Thioredoxin-1 attenuates post-ischemic neuronal apoptosis via reducing oxidative/nitrative stress |
| |
Authors: | Ma Y H Su Ning Chao X D Zhang Y Q Zhang Lei Han Feng Luo Peng Fei Zhou Qu Yan |
| |
Institution: | Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. |
| |
Abstract: | Recent studies show that Thioredoxin (Trx) possesses a neuronal protective effect and that Trx inactivation is closely related to cerebral ischemia injury. Peroxynitrite (ONOO?) formation may trigger oxidative/nitrative stress and represent a major cytotoxic effect in cerebral ischemia. The present study was conducted to validate whether treatment with recombinant human Trx-1 (rhTrx-1) would attenuate ONOO? generation and oxidative/nitrative stress in focal transient cerebral ischemia. The results showed that intravenously administered rhTrx-1 (10 mg/kg) significantly improved neurological functions and reduced cerebral infarction and apoptotic cell death following cerebral ischemia. Neuronal ONOO? formation was significantly attenuated after rhTrx-1 treatment. Moreover, rhTrx-1 resulted in a significant decrease in antioxidant capacity and p38 mitogen activated protein kinase (MAPK) activity in ischemic brain tissue. Furthermore, the suppression on ONOO? formation by either rhTrx-1 or an ONOO? scavenger uric acid reduced cerebral infarct size in mice subjected to cerebral ischemia. Peroxynitrite donor SIN-1 not only blocked the neuronal protection of rhTrx-1 but also markedly attenuated rhTrx-1-induced antioxidative/antinitrative effect. We concluded that rhTrx-1 exerts an antioxidative/antinitrative effect against cerebral ischemia injury by blocking ONOO? and superoxide anion formation. These results provide the information that thioredoxin is much more likely to succeed as a therapeutic approach to diminish oxidative/nitrative stress-induced neuronal apoptotic cell death in the ischemic brain. |
| |
Keywords: | Thioredoxin MCAO Apoptosis Oxidative/nitrative stress |
本文献已被 ScienceDirect PubMed 等数据库收录! |