mtROS-mediated Akt/AMPK/mTOR pathway was involved in Copper-induced autophagy and it attenuates Copper-induced apoptosis in RAW264.7 mouse monocytes
Qin Luo,
Yuzhen Song,
Jingjing Kang,
Yuchen Wu,
Fengsun Wu,
Yueqin Li,
Qing Dong,
Jun Wang,
Chao Song,
Hongrui Guo
Affiliations
Qin Luo
College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, Henan, China; Key Laboratory of Animal Nutrition Metabolic and Poisoning Diseases of Zhengzhou, 450046, Henan, China
Yuzhen Song
College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, Henan, China; Key Laboratory of Animal Nutrition Metabolic and Poisoning Diseases of Zhengzhou, 450046, Henan, China
Jingjing Kang
College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, Henan, China; Key Laboratory of Animal Nutrition Metabolic and Poisoning Diseases of Zhengzhou, 450046, Henan, China
Yuchen Wu
College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, Henan, China; Key Laboratory of Animal Nutrition Metabolic and Poisoning Diseases of Zhengzhou, 450046, Henan, China
Fengsun Wu
College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, Henan, China; Key Laboratory of Animal Nutrition Metabolic and Poisoning Diseases of Zhengzhou, 450046, Henan, China
Yueqin Li
College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, Henan, China; Key Laboratory of Animal Nutrition Metabolic and Poisoning Diseases of Zhengzhou, 450046, Henan, China
Qing Dong
College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, Henan, China; Key Laboratory of Animal Nutrition Metabolic and Poisoning Diseases of Zhengzhou, 450046, Henan, China
Jun Wang
College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, Henan, China; Key Laboratory of Animal Nutrition Metabolic and Poisoning Diseases of Zhengzhou, 450046, Henan, China
Chao Song
College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450046, Henan, China; Key Laboratory of Animal Nutrition Metabolic and Poisoning Diseases of Zhengzhou, 450046, Henan, China
Hongrui Guo
Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, China; Corresponding author. College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, China.
Copper (Cu) is a trace element necessary in animals as well as human beings. However, excessive Cu is toxic to immunocytes, but the precise mechanism is largely unclear so far. This work was conducted aiming to examine the Cu-mediated autophagy mechanism together with its role in Cu toxicology in RAW264.7 cells. Here, we demonstrated that CuSO4 reduced the cell viability depending on its dose. CuSO4 could obviously increase autophagy in RAW264.7 cells. According to the obtained results, CuSO4 induced autophagy through Akt/AMPK/mTOR pathway which characterized by down regulation of p-Akt (Ser473)/Akt, p-mTOR/mTOR, p-ULK1(Ser757)/ULK1 and subsequent up-regulation of p-AMPKα/AMPKα and p-ULK1(Ser555)/ULK1. Furthermore, CuSO4 significantly induced the production of mitochondrial reactive oxygen species (mtROS). In addition, CuSO4-mediated apoptosis and autophagy might be suppressed through suppressing mtROS generation by exposure to Mito-TEMPO. Intriguingly, autophagy promotion with rapamycin could decrease the apoptosis and the inhibition of autophagy with knock down Atg5 could enhance the apoptosis induced by CuSO4. Moreover, our results suggested that mtROS is the original cause in CuSO4-induced apoptosis and autophagy. Additionally, CuSO4 induced autophagy through mtROS-dependent Akt/AMPK/mTOR signalling pathwayin RAW264.7 cells. Moreover, autophagy activation might potentially generate a protection mechanism for improving CuSO4-induced RAW264.7 cell apoptosis.
