Differential activation of MAPK/ERK and p38/SAPK in neurones and glia following focal cerebral ischaemia in the rat
Differential activation of MAPK/ERK and p38/SAPK in neurones and glia following focal cerebral ischaemia in the rat
复制标题
DOI：
10.1016/s0169-328x(00)00043-7
复制
发表时间：
2000-04-14
期刊：
影响因子：
--
通讯作者：
Parsons, AA
中科院分区：
文献类型：
--
作者：
Irving, EA;Barone, FC;Parsons, AA
两种表征相对较好的激酶信号通路是涉及MAPK/ERK和p38/SAPK2的激酶信号通路，已知它们在体外被各种已知在中风后增加的因子激活，如谷氨酸、IL-1和TNF。本研究旨在利用磷特异性抗体研究局灶性脑缺血后磷酸化- erk1 /2、-p38和转录因子CREB的激活和细胞分布。在短暂MCAO后24小时（90分钟）和永久MCAO后6小时，神经元核周“半影状”区域的细胞质内磷酸化- erk1 /2染色明显增加。相比之下，在“核心”和“半影状”区域具有星形细胞样形态的细胞中，phospho-p38免疫染色明显增加。在短暂MCAO后24小时内，在“半影样”区域的一些神经元中也检测到Phospho-p38染色。CREB激活仅限于“半影状”区域的神经元。在闭塞的MCAO同侧皮质下白质中的星形细胞样细胞中检测到磷酸化-p38免疫反应性增加，而磷酸化- creb和-ERK1/2染色则局限于形态学上呈少突胶质细胞的细胞。该研究表明，瞬时和永久性MCAO发生后，MAPK和p38通路均发生磷酸化，表明其激活。然而，每种途径在缺血组织中都显示出不同的细胞和空间分布。综上所述，这些数据表明，针对ERK1/2通路的药物提供的神经保护可能直接通过保护神经元和少突胶质细胞起作用，而针对p38通路激酶信号通路的药物可能间接通过抑制细胞因子和其他参与脑损伤反应的介质起作用。(C) 2000 Elsevier Science B.V.版权所有
Two relatively well characterised kinase signalling pathways are those involving MAPK/ERK and p38/SAPK2, that are known to be activated in vitro by various factors known to increase following stroke, such as glutamate, IL-1 and TNF. The present study was designed to investigate the activation and cellular distribution of phosphorylated-ERK1/2, -p38 and the transcription factor CREB following focal cerebral ischaemia using phosphospecific antibodies. Up to 24 h following transient MCAO (90 min) and 6 h following permanent MCAO, phospho-ERK1/2 staining was markedly increased within the cytoplasm of neuronal perikarya in 'penumbral-like' regions. In contrast, phospho-p38 immunostaining was markedly increased in cells with astrocyte-like morphology in both 'core' and 'penumbral-like' regions. Phospho-p38 staining was also detected in some neurones within 'penumbral-like' regions up to 24 h following transient MCAO. CREB activation was confined to neurones in 'penumbral-like' regions. Increased phospho-p38 immunoreactivity was detected in astrocyte-like cells present in the subcortical white matter ipsilateral to the occluded MCAO, while phospho-CREB and -ERK1/2 staining was localised to cells with the morphological appearance of oligodendrocytes. This study demonstrates phosphorylation, indicative of activation, of both the MAPK and p38 pathways following transient and permanent MCAO. However, each pathway shows a distinct cellular and spatial distribution within ischaemic tissue. Together these data indicate that neuroprotection offered by agents directed towards the ERK1/2 pathway may act directly through protection of neurones and oligodendrocytes, while those directed towards the p38 pathway kinase signalling pathways may be indirectly via inhibition of cytokines and other mediators involved in the brains response to injury. (C) 2000 Elsevier Science B.V. All rights reserved.