Oxidative damage to skeletal muscle DNA from patients with mitochondrial encephalomyopathies

• Published in: Journal of the neurological sciences 1996-07, Vol.139 (1), p.111-116
• Main Authors: Mitsui, Takao, Kawai, Hisaomi, Nagasawa, Masakazu, Kunishige, Makoto, Akaike, Masashi, Kimura, Yuzo, Saito, Shiro
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-deoxyguanosine; Adult; Aged; Biological and medical sciences; Biopsy, Needle; Chromatography, High Pressure Liquid; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - analysis; Diseases of striated muscles. Neuromuscular diseases; DNA Damage; DNA, Mitochondrial - chemistry; DNA, Mitochondrial - genetics; Encephalomyopathy; Female; Humans; Kearns-Sayre Syndrome - enzymology; Kearns-Sayre Syndrome - genetics; Kearns-Sayre Syndrome - pathology; Male; Medical sciences; Middle Aged; Mitochondrial Myopathies - genetics; Mitochondrial Myopathies - pathology; Muscle, Skeletal - pathology; Neurology; Ophthalmoplegia, Chronic Progressive External - enzymology; Ophthalmoplegia, Chronic Progressive External - genetics; Ophthalmoplegia, Chronic Progressive External - pathology; Oxygen radical; Skeletal muscle; Superoxide dismutase; Superoxide Dismutase - metabolism
• ISSN: 0022-510X; 1878-5883
• DOI: 10.1016/0022-510X(96)00043-3

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.