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

广盐硬骨鱼中的肌醇代谢：有机农药在渗透调节和破坏中的作用

• 批准号: NE/J010081/1
• 负责人: Gordon Cramb
• 金额: $ 60.84万
• 依托单位: University of St Andrews
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FJ010081%2F1
• 关键词: Inositol; metabolism; euryhaline; teleosts; roles

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.

水生生物在许多不同的淡水（FW）和海水（SW）栖息地的进化成功和生存，是由于复杂的相互关联的离子和水运输系统的发展，使动植物能够在极端低渗和高渗环境中渗透调节和生存。这方面的研究很充分的例子是广盐硬骨鱼，如欧洲鳗鱼和大西洋鲑鱼，它们表现出遗传可塑性，使它们能够在FW和SW中生存，而体液的渗透压和离子组成只有很小的变化。为了实现这一目标，泛盐硬骨鱼已经进化出适应渗透调节策略的能力，允许排泄多余的水，并从缺乏离子的FW栖息地清除盐，同时在进入SW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SW环境能力的核心。这种多元醇在鳃、皮肤和鳍等多种组织中合成和积累，在许多激素信号通路中起作用，同时也是一种有机渗透剂，防止水的渗透损失和随后的鱼类脱水。积累肌醇的体表上皮细胞可以作为鱼体内低渗透环境和高渗透外部环境之间的屏障。本项目将研究两种模式物种鳗鱼和鲑鱼中肌醇生产和分布相关基因的表达和功能，以确定这种渗透物在适应FW和sw的硬鱼中所起的作用。虽然鳗鱼和鲑鱼都能够在FW和SW之间移动，但盐度适应的生理模式略有不同。虽然性成熟的FW“黄”鳗可以成功地适应向SW的急性转移，但性成熟的FW鲑鱼伴侣必须首先经历一个被称为smoltification的内分泌诱导的成熟过程，然后鱼类才能在SW中存活。鳗鱼和鲑鱼的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将被研究，皮质醇的影响也将被研究，皮质醇是一种已知参与鱼类性成熟和盐度适应的激素。此外，我们最近发现，肌醇单磷酸酶（IMPA）是负责细胞生成肌醇的一种必需酶，它可以被FW中已知的各种低浓度有机毒素抑制或在某些情况下被刺激。任何环境毒素对这种关键酶活性的扰动都可能对鱼类随后的渗透调节能力产生深远的影响。最近的证据表明，IMPA的酶活性被细胞骨架的一种未知的蛋白质成分所抑制，并且至少一些刺激性毒素似乎破坏了这种正常的调节系统。毒素对渗透调节和激素信号传导的潜在有害影响可能与鱼类在FW时酶的过度刺激和/或鱼类洄游到SW后酶的抑制有关。这种扰动肯定会损害鱼类的渗透调节能力，这可能会对鱼类洄游和物种的整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。虽然这两种鱼类数量减少的原因尚不确定，但许多研究表明，鱼类接触各种人为毒素是有关系的。该项目将确定是否有任何主要的持久性环境毒素对负责这种基本有机渗透物和信号分子的生产和组织分布的酶有任何影响。

项目成果

Myo-inositol phosphate synthase expression in the European eel (Anguilla anguilla) and Nile tilapia (Oreochromis niloticus): effect of seawater acclimation.

• DOI: 10.1152/ajpregu.00056.2016
• 发表时间: 2016-08-01
• 期刊: American journal of physiology. Regulatory, integrative and comparative physiology
• 作者: Kalujnaia S;Hazon N;Cramb G
• 通讯作者: Cramb G