N-acetyl-L-cysteine protects against cadmium-induced neuronal apoptosis by inhibiting ROS-dependent activation of Akt/mTOR pathway in mouse brain.
N-acetyl-L-cysteine protects against cadmium-induced neuronal apoptosis by inhibiting ROS-dependent activation of Akt/mTOR pathway in mouse brain.
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DOI：
10.1111/nan.12103
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发表时间：
2014-10
影响因子：
5
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Chen S;Ren Q;Zhang J;Ye Y;Zhang Z;Xu Y;Guo M;Ji H;Xu C;Gu C;Gao W;Huang S;Chen L
本研究探讨了N-乙酰-L-半胱氨酸（NAC）对镉（Cd）染毒小鼠的神经保护作用及其机制。小鼠经腹腔注射NAC（150 mg/kg），染毒6周。观察脑神经元损伤和死亡、活性氧（ROS）、抗氧化酶以及Akt/mTOR信号通路的变化。为了验证mTOR激活在Cd诱导的神经毒性中的作用，小鼠还接受了亚急性方案，即腹膜内施用Cd（1 mg/kg），伴随/不伴随雷帕霉素（7.5 mg/kg），持续11天。慢性暴露于镉诱导小鼠脑损伤或神经细胞死亡，由于活性氧诱导。NAC的共同管理显着降低镉水平的血浆和大脑的动物。NAC阻止镉诱导的ROS，并显着衰减镉诱导的脑损伤或神经细胞死亡。NAC的保护作用是介导的，至少部分地，通过提高铜/锌-超氧化物歧化酶，过氧化氢酶和谷胱甘肽过氧化物酶的活性，以及谷胱甘肽在大脑中的水平。此外，NAC还能抑制Cd诱导的Akt/mTOR通路的激活。雷帕霉素在体外和体内保护镉诱导的神经毒性。NAC通过抑制ROS依赖的Akt/mTOR通路对镉诱导的小鼠脑神经元凋亡的保护作用。研究结果强调，NAC可用于预防和治疗镉诱导的神经退行性疾病。
This study explores the neuroprotective effects and mechanisms of N-acetyl-L-cysteine (NAC) in mice exposed to cadmium (Cd). NAC (150 mg/kg) was intraperitoneally administered to mice exposed to Cd (10-50 mg/L) in drinking water for 6 weeks. The changes of cell damage and death, reactive oxygen species (ROS), antioxidant enzymes, as well as Akt/mammalian target of rapamycin (mTOR) signaling pathway in brain neurons were assessed. To verify the role of mTOR activation in Cd-induced neurotoxicity, mice also received a subacute regimen of intraperitoneally administered Cd (1 mg/kg) with/without rapamycin (7.5 mg/kg) for 11 days. Chronic exposure of mice to Cd induced brain damage or neuronal cell death, due to ROS induction. Co-administration of NAC significantly reduced Cd levels in the plasma and brain of the animals. NAC prevented Cd-induced ROS and significantly attenuated Cd-induced brain damage or neuronal cell death. The protective effect of NAC was mediated, at least partially, by elevating the activities of Cu/Zn-superoxide dismutase, catalase and glutathione peroxidase, as well as the level of glutathione in the brain. Furthermore, Cd-induced activation of Akt/mTOR pathway in the brain was also inhibited by NAC. Rapamycin in vitro and in vivo protected against Cd-induced neurotoxicity. NAC protects against Cd-induced neuronal apoptosis in mouse brain partially by inhibiting ROS-dependent activation of Akt/mTOR pathway. The findings highlight that NAC may be exploited for prevention and treatment of Cd-induced neurodegenerative diseases.
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影响因子：
7.4
作者：
Chen, Long;Xu, Baoshan;Liu, Lei;Luo, Van;Zhou, Hongyu;Chen, Wenxing;Shen, Tao;Han, Xiuzhen;Kontos, Christopher D.;Huang, Shile
通讯作者：
Huang, Shile
影响因子：
10.3
作者：
Alonso-Gonzalez, C.;Gonzalez, A.;Mediavilla, M. D.
通讯作者：
Mediavilla, M. D.
影响因子：
4.2
作者：
Huang, Quanzhen;Aluise, Christopher D.;Butterfield, D. Allan
通讯作者：
Butterfield, D. Allan
影响因子：
6.1
作者：
Brzóska, MM;Kaminski, M;Moniuszko-Jakoniuk, J
通讯作者：
Moniuszko-Jakoniuk, J
影响因子：
4.8
作者：
Choi, J;Rees, HD;Li, L
通讯作者：
Li, L