Alterations in the expression of
free radical scavenging
enzymes and production of
reactive oxygen species (ROS) in tissue cells may contribute to the pathogenesis of
mitochondrial diseases such as
chronic progressive external ophthalmoplegia (
CPEO) syndrome. Since the mitochondria with impaired respiratory function in affected tissues generate more ROS via electron leakage, we examined the expression levels of
free radical scavenging
enzymes in primary culture of muscle fibroblasts of eight patients with
CPEO syndrome. The results showed that the
enzyme activity and
protein levels of
Mn-SOD of the fibroblasts from
CPEO patients were significantly increased but those of Cu,Zn-SOD,
catalase and
glutathione peroxidase (GPx) were not increased compared with controls. A similar pattern was observed in the
mRNA levels of
Mn-SOD and GPx in muscle fibroblasts of all
CPEO patients. The activity ratios of
Mn-SOD/
catalase and
Mn-SOD/GPx in muscle fibroblasts of the
CPEO patients were increased 1.7-3.4 and 1.8- to 5.3-fold, respectively, compared to those of the controls. Moreover, by using flow cytometry we found that the production of O2(*-) and H2O2 in the fibroblasts was about 2 times higher than those of controls. The 8-OHdG/dG ratios in total
DNA of muscle biopsies from three
CPEO patients were much higher than those of age-matched controls as determined by high performance liquid chromatography (HPLC). In the light of these findings, we suggest that the increase in expression of
Mn-SOD, ROS production and oxidative damage in affected tissues may play an important role in the pathogenesis and progression of the
CPEO syndrome.