Department of Endocrinology and Metabolism, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People's Republic of China.
Department of Pediatrics Cardiology, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People's Republic of China.
Biol Trace Elem Res. 2022 Jan;200(1):122-133. doi: 10.1007/s12011-021-02643-z. Epub 2021 Mar 18.
Nickel is an industrial and environmental toxic metal, which is toxic to humans in certain forms at high doses. Here, we investigated the cytotoxic effects of nickel sulfate (NiSO) exposure on the human thyroid follicular epithelial cells (Nthy-ori 3-1) and its underlying toxicological mechanisms. The results showed that NiSO reduced the cell viability of Nthy-ori 3-1 cells in a dose- and time-dependent manner, inducing S and G2/M phases cell-cycle arrest and apoptosis. Electron microscopy demonstrated that abundant autophagic vacuoles were found in Nthy-ori 3-1 cells after NiSO treatment. Accordingly, exposure of Nthy-ori 3-1 cells to NiSO resulted in a dose-dependent increase of LC3II/I ratio, an induction of Beclin-1 expression, and a decrease in p62 levels. Blockade of autophagy with 3-methyladenine (3-MA) potentiated the NiSO-induced apoptotic cell death, while induction of autophagy significantly alleviated toxicity of NiSO. From a molecular standpoint, NiSO markedly promoted the activation of p38 and IKKβ by increasing their phosphorylation. In conclusion, we showed that autophagy was induced to protect thyroid cells from Ni mediated apoptosis, thus providing rational strategy to prevent against nickel toxicity in the thyroid.
镍是一种工业和环境毒物金属，在高剂量的某些形式下对人类有毒。在这里，我们研究了硫酸镍（NiSO）暴露对人甲状腺滤泡上皮细胞（Nthy-ori 3-1）的细胞毒性作用及其潜在的毒理学机制。结果表明，NiSO 以剂量和时间依赖的方式降低了 Nthy-ori 3-1 细胞的活力，诱导 S 和 G2/M 期细胞周期停滞和细胞凋亡。电子显微镜显示，NiSO 处理后 Nthy-ori 3-1 细胞中发现大量自噬空泡。因此，Nthy-ori 3-1 细胞暴露于 NiSO 导致 LC3II/I 比值呈剂量依赖性增加，Beclin-1 表达诱导和 p62 水平降低。用 3-甲基腺嘌呤（3-MA）阻断自噬增强了 NiSO 诱导的凋亡细胞死亡，而自噬的诱导则显著减轻了 NiSO 的毒性。从分子角度来看，NiSO 通过增加其磷酸化明显促进了 p38 和 IKKβ的激活。总之，我们表明自噬被诱导以保护甲状腺细胞免受 Ni 介导的凋亡，从而为防止甲状腺中镍毒性提供了合理的策略。
