Mitsui T, Kawai H, Nagasawa M, Kunishige M, Akaike M, Kimura Y, Saito S
First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
J Neurol Sci. 1996 Jul;139(1):111-6.
To estimate the oxidative damage to skeletal muscle DNA in mitochondrial encephalomyopathies, we studied the amount of 8-hydroxy-deoxyguanosine (8-OH-dG) and the localization of superoxide dismutase (SOD) in the skeletal muscles of patients with progressive external ophthalmoplegia (PEO) or Kearns-Sayre syndrome (KSS). The molar ratio of 8-OH-dG/deoxyguanosine in skeletal muscle from PEO or KSS patients was significantly higher than the control value. The ratio from patients with polymyositis or Duchenne's muscular dystrophy was not significantly elevated. Immunohistochemical staining for both Mn-SOD and Cu,Zn-SOD showed pronounced staining in the subsarcolemmal and intermyofibrillar regions of cytochrome-oxidase-negative ragged red fibers of KSS or PEO muscles. Our findings suggest that overproduction of 8-OH-dG and mitochondrial dysfunction with gene deletions are associated with each other in muscle cells of patients with PEO or KSS, and that free radicals may play an important role in the pathophysiology of mitochondrial encephalomyopathies.
为评估线粒体脑肌病中骨骼肌DNA的氧化损伤情况，我们研究了进行性眼外肌麻痹（PEO）或凯-塞尔综合征（KSS）患者骨骼肌中8-羟基脱氧鸟苷（8-OH-dG）的含量以及超氧化物歧化酶（SOD）的定位。PEO或KSS患者骨骼肌中8-OH-dG与脱氧鸟苷的摩尔比显著高于对照值。多发性肌炎或杜兴氏肌营养不良患者的该比值未显著升高。对锰超氧化物歧化酶（Mn-SOD）和铜锌超氧化物歧化酶（Cu,Zn-SOD）进行免疫组织化学染色显示，KSS或PEO肌肉中细胞色素氧化酶阴性的破碎红纤维在肌膜下和肌原纤维间区域有明显染色。我们的研究结果表明，在PEO或KSS患者的肌肉细胞中，8-OH-dG的过量产生与基因缺失导致的线粒体线粒体功能障碍相互关联，并且自由基可能在线粒体脑肌病的病理生理学中起重要作用。
