铜过载介导骨骼肌萎缩的机制及治疗新进展  

Updated progress in mechanism and treatment of copper overload-mediated skeletal muscle atrophy

作　　者：杨威[1] 李畅 邓云锋 胡昊 王娟[1] 范晶晶 YANG Wei;LI Chang;DENG Yun-feng;HU Hao;WANG Juan;FAN Jing-jing(School of Sports Medicine,Wuhan Sports University,Wuhan 430079,China;Department of Public Class Teaching,Changsha Health Vocational College,Changsha 410100,China;Department of spine surgery,Hubei Hospital of Traditional Chinese Medicine,Wuhan 430074,China)

机构地区：[1]武汉体育学院运动医学院,湖北武汉430079 [2]长沙卫生职业学院公共教学部,湖南长沙410100 [3]湖北省中医院脊柱外科,湖北武汉430074

出　　处：《中国病理生理杂志》2022年第12期2268-2277,共10页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金青年基金资助项目(No.81701391);湖北省教育厅科学研究计划项目中青年人才项目(No.Q20224104);武汉体育学院中青年科研团队项目(No.21KT08);武汉体育学院“东湖学子”资助项目;武汉体育学院青年教师科研基金项目(No.20S03)。

摘　　要：铜是一种必需的微量元素,同时也是一种过渡金属,具有氧化还原属性,通过接受和转移电子并以离子形式参与所有的生物学事件,对哺乳动物的能量代谢、活性氧去除、铁吸收和信号转导等生命过程至关重要[1]。铜的内稳态受肝脏代谢的严格调控,在糖尿病、肥胖、心力衰竭、神经退行性疾病、肿瘤等病理状态下表现为含量显著升高即铜过载.Skeletal muscle atrophy is a common complication for chronic diseases,which is mediated by imbalanced metabolic homeostasis of protein and mitochondria.Copper is a physiological yet toxicological trace element mainly from food,whose overload usually accompanies with skeletal muscle atrophy under multiple pathological conditions(such as diabetes,heart failure,cancer,etc.).Moreover,recent research has revealed that copper ions could induce cuproptosis process by targeting lipoacylated proteins of tricarboxylic acid cycle,which provides a novel mechanism for copper overload-mediated skeletal muscle atrophy.At present,copper chelation treatment has been clinically carried out for diabetes,cancers and other diseases.However,whether this pharmacological treatment benefits skeletal muscle atrophy and its underlying mechanism are still unclear.Here we review the fundamental biological functions of copper in skeletal muscle under physiological and pathological condition,highlight the regulation of intracellular copper homeostasis,and discuss the general mechanisms of copper overload and cuproptosis in disordered skeletal muscle protein metabolism as well as mitochondrial fusion/fission homeostasis.We aim to provide potential molecular targets and reference materials for copper chelation therapy in skeletal muscle atrophy.

关 键 词：铜过载 肌萎缩 线粒体 自噬 细胞凋亡 铜螯合 

分 类 号：R685[医药卫生—骨科学] R363[医药卫生—外科学]