期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 515, 期 1-2, 页码 89-98出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2011.07.016
关键词
Cerebral ischemia; Daxx trafficking; Ask1; Fas; NAC; SP600125
资金
- National Natural Science Foundation of China [90608015, 30870543, 31000360]
- Natural Science Funds of Jiangsu Province [BK2010171, BK2010176]
- Six Talent Peaks Program of Jiangsu Province of China
Previous studies have shown that the death-associated protein (Daxx) shuttles between nucleus and cytoplasm under ischemic stress, and the subcellular localization of Daxx plays an important role in ischemic neuron death. In this study, by blocking the Daxx trafficking, the rat hippocampus CA1 neurons were protected against cerebral ischemia/reperfusion, and the molecular mechanism underlying this neuroprotection was studied. We found that pretreatment of SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), or an anti-oxidant, N-acetylcysteine (NAC), could not only prevent Daxx from trafficking but also increase the number of the surviving CA1 pyramidal cells of hippocampus at 5 days of reperfusion. Furthermore, knock-down of endogenous Daxx exerted similar neuroprotective effect during ischemia/reperfusion. We found the treatment of SP600125 or NAC could decrease the activation of Ask1 during ischemia/reperfusion and suppress the assembly of the Fas.Daxx.Ask1 signaling module, and in succession inhibit JNK activation and c-Jun phosphorylation. This study provides the Daxx trafficking as a new potential therapeutic target for ischemic brain injury. (C) 2011 Elsevier Inc. All rights reserved.
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