Bidirectional effect of uric acid on C2C12 myotubes and its partial mechanism

作者全名："Li, Yuanfen; Zhang, Yingxiao; Wu, Yaoxuan; Yu, Jing; Guo, Ai; Fu, Rao; Xiao, Qian"

作者地址："[Li, Yuanfen; Zhang, Yingxiao; Wu, Yaoxuan; Yu, Jing; Guo, Ai; Fu, Rao; Xiao, Qian] Chongqing Med Univ, Dept Geriatr, Affiliated Hosp 1, Chongqing, Peoples R China; [Xiao, Qian] Chongqing Med Univ, Dept Geriatr, Affiliated Hosp 1, Chongqing 400016, Peoples R China"

通信作者："Xiao, Q (通讯作者)，Chongqing Med Univ, Dept Geriatr, Affiliated Hosp 1, Chongqing 400016, Peoples R China."

来源：GERIATRICS & GERONTOLOGY INTERNATIONAL

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001182745400001

JCR分区：Q2

影响因子：2.4

年份：2024

卷号：24

期号：4

开始页：430

结束页：439

文献类型：Article

关键词：autophagy; cGAS-Sting signal pathway; hyperuricemia; sarcopenia

摘要："Aim: To explore the effects and mechanisms of different concentrations of uric acid on skeletal muscle cells. Methods: C2C12 myoblasts were differentiated into myotubes and then exposed to a medium containing uric acid (0 mu M, 200 mu M, 400 mu M, 600 mu M, 800 mu M, 1000 mu M, 1200 mu M, 1400 mu M). The myotube diameters were observed under light microscopy; the expressions of myosin heavy chain (MyHC), autophagy-related proteins (LC3BII/LC3BI, P62), cGAS, and p-Sting/Sting proteins were analyzed using Western blotting or immunoprecipitation; and oxidative stress and mitochondrial damage were evaluated using ROS, mtDNA and JC-1 assays. Cell viability was measured via CCK8 assay, and 1000-mu M uric acid was selected for follow-up experiments. Furthermore, C2C12 myotubes were divided into a blank control group (Ctrl), a high-uric-acid group (HUA), and an HUA plus cGASn inhibitor group (HUA + RU.521). Then, the myotube diameter was observed, oxidative stress and mitochondrial damage were evaluated, and MyHC and autophagy-related protein expressions were analysed. Results: C2C12 myotubes cultured in 400-mu M uric acid medium had the greatest myotube diameter and the highest MyHC protein expression. At 1000-mu M uric acid, the diameter and MyHC protein expression were significantly decreased, LCB3II/LCB3I expression was notably increased, and the level of p62 protein expression was considerably decreased. RU.521 partially alleviated the HUA-induced C2C12 myotubes changes. Conclusions: Uric acid bidirectionally affected C2C12 myotubes: 400-mu M uric acid promoted myotube growth, while 1000-mu M uric acid triggered myotube atrophy with increased autophagy. Inhibiting cGAS-Sting signaling attenuated HUA-induced C2C12 myotube autophagy and atrophy. Geriatr Gerontol Int 2024; center dot center dot: center dot center dot-center dot center dot."

基金机构：The First Affiliated Hospital of Chongqing Medical University [PYJJ2022-01]; First Affiliated Hospital of Chongqing Medical University [2022TQ0398]; Postdoctoral Science Foundation of China

基金资助正文："The First Affiliated Hospital of Chongqing Medical University (PYJJ2022-01), the Postdoctoral Science Foundation of China (2022TQ0398)."