Close regulation of peroxiredoxin oxidation is essential for maintenance of muscle mass and function in the elderly.

众所周知，骨骼肌以一种积极的方式对运动做出反应，使肌肉变得更强壮，工作更有效。肌肉通过增加或减少不同蛋白质的含量来做到这一点，但我们仍然不知道锻炼肌肉产生的关键因素是什么，这些因素刺激了导致蛋白质含量变化的信号传递过程。当肌肉运动时，它会产生被称为活性氧的分子，这些分子是启动对运动的积极适应的潜在信号。关键的活性氧物种是过氧化氢，我们的研究团队在研究肌肉中的这种分子方面有丰富的经验。我们已经证明，肌肉收缩过程中产生的极低水平的过氧化氢可以氧化三种高活性的蛋白质，称为过氧化还蛋白1、2和3。我们认为这些蛋白质充当效应器(或中间体)并激活信号通路，导致肌肉适应。我们需要了解这些过氧化还蛋白的作用，以及它们介导的运动适应，因为它们可能为干预提供新的靶点，以帮助在受试者无法有效锻炼和适应的情况下，例如在衰老和各种疾病状态下，帮助维持肌肉质量和功能。因此，我们的详细研究将研究不同过氧化还蛋白缺失的人类肌肉细胞和小鼠肌肉细胞，以实现以下目的：表征人类肌肉细胞对电诱导的收缩和当单个过氧化还蛋白从细胞中删除时对过氧化氢的反应方式。确定缺乏单独的过氧化还蛋白如何影响通过转基因技术缺失特定过氧化还蛋白的小鼠对运动的功能反应。确定骨骼肌收缩活动中过氧化氧还蛋白氧化的关键调节因素，以发现如何控制氧化作为一种潜在的方法来改善老年人肌肉对运动的反应。

It is well known that skeletal muscle responds to exercise in a positive way to make the muscle stronger and work more efficiently. Muscle does this by increasing or decreasing the content of different proteins, but we still do not understand the key factors produced by exercising muscle which stimulate the signalling processes leading to changes in protein content. As muscle exercises it generates molecules, called reactive oxygen species, which are potential signals that initiate positive adaptations to exercise. The key reactive oxygen species is hydrogen peroxide and our research team have a great deal of experience of studying this molecule in muscle. We have shown that the very low levels of hydrogen peroxide generated in muscle during contraction can oxidise three highly reactive proteins, called peroxiredoxins 1, 2 and 3. We believe that these proteins act as effectors (or intermediaries) and activate signalling pathways that lead to adaptations to the muscle. We need to understand the roles of these peroxiredoxins, and which adaptations to exercise they mediate, since they may provide novel targets for interventions to help maintain muscle mass and function in situations where subjects cannot exercise and adapt efficiently, such as in ageing and in various disease states. Our detailed studies will therefore examine muscle cells from humans and muscles from mice in which the different peroxiredoxins are deleted to achieve the following: To characterise the way that human muscle cells respond to electrically induced contractions and to hydrogen peroxide when individual peroxiredoxins are deleted from the cells.To determine how a lack of individual peroxiredoxins affects the functional responses to exercise in mice in which specific peroxiredoxins have been deleted by transgenic techniques. To identify the key regulators of peroxiredoxin oxidation during contractile activity in skeletal muscle in order to find how the oxidation can be controlled as a potential approach to improve the way that muscle responds to exercise in the elderly.