Redox responses are preserved across muscle fibres with differential susceptibility to aging.
Redox responses are preserved across muscle fibres with differential susceptibility to aging.
复制标题
氧化还原反应在对衰老的敏感性不同的肌肉纤维中得以保留。
DOI：
10.1016/j.jprot.2018.02.015
复制
发表时间：
2018
影响因子：
3.3
通讯作者：
McDonagh,Brian
中科院分区：
文献类型：
--
作者：
Smith,NeilT;Soriano-Arroquia,Ana;Goljanek-Whysall,Katarzyna;Jackson,MalcolmJ;McDonagh,Brian
与年龄相关的肌肉质量和功能丧失与身体虚弱和独立性丧失有关。不同肌肉类型对年龄相关性萎缩的易感性机制尚不完全清楚。活性氧 (ROS) 被认为是健康肌肉中重要的信号分子，氧化还原敏感蛋白可以响应细胞内 ROS 浓度的变化，从而修饰半胱氨酸 (Cys) 残基上的活性硫醇基团。保守的半胱氨酸残基往往出现在功能上重要的位置，并且可以通过活性位点的修饰或确定蛋白质构象对蛋白质功能产生直接影响。这项工作的目的是确定两种代谢不同的小鼠骨骼肌氧化还原蛋白质组与年龄相关的变化，股四头肌是主要的糖酵解肌肉，比目鱼肌含有较高比例的线粒体。为了检查衰老对整体蛋白质组和单个氧化还原敏感的半胱氨酸残基氧化态的影响，我们采用了无标记蛋白质组学方法，包括还原和可逆氧化半胱氨酸残基的差异标记。我们的结果表明，对衰老的蛋白质组反应取决于肌肉类型，但主要发生在代谢和细胞骨架蛋白中的氧化还原变化通常保留在代谢不同的组织之间。生物学意义与含有较高比例的氧化慢肌纤维的肌肉相比，含有快肌糖酵解纤维的骨骼肌更容易出现与年龄相关的萎缩。收缩的骨骼肌会产生活性氧，这是正确的信号传导和适应运动所必需的，并且众所周知，细胞内的氧化还原环境会随着年龄的增长而变化。为了确定对年龄的不同反应的潜在机制，本文结合了整体蛋白质组学方法和对成年和老年小鼠两种代谢不同的骨骼肌（股四头肌和比目鱼肌）中还原和可逆氧化半胱氨酸残基的差异标记。我们的结果表明，骨骼肌中随年龄增长的整体蛋白质组变化取决于纤维类型。然而，氧化还原特异性变化在不同肌肉类型中得以保留，并伴随着氧化还原敏感半胱氨酸残基数量的减少。
Age-related loss of muscle mass and function is associated with increased frailty and loss of independence. The mechanisms underlying the susceptibility of different muscle types to age-related atrophy are not fully understood. Reactive oxygen species (ROS) are recognised as important signalling molecules in healthy muscle and redox sensitive proteins can respond to intracellular changes in ROS concentrations modifying reactive thiol groups on Cysteine (Cys) residues. Conserved Cys residues tend to occur in functionally important locations and can have a direct impact on protein function through modifications at the active site or determining protein conformation. The aim of this work was to determine age-related changes in the redox proteome of two metabolically distinct murine skeletal muscles, the quadriceps a predominantly glycolytic muscle and the soleus which contains a higher proportion of mitochondria. To examine the effects of aging on the global proteome and the oxidation state of individual redox sensitive Cys residues, we employed a label free proteomics approach including a differential labelling of reduced and reversibly oxidised Cys residues. Our results indicate the proteomic response to aging is dependent on muscle type but redox changes that occur primarily in metabolic and cytoskeletal proteins are generally preserved between metabolically distinct tissues.Biological significanceSkeletal muscle containing fast twitch glycolytic fibres are more susceptible to age related atrophy compared to muscles with higher proportions of oxidative slow twitch fibres. Contracting skeletal muscle generates reactive oxygen species that are required for correct signalling and adaptation to exercise and it is also known that the intracellular redox environment changes with age. To identify potential mechanisms for the distinct response to age, this article combines a global proteomic approach and a differential labelling of reduced and reversibly oxidised Cysteine residues in two metabolically distinct skeletal muscles, quadriceps and soleus, from adult and old mice. Our results indicate that the global proteomic changes with age in skeletal muscles are dependent on fibre type. However, redox specific changes are preserved across muscle types and accompanied with a reduction in the number of redox sensitive Cysteine residues.