虽然这两个物种种群数量减少的原因尚不确定，但许多研究表明，鱼类暴露于各种人为毒素中。该项目将确定是否有任何主要的持久性环境毒素对负责生产和组织分布这种基本的有机渗透分子和信号分子的酶有任何影响。

The evolutionary success and survival of aquatic organisms in many diverse freshwater (FW) and sea water (SW) habitats has been made possible by the development of complex interrelated ion and water transport systems which allow animals and plants to osmoregulate and survive in extreme hypotonic and hypertonic environments. Well-studied examples of this are the euryhaline teleosts, such as the European eel and the Atlantic salmon, which exhibit the genetic plasticity to enable survival in both FW and SW with only minimal changes in the osmolality and ionic composition of their body fluids. In order to accomplish this, euryhaline teleosts have evolved the capacity to adapt their osmoregulatory strategies to allow the excretion of excess water and the scavenging of salts from ion-poor FW habitats while reversing these functions when entering SW. Recent evidence has suggested that the simple organic alcohol, inositol, is central to the ability of eels to adapt to SW environments. This polyol, which is synthesised and accumulated in a variety of tissues such as the gill, skin and fins, acts in many hormonal signalling pathways and also as an organic osmolyte, preventing the osmotic loss of water and the subsequent desiccation of fish when in SW. Body surface epithelial cells, which accumulate inositol can then act as a barrier between the hypo-osmotic internal environment of the fish and the hyperosmotic external environment.This project will investigate the expression and function of genes involved in inositol production and distribution in two model species, the eel and the salmon, to determine the roles of this osmolyte in both FW- and SW-adapted teleosts. Although both eel and salmon are capable of movement between FW and SW, the physiological patterns of salinity adaptation are slightly different. Although sexually immature FW "yellow" eels can successfully acclimate to acute transfers to SW, the sexually immature FW salmon parr must first go through an endocrine-induced maturation process called smoltification before fish can survive in SW. The ability of mature and immature life stages of both eels and salmon to regulate inositol production in response to increased environmental salinities will be investigated as will the effects of cortisol, a hormone known to be involved in sexual maturation and salinity adaptation in fish. In addition we have recently discovered that an essential enzyme responsible for the cellular production of inositol, inositol monophosphatase (IMPA), can be inhibited or in some cases stimulated by low concentrations of a wide range of organic toxins known to be found in FW. Any perturbations in the activity of this key enzyme by any environmental toxins are likely to have profound effects on the subsequent ability of fish to osmoregulate. Recent evidence suggests that enzymatic activity of IMPA is inhibited by an unknown protein component(s) of the cytoskeleton, and that at least some stimulatory toxins appear to disrupt this normal regulatory system. Potential deleterious effects of toxins on osmoregulation and hormonal signalling could be associated with over-stimulation of the enzyme when fish are in FW and/or inhibition of the enzyme after fish migrate to SW. Such perturbations would certainly compromise the ability of fish to osmoregulate and this is likely to have severe implications with respect to fish migration and the overall fecundity of the species. Over the last 30 years there has been dramatic declines in both salmon and in eel populations. Although the reasons for the decrease in the populations of both species are undetermined, exposures of fish to a variety of anthropogenic toxins have been implicated in a number of studies. This project will determine if any of the major persistent environmental toxins have any effects on the enzymes responsible for the production and tissue distribution of this essential organic osmolyte and signalling molecule.