Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be el...Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be elucidated.Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction.Besides,oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy,whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress.Nevertheless,whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown.Here we show that six-week resistance exercise training significantly improved muscle function,muscle mass,and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice.Mechanistically,Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes.Furthermore,an emerging regulator of cellular defense against toxic and oxidative insults,nuclear factor erythroid2–related factor 2(Nrf2)controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the pathophysiological outcomes of oxidant exposure.In this study,we found that Nrf2 is a target of Sestrin1,and Nrf2 nuclear translocation is facilitated by Sestrin1.ML385(an Nrf2 inhibitor)treatment mitigated the regulatory effects of overexpression-Sestrin1.Therefore,Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy,which may be closely related to its antioxidant capacity,revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.展开更多
目的:探讨不同运动方式对C57BL/6J小鼠骨骼肌应激诱导蛋白Sestrin1-mTOR通路及相关蛋白的影响。方法:18只6周龄雄性C57BL/6J小鼠随机分为安静对照组(CON组)、有氧运动组(AE组)和抗阻运动组(RE组),每组6只。AE组进行12周的有氧跑台运动(6...目的:探讨不同运动方式对C57BL/6J小鼠骨骼肌应激诱导蛋白Sestrin1-mTOR通路及相关蛋白的影响。方法:18只6周龄雄性C57BL/6J小鼠随机分为安静对照组(CON组)、有氧运动组(AE组)和抗阻运动组(RE组),每组6只。AE组进行12周的有氧跑台运动(60分钟/次,5次/周,14米/分钟,坡度0°),RE组进行12周的递增负荷爬梯运动(5组×3次,3次/周)。采用苏木精伊红染色(HE)分析腓肠肌横截面积等形态学特征;蛋白质印记法(Western Blot)检测骨骼肌Sestrin1、Sestrin2、Sestrin3、蛋白激酶B(protein kinase B,AKT)、AMP活化蛋白激酶(AMP-activated protein kinase,AMPK)、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)、m TOR调节相关蛋白(regulatory-associated protein of mTOR,Raptor)、p70核糖体蛋白S6激酶(p70 ribosomal S6 kinase ,p70S6K)的蛋白表达。结果:(1)与CON组相比,AE组和RE组小鼠体重均降低;与CON组相比,RE组腓肠肌湿重较高;与AE组相比,RE组腓肠肌纤维横截面积(cross sectional area,CSA)较大(P<0.05)。(2)腓肠肌中仅表达Sestrin1,并未表达Sestrin2和Sestirn3;与CON组和AE组相比,RE组Sestrin1的表达较高(P<0.05)。(3)与CON组相比,AE组AMPK蛋白表达较高(P<0.05),RE组中mTOR表达较高(P<0.05);与AE组相比,RE组AKT、p70S6K表达较高(P<0.05)。结论:12周有氧运动和抗阻运动均能降低C57BL/6J小鼠体重,但抗阻运动对肌纤维CSA的影响更为显著。腓肠肌中仅表达Sestrin1,且与有氧运动相比,抗阻运动能显著提高Sestrin1蛋白表达。抗阻运动对骨骼肌产生积极影响的潜在机制涉及Sestrin1-mTOR通路的上调。展开更多
基金funded by research grant from National Natural Science Foundation of China(32171135).
文摘Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be elucidated.Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction.Besides,oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy,whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress.Nevertheless,whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown.Here we show that six-week resistance exercise training significantly improved muscle function,muscle mass,and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice.Mechanistically,Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes.Furthermore,an emerging regulator of cellular defense against toxic and oxidative insults,nuclear factor erythroid2–related factor 2(Nrf2)controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the pathophysiological outcomes of oxidant exposure.In this study,we found that Nrf2 is a target of Sestrin1,and Nrf2 nuclear translocation is facilitated by Sestrin1.ML385(an Nrf2 inhibitor)treatment mitigated the regulatory effects of overexpression-Sestrin1.Therefore,Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy,which may be closely related to its antioxidant capacity,revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.
文摘目的:探讨不同运动方式对C57BL/6J小鼠骨骼肌应激诱导蛋白Sestrin1-mTOR通路及相关蛋白的影响。方法:18只6周龄雄性C57BL/6J小鼠随机分为安静对照组(CON组)、有氧运动组(AE组)和抗阻运动组(RE组),每组6只。AE组进行12周的有氧跑台运动(60分钟/次,5次/周,14米/分钟,坡度0°),RE组进行12周的递增负荷爬梯运动(5组×3次,3次/周)。采用苏木精伊红染色(HE)分析腓肠肌横截面积等形态学特征;蛋白质印记法(Western Blot)检测骨骼肌Sestrin1、Sestrin2、Sestrin3、蛋白激酶B(protein kinase B,AKT)、AMP活化蛋白激酶(AMP-activated protein kinase,AMPK)、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,m TOR)、m TOR调节相关蛋白(regulatory-associated protein of mTOR,Raptor)、p70核糖体蛋白S6激酶(p70 ribosomal S6 kinase ,p70S6K)的蛋白表达。结果:(1)与CON组相比,AE组和RE组小鼠体重均降低;与CON组相比,RE组腓肠肌湿重较高;与AE组相比,RE组腓肠肌纤维横截面积(cross sectional area,CSA)较大(P<0.05)。(2)腓肠肌中仅表达Sestrin1,并未表达Sestrin2和Sestirn3;与CON组和AE组相比,RE组Sestrin1的表达较高(P<0.05)。(3)与CON组相比,AE组AMPK蛋白表达较高(P<0.05),RE组中mTOR表达较高(P<0.05);与AE组相比,RE组AKT、p70S6K表达较高(P<0.05)。结论:12周有氧运动和抗阻运动均能降低C57BL/6J小鼠体重,但抗阻运动对肌纤维CSA的影响更为显著。腓肠肌中仅表达Sestrin1,且与有氧运动相比,抗阻运动能显著提高Sestrin1蛋白表达。抗阻运动对骨骼肌产生积极影响的潜在机制涉及Sestrin1-mTOR通路的上调。
