Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, Shanxi, China.
Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, Taigu 030801, Shanxi, China.
Toxicol In Vitro. 2021 Apr;72:105074. doi: 10.1016/j.tiv.2020.105074. Epub 2020 Dec 19.
Arsenic (As), a potent toxicant, is known to be a hepatotoxicant. Although As induced liver apoptosis and autophagy, the relationship between apoptosis and autophagy of hepatocytes caused by As remains largely unknown. 3-methyladenine (3-MA) and rapamycin can inhibit and promote autophagy of AML-12 cells, respectively. Hence, in this study, AML-12 cells were treated with different concentrations (0, 2, 4, 6, 8, 10 and 12 μmol/L) of AsO, and 5 mmol/L 3-MA or 100 nmol/L rapamycin were applied to distinguish the effect of autophagy on apoptosis in AML-12. Results showed that exposure to As induced cell apoptosis and autophagy, which were mediated by the significantly altered expression levels of autophagy markers (mTOR, LC3, PI3K and P62), and apoptosis markers (Bcl-2 and caspase-3). Further analysis indicated that a certain dosage of 3-MA and rapamycin decreased apoptosis and the caspase-3 expression, which suggested that As-induced autophagy regulated AML-12 cells apoptosis through the expressions of PI3K, mTOR, P62 and Bcl-2.
砷（As）是一种毒性很强的物质，已知具有肝毒性。虽然砷能诱导肝细胞凋亡和自噬，但砷诱导的肝细胞凋亡和自噬之间的关系在很大程度上尚不清楚。3-甲基腺嘌呤（3-MA）和雷帕霉素分别可以抑制和促进 AML-12 细胞的自噬。因此，在本研究中，用不同浓度（0、2、4、6、8、10 和 12μmol/L）的砷酸盐（AsO）处理 AML-12 细胞，并应用 5mmol/L 的 3-MA 或 100nmol/L 的雷帕霉素来区分自噬对 AML-12 细胞凋亡的影响。结果表明，砷暴露诱导细胞凋亡和自噬，这是通过自噬标志物（mTOR、LC3、PI3K 和 P62）和凋亡标志物（Bcl-2 和 caspase-3）表达的显著改变介导的。进一步的分析表明，一定剂量的 3-MA 和雷帕霉素可减少凋亡和 caspase-3 的表达，这表明砷诱导的自噬通过 PI3K、mTOR、P62 和 Bcl-2 的表达来调节 AML-12 细胞的凋亡。
