Prestage Department of Poultry Science, North Carolina State University, Raleigh, NC 27695, USA.
Department of Histology and Embryology, Poznan University of Medical Sciences, 6 Święcickiego St., 60-781 Poznan, Poland.
Genes (Basel). 2020 Jul 24;11(8):840. doi: 10.3390/genes11080840.
Ammonia is very toxic to the body and has detrimental effects on many different organ systems. Using cultured myoblast cells, we examined ammonia's effect on myostatin expression, a negative regulator of skeletal muscle growth, and myotube diameters. The objective of this study was to examine how murine, avian, and fish cells respond to increasing levels of ammonia up to 50 mM. The murine myoblast cell line (C2C12), primary chick, and primary tilapia myoblast cells were cultured and then exposed to 10, 25, and 50 mM ammonium acetate, sodium acetate, and an untreated control for 24 h. High levels of ammonia were detrimental to the C2C12 cells, causing increased Myostatin (MSTN) expression and decreased myotube diameters between 10 and 25 mM ( < 0.002). Ammonia at 10 mM continued the positive myogenic response in the chick, with lower MSTN expression than the C2C12 cells and larger myotube diameters, but the myotube diameter at 50 mM ammonium acetate was significantly smaller than those at 10 and 25 mM ( < 0.001). However, chick myotubes at 50 mM were still significantly larger than the sodium acetate-treated and untreated control ( < 0.001). The tilapia cells showed no significant difference in MSTN expression or myotube diameter in response to increasing the concentrations of ammonia. Overall, these results confirm that increasing concentrations of ammonia are detrimental to mammalian skeletal muscle, while chick cells responded positively at lower levels but began to exhibit a negative response at higher levels, as the tilapia experienced no detrimental effects. The differences in ammonia metabolism strategies between fish, avian, and mammalian species could potentially contribute to the differences between species in response to high levels of ammonia. Understanding how ammonia affects skeletal muscle is important for the treatment of muscle wasting observed in liver failure patients.
氨对身体非常有毒，对许多不同的器官系统都有不利影响。我们使用培养的成肌细胞研究了氨对肌肉生长负调控因子肌抑素表达和肌管直径的影响。本研究的目的是研究在高达 50mM 的氨浓度下，鼠、禽和鱼类细胞如何响应。我们培养了鼠成肌细胞系（C2C12）、原代鸡和原代罗非鱼成肌细胞，然后用 10、25 和 50mM 的醋酸铵、醋酸钠和未经处理的对照培养基培养 24 小时。高浓度的氨对 C2C12 细胞有害，导致 Myostatin (MSTN) 表达增加和肌管直径减小 10-25mM（<0.002）。10mM 氨在鸡中继续产生正向成肌作用，MSTN 表达低于 C2C12 细胞，肌管直径较大，但 50mM 醋酸铵的肌管直径明显小于 10 和 25mM（<0.001）。然而，鸡的肌管在 50mM 时仍明显大于醋酸钠处理和未处理的对照组（<0.001）。罗非鱼细胞在响应增加氨浓度时，MSTN 表达或肌管直径没有显著差异。总的来说，这些结果证实增加的氨浓度对哺乳动物骨骼肌有害，而鸡细胞在较低水平下反应积极，但在较高水平下开始表现出负反应，因为罗非鱼没有受到有害影响。鱼类、禽类和哺乳动物物种之间氨代谢策略的差异可能导致它们对高浓度氨的反应不同。了解氨如何影响骨骼肌对于治疗肝衰竭患者中观察到的肌肉消耗非常重要。
