Environmental and contaminant influences on cardiorespiratory function and metabolism in fish

环境和污染物对鱼类心肺功能和新陈代谢的影响

• 批准号: RGPIN-2016-05812
• 负责人: Weber, Lynn
• 金额: $ 2.55万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=685494
• 关键词: Environmental; contaminant; influences; cardiorespiratory; function

Fish are facing increasing impacts not only from aquatic contaminants, but simultaneously also from thermal stresses due to global warming. Increasing our understanding of how these factors interact is critical for survival of fish species. There is a fundamental need for fish to be able to adjust cardiac, respiratory and metabolic function to meet environmental demands in order to obtain food, avoid predators, grow, reproduce and survive. Fish are exposed to persistent dioxins (a by-product of industrial processes and fires) or to rapidly degraded polycyclic aromatic hydrocarbons (PAHs) that come from oil spills, boat activity and urban run-off. These contaminants cause lethal cardiac defects if exposure occurs during a critical period of development in larval fish. However, they are also increasingly recognized to alter metabolism, cause cardiac arrhythmias and impair swimming in adult fish. The aryl hydrocarbon receptor (AhR) is a transcription factor receptor activated by certain dioxins and PAHs. AhR increases expression of many genes, including cytochrome P450 1A (CYP1A). Both AhR and CYP1A have been implicated in normal cardiac development via an unknown endogenous signal, while a similar endogenous role in metabolism is unknown. Moreover, recent evidence suggests epigenetic mechanisms may be involved in normal AhR-mediated signals when stimulated by dioxins or PAHs. Finally, both developmental and functional toxicity of PAHs have recently been hypothesized to involve inhibition of the inward delayed rectifier potassium current in fish cardiomyocytes. The proposed research will utilize state-of-the-art ultrasound biomicroscopy combined with swim tunnel respirometry to assess cardiorespiratory performance in zebrafish (Danio rerio) and rainbow trout (Oncorhynchus mykiss) exposed to these contaminants in developmental and acute exposure scenarios. This will be combined with pharmacological, biochemical, molecular and whole cell channel recording techniques that will increase our understanding of the basic biological role of AhR, the mechanisms of dioxin and PAH toxicity as well as their interaction with thermal stress in fish. With better understanding of how toxicants and thermal stress interact, we can set better environmental regulations to protect our fisheries resources in Canada.**

鱼类不仅面临着越来越多的水生污染物的影响，而且同时也面临着全球变暖造成的热应力的影响。增加我们对这些因素如何相互作用的理解对于鱼类的生存至关重要。鱼类基本上需要能够调整心脏、呼吸和代谢功能，以满足环境需求，从而获得食物、躲避捕食者、生长、繁殖和生存。鱼类暴露于持久性二恶英（工业过程和火灾的副产品）或来自石油泄漏、船只活动和城市径流的快速降解的多环芳烃。如果在幼鱼发育的关键时期接触这些污染物，会造成致命的心脏缺陷。然而，它们也越来越多地被认识到改变代谢，导致心律失常和损害成鱼的游泳。芳烃受体（Aryl Hydrocarbon Receptor，AhR）是一种转录因子受体，可被二恶英和多环芳烃激活。AhR增加许多基因的表达，包括细胞色素P450 1A（CYP1A）。AhR和CYP1A均通过未知的内源性信号参与正常心脏发育，而在代谢中的类似内源性作用尚不清楚。此外，最近的证据表明，表观遗传机制可能参与正常AhR介导的信号时，刺激二恶英或多环芳烃。最后，多环芳烃的发育和功能毒性最近被假设为涉及抑制鱼类心肌细胞的内向延迟整流钾电流。拟议的研究将利用最先进的超声生物显微镜结合游泳隧道呼吸测定法来评估斑马鱼（Danio rerio）和虹鳟鱼（Oncorhynchus mykiss）在发育和急性暴露情况下暴露于这些污染物的心肺功能。这将与药理学，生物化学，分子和全细胞通道记录技术相结合，将增加我们对AhR的基本生物学作用，二恶英和PAH毒性的机制以及它们与鱼类热应激的相互作用的理解。通过更好地了解有毒物质和热应力如何相互作用，我们可以制定更好的环境法规，以保护我们在加拿大的渔业资源。