Environmental and contaminant influences on cardiorespiratory function and metabolism in fish

鱼类正面临着越来越多的影响，不仅来自水生污染物，同时还来自全球变暖造成的温度压力。增加我们对这些因素如何相互作用的理解对鱼类物种的生存至关重要。鱼类的基本需求是能够调节心脏、呼吸和代谢功能，以满足环境需求，以便获得食物、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(PAHs)。如果暴露在幼鱼发育的关键时期，这些污染物会导致致命的心脏缺陷。然而，它们也被越来越多地认识到可以改变新陈代谢，导致心律失常，并损害成年鱼的游泳。芳香烃受体(AhR)是一种被某些二恶英和多环芳烃激活的转录因子受体。AHR可促进多种基因的表达，其中包括细胞色素P4501a(CyP1a)。AhR和CyP1A都通过一种未知的内源性信号参与心脏的正常发育，而类似的内源性代谢作用尚不清楚。此外，最近的证据表明，当受到二恶英或多环芳烃刺激时，表观遗传机制可能涉及正常的AhR介导的信号。最后，多环芳烃的发育毒性和功能毒性最近被认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波生物显微镜结合游泳隧道呼吸测量来评估斑马鱼(Danio Rerio)和虹鲑鱼(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、生化、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相互作用的了解。通过更好地了解毒物和热应激是如何相互作用的，我们可以制定更好的环境法规来保护我们在加拿大的渔业资源。

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.