PDF(Pubmed)
Abstract：
Advanced glycation end products (AGEs) have been implicated in several skeletal muscle dysfunctions. However, whether the adverse effects of AGEs on skeletal muscle are because of their direct action on the skeletal muscle tissue is unclear. Therefore, this study aimed to investigate the direct and acute effects of AGEs on skeletal muscle using an isolated mouse skeletal muscle to eliminate several confounders derived from other organs. The results showed that the incubation of isolated mouse skeletal muscle with AGEs (1 mg/mL) for 2-6 h suppressed protein synthesis and the mechanistic target of rapamycin signaling pathway. Furthermore, AGEs showed potential inhibitory effects on protein degradation pathways, including autophagy and the ubiquitin-proteasome system. Additionally, AGEs stimulated endoplasmic reticulum (ER) stress by modulating the activating transcription factor 6, PKR-like ER kinase, C/EBP homologous protein, and altered inflammatory cytokine expression. AGEs also stimulated receptor for AGEs (RAGE)-associated signaling molecules, including mitogen-activated protein kinases. These findings suggest that AGEs have direct and acute effect on skeletal muscle and disturb proteostasis by modulating intracellular pathways such as RAGE signaling, protein synthesis, proteolysis, ER stress, and inflammatory cytokines.
摘要：
晚期糖基化终产物（AGEs）与几种骨骼肌功能障碍有关。然而,AGEs对骨骼肌的不良影响是否是因为它们对骨骼肌组织的直接作用尚不清楚.因此,这项研究的目的是研究AGEs对骨骼肌的直接和急性影响，使用分离的小鼠骨骼肌，以消除来自其他器官的多种混杂因素。结果表明，将分离的小鼠骨骼肌与AGEs（1mg/mL）孵育2-6h可抑制蛋白质合成和雷帕霉素信号通路的机制靶标。此外，AGEs对蛋白质降解途径显示出潜在的抑制作用，包括自噬和泛素-蛋白酶体系统。此外,AGEs通过调节激活转录因子6,PKR样ER激酶刺激内质网(ER)应激,C/EBP同源蛋白,和改变的炎性细胞因子表达。AGEs还刺激AGEs（RAGE）相关信号分子的受体，包括丝裂原激活的蛋白激酶。这些发现表明，AGEs对骨骼肌有直接和急性的作用，并通过调节细胞内途径如RAGE信号传导来干扰蛋白质平衡。蛋白质合成，蛋白水解，ER压力,和炎性细胞因子。
