Modulation of autophagy and ubiquitin-proteasome pathways during ultra-endurance running
Modulation of autophagy and ubiquitin-proteasome pathways during ultra-endurance running
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DOI：
10.1152/japplphysiol.00952.2011
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发表时间：
2012-05-01
影响因子：
3.3
通讯作者：
Feasson, Leonard
中科院分区：
文献类型：
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作者：
Jamart, Cecile;Francaux, Marc;Feasson, Leonard
[10]杨文，李文.超耐力跑过程中自噬和泛素-蛋白酶体通路的调节。J Appl Physiol 112：1529-1537，2012.首次发表于2012年2月16日; doi：10.1152/japplphysiol.00952.2011。在这项研究中，协调激活的泛素-蛋白酶体途径（UPP），自噬-溶酶体途径（ALP），和线粒体重塑包括线粒体自噬的蛋白质标记物的测量在超耐力跑运动中评估人骨骼肌。11名男性，经验丰富的超耐力运动员在跑步机上跑了24小时。肌肉活检样品取自股外侧肌2小时前开始和结束后立即运动。运动员跑了149.8 +/- 16.3公里，有效跑步时间为18小时42分钟（+/-41分钟）。Akt的磷酸化状态（-74 +/- 5%; P < 0.001），FOXO 3a（-49 +/- 9%; P < 0.001），mTOR Ser2448（-32 +/-14%; P = 0.028）和4 E-BP 1（-34 +/-7%; P < 0.001）降低，而AMPK磷酸化状态增加了247 +/-170%（P = 0.042）。蛋白酶体β 2亚基活性增加了95 +/- 44%（P = 0.028），而与β 1和β 5亚基相关的活性保持不变。MuRF 1蛋白水平增加了55 +/- 26%（P = 0.034），而MAFbx蛋白和泛素结合蛋白水平没有变化。LC 3bII增加了554 +/- 256%（P = 0.005），与ATG 5缀合的ATG 12的形式增加了36 +/- 17%（P = 0.042）。线粒体分裂标志物磷酸-DRP 1增加了110 +/- 47%（P = 0.003），而融合标志物Mfn 1和线粒体自噬标志物Parkin和PINK 1保持不变。这些结果与超耐力运动期间FOXO 3和AMPK触发的ALP和UPP的协调调节非常吻合。
Jamart C, Francaux M, Millet GY, Deldicque L, Frere D, Feasson L. Modulation of autophagy and ubiquitin-proteasome pathways during ultra-endurance running. J Appl Physiol 112: 1529-1537, 2012. First published February 16, 2012; doi:10.1152/japplphysiol.00952.2011.-In this study, the coordinated activation of ubiquitin-proteasome pathway (UPP), autophagy-lysosomal pathway (ALP), and mitochondrial remodeling including mitophagy was assessed by measuring protein markers during ultra-endurance running exercise in human skeletal muscle. Eleven male, experienced ultra-endurance athletes ran for 24 h on a treadmill. Muscle biopsy samples were taken from the vastus lateralis muscle 2 h before starting and immediately after finishing exercise. Athletes ran 149.8 +/- 16.3 km with an effective running time of 18 h 42 min (+/- 41min). The phosphorylation state of Akt (-74 +/- 5%; P < 0.001), FOXO3a (-49 +/- 9%; P < 0.001), mTOR Ser2448 (-32 +/- 14%; P = 0.028), and 4E-BP1 (-34 +/- 7%; P < 0.001) was decreased, whereas AMPK phosphorylation state increased by 247 +/- 170% (P = 0.042). Proteasome beta 2 subunit activity increased by 95 +/- 44% (P = 0.028), wheras the activities associated with the beta 1 and beta 5 subunits remained unchanged. MuRF1 protein level increased by 55 +/- 26% (P = 0.034), whereas MAFbx protein and ubiquitin-conjugated protein levels did not change. LC3bII increased by 554 +/- 256% (P = 0.005), and the form of ATG12 conjugated to ATG5 increased by 36 +/- 17% (P = 0.042). The mitochondrial fission marker phospho-DRP1 increased by 110 +/- 47% (P = 0.003), whereas the fusion marker Mfn1 and the mitophagy markers Parkin and PINK1 remained unchanged. These results fit well with a coordinated regulation of ALP and UPP triggered by FOXO3 and AMPK during ultra-endurance exercise.