Ageing-induced changes in the redox status of peripheral motor nerves imply an effect on redox signalling rather than oxidative damage.
Ageing-induced changes in the redox status of peripheral motor nerves imply an effect on redox signalling rather than oxidative damage.
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DOI：
10.1016/j.freeradbiomed.2016.02.008
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发表时间：
2016-05
影响因子：
7.4
通讯作者：
Jackson MJ
中科院分区：
文献类型：
--
作者：
McDonagh B;Scullion SM;Vasilaki A;Pollock N;McArdle A;Jackson MJ
衰老与骨骼肌纤维的丧失、剩余纤维的萎缩和虚弱有关。肌肉的这些变化伴随着运动神经元和神经肌肉连接的中断，尽管神经和肌肉退化之间的直接关系尚不清楚。氧化变化与导致与年龄相关的肌肉质量丧失和中枢神经系统退化的机制有关，但对供应受衰老影响的肌肉的特定外周神经中与年龄相关的氧化变化知之甚少。因此，我们在胫前肌质量和功能明显丧失的年龄对老年小鼠的坐骨神经进行了检查。老年小鼠坐骨神经的氧化损伤没有明显增加，但电子顺磁共振(EPR)研究表明，静息状态下老年小鼠神经中超氧化物和/或过氧亚硝酸根的活性增加，而电刺激神经以激活肌肉收缩进一步加剧了这种活性。蛋白质组学分析表明，老年小鼠神经中特定的氧化还原敏感蛋白含量增加，这可能反映了一种适应，以调节增加的超氧化物/过氧亚硝酸盐，并维持氧化还原稳态。对氧化还原活性半胱氨酸的分析表明，老年小鼠神经中特定蛋白质的可逆氧化增加了一些，但这并不是所有氧化还原活性半胱氨酸都普遍存在的。对老年小鼠神经中氧化还原活性半胱氨酸的详细分析表明，可逆氧化作用略有增加，这将与其氧化还原信号功能的变化相适应。总而言之，目前的数据表明，老年小鼠的坐骨神经并没有表现出与TA和它所支配的其他肌肉类似的氧化损伤的显著增加。我们的结果表明，随着关键半胱氨酸氧化的微小变化，适应了氧化增加的情况，这可能有助于神经中有缺陷的氧化还原信号。骨质疏松症伴随运动神经元和神经肌肉接头的破坏。陈旧的神经减少了轴突的数量和直径。EPR研究表明，老年神经中的超氧化物/过亚硝酸根活性增加。陈旧的神经表现出氧化还原敏感蛋白的变化，而不会造成重大的氧化损伤。结果表明，老年小鼠神经中的氧化还原信号通路发生了变化。
Ageing is associated with loss of skeletal muscle fibres, atrophy of the remaining fibres and weakness. These changes in muscle are accompanied by disruption of motor neurons and neuromuscular junctions although the direct relationship between the nerve and muscle degeneration is not understood. Oxidative changes have been implicated in the mechanisms leading to age-related loss of muscle mass and in degeneration of the central nervous system, but little is known about age-related changes in oxidation in specific peripheral nerves that supply muscles that are affected by ageing. We have therefore examined the sciatic nerve of old mice at an age when loss of tibialis anterior muscle mass and function is apparent. Sciatic nerve from old mice did not show a gross increase in oxidative damage, but electron paramagnetic resonance (EPR) studies indicated an increase in the activity of superoxide and/or peroxynitrite in the nerves of old mice at rest that was further exacerbated by electrical stimulation of the nerve to activate muscle contractions. Proteomic analyses indicated that specific redox-sensitive proteins are increased in content in the nerves of old mice that may reflect an adaptation to regulate the increased superoxide/peroxynitrite and maintain redox homoeostasis. Analysis of redox active cysteines showed some increase in reversible oxidation in specific proteins in nerves of old mice, but this was not universally seen across all redox-active cysteines. Detailed analysis of the redox-active cysteine in one protein in the nerve of old mice that is key to redox signalling (Peroxiredoxin 6, Cys 47) showed a minor increase in reversible oxidation that would be compatible with a change in its redox signalling function. In conclusion, the data presented indicate that sciatic nerve from old mice does not show a gross increase in oxidative damage similar to that seen in the TA and other muscles that it innervates. Our results indicate an adaptation to increased oxidation with minor changes in the oxidation of key cysteines that may contribute to defective redox signalling in the nerve. Sarcopenia is accompanied by disruption of motor neurons and neuromuscular junctions. Old nerves have decreased axon numbers and diameter. EPR studies showed increased superoxide/peroxynitrite activities in old nerves. Old nerves show changes in redox sensitive proteins without major oxidative damage. Results indicate altered redox signalling pathways in nerves from old mice.