Denervated muscle fibers induce mitochondrial peroxide generation in neighboring innervated fibers: Role in muscle aging.
Denervated muscle fibers induce mitochondrial peroxide generation in neighboring innervated fibers: Role in muscle aging.
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DOI：
10.1016/j.freeradbiomed.2017.07.017
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发表时间：
2017-11
影响因子：
7.4
通讯作者：
Jackson MJ
中科院分区：
文献类型：
--
作者：
Pollock N;Staunton CA;Vasilaki A;McArdle A;Jackson MJ
在老化的骨骼肌中，神经肌肉连接的破坏和一些肌肉纤维的去神经支配发生，并导致肌肉质量和功能的损失。衰老与线粒体功能障碍有关，氧化还原稳态的丧失可能通过线粒体产生活性氧（ROS）的增加而发生。在肌肉老化中，线粒体ROS生成增加和去神经支配之间没有明确的联系。为了解决这个问题，我们研究了小鼠胫骨前肌（TA）中所有纤维或部分纤维的实验性去神经支配对肌肉线粒体过氧化生成的影响。横断小鼠腓神经在1-3天内造成突触前轴突的损失，直到术后10天突触后结构没有明显的形态学改变，TA质量和纤维大小明显减少。去神经支配肌肉中的线粒体在横断后3天显示过氧化氢生成增加。电子传递链（ETC）底物和特定途径抑制剂的使用表明ETC不太可能增加ROS的产生，但单胺氧化酶B、NADPH氧化酶和磷脂酶都有牵连。腓神经3支之一的横断导致部分TA肌纤维去神经支配，而另一些保留了神经支配，但在去神经支配和神经支配的纤维中线粒体过氧化生成均增加。因此，新近失神经纤维的存在导致邻近神经支配纤维中线粒体产生的ROS增加，这为骨骼肌中线粒体氧化应激和衰老损伤的增加提供了新的解释。去神经支配导致肌纤维中线粒体过氧化物释放增加。增加线粒体过氧化物释放先于骨骼肌质量的损失。增加的过氧化物释放不是由于ETC复合物产生的超氧化物增加。过氧化氢释放增加发生在去神经纤维和邻近的神经支配纤维中。数据提供了衰老肌肉中线粒体过氧化物增加的解释。
Disruption of neuromuscular junctions and denervation of some muscle fibers occurs in ageing skeletal muscle and contribute to loss of muscle mass and function. Aging is associated with mitochondrial dysfunction and loss of redox homeostasis potentially occurs through increased mitochondrial generation of reactive oxygen species (ROS). No specific link between increased mitochondrial ROS generation and denervation has been defined in muscle ageing. To address this, we have examined the effect of experimental denervation of all fibers, or only a proportion of the fibers, in the mouse tibialis anterior (TA) muscle on muscle mitochondrial peroxide generation. Transection of the peroneal nerve of mice caused loss of pre-synaptic axons within 1–3 days with no significant morphological changes in post-synaptic structures up to 10 days post-surgery when decreased TA mass and fiber size were apparent. Mitochondria in the denervated muscle showed increased peroxide generation by 3 days post-transection. Use of electron transport chain (ETC) substrates and inhibitors of specific pathways indicated that the ETC was unlikely to contribute to increased ROS generation, but monoamine oxidase B, NADPH oxidase and phospholipase enzymes were implicated. Transection of one of the 3 branches of the peroneal nerve caused denervation of some TA muscle fibers while others retained innervation, but increased mitochondrial peroxide generation occurred in both denervated and innervated fibers. Thus the presence of recently denervated fibers leads to increased ROS generation by mitochondria in neighboring innervated fibers providing a novel explanation for the increased mitochondrial oxidative stress and damage seen with aging in skeletal muscles. Denervation causes increased mitochondrial peroxide release in muscle fibers. Increased mitochondrial peroxide release precedes loss of skeletal muscle mass. Increased peroxide release is not due to increased superoxide generation by ETC complexes. Increased peroxide release occurs in both denervated and neighboring innervated fibers. Data provide an explanation for increased mitochondrial peroxide seen in aging muscle.
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影响因子：
3.7
作者：
Chai RJ;Vukovic J;Dunlop S;Grounds MD;Shavlakadze T
通讯作者：
Shavlakadze T
DOI：
10.1152/ajpcell.2001.280.3.c621
发表时间：
2001-03-01
影响因子：
5.5
作者：
McArdle, A;Pattwell, D;Jackson, MJ
通讯作者：
Jackson, MJ
DOI：
10.1073/pnas.82.13.4544
发表时间：
1985-01-01
影响因子：
11.1
作者：
COVAULT, J;SANES, JR
通讯作者：
SANES, JR
影响因子：
7.8
作者：
Sakellariou GK;Pye D;Vasilaki A;Zibrik L;Palomero J;Kabayo T;McArdle F;Van Remmen H;Richardson A;Tidball JG;McArdle A;Jackson MJ
通讯作者：
Jackson MJ
影响因子：
2.5
作者：
Kostrominova, Tatiana Y.
通讯作者：
Kostrominova, Tatiana Y.