Role of proteasomes in the formation of neurofilamentous inclusions in spinal motor neurons of aluminum-treated rabbits
Role of proteasomes in the formation of neurofilamentous inclusions in spinal motor neurons of aluminum-treated rabbits
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DOI：
10.1111/j.1440-1789.2007.00822.x
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发表时间：
2007-12-01
期刊：
影响因子：
2.3
通讯作者：
Ohama, Eisaku
中科院分区：
文献类型：
--
作者：
Kimura, Noriyuki;Kumamoto, Toshihide;Ohama, Eisaku
我们研究了20S蛋白酶体在铝处理的兔脊髓运动神经细胞的病理变化中的作用，包括磷酸化神经丝的异常聚集。20S蛋白酶体免疫组织化学染色显示，染铝组兔腰段脊髓运动神经元胞浆内无神经丝状包涵体或有小包涵体的神经元较对照组染色更深，而含有大的神经丝状包涵体的部分增大神经元的免疫反应性明显降低。与对照组相比，铝处理组兔全脊髓提取液中的蛋白酶体活性显著增加。此外，Western印迹分析表明，20S蛋白酶体在体外降解了非磷酸化的高分子神经细丝(NFH)蛋白。这些结果表明，铝不抑制20S蛋白酶体的活性，而20S蛋白酶体能降解神经细丝-H蛋白。我们认为，在铝处理的兔中，磷酸化神经丝的异常聚集是由铝直接诱导的，而不是通过蛋白酶体的抑制而诱导的。蛋白酶体激活可能参与了细胞内蛋白分解，特别是在铝处理的兔运动神经元变性的早期阶段。
We examined the role of the 20S proteasome in pathologic changes, including abnormal aggregation of phosphorylated neurofilaments, of spinal motor nerve cells from aluminum-treated rabbits. Immunohistochemistry for the 20S proteasome revealed that many lumbar spinal motor neurons without intracytoplasmic neurofilamentous inclusions or with small inclusions were more intensely stained in aluminum-treated rabbits than in controls, whereas the immunoreactivity was greatly decreased in some enlarged neurons containing large neurofilamentous inclusions. Proteasome activity in whole spinal cord extracts was significantly increased in aluminum-treated rabbits compared with controls. Furthermore, Western blot analysis indicated that the 20S proteasome degraded non-phosphorylated high molecular weight neurofilament (neurofilament-H) protein in vitro. These results suggest that aluminum does not inhibit 20S proteasome activity, and the 20S proteasome degrades neurofilament-H protein. We propose that abnormal aggregation of phosphorylated neurofilaments is induced directly by aluminum, and is not induced by the proteasome inhibition in the aluminum-treated rabbits. Proteasome activation might be involved in intracellular proteolysis, especially in the earlier stages of motor neuron degeneration in aluminum-treated rabbits.