Department of Aerospace Physiology, Fourth Military Medical University, Xi'an, China.
Mol Cell Biochem. 2012 Aug;367(1-2):113-24. doi: 10.1007/s11010-012-1325-8. Epub 2012 May 1.
Unloading in spaceflight or long-term bed rest induces to pronounced atrophy of anti-gravity skeletal muscles. Passive stretch partially resists unloading-induced atrophy of skeletal muscle, but the mechanism remains elusive. The aims of this study were to investigate the hypotheses that stretch tension might increase protein level of neuronal nitric oxide synthase (nNOS) in unloaded skeletal muscle, and then nNOS-derived NO alleviated atrophy of skeletal muscle by inhibiting calpain activity. The tail-suspended rats were used to unload rat hindlimbs for 2 weeks, at the same time, left soleus muscle was stretched by applying a plaster cast to fix the ankle at 35° dorsiflexion. Stretch partially resisted atrophy and inhibited the decreased protein level and activity of nNOS in unloaded soleus muscles. Unloading increased frequency of calcium sparks and elevated intracellular resting and caffeine-induced Ca(2+) concentration ([Ca(2+)]i) in unloaded soleus muscle fibers. Stretch reduced frequency of calcium sparks and restored intracellular resting and caffeine-induced Ca(2+) concentration to control levels in unloaded soleus muscle fibers. The increased protein level and activity of calpain as well as the higher degradation of desmin induced by unloading were inhibited by stretch in soleus muscles. In conclusion, these results suggest that stretch can preserve the stability of sarcoplasmic reticulum Ca(2+) release channels which prevents the elevated [Ca(2+)]i by means of keeping nNOS activity, and then the enhanced protein level and activity of calpain return to control levels in unloaded soleus muscles. Therefore, stretch can resist in part atrophy of unloaded soleus muscles.
在太空飞行或长期卧床休息中，承重骨骼肌肉会出现明显的萎缩。被动拉伸可部分抵抗骨骼肌肉失重大鼠的萎缩，但具体机制尚不清楚。本研究旨在验证以下假设：拉伸张力可能会增加失重大鼠骨骼肌中神经元型一氧化氮合酶（nNOS）的蛋白水平，然后 nNOS 衍生的一氧化氮（NO）通过抑制钙蛋白酶活性来减轻骨骼肌萎缩。采用尾部悬吊大鼠来使大鼠后肢负重 2 周，同时通过将石膏固定在踝关节处使左比目鱼肌拉伸至 35°背屈位。拉伸部分抵抗了萎缩，并抑制了失重大鼠比目鱼肌中 nNOS 蛋白水平和活性的降低。失重则增加了钙火花的频率，并升高了失重大鼠比目鱼肌纤维中的细胞内静息状态和咖啡因诱导的 Ca²⁺浓度([Ca²⁺]i)。拉伸降低了钙火花的频率，并将失重大鼠比目鱼肌纤维中的细胞内静息状态和咖啡因诱导的 Ca²⁺浓度恢复至对照水平。拉伸抑制了钙蛋白酶的蛋白水平和活性的增加，以及失重大鼠比目鱼肌中肌联蛋白的降解。总之，这些结果表明，拉伸可以维持肌浆网 Ca²⁺释放通道的稳定性，防止因[Ca²⁺]i 升高而引起的钙蛋白酶蛋白水平和活性的增强，从而在失重大鼠比目鱼肌中部分抵抗萎缩。
