Interactive mechanism between connexin43 and Cd-induced autophagic flux blockage and gap junctional intercellular communication dysfunction in rat hepatocytes
Yuntian Duan,
Yi Zhang,
Tao Wang,
Jian Sun,
Waseem Ali,
Yonggang Ma,
Yan Yuan,
Jianhong Gu,
Jianchun Bian,
Zongping Liu,
Hui Zou
Affiliations
Yuntian Duan
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China
Yi Zhang
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Joint International Research Laboratory of Agriculture and Agri−Product Safety of the Ministry of Education of China, Yangzhou 225009, China; Jiangsu Co−Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
Tao Wang
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Joint International Research Laboratory of Agriculture and Agri−Product Safety of the Ministry of Education of China, Yangzhou 225009, China; Jiangsu Co−Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
Jian Sun
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Joint International Research Laboratory of Agriculture and Agri−Product Safety of the Ministry of Education of China, Yangzhou 225009, China; Jiangsu Co−Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
Waseem Ali
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Joint International Research Laboratory of Agriculture and Agri−Product Safety of the Ministry of Education of China, Yangzhou 225009, China; Jiangsu Co−Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
Yonggang Ma
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Joint International Research Laboratory of Agriculture and Agri−Product Safety of the Ministry of Education of China, Yangzhou 225009, China; Jiangsu Co−Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
Yan Yuan
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Joint International Research Laboratory of Agriculture and Agri−Product Safety of the Ministry of Education of China, Yangzhou 225009, China; Jiangsu Co−Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
Jianhong Gu
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Joint International Research Laboratory of Agriculture and Agri−Product Safety of the Ministry of Education of China, Yangzhou 225009, China; Jiangsu Co−Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
Jianchun Bian
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Joint International Research Laboratory of Agriculture and Agri−Product Safety of the Ministry of Education of China, Yangzhou 225009, China; Jiangsu Co−Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
Zongping Liu
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Joint International Research Laboratory of Agriculture and Agri−Product Safety of the Ministry of Education of China, Yangzhou 225009, China; Jiangsu Co−Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China
Hui Zou
College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China; Joint International Research Laboratory of Agriculture and Agri−Product Safety of the Ministry of Education of China, Yangzhou 225009, China; Jiangsu Co−Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China; Corresponding author. College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Cadmium (Cd) is a significant environmental contaminant known for its potential hepatotoxic effects. However, the precise mechanisms underlying Cd-induced hepatotoxicity have yet to be fully understood. Therefore, the purpose of this study was to investigate the dynamic role of connexin 43 (Cx43) in response to Cd exposure, particularly its impact on gap junctional intercellular communication (GJIC) and autophagy in hepatocytes. To establish an in vitro model of Cd-induced hepatocyte injury, the Buffalo rat liver 3A cell line (BRL3A) was utilized.In order to elucidate the mechanism by which Cx43 influences Cd-induced hepatocyte toxic injury, inhibitors of Cx43 (Dynasore) and P-Cx43 (Ro318220) were employed in the model. The findings revealed that inhibiting Cx43 and its phosphorylation further compromised GJIC function, exacerbating the impairment, while also intensifying the blockage of autophagic flux. To gain further insight into the role of Cx43, siRNA was utilized to knock down Cx43 expression, yielding similar results. The down-regulation of Cx43 expression was found to worsen the morphological damage induced by cadmium exposure, diminish the cell proliferation capacity of BRL3A cells, and exacerbate the disruption of GJIC and autophagic flow caused by Cd.These findings suggest that Cx43 may serve as a potential therapeutic target for the treatment of liver damage resulting from Cd exposure. By targeting Cx43, it may be possible to mitigate the adverse effects of Cd on hepatocytes.
