Oxidative damage to skeletal muscle DNA from patients with mitochondrial encephalomyopathies.
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.
Mitsui
T
T
First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
Kawai
H
H
Nagasawa
M
M
Kunishige
M
M
Akaike
M
M
Kimura
Y
Y
Saito
S
S
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000032:analysis; D005260:Female; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D017240:Mitochondrial Myopathies / Q000235:genetics* / Q000473:pathology; D018482:Muscle, Skeletal / Q000473:pathology; D017246:Ophthalmoplegia, Chronic Progressive External / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
D004272:DNA, Mitochondrial; D000080242:8-Hydroxy-2'-Deoxyguanosine; D013482:Superoxide Dismutase; D003849:Deoxyguanosine