Dixon Toni-Anne M, Rhyno Emma-Lee M, El Nir, McGaw Samuel P, Otley Nathan A, Parker Katya S, Buldo Elena C, Pabody Claire M, Savoie Mireille, Cockshutt Amanda, Morash Andrea J, Lamarre Simon G, MacCormack Tyson J
Department of Chemistry and Biochemistry, Mount Allison University, Sackville, NB, Canada, E4L 1E4.
Department of Biology, Mount Allison University, Sackville, NB, Canada, E4L 1E4.
J Exp Biol. 2023 Feb 15;226(4). doi: 10.1242/jeb.245092. Epub 2023 Feb 23.
Physiological and environmental stressors can cause osmotic stress in fish hearts, leading to a reduction in intracellular taurine concentration. Taurine is a β-amino acid known to regulate cardiac function in other animal models but its role in fish has not been well characterized. We generated a model of cardiac taurine deficiency (TD) by feeding brook char (Salvelinus fontinalis) a diet enriched in β-alanine, which inhibits cardiomyocyte taurine uptake. Cardiac taurine levels were reduced by 21% and stress-induced changes in normal taurine handling were observed in TD brook char. Responses to exhaustive exercise and acute thermal and hypoxia tolerance were then assessed using a combination of in vivo, in vitro and biochemical approaches. Critical thermal maximum was higher in TD brook char despite significant reductions in maximum heart rate. In vivo, TD brook char exhibited a lower resting heart rate, blunted hypoxic bradycardia and a severe reduction in time to loss of equilibrium under hypoxia. In vitro function was similar between control and TD hearts under oxygenated conditions, but stroke volume and cardiac output were severely compromised in TD hearts under severe hypoxia. Aspects of mitochondrial structure and function were also impacted in TD permeabilized cardiomyocytes, but overall effects were modest. High levels of intracellular taurine are required to achieve maximum cardiac function in brook char and cardiac taurine efflux may be necessary to support heart function under stress. Taurine appears to play a vital, previously unrecognized role in supporting cardiovascular function and stress tolerance in fish.
生理和环境应激源可导致鱼类心脏出现渗透应激，从而导致细胞内牛磺酸浓度降低。牛磺酸是一种β-氨基酸，已知在其他动物模型中可调节心脏功能，但其在鱼类中的作用尚未得到充分表征。我们通过给溪红点鲑（Salvelinus fontinalis）喂食富含β-丙氨酸的饲料来建立心脏牛磺酸缺乏（TD）模型，β-丙氨酸会抑制心肌细胞对牛磺酸的摄取。TD溪红点鲑的心脏牛磺酸水平降低了21%，并且在TD溪红点鲑中观察到应激诱导的正常牛磺酸处理变化。然后使用体内、体外和生化方法相结合的方式评估对力竭运动、急性热耐受性和缺氧耐受性的反应。尽管最大心率显著降低，但TD溪红点鲑的临界热最大值更高。在体内，TD溪红点鲑的静息心率较低，缺氧性心动过缓减弱，并且在缺氧状态下失去平衡的时间严重缩短。在有氧条件下，对照心脏和TD心脏的体外功能相似，但在严重缺氧条件下，TD心脏的每搏输出量和心输出量严重受损。TD透化心肌细胞的线粒体结构和功能方面也受到影响，但总体影响较小。在溪红点鲑中，需要高水平的细胞内牛磺酸才能实现最大心脏功能，并且心脏牛磺酸外流可能是在应激状态下支持心脏功能所必需的。牛磺酸似乎在支持鱼类心血管功能和应激耐受性方面发挥着至关重要但此前未被认识到的作用。
