Increased expression of manganese-superoxide dismutase in fibroblasts of patients with CPEO syndrome

Ching You Lu, Edward K. Wang, Hsin Chen Lee, Huey Jen Tsay, Yau Huei Wei*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)321-329
Number of pages9
JournalMolecular Genetics and Metabolism
Volume80
Issue number3
DOIs
StatePublished - Nov 2003

Keywords

  • CPEO syndrome
  • Free radical scavenging enzyme
  • Mitochondrial DNA
  • Mn-superoxide dismutase
  • Muscle fibroblasts
  • Oxidative stress

Fingerprint

Dive into the research topics of 'Increased expression of manganese-superoxide dismutase in fibroblasts of patients with CPEO syndrome'. Together they form a unique fingerprint.

Cite this