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癫痫持续状态后未成熟大鼠脑中葡萄糖调节蛋白(葡萄糖调节蛋白78/免疫球蛋白重链结合蛋白和葡萄糖调节蛋白94)及热休克蛋白70转录本的诱导

Induction of glucose-regulated protein (glucose-regulated protein 78/BiP and glucose-regulated protein 94) and heat shock protein 70 transcripts in the immature rat brain following status epilepticus.

作者信息

Little E, Tocco G, Baudry M, Lee A S, Schreiber S S

机构信息

Department of Biochemistry, University of Southern California, School of Medicine, Los Angeles 90033, USA.

出版信息

Neuroscience. 1996 Nov;75(1):209-19. doi: 10.1016/0306-4522(96)00267-9.

Abstract

Prior to 21 days of age, the immature rat brain is relatively resistant to excitotoxicity caused by the glutamate analogue, kainate. As stress-inducible proteins (GRP78, GRP94 and HSP70) have been proposed to possess molecular chaperone activity and protect cells from the deleterious effects of damaged proteins, we examined the pattern of expression of their respective messenger RNAs following systemic kainate at different postnatal ages. In untreated rats between seven and 21 days old, there was a higher basal level of grp78 and grp94 expression compared to hsp70. Unlike hsp70, which was inducible only in 21-day-old rats, kainate-mediated grp94 induction occurred in several regions of the brain as early as postnatal day 7. Grp78 messenger RNA expression was also increased by kainate treatment in 14-day-old rats, and the induction was most pronounced in the kainate-resistant dentate gyrus. With increasing age, longer lasting expression of both grp78 and grp94 messenger RNAs was observed in kainate-vulnerable regions, similar to observations in the adult rat brain. These results demonstrate non-overlapping expression patterns of glucose-regulated proteins and HSP70 in the immature central nervous system, suggesting that they serve different functions. While hsp70 induction could be a marker for potential cell injury and death, increased expression of grp78 and grp94 could play a neuroprotective role in the developing rat brain.

摘要

在21日龄之前,未成熟大鼠的大脑对谷氨酸类似物海藻酸酯引起的兴奋性毒性相对具有抗性。由于应激诱导蛋白(GRP78、GRP94和HSP70)被认为具有分子伴侣活性并保护细胞免受受损蛋白质的有害影响,我们研究了在不同出生后年龄全身给予海藻酸酯后它们各自信使RNA的表达模式。在7至21日龄的未处理大鼠中,与hsp70相比,grp78和grp94的基础表达水平更高。与仅在21日龄大鼠中可诱导的hsp70不同,海藻酸酯介导的grp94诱导早在出生后第7天就在大脑的几个区域发生。在14日龄大鼠中,海藻酸酯处理也增加了grp78信使RNA的表达,并且在对海藻酸酯有抗性的齿状回中诱导最为明显。随着年龄的增长,在对海藻酸酯敏感的区域观察到grp78和grp94信使RNA的表达持续时间更长,这与成年大鼠大脑中的观察结果相似。这些结果表明未成熟中枢神经系统中葡萄糖调节蛋白和HSP70的表达模式不重叠,表明它们具有不同的功能。虽然hsp70诱导可能是潜在细胞损伤和死亡的标志物,但grp78和grp94表达的增加可能在发育中的大鼠大脑中发挥神经保护作用。

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