Kaczor Jan J, Robertshaw Holly A, Tarnopolsky Mark A
Department of Pediatrics, McMaster University, Hamilton, Ontario L8N 3Z5, Canada.
Department of Neurobiology of Muscle, Gdansk University of Physical Education and Sport, Gdansk, Poland.
Mol Genet Metab Rep. 2017 Jun 9;12:69-75. doi: 10.1016/j.ymgmr.2017.05.009. eCollection 2017 Sep.
McArdle disease (MCD) is an autosomal recessive condition resulting from skeletal muscle glycogen phosphorylase deficiency. The resultant block in glycogenolysis leads to an increased flux through the xanthine oxidase pathway (myogenic hyperuricemia) and could lead to an increase in oxidative stress. We examined markers of oxidative stress (8-isoprostane and protein carbonyls), NAD(P)H-oxidase, xanthine oxidase and antioxidant enzyme (superoxide dismutase, catalase and glutathione peroxidase) activity in skeletal muscle of MCD patients (N = 12) and controls (N = 12). Eight-isoprostanes and protein carbonyls were higher in MCD patients as compared to controls (p < 0.05). There was a compensatory up-regulation of catalase protein content and activity (p < 0.05), mitochondrial superoxide dismutase (MnSOD) protein content (p < 0.01) and activity (p < 0.05) in MCD patients, yet this increase was not sufficient to protect the muscle against elevated oxidative damage. These results suggest that oxidative stress in McArdle patients occurs and future studies should evaluate a potential role for oxidative stress contributing to acute pathology (rhabdomyolysis) and possibly later onset fixed myopathy.
麦克尔迪氏病（MCD）是一种常染色体隐性疾病，由骨骼肌糖原磷酸化酶缺乏所致。糖原分解过程中由此产生的阻断会导致通过黄嘌呤氧化酶途径的通量增加（肌源性高尿酸血症），并可能导致氧化应激增加。我们检测了MCD患者（N = 12）和对照组（N = 12）骨骼肌中的氧化应激标志物（8-异前列腺素和蛋白质羰基）、NAD(P)H氧化酶、黄嘌呤氧化酶以及抗氧化酶（超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶）的活性。与对照组相比，MCD患者的8-异前列腺素和蛋白质羰基含量更高（p < 0.05）。MCD患者的过氧化氢酶蛋白含量和活性（p < 0.05）、线粒体超氧化物歧化酶（MnSOD）蛋白含量（p < 0.01）和活性（p < 0.05）出现代偿性上调，但这种增加不足以保护肌肉免受氧化损伤的加剧。这些结果表明，麦克尔迪氏病患者存在氧化应激，未来的研究应评估氧化应激在导致急性病理（横纹肌溶解）以及可能在后期发生的固定性肌病中所起的潜在作用。
