Integrated mechanistic models for the study of skeletal muscle protein turnover

用于研究骨骼肌蛋白质周转的综合机制模型

• 批准号: 227870-2010
• 负责人: Phillips, Stuart
• 金额: $ 3.06万
• 依托单位: McMaster University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=546849
• 关键词: Integrated; mechanistic; models; study; skeletal

Skeletal muscle has an obvious role in helping us get around. However, an underappreciated aspect of skeletal muscle is that it is a very metabolically active tissue, is a large contributor to our basal metabolic rate, and is the biggest consumer of blood sugar after we have eaten. As such, maintaining a relatively large and metabolically active amount of muscle is very protective in terms of lowering our risk for development of chronic diseases such as overweight/obesity, type II diabetes, and the simple loss of muscle as we age. Muscle growth in adulthood is known as hypertrophy and occurs when muscles are stressed by having to move heavy external loads. The easiest practical example of this is a weightlifter in who, through regularly lifting heavy loads, we can observe an increase in muscle size of their muscles. Interestingly, this occurs for a large part due to the net addition of new proteins within pre-existing muscle cells; this because muscle cells cannot divide and thus they must accrue protein within their existing cellular size to grow. A net accretion of new muscle proteins occurs therefore when the rate of making new muscle proteins - muscle protein synthesis (MPS) - is elevated. We know that nutrients, in particular protein, and weightlifting are both potent stimulators of MPS. However, stimulation of MPS alone is not enough since proteins within muscles are also continually broken down to maintain efficiently functioning proteins. Thus, muscle growth occurs when the rate of MPS exceeds the rate of muscle protein breakdown. In this proposal experiments will be conducted to help understand what processes are involved in increasing muscle size or, viewed alternatively, in slowing/preventing muscle protein loss. We will use, as potent stimulators of MPS, exercise and protein as well as the active components of protein, amino acids in cells grown in petri dishes. To obtain an integrated view we will also, however, compliment the experiments in cells with experiments in humans to ascertain whether the processes we see in cells are operating in a similar fashion. Our findings have substantial implications for understanding how we might slow muscle loss in, for example, aging.

骨骼肌在帮助我们走动方面起着明显的作用。然而，骨骼肌被低估的一个方面是，它是一种非常活跃的新陈代谢组织，对我们的基础代谢率有很大贡献，而且是我们进食后最大的血糖消耗者。因此，保持相对较大的新陈代谢活跃的肌肉数量是非常有保护作用的，因为它可以降低我们患慢性疾病的风险，如超重/肥胖、II型糖尿病，以及随着年龄的增长而出现的简单的肌肉损失。成年期的肌肉生长被称为肥大，当肌肉因不得不移动沉重的外部负荷而受到压力时就会发生。最简单的实际例子是举重运动员，通过经常举起重物，我们可以观察到他们肌肉的大小增加。有趣的是，这在很大程度上是由于预先存在的肌肉细胞中净添加了新的蛋白质；这是因为肌肉细胞不能分裂，因此它们必须在现有细胞大小内积累蛋白质才能生长。因此，当制造新肌肉蛋白质的速度-肌肉蛋白质合成(MPS)-提高时，新肌肉蛋白质的净增加就会发生。我们知道，营养素，特别是蛋白质和举重都是MPS的有力刺激因素。然而，仅仅刺激MPS是不够的，因为肌肉中的蛋白质也会不断被分解，以维持有效的蛋白质功能。因此，当MPS的速率超过肌肉蛋白质分解的速率时，肌肉就会生长。在这项提案中，将进行实验，以帮助了解增加肌肉尺寸或从另一种角度来看，在减缓/防止肌肉蛋白质损失方面涉及哪些过程。我们将使用培养皿中培养的细胞中的氨基酸作为MPS的有效刺激物，运动和蛋白质以及蛋白质的活性成分。然而，为了获得一个完整的观点，我们还将用人体实验来补充细胞实验，以确定我们在细胞中看到的过程是否以类似的方式运行。我们的发现对理解我们如何减缓肌肉老化等方面的损失具有重要意义。