The phosphatase inhibitor, okadaic acid, strongly protects primary rat cortical neurons from lethal oxygen-glucose deprivation
The phosphatase inhibitor, okadaic acid, strongly protects primary rat cortical neurons from lethal oxygen-glucose deprivation
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DOI：
10.1016/j.bbrc.2008.11.036
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发表时间：
2009-01-16
影响因子：
3.1
通讯作者：
Chakravarthy, Balu
中科院分区：
文献类型：
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作者：
Atkinson, Trevor;Whitfield, James;Chakravarthy, Balu
IGF-1和bFGF等多肽生长因子的蛋白激酶介导的作用保护培养的神经元免受普遍存在于中风脑中的氧气和葡萄糖剥夺(OGD)的破坏。在这里，我们证明了IGF-1的神经保护作用是通过PI-3K/Akt介导的，而碱性成纤维细胞生长因子的神经保护是通过MAPK介导的。胰岛素样生长因子-1和碱性成纤维细胞生长因子一起并没有进一步增加保护作用，这表明它们的通路在下游汇聚。由于蛋白激酶介导了这种保护作用，磷酸酶抑制剂冈田酸(OA)可能与生长因子一样对OGD具有保护作用。在这里，我们展示了办公自动化实际上是一个更有效的保护者。增加PI-3K/Akt和MAPK的磷酸化，刺激新的蛋白质合成。OA的作用也独立于CREB激活和FKHRL1和GSK-3失活，后者与IGF-1的作用有关。皇冠版权所有(C)2008由爱思唯尔公司出版。保留所有权利。
The protein kinase-mediated actions of peptide growth factors such as IGF-1 and bFGF protect cultured neurons from being killed by the oxygen and glucose deprivations (OGD) that prevail in the 'stroked brain'. Here, we show that neuroprotection by IGF-1 is mediated by PI-3K/Akt, whereas that of bFGF is mediated by MAPK. IGF-1 and bFGF together did not further increase protection suggesting a downstream convergence of their pathways. Since protein kinases mediated the protection, a phosphatase inhibitor such as okadaic acid (OA) might be as protective as the growth factors against OGD. Here, we show that OA is actually a Much more effective protector. It increased the phosphorylation of both PI-3K/Akt and MAPK, and stimulated new protein synthesis. OA also acted independently of the CREB activation and FKHRL1 and GSK-3 inactivation which have been implicated in IGF-1 actions. Crown Copyright (C) 2008 Published by Elsevier Inc. All rights reserved.