Cadmium (Cd) is an important environmental pollutant. Previous studies have shown that Cd can induce liver cell injury; however, the toxicity mechanisms of Cd have not been fully elucidated. This study aimed to further confirm the hepatotoxic effects of Cd in mouse liver cells by various methods both in vivo and in vitro. In addition, it found that Cd induced autophagy but also caused autophagy blockade, and autophagy blockade intensified Cd-induced injury in liver cells. Subsequently, the study investigated the effects of Cd on lysosomes and found that Cd induced lysosomal acidification, promoted the expression of lysosomal-associated membrane protein 2 and lysosomal hydrolase cathepsin B both in vivo and in vitro, and enhanced the lysosomal degradation capacity. It indicated that Cd triggered lysosomal activation. However, the fusion of autophagosomes with lysosomes was inhibited by Cd both in vivo and in vitro. Next, the expression of Rab7, a key protein that regulates autophagosome-lysosome fusion, was examined. Cd was found to inhibit Rab7 expression both in vivo and in vitro. In conclusion, the results indicated that Cd obstructed the autophagic flux by inhibiting the fusion of autophagosomes with lysosomes, thus exacerbating the Cd-induced hepatotoxicity. Moreover, the molecular mechanism of Cd-induced inhibition of autophagosome-lysosome fusion is probably related to the Cd-induced downregulation of Rab7.

中文翻译：

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镉诱导的小鼠肝细胞细胞毒性与通过抑制自噬体和溶酶体融合破坏自噬通量有关

镉 (Cd) 是一种重要的环境污染物。以前的研究表明，Cd 可以诱导肝细胞损伤；然而，Cd 的毒性机制尚未完全阐明。本研究旨在通过体内和体外的各种方法进一步证实镉对小鼠肝细胞的肝毒性作用。此外，发现Cd诱导自噬的同时也引起自噬阻断，自噬阻断加剧了Cd诱导的肝细胞损伤。随后，该研究调查了 Cd 对溶酶体的影响，发现 Cd 诱导溶酶体酸化，促进溶酶体相关膜蛋白 2 和溶酶体水解酶组织蛋白酶 B 在体内和体外的表达，并增强溶酶体降解能力。这表明 Cd 触发了溶酶体活化。然而，自噬体与溶酶体的融合在体内和体外都被 Cd 抑制。接下来，检查了调节自噬体-溶酶体融合的关键蛋白 Rab7 的表达。发现 Cd 在体内和体外均抑制 Rab7 表达。总之，结果表明镉通过抑制自噬体与溶酶体的融合来阻碍自噬通量，从而加剧了镉诱导的肝毒性。此外，镉诱导抑制自噬体-溶酶体融合的分子机制可能与镉诱导的 Rab7 下调有关。结果表明，镉通过抑制自噬体与溶酶体的融合来阻碍自噬通量，从而加剧了镉诱导的肝毒性。此外，镉诱导抑制自噬体-溶酶体融合的分子机制可能与镉诱导的 Rab7 下调有关。结果表明，镉通过抑制自噬体与溶酶体的融合来阻碍自噬通量，从而加剧了镉诱导的肝毒性。此外，镉诱导抑制自噬体-溶酶体融合的分子机制可能与镉诱导的 Rab7 下调有关。