Liu Hongliang, Wang Lingzhi, Zeng Qiang, Zhao Liang, Cui Yushan, Hou Changchun, Zhang Bin, Zhang Zushan, Zhang Shun, Chen Xuemin, Wang Aiguo
Tianjin Centers for Disease Control and Prevention, 6 Huayue Road, Hedong District, Tianjin, 300011, People's Republic of China.
School of Public Health, Tianjin Medical University, 22 Qixiangtai Road, HepingDistrict, Tianjin, 300070, People's Republic of China.
Environ Toxicol. 2018 Jun 19. doi: 10.1002/tox.22571.
Excessive iodide could induce intellectual damage in children, which has attracted broad attention. To investigate the neurotoxic effect of iodide and its mechanism, a human dopaminergic neuroblastoma cell line (SH-SY5Y) was treated with different concentrations of potassium iodide (KI). The results showed that excessive iodide could decrease cell viability, reduce glutathione (GSH) and superoxide dismutase (SOD), and increase the degree of autophagy (by changing the cellular ultrastructure and raising the autophagy-related mRNA and protein expression of LC3, Beclin1, and p62), which were correlated with the immunofluorescence labeling. Furthermore, treatment with the autophagy inhibitor 3-methyladenine (3MA), antioxidant N-acetylcysteine (NAC) and 30 mM KI for 24 h was conducted in the following research. 3MA significantly decreased autophagy-related mRNA and protein expression and improved cell viability, indicating that excess iodide induced autophagic cell death. In addition, oxidative stress regulated autophagy, reflected by the results that NAC decreased the mRNA and protein expression of LC3, Beclin1, and p62. In summary, autophagic cell death mediated by oxidative stress may participate in excessive iodide-induced SH-SY5Y cell death.
过量碘化物可导致儿童智力损伤，这已引起广泛关注。为研究碘化物的神经毒性作用及其机制，用不同浓度的碘化钾（KI）处理人多巴胺能神经母细胞瘤细胞系（SH-SY5Y）。结果显示，过量碘化物可降低细胞活力，减少谷胱甘肽（GSH）和超氧化物歧化酶（SOD），并增加自噬程度（通过改变细胞超微结构以及提高自噬相关mRNA和LC3、Beclin1、p62的蛋白表达），这与免疫荧光标记相关。此外，在后续研究中用自噬抑制剂3-甲基腺嘌呤（3MA）、抗氧化剂N-乙酰半胱氨酸（NAC）和30 mM KI处理24小时。3MA显著降低自噬相关mRNA和蛋白表达并提高细胞活力，表明过量碘化物诱导自噬性细胞死亡。此外，氧化应激调节自噬，NAC降低LC3、Beclin1和p62的mRNA和蛋白表达的结果反映了这一点。总之，氧化应激介导的自噬性细胞死亡可能参与过量碘化物诱导的SH-SY5Y细胞死亡。
