Effects of cathepsins B and L inhibition on postischemic protein alterations in the brain
Effects of cathepsins B and L inhibition on postischemic protein alterations in the brain
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DOI：
10.1016/j.bbrc.2007.11.104
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发表时间：
2008-02-01
影响因子：
3.1
通讯作者：
Seyfried, Donald
中科院分区：
文献类型：
--
作者：
Anagli, John;Abounit, Kadija;Seyfried, Donald
在大鼠大脑中动脉闭塞(MCAO)模型上观察了选择性抑制组织蛋白酶B和L对脑缺血后蛋白质变化的影响。组织蛋白酶B活性主要在缺血侧皮质下区域升高，塌陷介质反应蛋白2、热休克相关蛋白70 kDa、60 kDa热休克蛋白、蛋白二硫键异构酶A3和白蛋白水平显著升高。使用半胱氨酸蛋白酶抑制剂1(CP-1)的CBZ-Phe-Ser(OBzl)-CHN2进行缺血后治疗，可减少脑梗塞体积、神经功能障碍和组织蛋白酶B活性，并减少脑中发现的热休克蛋白和白蛋白的数量。我们的数据有力地表明，CP-1急性治疗后热休克蛋白水平的降低和血清白蛋白向脑内渗漏的显著减少表明继发性脑缺血损伤较少，这最终与减少脑组织丢失和改善动物的神经恢复有关。(C)2007 Elsevier Inc.保留所有权利。
The effects of selective inhibition of cathepsins B and L on postischemic protein alterations in the brain were investigated in a rat model of middle cerebral artery occlusion (MCAO). Cathepsin B activity increased predominantly in the subcortical region of the ischemic hemisphere where the levels of collapsing mediator response protein 2, heat shock cognate 70 kDa protein, 60 kDa heat shock protein, protein disulfide isomerase A3 and albumin, were found to be significantly elevated. Postischemic treatment with Cbz-Phe-Ser(OBzl)-CHN2, cysteine protease inhibitor 1 (CP-1),reduced infarct volume, neurological deficits and cathepsin B activity as well as the amount of heat shock proteins and albumin found in the brain. Our data strongly suggests that the decrease in heat shock protein levels and the significant reduction of serum albumin leakage into the brain following acute treatment with CP-1 is indicative of less secondary ischemic damage, which ultimately, is related to less cerebral tissue loss and improved neurological recovery of the animals. (C) 2007 Elsevier Inc. All rights reserved.