Activated mTOR signaling pathway in myofibers with inherited metabolic defect might be an evidence for mTOR inhibition therapies  

作　　者：Jing-Wei Lyu Xue-Bi Xu Kun-Qian Ji Na Zhang Yuan Sun Dan-Dan Zhao Yu-Ying Zhao Chuan-Zhu Yan 

机构地区：[1]Institute of Neuromuscular and Neurodegenerative Diseases,Department of Neurology,Qilu Hospital,Shandong University,Jinan,Shandong 250012,China [2]Brain Science Research Institute,Shandong University,Jinan,Shandong 250012,China [3]Department of Neurology,Qilu Hospital (Qingdao),Shandong University,Qingdao,Shandong 266035,China [4]Mitochondrial Medicine Laboratory,Qilu Hospital (Qingdao),Shandong University,Qingdao,Shandong 266035,China

出　　处：《Chinese Medical Journal》2019年第7期805-810,共6页中华医学杂志（英文版）

摘　　要：Background:Abnormally activated mechanistic target of rapamycin(mTOR)pathway has been reported in several model animals with inherited metabolic myopathies(IMMs).However,the profiles of mTOR pathway in skeletal muscles from patients are still unknown.This study aimed to analyze the activity of mTOR pathway in IMMs muscles.Methods:We collected muscle samples from 25 patients with mitochondrial myopathy(MM),lipid storage disease(LSD)or Pompe disease(PD).To evaluate the activity of mTOR pathway in muscle specimens,phosphorylation of S6 ribosomal protein(p-S6)and p70S6 kinase(p-p70S6K)were analyzed by Western blotting and immunohistochemistry.Results:Western blotting results showed that p-p70S6K/p70S6K in muscles from LSD and MM was up-regulated when compared with normal controls(NC)(NC vs.LSD,U=2.000,P=0.024;NC vs.MM:U=6.000,P=0.043).Likewise,p-S6/S6 was also upregulated in muscles from all three subgroups of IMMs(NC vs.LSD,U=0.000,P=0.006;NC vs.PD,[7=0.000,P=0.006;NC vs.MM,U=1.000,P=0.007).Immunohistochemical study revealed that p-S6 was mainly expressed in fibers with metabolic defect.In MM muscles,most p-S6 positive fibers showed cytochrome C oxidase(COX)deficiency(U=5.000,P=0.001).In LSD and PD muscles,p-S6 was mainly overexpressed in fibers with intramuscular vacuoles containing lipid droplets(17=0.000,P=0.002)or basophilic materials(U=0.000,P=0.002).Conclusion:The mTOR pathway might be activated in myofibers with various metabolic defects,which might provide evidence for mTOR inhibition therapy in human IMMs.

关 键 词：MTOR pathway MITOCHONDRIAL MYOPATHY Lipid storage DISEASE Pompe DISEASE 

分 类 号：R[医药卫生]