These authors contributed equally to this work.
N-acetyl-L-cysteine protects against cadmium-induced neuronal apoptosis by inhibiting ROS-dependent activation of Akt/mTOR pathway in mouse brain
Article first published online: 25 SEP 2014
© 2013 British Neuropathological Society
Neuropathology and Applied Neurobiology
Volume 40, Issue 6, pages 759–777, October 2014
How to Cite
Chen, S., Ren, Q., Zhang, J., Ye, Y., Zhang, Z., Xu, Y., Guo, M., Ji, H., Xu, C., Gu, C., Gao, W., Huang, S. and Chen, L. (2014), N-acetyl-L-cysteine protects against cadmium-induced neuronal apoptosis by inhibiting ROS-dependent activation of Akt/mTOR pathway in mouse brain. Neuropathology and Applied Neurobiology, 40: 759–777. doi: 10.1111/nan.12103
- Issue published online: 25 SEP 2014
- Article first published online: 25 SEP 2014
- Accepted manuscript online: 3 DEC 2013 02:25AM EST
- Manuscript Accepted: 27 NOV 2013
- Manuscript Received: 2 SEP 2013
- National Natural Science Foundation of China. Grant Number: 30971486, 81271416
- Scientific Research Foundation of State Education Ministry of China. Grant Number: SEMR20091341
- Project for the Priority Academic Program Development and Natural Science Foundation of Jiangsu Higher Education Institutions of China. Grant Number: 10KJA180027
- NIH. Grant Number: CA115414
- American Cancer Society. Grant Number: RSG-08–135-01-CNE
- Louisiana Board of Regents. Grant Number: NSF-2009-PFUND-144
- NSFC for Talents Training in Basic Science. Grant Number: J1103507, J1210025
- Innovative Research Program of Jiangsu College Graduate of China. Grant Number: CXZZ11–0888
- mammalian target of rapamycin;
- neuronal apoptosis;
- reactive oxygen species
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) signalling pathway in brain neurones 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.