College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, Guangdong, PR China.
College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, Guangdong, PR China; Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, Nanchang, 330045, PR China.
Ecotoxicol Environ Saf. 2020 Dec 15;206:111366. doi: 10.1016/j.ecoenv.2020.111366. Epub 2020 Sep 30.
To explore the effects of copper (Cu) on energy metabolism and AMPK-mTOR pathway-mediated autophagy in kidney, a total of 240 one-day-old broiler chickens were randomized into four equal groups and fed on the diets with different levels of Cu (11, 110, 220, and 330 mg/kg) for 49 d. Results showed that excess Cu could induce vacuolar degeneration and increase the number of autophagosomes in kidney, and the adenosine triphosphate (ATP) level and mRNA levels of energy metabolism-related genes were decreased with the increasing dietary Cu level. Moreover, immunohistochemistry and immunofluorescence showed that the positive expressions of Beclin1 and LC3-II were mainly located in cytoplasm of renal tubular epithelial cells and increased significantly with the increasing levels of Cu. The mRNA levels of Beclin1, Atg5, LC3-I, LC3-II, Dynein and the protein levels of Beclin1, Atg5, LC3-II/LC3-I and p-AMPKα1/AMPKα1 were markedly elevated in treated groups compared with control group (11 mg/kg Cu). However, the mRNA and protein levels of p62 and p-mTOR/mTOR were significantly decreased with the increasing levels of Cu. These results suggest that impaired energy metabolism induced by Cu may lead to autophagy via AMPK-mTOR pathway in kidney of broiler chickens.
为了探究铜（Cu）对能量代谢和 AMPK-mTOR 通路介导的自噬的影响，将 240 只 1 日龄肉鸡随机分为 4 组，每组 60 只，分别饲喂添加不同水平 Cu（11、110、220 和 330mg/kg）的日粮 49d。结果表明，过量 Cu 可诱导肾脏空泡变性和自噬体数量增加，随着日粮 Cu 水平的升高，三磷酸腺苷（ATP）水平和能量代谢相关基因的 mRNA 水平降低。此外，免疫组织化学和免疫荧光结果显示，Beclin1 和 LC3-II 的阳性表达主要位于肾小管上皮细胞的细胞质中，且随着 Cu 水平的升高而显著增加。与对照组（11mg/kg Cu）相比，处理组的 Beclin1、Atg5、LC3-I、LC3-II、Dynein 的 mRNA 水平和 Beclin1、Atg5、LC3-II/LC3-I 和 p-AMPKα1/AMPKα1 的蛋白水平显著升高。然而，p62 和 p-mTOR/mTOR 的 mRNA 和蛋白水平随着 Cu 水平的升高而显著降低。这些结果表明，Cu 引起的能量代谢障碍可能通过 AMPK-mTOR 通路导致肉鸡肾脏发生自噬。
