Increased autophagy in transgenic mice with a G93A mutant SOD1 gene
Increased autophagy in transgenic mice with a G93A mutant SOD1 gene
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DOI：
10.1016/j.brainres.2007.06.045
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发表时间：
2007-09-05
期刊：
影响因子：
2.9
通讯作者：
Abe, Koji
中科院分区：
文献类型：
--
作者：
Morimoto, Nobutoshi;Nagai, Makiko;Abe, Koji
自噬与泛素-蛋白酶体系统一样，被认为在防止异常蛋白的积累中起着重要作用。大鼠微管相关蛋白1轻链3 （microtutube -associated protein 1 light chain 3, LC3）在自噬过程中起重要作用，LC3- i转化为LC3- ii被认为是监测自噬过程的一种简单方法。我们研究了SODIG93A转基因肌萎缩性侧索硬化症（ALS）小鼠模型，以考虑自噬与ALS之间可能的关系。在我们的研究中，我们通过免疫分析分析了LC3和哺乳动物雷帕霉素靶点（mTOR），一种自噬抑制剂。与非转基因或人野生型SOD1转基因动物相比，症状期SOD1转基因小鼠的LC3-II水平升高，而LC3-II与自噬体形成程度相关。此外，SOD1G93A-Tg小鼠磷酸化mTOR/ser（2448）免疫阳性运动神经元与总运动神经元的比例降低。目前的数据显示ALS动物模型中自噬增加的可能性。在这些动物中，自噬可能部分受到mTOR信号通路的调节。(c) 2007 Elsevier B.V.版权所有
Autophagy, like the ubiquitin-proteasome system, is considered to play an important role in preventing the accumulation of abnormal proteins. Rat microtubule-associated protein 1 light chain 3 (LC3) is important for autophagy, and the conversion from LC3-I into LC3-II is accepted as a simple method for monitoring autophagy. We examined a SODIG93A transgenic mouse model for amyotrophic lateral sclerosis (ALS) to consider a possible relationship between autophagy and ALS. In our study we analyzed LC3 and mammalian target of rapamycin (mTOR), a suppressor of autophagy, by immunoassays. The level of LC3-II, which is known to be correlated with the extent of autophagosome formation, was increased in S0D1G93A transgenic mice at symptomatic stage compared with non-transgenic or human wild-type SOD1 transgenic animals. Moreover, the ratio of phosphorylated mTOR/ser(2448) immunopositive motor neurons to total motor neurons was decreased in SOD1G93A-Tg mice. The present data show the possibility of increased autophagy in an animal model for ALS. And autophagy may be partially regulated by an mTOR signaling pathway in these animals. (c) 2007 Elsevier B.V. All rights reserved.