|本期目录/Table of Contents|

[1]熊薇,王倩,牛燕媚,等.有氧运动经由泛素-蛋白酶体降解HDAC4/5改善骨骼肌能量代谢[J].天津医科大学学报,2026,32(03):236-241.[doi:10.20135/j.issn.1006-8147.2026.03.0236]
　XIONG Wei,WANG Qian,NIU Yanmei,et al.Aerobic exercise improving skeletal muscle energy metabolism via ubiquitin-proteasome-mediated degra-dation of HDAC4/5[J].Journal of Tianjin Medical University,2026,32(03):236-241.[doi:10.20135/j.issn.1006-8147.2026.03.0236]
点击复制

有氧运动经由泛素-蛋白酶体降解HDAC4/5改善骨骼肌能量代谢(PDF)

《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:
32卷
期数:
2026年03期
页码:
236-241
栏目:
基础医学
出版日期:
2026-05-20

文章信息/Info

Title:
Aerobic exercise improving skeletal muscle energy metabolism via ubiquitin-proteasome-mediated degra-dation of HDAC4/5
文章编号:
1006-8147（2026）03-0236-06
作者:
熊薇1; 王倩1; 牛燕媚2; 3; 傅力1; 2; 邵珩1
1.天津医科大学基础医学院人体解剖学系，天津300070;2.天津医科大学医学技术学院，天津300203;3.天津医科大学总医院康复医学科，天津300052
Author(s):
XIONG Wei1; WANG Qian1; NIU Yanmei2; 3; FU Li1; 2; SHAO Heng1
1.Department of Human Anatomy， School of Basic Medical Sciences， Tianjin Medical University， Tianjin 300070， China;2.School of Medical Technology， Tianjin Medical University， Tianjin 300203， China;3.Department of Rehabilitation Medicine， Tianjin Medical University General Hospital， Tianjin 300052， China
关键词:
泛素-蛋白酶体系统; 有氧运动; 组蛋白去乙酰化酶; 骨骼肌; 能量代谢
Keywords:
ubiquitin-proteasome system;  aerobic exercise;  histone deacetylase;  skeletal muscle;  energy metabolism
分类号:
R87
DOI:
10.20135/j.issn.1006-8147.2026.03.0236
文献标志码:
A
摘要:
目的：探究有氧运动是否通过泛素-蛋白酶体系统（UPS）介导组蛋白去乙酰化酶4/5（HDAC4/5）降解，从而改善骨骼肌细胞能量代谢。方法：采用随机数字表法将60只4周龄雄性C57BL/6小鼠分为安静对照组（C组）、安静+MG132组（C+M组）、运动组（E组）和运动+MG132组（E+M组），每组小鼠15只。E组和E+M组小鼠均进行6周75%最大摄氧量强度跑台运动。C+M和E+M组小鼠腹腔注射蛋白酶体抑制剂MG132[10μg/（kg·d）]。小鼠经注射干预后检测体成分；采用Western印迹分别检测比目鱼肌和腓肠肌组织HDAC4/5、20S蛋白酶体、肌肉环指蛋白1（MuRF1）及有氧代谢标志物的表达；免疫共沉淀（Co-IP）检测HDAC4/5泛素化水平；实时PCR检测葡萄糖转运体4（Glut4）和肉毒碱棕榈酰转移酶1b（Cpt1b）mRNA表达。结果：与C组小鼠相比，E组体重、体脂显著降低（t=2.231、2.097，均P<0.05），去脂体重显著增加（t=2.163，P<0.05），在比目鱼肌中细胞色素C（CytoC）表达升高（t=2.964，P<0.05），HDAC4/5蛋白表达降低（t=7.055、3.249，均P<0.05），Glut4和Cpt1bmRNA表达增加（t=2.639、2.138，均P<0.05），HDAC4/5泛素化水平升高。与E组小鼠相比，E+M组上述运动效应被MG132部分逆转。上述变化在腓肠肌中均不显著。结论：有氧运动通过激活UPS，促进骨骼肌HDAC4/5的泛素化降解，以I型肌纤维尤为显著，从而解除其对下游Glut4和Cpt1b基因的转录抑制，改善骨骼肌能量代谢。
Abstract:
Objective： To investigate whether aerobic exercise improves skeletal muscle energy metabolism by promoting the ubiqui-tin-proteasome system（UPS）-mediated degradation of histone deacetylase 4/5（HDAC4/5）. Methods： Sixty 4-week-old male C57BL/6 mice were assigned to sedentary control（C）， sedentary+MG132（C+M）， exercise（E）， and exercise+MG132（E+M） groups accord-ing to the random number table method. Mice in E group and E+M group performed 6 weeks of treadmill running at 75% maximal oxygen uptake intensity. The C+M group and E+M group received intraperitoneal injections of the proteasome inhibitor MG132 [10 μg/（kg·d）]. After the intervention， body composition was analyzed. The protein expressions of HDAC4/5， 20S proteasome， muscle RING-finger protein-1（MuRF1）， and aerobic metabolism markers in soleus and gastrocnemius muscles were detected by Western blotting. The ubiquitination levels of HDAC4/5 were detected by co-immunoprecipitation（Co-IP）. The mRNA expressions of glucose transporter type 4（Glut4） and carnitine palmitoyltransferase 1b（Cpt1b） were measured by real-time PCR. Results： Compared with group C， group E showed significantly decreased body weight and fat mass（t=2.231， 2.097， both P<0.05）， increased free fat mass （t=2.163， P<0.05）， elevated cytochrome C（Cyto C） expression in soleus（t=2.964， P<0.05）， decreased HDAC4/5 protein ex-pression（t=7.055， 3.249， both P<0.05）， increased Glut4 and Cpt1b mRNA expressions（t=2.639， 2.138， both P<0.05）， and en-hanced HDAC4/5 ubiquitination levels. Compared with E group， these exercise-induced effects were partially reversed by MG132 in E+M group. No significant changes were observed in the gastrocnemius. Conclusion： Aerobic exercise activates the UPS to promote the ubiquitination and degradation of HDAC4/5 protein， primarily in type I oxidative muscle fibers， thereby relieving their transcrip-tional inhibition on downstream Glut4 and Cpt1b genes and improving skeletal muscle energy metabolism.

参考文献/References:

[1] DING Y， WAN Q， LIU W. Effects of atmospherically relevant PM2.5 on skeletal muscle mitochondria： a review of damage mecha-nisms and pot ential of exercise interventions [ J ] . Front Pub-lic Health， 2025， 13： 1615363.
[2] SHIN J， NUNOMIYA A， GONDA K， et al. Specification of skeletal muscle fiber-type is determined by the calcineurin/NFATc1 signal-ing pathway during muscle regeneration[J]. Biochem Biophys Res Commun， 2023， 659： 20-28.
[3] PHILP A M， SANER N J， LAZAROU M， et al. The influence of aerobic exercise on mitochondrial quality control in skeletal muscle [J]. J Physiol， 2021， 599（14）：3463-3476.
[4] MOCHALOVA E P， BELOVA S P， KOSTROMINOVA T Y， et al. Differences in the role of HDACs 4 and 5 in the modulation of pro-cesses regulating MAFbx and MuRF1 expression during muscle un-loading[J]. Int J Mol Sci， 2020， 21（13）： 4815.
[5] MA W， CAI Y， SHEN Y， et al. HDAC4 knockdown alleviates den-ervation-induced muscle atrophy by inhibiting myogenin-depen-dent atrogene activation[J]. Front Cell Neurosci， 2021， 15： 663384.
[6] LIN Y， LI Y， KE C， et al. HDAC4： an emerging target in diabetes mellitus and diabetic complications[J]. Eur J Med Res， 2025， 30 （1）： 429.
[7] LI Z， SONG Y， LI Z， et al. Role of protein lysine acetylation in the pathogenesis and treatment of obesity and metabolic syndrome [J]. Curr Obes Rep， 2025， 14（1）： 24.
[8] NIU Y， WANG T， LIU S， et al. Exercise-induced GLUT4 tran-scription via inactivation of HDAC4/5 in mouse skeletal muscle in an AMPKα2-dependent manner[J]. Biochim Biophys Acta Mol Ba-sis Dis， 2017， 1863（9）： 2372-2381.
[9] MARTIN S D， CONNOR T， SANIGORSKI A， et al. Class IIa HDACs inhibit cell death pathways and protect muscle integrity in response to lipotoxicity[J]. Cell Death Dis， 2023， 14（12）： 787.
[10] SCHIAFFINO S， CHEMELLO F， REGGIANI C. The diversity of skeletal muscle fiber types[J]. Cold Spring Harb Perspect Biol， 2025，17（8）：41477.
[11] MORESI V， WILLIAMS A H， MEADOWS E， et al. Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases[J]. Cell， 2010，143（1）： 35-45.
[12] M覫LMEN K S， ALMQUISTt N W， SKATTEBO覫. Effects of exer-cise training on mitochondrial and capillary growth in human skele-tal muscle： a systematic review and meta-regression[J]. Sports Med， 2025， 55（1）：115-144.
[13] LUNDBERG T R， FEUERBACHER J F， S譈NKELER M， et al. The effects of concurrent aerobic and strength training on muscle fiber hypertrophy： a systematic review and meta-analysis[J]. Sports Med， 2022，52（10）： 2391-2403.
[14] LI Y， LI S， WU H. Ubiquitination-proteasome system（UPS） and autophagy two main protein degradation machineries in response to cell stress[J]. Cells， 2022， 11（5）： 851.
[15] BODINE S C， LATRES E， BAUMHUETER S， et al. Identification of ubiquitin ligases required for skeletal muscle atrophy[J]. Science， 2001， 294（5547）： 1704-1708.
[16] GUO N， PENG Z. MG132， a proteasome inhibitor， induces apopto-sis in tumor cells[J]. Asia Pac J Clin Oncol， 2013， 9（1）：6-11.
[17] HUANG S， ZHENG X， ZHANG X， et al. Exercise improves high-fat diet-induced metabolic disorder by promoting HDAC5 degrada-tion through the ubiquitin-proteasome system in skeletal muscle[J]. Appl Physiol Nutr Metab， 2022， 47（11）： 1062-1074.
[18] ZHANG Y， WU X， LI R， et al. Sodium danshensu modulates skeletal muscle fiber type formation and metabolism by inhibiting pyruvate kinase M1[J]. Front Pharmacol， 2024， 15： 1467620.

相似文献/References:

备注/Memo

备注/Memo:
基金项目 国家自然科学基金资助项目（31671237）
作者简介 熊薇（2001-），女，硕士在读，研究方向：有氧运动改善骨骼肌能量代谢的机制研究；通信作者：邵珩，E-mail：shaoh@tmu.edu.cn。
（2025-10-27收稿）
更新日期/Last Update: 2026-05-25