Tan, Min; Ouyang, Ying; Jin, Minghua; Chen, Meihui; Liu, Peiqing; Chao, Xiaojuan; Chen, Ziwei; Chen, Xiaohong; Ramassamy, Charles; Gao, Youheng et Pi, Rongbiao (2013). Downregulation of Nrf2/HO-1 pathway and activation of JNK/c-Jun pathway are involved in homocysteic acid-induced cytotoxicity in HT-22 cells Toxicology Letters , vol. 223 , nº 1. pp. 1-8. DOI: 10.1016/j.toxlet.2013.08.011.
Ce document n'est pas hébergé sur EspaceINRS.Résumé
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/c-Jun pathway, supporting that HCA might be a therapeutic target for AD.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | Cytotoxicity; HO-1; Homocysteic acid; JNK; Nrf2; c-Jun |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 29 mai 2017 15:52 |
| Dernière modification: | 29 mai 2017 16:03 |
| URI: | https://espace.inrs.ca/id/eprint/2982 |
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