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: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=615916
• 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.

鱼类不仅面临着来自水生污染物的越来越大的影响，同时也面临着全球变暖造成的热应力的影响。加深我们对这些因素如何相互作用的理解对鱼类的生存至关重要。为了获得食物、躲避捕食者、生长、繁殖和生存，鱼类需要能够调整心脏、呼吸和代谢功能以满足环境需求。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（PAHs）中。如果在幼鱼发育的关键时期接触这些污染物，会导致致命的心脏缺陷。然而，人们也越来越认识到它们会改变成年鱼的新陈代谢，导致心律失常和损害游泳能力。芳烃受体（AhR）是由某些二恶英和多环芳烃激活的转录因子受体。AhR增加许多基因的表达，包括细胞色素P450 1A （CYP1A）。AhR和CYP1A都通过一种未知的内源性信号与正常心脏发育有关，而在代谢中类似的内源性作用尚不清楚。此外，最近的证据表明，当二恶英或多环芳烃刺激时，正常的ahr介导信号可能涉及表观遗传机制。最后，多环芳烃的发育毒性和功能毒性最近被假设与鱼类心肌细胞内向延迟整流钾电流的抑制有关。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量法来评估斑马鱼（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、二恶英和多环芳烃毒性的机制以及它们与鱼类热应激的相互作用的理解。随着对有毒物质和热应力相互作用的更好理解，我们可以制定更好的环境法规来保护加拿大的渔业资源。