Expression of autophagy-associated genes in skeletal muscle: An experimental model of chloroquine-induced myopathy
Expression of autophagy-associated genes in skeletal muscle: An experimental model of chloroquine-induced myopathy
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DOI：
10.1159/000103376
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发表时间：
2007-01-01
期刊：
影响因子：
5
通讯作者：
Arakawa, Ryuki
中科院分区：
文献类型：
--
作者：
Kimura, Noriyuki;Kumamoto, Toshihide;Arakawa, Ryuki
目的：氯喹调节溶酶体系统中的自噬细胞蛋白质降解，从而诱导骨骼肌中由自噬体和自溶酶体组成的边缘空泡的形成。本研究的目的是研究溶酶体系统，特别是自噬体形成（自噬过程）在分子水平上的贡献，在氯喹诱导的肌病的实验模型中的空泡异常积累。研究方法：组织学，免疫组织化学和半定量逆转录聚合酶链反应研究进行神经支配和去神经大鼠比目鱼肌治疗后，无论是生理盐水或氯喹。结果：仅在氯喹处理的失神经肌肉中观察到边缘空泡的积聚。微管相关蛋白-1轻链-3（LC 3）蛋白和mRNA水平显着增加，仅在去神经肌肉氯喹治疗的大鼠，而Apg 5和Apg 12 mRNA水平没有显着变化。此外，在用氯喹处理的去神经肌肉中，与骨骼肌中具有许多有缘空泡的有缘空泡的远端肌病相关的UDP-N-乙酰葡糖胺2-差向异构酶/N-乙酰甘露糖胺激酶（GNE）的mRNA水平没有降低。结论：LC 3 mRNA的增加可能与氯喹处理大鼠失神经肌肉中边缘空泡的形成有关，这表明在分子水平上自噬增加。在这种肌病中，边缘空泡的异常积聚似乎不是由自噬体相关基因或GNE基因的抑制介导的。版权所有（c）2007 S. Karger AG，巴塞尔。
Objective: Chloroquine modulates autophagocytic protein degradation in the lysosome system, thereby inducing the formation of rimmed vacuoles consisting of autophagosomes and autolysosomes in skeletal muscle. The goal of this study was to investigate the contribution of the lysosomal system, particularly autophagosome formation (an autophagic process) at the molecular level, to the abnormal accumulation of vacuoles in an experimental model of chloroquine-induced myopathy. Methods: Histological, immunohistochemical and semiquantitative reverse transcriptase-polymerase chain reaction studies were performed on innervated and denervated rat soleus muscles after treatment with either saline or chloroquine. Results: Accumulation of rimmed vacuoles was observed only in chloroquine-treated denervated muscles. Microtubule-associated protein-1 light chain-3 (LC3) protein and mRNA levels were significantly increased exclusively in denervated muscles from chloroquine-treated rats, whereas Apg5 and Apg12 mRNA levels did not change significantly. Further, the mRNA levels of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE), which are associated with distal myopathy with rimmed vacuoles showing numerous rimmed vacuoles in its skeletal muscle, were not decreased in denervated muscles treated with chloroquine. Conclusions: LC3 mRNA may increase in association with rimmed vacuole formation in denervated muscles from chloroquine-treated rats, suggesting an increase in autophagy at the molecular level. Abnormal accumulation of rimmed vacuoles in this myopathy does not appear to be mediated by inhibition of autophagosome-related genes or GNE gene. Copyright (c) 2007 S. Karger AG, Basel.