Elevation of cytoskeletal protein breakdown in aged Wistar rat brain

Elevation of cytoskeletal protein breakdown in aged Wistar rat brain
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DOI:
10.1016/j.neurobiolaging.2005.02.013
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发表时间:
2006-04-01
影响因子:
4.2
通讯作者:
Wang, KKW
Wang, KKW
中科院分区:
医学2区
文献类型:
--
作者:
Bernath, E;Kupina, N;Wang, KKW

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先前的研究表明,衰老大鼠大脑中的蛋白水解作用总体增加。我们监测了取自年轻(3 个月)和老年(17、21 和 23.5 个月)Wistar 大鼠大脑皮层和小脑的神经组织中细胞骨架蛋白的潜在降解。我们发现大脑皮层和小脑中细胞骨架蛋白(全血影蛋白和微管相关蛋白 MAP-2A/B)存在显着的年龄依赖性蛋白水解作用。 α II-血影蛋白分解的模式显示 150-和 145-kDa 片段(分别为 SBDP150 和 SBDP145)显着增加,但我们没有在老年大鼠大脑中检测到 caspase-3 介导的 120-kDa 片段(SBDP120),这表明钙蛋白酶的参与。老年大鼠大脑中 MAP-2A/B 的分解模式与体外钙蛋白酶消化 3 个月对照大鼠大脑 MAP-2A/B 所产生的模式一致。在老年大鼠大脑中,Caspase-3 前体的加工没有显着增加;相反,皮质中的 caspase-3 蛋白原和 caspase-3 水解活性适度降低。这些结果表明细胞骨架蛋白对猫痛介导的降解具有选择性敏感性,但衰老大鼠大脑中的 caspase-3 则不然。 (C) 2005 Elsevier Inc. 保留所有权利。
Previous studies indicated there is an overall increase of proteolysis in aging ratbrains. We monitored the potential degradation of cytoskeletal proteins in neuronal tissue taken from cerebral cortex and cerebellum of young (3 month) and aging (17, 21 and 23.5 month) Wistar rats. We found significant age-dependent proteolysis of cytoskeletal proteins (all-spectrin and microtubule-associated protein MAP-2A/B) in the cerebral cortex and the cerebellum. The pattern of alpha II-spectrin breakdown shows a marked increase in 150- and 145-kDa fragments (SBDP150 and SBDP145, respectively), but we did not detect the caspase-3-mediated 120-kDa fragment (SBDP120) in aged rat brains, suggesting the involvement of the calpain proteases. The pattern of MAP-2A/B breakdown in aged rat brains mirrors that produced by in vitro calpain digestion of 3-month control rat brain MAP-2A/B. In aged rat brains, there is no significant increase in pro-caspase-3 processing; rather, there is a moderate reduction in pro-caspase-3 protein and caspase-3 hydrolytic activity in the cortex. These results point to selective susceptibility of cytoskeletal proteins to cat pain-mediated degradation, but not caspase-3 in aging rat brains. (C) 2005 Elsevier Inc. All rights reserved.