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Blocking Daxx trafficking attenuates neuronal cell death following ischemia/reperfusion in rat hippocampus CA1 region.
MedLine Citation:
PMID:  21843499     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 5days 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.
Authors:
Yu-Lan Niu; Chong Li; Guang-Yi Zhang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-6
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  -     ISSN:  1096-0384     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Inc.
Affiliation:
Research Center for Biochemistry and Molecular Biology, Jiangsu Key Laboratory of Brain Disease Bioinformation, Xuzhou Medical College, Xuzhou 221002, China.
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