Neuroprotection against ischemic brain injury by a small peptide inhibitor of c-Jun N-terminal kinase (JNK) via nuclear and non-nuclear pathways

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	Neuroprotection against ischemic brain injury by a small peptide inhibitor of c-Jun N-terminal kinase (JNK) via nuclear and non-nuclear pathways
	Guan, QH ; Pei, DS ; Zong, YY ; Xu, TL(徐天乐) ; Zhang, GY
刊名	NEUROSCIENCE
	2006
卷号	139 期号:2 页码:609-627
关键词	c-jun N-terminal protein kinase JNK JNK interacting protein-1 JIP-11 Tat-JBD cerebral ischemia/reperfusion TRANSIENT CEREBRAL-ISCHEMIA POSTSYNAPTIC DENSITY PROTEIN-95 BAX-DEPENDENT APOPTOSIS CELL-DEATH NEURONAL APOPTOSIS SIGNALING PATHWAY RAT HIPPOCAMPUS MIXED LINEAGE CNS NEURONS ACTIVATION
ISSN号	0306-4522
通讯作者	Zhang, GY (reprint author), Xuzhou med Coll, Res Ctr Biochem & Mol Biol, 84 W Huai Hai Rd, Xuzhou 221002, Jiangsu, Peoples R China,gyzhang@xzmc.edu.cn
英文摘要	Our previous studies and the others have strongly suggested that c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in ischemic brain injury. Here we reported that Tat-JNK binding domain (JBD) of JNK-interacting protein-1 (JIP-1), a smaller 11-mer peptide corresponding to residues 153-163 of murine JIP-1 conjugated to Tat peptide, perturbed the assembly of JIP-1-JNK3 complexes, thus inhibiting the activation of JNK3 induced by ischemia/reperfusion in the vulnerable hippocampal CA1 subregion. As a result, Tat-JBD diminished the increased phosphorylation of c-Jun (a nuclear substrate of JNK) and the increased expression of Fas ligand induced by ischemia/reperfusion in the vulnerable hippocampal CA1 subregion. At the same time, through inhibiting phosphorylation of Bcl-2 (a cytosolic target of JNK) and the release of Bax from Bcl-2/Bax dimers, Tat-JBD attenuated Bax translocation to mitochondria and the release of cytochrome c induced by ischemia/reperfusion. Furthermore, the activation of caspase3 and hydrolyzation of poly-ADP-ribose-polymerase induced by brain ischemia/reperfusion were also significantly suppressed by preinfusion of the peptide Tat-JBD. Importantly, Tat-JBD showed neuroprotective effects on ischemic brain damage in vivo, and administration of the peptide after ischemia also achieved the same effects as preinfusion of the peptide did. Thus, our findings imply that Tat-JBD induced neuroprotection against ischemia/reperfusion in rat hippocampal CA1 region via inhibiting nuclear and non-nuclear pathways of JNK signaling. Taken together, these results indicate that Tat-JBD peptide provides a promising therapeutic approach for ischemic brain injury. (C) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.
学科主题	Neurosciences & Neurology
收录类别	SCI
语种	英语
公开日期	2012-07-23
内容类型	期刊论文
源URL	[http://ir.sibs.ac.cn/handle/331001/1853]
专题	上海神经科学研究所_神经所(总)
推荐引用方式 GB/T 7714	Guan, QH,Pei, DS,Zong, YY,et al. Neuroprotection against ischemic brain injury by a small peptide inhibitor of c-Jun N-terminal kinase (JNK) via nuclear and non-nuclear pathways[J]. NEUROSCIENCE,2006,139(2):609-627.
APA	Guan, QH,Pei, DS,Zong, YY,Xu, TL,&Zhang, GY.(2006).Neuroprotection against ischemic brain injury by a small peptide inhibitor of c-Jun N-terminal kinase (JNK) via nuclear and non-nuclear pathways.NEUROSCIENCE,139(2),609-627.
MLA	Guan, QH,et al."Neuroprotection against ischemic brain injury by a small peptide inhibitor of c-Jun N-terminal kinase (JNK) via nuclear and non-nuclear pathways".NEUROSCIENCE 139.2(2006):609-627.