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

过氧化还原蛋白氧化的密切调节对于维持老年人的肌肉质量和功能至关重要。

• 批准号: MR/V03412X/1
• 负责人: Malcolm Jackson
• 金额: $ 62.5万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV03412X%2F1
• 关键词: Close; regulation; peroxiredoxin; oxidation; essential

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.

众所周知，骨骼肌以积极的方式对运动做出反应，使肌肉更强壮，更有效地工作。肌肉通过增加或减少不同蛋白质的含量来做到这一点，但我们仍然不了解运动肌肉刺激导致蛋白质含量变化的信号传导过程所产生的关键因素。当肌肉运动时，它会产生分子，称为活性氧，这是启动积极适应运动的潜在信号。关键的活性氧是过氧化氢，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非常低水平的过氧化氢可以氧化三种高活性蛋白质，称为过氧化物酶1，2和3。我们认为这些蛋白质作为效应物（或中介物）并激活导致肌肉适应的信号通路。我们需要了解这些过氧化物酶的作用，以及它们介导的运动适应性，因为它们可能为干预提供新的目标，以帮助在受试者无法有效运动和适应的情况下保持肌肉质量和功能，例如在衰老和各种疾病状态下。因此，我们的详细研究将检查来自人类的肌肉细胞和来自小鼠的肌肉，其中删除了不同的过氧化物酶，以实现以下目标：为了阐明当单个过氧化物酶从细胞中删除时，人类肌肉细胞对电诱导收缩和过氧化氢的反应方式，为了确定单个过氧化物酶的缺乏如何影响小鼠对运动的功能反应，已经通过转基因技术删除了过氧化物氧还蛋白。确定骨骼肌收缩活动期间过氧化物氧还蛋白氧化的关键调节因子，以发现如何控制氧化作为改善老年人肌肉对运动反应的潜在方法。

项目成果

Redox Control of Signalling Responses to Contractile Activity and Ageing in Skeletal Muscle.

• DOI: 10.3390/cells11101698
• 发表时间: 2022-05-20
• 期刊: Cells
• 影响因子: 6

Redox control of signalling responses to contractile activity and aging in skeletal muscle

骨骼肌收缩活动和衰老信号反应的氧化还原控制

• DOI: 10.1530/rem-23-0014
• 发表时间: 2023
• 期刊: Redox Experimental Medicine
• 作者: Jackson M