Nickel Sulfate Induces Autophagy in Human Thyroid Follicular Epithelial Cells

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 (NiSO₄) exposure on the human thyroid follicular epithelial cells (Nthy-ori 3-1) and its underlying toxicological mechanisms. The results showed that NiSO₄ 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 NiSO₄ treatment. Accordingly, exposure of Nthy-ori 3-1 cells to NiSO₄ 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 NiSO₄-induced apoptotic cell death, while induction of autophagy significantly alleviated toxicity of NiSO₄. From a molecular standpoint, NiSO₄ 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 Ni²⁺ mediated apoptosis, thus providing rational strategy to prevent against nickel toxicity in the thyroid.