HyPer2 imaging reveals temporal and heterogeneous hydrogen peroxide changes in denervated and aged skeletal muscle fibers in vivo

HyPer2 imaging reveals temporal and heterogeneous hydrogen peroxide changes in denervated and aged skeletal muscle fibers in vivo
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HyPer2 成像揭示体内去神经和老化骨骼肌纤维中过氧化氢的时间和异质变化

DOI:
10.1038/s41598-019-51035-w
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发表时间:
2019
期刊:
影响因子:
4.6
通讯作者:
M. Jackson
M. Jackson
中科院分区:
综合性期刊3区
文献类型:
--
作者:
C. Staunton;E. Owen;N. Pollock;A. Vasilaki;R. Barrett;A. Mcardle;M. Jackson

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为了确定去神经支配和运动单位周转在骨骼肌氧化应激的年龄相关性增加中的作用,过氧化氢(H2 O2)特异性的、遗传编码的荧光细胞-Hyper 2探针在小鼠胫骨前肌(AT)中表达,并与线粒体氧化剂生成的离体测量进行比较。腓神经挤压诱导线粒体过氧化物生成增加,在离体透化AT纤维中测量,细胞-Hyper 2荧光的活体共聚焦显微镜显示与纤维萎缩发作相关的单个纤维的子集(~24%)中细胞溶质H2 O2增加。相比之下,与成年(6-8个月)小鼠相比,老年(26个月)小鼠静息肌肉中线粒体过氧化物的产生也增加,但未观察到体内纤维细胞溶质H2 O2的年龄效应。因此,衰老与肌纤维在去神经诱导的线粒体过氧化物产生增加的情况下维持细胞溶质氧化还原稳态的能力增加有关。
To determine the role of denervation and motor unit turnover in the age-related increase in skeletal muscle oxidative stress, the hydrogen peroxide (H2O2) specific, genetically-encoded, fluorescent cyto-HyPer2 probe was expressed in mouse anterior tibialis (AT) muscle and compared with ex vivo measurements of mitochondrial oxidant generation. Crush of the peroneal nerve induced increased mitochondrial peroxide generation, measured in permeabilised AT fibers ex vivo and intra vital confocal microscopy of cyto-HyPer2 fluorescence showed increased cytosolic H2O2 in a sub-set (~24%) of individual fibers associated with onset of fiber atrophy. In comparison, mitochondrial peroxide generation was also increased in resting muscle from old (26 month) mice compared with adult (6–8 month) mice, but no age effect on fiber cytosolic H2O2in vivo was seen. Thus ageing is associated with an increased ability of muscle fibers to maintain cytosolic redox homeostasis in the presence of denervation-induced increase in mitochondrial peroxide generation.
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