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Nickel Sulfate Induces Autophagy in Human Thyroid Follicular Epithelial Cells

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Abstract

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.

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Acknowledgements

The authors thank all those who participated in this study.

Funding

This study was supported by the Program for National Natural Science Foundation of China (31670518).

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of China

    Tao Zhang & Hui Chen

  2. Department of Pediatrics Cardiology, Lanzhou University Second Hospital, Lanzhou, Gansu, 730030, People’s Republic of China

    Yahong Liu

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  1. Tao Zhang
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Correspondence to Hui Chen.

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Zhang, T., Chen, H. & Liu, Y. Nickel Sulfate Induces Autophagy in Human Thyroid Follicular Epithelial Cells. Biol Trace Elem Res 200, 122–133 (2022). https://doi.org/10.1007/s12011-021-02643-z

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