Duan Yuntian, Zhang Yi, Wang Tao, Sun Jian, Ali Waseem, Ma Yonggang, Yuan Yan, Gu Jianhong, Bian Jianchun, Liu Zongping, Zou Hui
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.
Heliyon. 2023 Oct 14;9(10):e21052. doi: 10.1016/j.heliyon.2023.e21052. eCollection 2023 Oct.
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.
镉（Cd）是一种重要的环境污染物，以其潜在的肝毒性作用而闻名。然而，Cd诱导肝毒性的精确机制尚未完全明确。因此，本研究的目的是探讨连接蛋白43（Cx43）在响应Cd暴露时的动态作用，特别是其对肝细胞间隙连接细胞间通讯（GJIC）和自噬的影响。为建立Cd诱导的肝细胞损伤体外模型，使用了布法罗大鼠肝3A细胞系（BRL3A）。为阐明Cx43影响Cd诱导的肝细胞毒性损伤的机制，在该模型中使用了Cx43抑制剂（Dynasore）和磷酸化Cx43抑制剂（Ro318220）。研究结果显示，抑制Cx43及其磷酸化会进一步损害GJIC功能，加剧损伤，同时还会增强自噬流的阻断。为进一步深入了解Cx43的作用，利用小干扰RNA（siRNA）敲低Cx43表达，得到了类似的结果。发现Cx43表达下调会加重镉暴露诱导的形态损伤，降低BRL3A细胞的增殖能力，并加剧Cd引起的GJIC和自噬流的破坏。这些发现表明，Cx43可能是治疗Cd暴露所致肝损伤的潜在治疗靶点。通过靶向Cx43，有可能减轻Cd对肝细胞的不利影响。
