Cen Yuyan, Yang Jianmin, Su Liyu, Wang Feng, Zhu Deyu, Zhao Lan, Li Yan
School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563000, PR China; Key Laboratory of Maternal & Child Health and Exposure Science of Guizhou Higher Education Institutes, Zunyi, Guizhou, 563000, PR China.
School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563000, PR China.
Food Chem Toxicol. 2024 Mar;185:114508. doi: 10.1016/j.fct.2024.114508. Epub 2024 Feb 7.
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 (MnCl). 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.
锰（Mn）是一种著名的环境污染物和职业毒物，可导致神经毒性，表现为类似神经退行性变的症状。然而，锰诱导神经元损伤的机制仍不清楚。在本研究中，我们探讨了锰诱导神经毒性的机制，重点关注mTOR信号通路。将表达靶向mTOR的短发夹RNA（shRNA）的质粒（shRNA-mTOR）体外转染到N27细胞中，并在体内使用雷帕霉素作为mTOR抑制剂来阻断mTOR信号通路。细胞用不同浓度的氯化锰（MnCl₂）处理。我们发现锰诱导细胞损伤和凋亡，并显著上调mTOR通路相关蛋白的表达。阻断mTOR后，4E-BP1、S6K1、Akt和SGK1的磷酸化显著降低，细胞凋亡也减少。此外，mTOR特异性抑制剂雷帕霉素在体内恢复了学习和记忆能力。本研究强调，抑制mTOR可能有助于预防锰诱导的类似神经退行性疾病。
