Reduced synthesis of muscle proteins in chronic renal failure
Reduced synthesis of muscle proteins in chronic renal failure
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DOI：
10.1152/ajpendo.2000.278.2.e219
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发表时间：
2000-02-01
影响因子：
5.1
通讯作者：
Nair, KS
中科院分区：
文献类型：
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作者：
Adey, D;Kumar, R;Nair, KS
慢性肾衰竭患者常发生肌肉萎缩和无力。这些异常发生的机制尚不清楚。我们假设这些发现是由于肌肉蛋白质合成缺陷。在相同的研究条件下，我们测量了12例慢性肾功能衰竭患者和10例健康对照者连续输注L[1-C-13]亮氨酸期间连续肌肉活检样本中混合肌肉蛋白、肌球蛋白重链和线粒体蛋白的合成率。慢性肾功能不全患者混合肌蛋白和肌球蛋白重链的合成率明显降低（分别降低27%和37%，P < 0.05和P < 0.02）。慢性肾功能不全患者肌肉线粒体蛋白合成率（27%）（P < 0.05）、细胞色素c氧化酶活性（42%）（P < 0.007）和柠檬酸合酶（27%）（P < 0.007）也明显下降。肌肉蛋白质合成速率和线粒体酶活性与肾功能衰竭程度呈负相关。这些结果表明，在慢性肾功能衰竭有一个减少的肌肉收缩和线粒体蛋白的合成和减少肌肉线粒体氧化酶。几种肌肉蛋白合成速率的降低可能是慢性肾功能衰竭患者肌肉损失和肌肉无力的生化基础。
Muscle wasting and weakness occur frequently in patients with chronic renal failure. The mechanism(s) by which these abnormalities occur is unclear. We hypothesized that such findings were due to defective muscle protein synthesis. We measured synthetic rates of mixed muscle proteins, myosin heavy chain, and mitochondrial proteins in serial muscle biopsy samples during a continuous infusion of L[1-C-13]leucine from 12 patients with chronic renal failure and 10 healthy control subjects under identical study conditions. Patients with chronic renal failure have significantly lower synthetic rates of mixed muscle proteins and myosin heavy chain (27 and 37% reductions, respectively, P < 0.05 and P < 0.02). Significant declines in the synthetic rates of muscle mitochondrial protein (27%) (P < 0.05), muscle cytochrome c-oxidase activity (42%) (P < 0.007), and citrate synthase (27%) (P < 0.007) were also observed in patients with chronic renal failure. The synthetic rates of muscle proteins and activity of mitochondrial enzymes were negatively correlated to the severity of renal failure. These results indicate that in chronic renal failure there is a decrease in the synthesis of muscle contractile and mitochondrial proteins and a decrease in muscle mitochondrial oxidative enzymes. Reduced synthetic rate of several muscle proteins is the likely biochemical basis of muscle loss and muscle weakness in people with chronic renal failure.