摘要
衰老性肌萎缩(sarcopenia)的防治已成为亟待解决的公共健康问题。内质网未折叠蛋白反应(endoplasmic reticulum unfolded protein response,UPR^(ER))是维持衰老骨骼肌蛋白质稳态的关键靶标,探究其在衰老性肌萎缩中的作用具有重要意义。运动可能介导UPR^(ER)削弱内质网应激(endoplasmic reticulum stress,ERS)发生,增加衰老骨骼肌蛋白质合成,维持蛋白质稳态,改善骨骼肌功能;急性运动可能介导UPR^(ER),活化PERK/ATF4、IRE1/Xbp1和ATF6信号轴,促进衰老骨骼肌蛋白质合成,最终改善蛋白质稳态,其特征凸显“时相性”--在运动后0~3 h作用不明显、12~48 h逐渐显著、48 h回落,其中尤以抗阻运动明显;长期耐力/抗阻运动亦可能介导UPR^(ER),活化PERK/ATF4和IRE1/Xbp1信号轴,促进衰老骨骼肌蛋白质合成,最终改善蛋白质稳态。提示,运动可能优化UPR^(ER),改善衰老骨骼肌PERK/ATF4和IRE1/Xbp1信号轴上相关蛋白的表达削弱ERS,进而维持骨骼肌稳态,确保衰老骨骼肌功能完整性。未来以运动介导UPR^(ER)调控衰老性肌萎缩为靶点的研究,有望为衰老性肌萎缩的防治提供有益参考。
The prevention and treatment of sarcopenia is an urgent public health problem.Endoplasmic reticulum unfolded protein response(UPR^(ER))is a key target to maintain protein homeostasis in aging skeletal muscle,so it is important to explore the role of UPR^(ER) in sarcopenia.Exercise is known to weaken endoplasmic reticulum stress(ERS),increase protein synthesis of aging skeletal muscle,maintain protein homeostasis and improve skeletal muscle function by regulating UPR^(ER).Acute exercise may have the role to activate protein kinase RNA-like ER kinase/activating transcription factor 4(PERK/ATF4),inositol-requiring protein 1/X-box binding protein 1(IRE1/Xbp1)and ATF6 signal axes via UPRE,and thus to promote protein synthesis of aging skeletal muscle,and finally to improve protein homeostasis.In addition,the"phasic"is the most important characteristic in the abovementioned effects,ie,the effect is not obvious at 0~3 h after exercise,gradually significant at 12~48 h,and fall back after 48 h,especially in resistance exercise.Long term endurance/resistance exercise may also mediate UPR^(ER) to activate PERK/ATF4 and IRE1/Xbp1 signal axis,and then promote protein synthesis of aging skeletal muscle,and finally improved protein homeostasis.It is suggested that exercise can optimize UPR,improve the expression of related proteins on PERK/ATF4 and IRE1/Xbp1 signal axis of aging skeletal muscle to weaken ERS,so as to maintain the skeletal muscle homeostasis and the functional integrity of aging skeletal muscle.In the future,the research on the regulation of sarcopenia by exercise-mediated UPR^(ER) is expected to provide useful references for the prevention and treatment of sarcopenia.
作者
柯志飞
尚画雨
王瑞元
李俊平
KE Zhifei;SHANG Huayu;WANG Ruiyuan;LI Junping(School of Sports and Human Sciences,Beijing Sport University,Bejing 100084,China;School of Sports Medicine and Health,Chengdu Sport Universit,Chengdu 610041,China)
出处
《体育科学》
CSSCI
北大核心
2021年第5期73-79,F0003,共8页
China Sport Science
基金
国家自然科学基金资助项目(31900842)
中央高校基本科研业务费专项资金资助(2019PT013)。
关键词
内质网未折叠蛋白反应
衰老性肌萎缩
运动
骨骼肌
endoplasmic reticulum unfolded protein response
sarcopenia
exercise
skeletal muscle
