Manganese induces neuronal apoptosis by activating mTOR signaling pathway in vitro and in vivo
Manganese induces neuronal apoptosis by activating mTOR signaling pathway in vitro and in vivo
复制标题
锰在体内外激活mTOR信号通路诱导神经细胞凋亡
DOI：
10.1016/j.fct.2024.114508
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发表时间：
2024-02-12
影响因子：
4.3
通讯作者：
Li，Yan
中科院分区：
文献类型：
--
作者：
Cen，Yuyan;Yang，Jianmin;Li，Yan
Manganese (Mn) is a well-known environmental pollutant and occupational toxicant that causes neurotoxicity, which present as neurodegenerative-like symptoms. However, the mechanism of Mn-induced neuronal injury remains unclear. In this research, we explored the mechanism of Mn-induced neurotoxicity, focusing on the mTOR signaling pathway. A plasmid expressing a short hairpin RNA (shRNA) targeting mTOR (shRNA-mTOR) was transfected into N27 cells in vitro, and rapamycin was used as an mTOR inhibitor in vivo to block the mTOR signaling pathway. Cells were treated with different concentrations of manganese (II) chloride (MnCl2). We found that Mn induced cell injury and apoptosis and markedly upregulated the expression of mTOR pathway-related proteins. The phosphorylation of 4E-BP1, S6K1, Akt and SGK1 was markedly decreased after blocking mTOR, and cell apoptosis was also reduced. Furthermore, the mTOR-specific inhibitor rapamycin restored learning and memory abilities in vivo. This research highlights that inhibiting mTOR might be useful for preventing Mn-induced neurodegenerative-like disorders.
