期刊
TOXICOLOGY LETTERS
卷 223, 期 1, 页码 1-8出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2013.08.011
关键词
Homocysteic acid; Cytotoxicity; Nrf2; HO-1; JNK; c-Jun
类别
资金
- Fundamental Research Funds for the Central Universities [10ykpy23]
- Guangdong Provincial International Cooperation Project of Science Technology [2012B050300015]
Previous studies have suggested that elevated blood homocysteic acid (HCA) levels increased the risk of Alzheimer's disease (AD), but the underlying mechanisms are unclear. Herein, we studied the neuronal toxicity of HCA and the underlying mechanisms in HT-22 cells. Results showed that HCA induced cell death in concentration-and time-dependent manners, but did not activate Caspase-3. Additionally, HCA increased ROS production, depleted GSH, inactivated the Nrf2/HO-1 pathway, decreased mitochondrial membrane potential and increased the ratio of Bax/Bcl-2, two apoptosis-related proteins. Furthermore, HCA significantly increased the levels of p-JNK and p-c-Jun and its toxicity dramatically attenuated by SP600125, a specific JNK pathway inhibitor. Taken together, our results provide evidence that HCA induced cytotoxicity in HT-22 cells through down-regulating of Nrf2/HO-1 pathway and activating JNK/cJun pathway, supporting that HCA might be a therapeutic target for AD. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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