Gene expression during inactivity-induced muscle atrophy: effects of brief bouts of a forceful contraction countermeasure

Gene expression during inactivity-induced muscle atrophy: effects of brief bouts of a forceful contraction countermeasure
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DOI:
10.1152/japplphysiol.90668.2008
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发表时间:
2008-10-01
影响因子:
3.3
通讯作者:
Edgerton, V. Reggie
Edgerton, V. Reggie
中科院分区:
医学2区
文献类型:
--
作者:
Kim, Soo J.;Roy, Roland R.;Edgerton, V. Reggie

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肌肉蛋白质代谢的合成代谢和分解代谢标志物进行了检查,在不活动引起的萎缩肌肉,每天短时间,高阻力等长收缩。通过脊髓隔离(SI)实现不活动,这导致后肢肌肉组织接近不活动,而不影响运动神经元-肌肉连接。成年大鼠被分配到对照组(Con)或SI组,其中一条肢体被刺激(SI-Stim,连续5天的高负荷等长收缩的短暂发作),而另一条肢体作为SI对照组(SI)。内侧腓肠肌(MG)和比目鱼肌重量(相对于体重)均与SI中Con的71%相似,但在SI-刺激组中维持在Con。IGF-1/磷脂酰肌醇3-激酶(PI 3 K)/Akt蛋白合成途径的活性在MG的所有组中相似。atrogin-1和肌肉环指-1(MuRF-1),蛋白质降解的标志物的表达,在MG和比目鱼肌的SI高于Con,并保持在Con的SI刺激。与Con相比,SI中MG和比目鱼肌中的抗生长因子肌肉生长抑制素不受影响,但SI-Stim的MG中的抗生长因子肌肉生长抑制素较低。这些结果表明,特定蛋白质分解代谢途径的上调在SI诱导的萎缩中起着关键作用,而这种反应被每天4分钟的高电阻机电刺激减弱,并且能够保留大部分肌肉质量。虽然蛋白合成代谢途径(IGF-1/PI 3 K/Akt)似乎在SI模型中调节质量中起次要作用,但增加的翻译能力可能有助于响应等长收缩的质量保持。
Anabolic and catabolic markers of muscle protein metabolism were examined in inactivity-induced atrophying muscles with and without daily short-duration, high-resistance isometric contractions. Inactivity was achieved via spinal cord isolation (SI), which results in near inactivity of the hindlimb musculature without compromising the motoneuron-muscle connectivity. Adult rats were assigned to a control (Con) or SI group in which one limb was stimulated (SI-Stim, 5 consecutive days of brief bouts of high-load isometric contractions) while the other served as a SI control (SI). Both the medial gastrocnemius (MG) and soleus weights (relative to body weight) were similar to 71% of Con in the SI, but maintained at Con in the SI-Stim group. Activity of the IGF-1/phosphatidylinositol 3-kinase (PI3K)/Akt pathway of protein synthesis was similar among all groups in the MG. Expression of atrogin-1 and muscle RING finger-1 (MuRF-1), markers of protein degradation, were higher in the MG and soleus of the SI than Con and maintained at Con in the SI-Stim. Compared with Con, the anti-growth factor myostatin was unaffected in the MG and soleus in the SI but was lower in the MG of the SI-Stim. These results demonstrate that upregulation of specific protein catabolic pathways plays a critical role in SI-induced atrophy, while this response was blunted by 4 min of daily high-resistance electromechanical stimulation and was able to preserve most of the muscle mass. Although the protein anabolic pathway (IGF-1/PI3K/Akt) appears to play a minor role in regulating mass in the SI model, increased translational capacity may have contributed to mass preservation in response to isometric contractions.