Effects of kainate-mediated excitotoxicity on the expression of rat counterparts of A170 and MSP23 stress proteins in the brain

Effects of kainate-mediated excitotoxicity on the expression of rat counterparts of A170 and MSP23 stress proteins in the brain
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DOI:
10.1016/s0169-328x(99)00093-5
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发表时间:
1999-06-08
期刊:
MOLECULAR BRAIN RESEARCH
影响因子:
--
通讯作者:
Yamada, K
Yamada, K
中科院分区:
其他
文献类型:
--
作者:
Nakaso, K;Kitayama, M;Yamada, K

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在细胞生存的关键条件下,应激蛋白在保护机制中起着重要作用。我们在这里报道了A170和MSP23这两种氧化应激诱导蛋白在kainate介导的兴奋性毒性大鼠脑中的表达。在给药后5-8 h, A170 mRNA在脑内被显著诱导。大鼠脑组织中MSP23 mRNA表达水平较低,且在给药24 h内未见MSP23 mRNA的诱导作用。免疫印迹分析显示,A170蛋白在治疗后8 h在脑各部位达到最高表达水平。MSP23蛋白在脑内组成性表达,且在给药24 h内MSP23蛋白水平显著降低。原位杂交和免疫组化研究表明,A170主要在神经元中表达,特别是在大脑和小脑浦肯野细胞的锥体神经元中表达,而MSP23在少突胶质细胞中表达。在受兴奋毒性影响的区域观察到A170的诱导,并且在细胞死亡早期观察到这种诱导。此外,海马锥体细胞层等高兴奋毒性易感性区域的A170表达低于海马齿状回等高兴奋毒性抗性区域。这些结果表明A170可能在海碱盐介导的兴奋性毒性脑中发挥保护作用。(C) 1999 Elsevier Science B.V.版权所有
Stress proteins play important roles in the protective mechanisms under critical conditions for cell survival. We report here the expression of A170 and MSP23, oxidative stress-inducible proteins, under kainate-mediated excitotoxicity in the rat brain. A170 mRNA was significantly induced in the brain 5-8 h after i.p. kainate administration. MSP23 mRNA was observed at quite a low level in the rat brain, and the induction of MSP23 mRNA was not observed during the period 24 h after kainate administration. Immunoblot analysis demonstrated that the maximal expression level of A170 protein occurred 8 h after treatment in each part of the brain. MSP23 protein was constitutively expressed in the brain and the level of this protein was significantly decreased during the period 24 h after kainate administration. In situ hybridization and immunohistochemical studies showed that A170 was expressed predominantly in neurons, especially in pyramidal neurons of the cerebrum and cerebellar Purkinje cells, while MSP23 was expressed in oligodendrocytes. The induction of A170 was observed in the regions which are affected by excitotoxicity and this induction was observed in the earlier phase than cell death. Also, the region which shows high vulnerability to excitotoxicity such as pyramidal cell layer in the hippocampus, showed lower A170 expression than that which shows resistance to excitotoxicity, such as the dentate gyrus in the hippocampus. These results suggest that A170 may play a protective role in the brain under kainate-mediated excitotoxicity. (C) 1999 Elsevier Science B.V. All rights reserved.