Ischemic preconditioning negatively regulates plenty of SH3s-mixed lineage kinase 3-Rac1 complex and c-Jun N-terminal kinase 3 signaling via activation of Akt
文献类型：期刊论文
| 作者 | Zhang, Q. -G. ; Han, D. ; Xu, J. ; Lv, Q. ; Wang, R. ; Yin, X. -H. ; Xu, T. -L. ; Zhang, G. -Y. |
| 刊名 | NEUROSCIENCE
 |
| 出版日期 | 2006 |
| 卷号 | 143期号:2页码:431-444 |
| 关键词 | Akt POSH Rac1 MLK3 apoptosis ischemic preconditioning INDUCED NEURONAL APOPTOSIS BINDING PROTEINS RAC1 IN-VIVO CEREBRAL-ISCHEMIA CELL-SURVIVAL SMALL GTPASES CYTOCHROME-C BAX PHOSPHORYLATION PATHWAY |
| 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 | Activation of Akt/protein kinase B has been recently reported to play an important role in ischemic tolerance. We here demonstrate that the decreased protein expression and phosphorylation of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) underlie the increased Akt-Ser-473 phosphorylation in the hippocampal CA1 subfield in ischemic preconditioning (IPC). Co-immuno-precipitation analysis reveals that Akt physically interacts with Rac1, a small Rho family GTPase required for mixed lineage kinase 3 (MLK3) autophosphorylation, and both this interaction and Rac1-Ser-71 phosphorylation induced by Akt are promoted in preconditioned rats. In addition, we show that Akt activation results in the disassembly of the plenty of SH3s (POSH)-MLK3-Rac1 signaling complex and down-regulation of the activation of MLK3/c-Jun N-terminal kinase (JNK) pathway. Akt activation results in decreased serine phosphorylation of 14-3-3, a cytoplasmic anchor of Bax, and prevents ischemia-induced mitochondrial translocation of Bax, release of cytochrome c, and activation of caspase-3. The expression of Fas ligand is also decreased in the CA1 region. Akt activation protects against apoptotic neuronal death as shown in TUNEL staining following IPC. Intracerebral infusion of LY294002 before IPC reverses the increase in Akt phosphorylation and the decrease in JNK signaling activation, as well as the neuroprotective action of IPC. Our results suggest that activation of pro-apoptotic MLK3/JNK3 cascade can be suppressed through activating anti-apoptotic phosphoinositide 3-kinase/Akt pathway induced by a sublethal ischemic insult, which provides a functional link between Akt and the JNK family of stress-activated kinases in ischemic tolerance. (c) 2006 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 |
| 源URL | [http://ir.sibs.ac.cn/handle/331001/1799]  |
| 专题 | 上海神经科学研究所_神经所(总) |
| 推荐引用方式 GB/T 7714 | Zhang, Q. -G.,Han, D.,Xu, J.,et al. Ischemic preconditioning negatively regulates plenty of SH3s-mixed lineage kinase 3-Rac1 complex and c-Jun N-terminal kinase 3 signaling via activation of Akt[J]. NEUROSCIENCE,2006,143(2):431-444. |
| APA | Zhang, Q. -G..,Han, D..,Xu, J..,Lv, Q..,Wang, R..,...&Zhang, G. -Y..(2006).Ischemic preconditioning negatively regulates plenty of SH3s-mixed lineage kinase 3-Rac1 complex and c-Jun N-terminal kinase 3 signaling via activation of Akt.NEUROSCIENCE,143(2),431-444. |
| MLA | Zhang, Q. -G.,et al."Ischemic preconditioning negatively regulates plenty of SH3s-mixed lineage kinase 3-Rac1 complex and c-Jun N-terminal kinase 3 signaling via activation of Akt".NEUROSCIENCE 143.2(2006):431-444. |
入库方式： OAI收割
来源：上海神经科学研究所
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