Implications of protease M/neurosin in myelination during experimental demyelination and remyelination
Implications of protease M/neurosin in myelination during experimental demyelination and remyelination
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DOI：
10.1016/j.neulet.2006.06.030
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发表时间：
2006-09-25
影响因子：
2.5
通讯作者：
Yoshida, Shigetaka
中科院分区：
文献类型：
--
作者：
Bando, Yoshio;Ito, Shinji;Yoshida, Shigetaka
蛋白酶M/神经素是由中枢神经系统（CNS）中的少突胶质细胞（OLG）表达的丝氨酸蛋白酶。为了研究蛋白酶M/神经素在实验性脱髓鞘和髓鞘再生过程中的作用，给小鼠喂食cuprizone（双-环己酮双二腙）。半定量RT-PCR分析和免疫组化结果显示，脱髓鞘时蛋白酶M/neurosin mRNA和蛋白表达迅速下降，而谷胱甘肽-S-转移酶（GST-pi）阳性OLG的pi型在髓鞘再生过程中蛋白酶M/neurosin表达增加。培养的原代OLG显示蛋白酶M/神经素和髓鞘碱性蛋白（MBP）之间的强相关性。在肿瘤坏死因子-α（TNF-α）和IFN-γ刺激后，这些蛋白质在少突胶质细胞过程中共定位。使用RNAi抑制蛋白酶M/neurosin降低了培养的OLG中MBP mRNA的水平。与此相反，蛋白酶M/neurosin水平的降低与培养的OLG中的少突胶质细胞死亡或分化无关。这项研究确定，蛋白酶M/neurosin在OLG是密切相关的MBP和PLP基因的表达。我们的数据强调，髓鞘形成的维护是一个重要的功能蛋白酶M/neurosin在OLG，这表明其关系到少突胶质细胞的髓鞘疾病的反应。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
Protease M/neurosin is a serine protease expressed by oligodendrocytes (OLGs) in the central nervous system (CNS). To investigate the role of protease M/neurosin during experimental demyelination and remyelination, mice were fed cuprizone (bis-cyclohexanon oxaldihydrazone). Semi-quantitative RT-PCR analysis and immunohistochemistry revealed that the expressions of protease M/neurosin mRNA and protein were rapidly reduced in demyelination, whereas the expression of protease M/neurosin was increased in pi form of glutathione-S-transferases (GST-pi)-positive OLGs during remyelination. Cultured primary OLGs displayed a strong correlation between protease M/neurosin and myelin basic protein (MBP). After tumor necrosis factor-alpha (TNF-alpha) and IFN-gamma stimulation, these proteins showed colocalization in the oligodendroglial process. The suppression of protease M/neurosin using RNAi reduced the level of MBP mRNA in cultured OLGs. In contrast, the reduced level of protease M/neurosin was not associated with oligodendroglial cell death or differentiation in cultured OLGs. This study identifies that protease M/neurosin in OLGs is closely associated with the expression of the MBP and the PLP gene. Our data emphasize that the maintenance of myelination is an important function of protease M/neurosin in OLGs, suggesting its relation to the oligodendroglial response to myelin disorders. (c) 2006 Elsevier Ireland Ltd. All rights reserved.