铜过载调控的细胞死亡方式在骨骼肌衰老萎缩中的作用
The Role of Cell Death Modes Regulated by Copper Overload in Aging-related Atrophy for Skeletal Muscles
杨威 1邓云锋 2范晶晶1
作者信息
- 1. 武汉体育学院运动医学院,武汉 430079;运动训练监控湖北省重点实验室,武汉 430079
- 2. 长沙卫生职业学院公共教学部,长沙 410100
- 折叠
摘要
骨骼肌衰老是机体衰老的相关生物学事件,以质量丢失和功能衰退为显著特征,金属组学尤其是铜金属组学在其中的功能角色正日益得到关注.铜金属组学在衰老状态下表现为铜过载,其触发的毒理效应具有激活骨骼肌细胞中发生凋亡、焦亡、铁死亡、铜死亡及并促进α突触核蛋白聚集的特异性分子潜力,相关的信号级联最终可诱导衰老肌纤维中蛋白质、线粒体和卫星细胞等内容物代谢失衡及裂解丢失,同时可触发神经肌肉接头(neuromuscular junction,NMJ)退化和异常,是骨骼肌衰老萎缩的新型病理生理机制.本综述首次系统地解码骨骼肌衰老萎缩调控网络中铜的分子生物学功能、衰老骨骼肌中铜过载的潜在机制,以及铜过载诱导的多种细胞死亡形式例如凋亡、焦亡、铁死亡及铜死亡的信号转导途径在骨骼肌衰老萎缩中的新角色,为临床上应用铜螯合改善和治疗骨骼肌衰老萎缩提供潜在分子靶点和方案选择.
Abstract
Skeletal muscle aging is a biological process that occurs as the body ages,characterized by mass loss and functional decline.The involvement of metallomics,particularly copper metallomics,is pivotal in understanding its functional roles.Copper metallomics manifests as copper overload with aging.It triggers toxic effects that activate apoptosis,pyroptosis,ferroptosis,cuproptosis and also promote α-sy-nuclein aggregation.The related signaling cascades can eventually promote metabolic turbulence and the loss of proteins,mitochondria,satellite cells and other cell contents in senescent myofibers,while cau-sing the degeneration and abnormality of neuromuscular junctions.This is a new physiopathgical mecha-nism of aging-related atrophy in skeletal muscles.Here we firstly review the molecular biological functions of copper in the regulatory networks of aging-related atrophy for skeletal muscles,the potential mecha-nisms of copper overload in senescent skeletal muscles,and the novel role of multiple signaling transduc-tion pathways associated with copper overload-induced cell death modes comprising apoptosis,pyroptosis,ferroptosis and cuproptosis in aging-related atrophy for skeletal muscles.We aim to provide potential mo-lecular targets and option choices for clinically applying copper chelation to improve and treat aging-relat-ed atrophy in skeletal muscles.
关键词
细胞死亡/铜金属组学/骨骼肌衰老萎缩/铜死亡/α突触核蛋白Key words
cell death/copper metallomics/aging-related atrophy in skeletal muscle/cuproptosis/α-synuclein(α-syn)引用本文复制引用
基金项目
国家自然科学基金青年基金(81701391)
湖北省自然科学基金(2023AFB700)
湖北省教育厅科研项目中青年人才项目(Q20224104)
武汉体育学院中青年科研团队项目(21KT08)
出版年
2024
NETL
NSTL
万方数据