Studies on oxidative damage and mitochondrial DNA mutations in patients with cardiomyopathy

• Main Authors: Chia-Ping Su, 蘇佳苹
• Other Authors: Yau-Huei Wei
• Format: Others
• Language: zh-TW
• Published: 1999
• Online Access: http://ndltd.ncl.edu.tw/handle/39435551997394154067

碩士 === 國立陽明大學 === 生物化學研究所 === 87 === Abstract Atrial fibrillation (AF), a commonly encountered arrhythmia, has been a subject of increasing interest and intensive clinical research. It was shown that, in dog model, severe changes in the architecture of both left atria and right atria occurred after 6 weeks of rapid atrial pacing. These changes were characterized by marked increase in the number and size of mitochondria and by disruption of the sarcoplasmic reticulum. The mitochondrion is the power plant of aerobic cells, and reactive oxygen species (ROS) are continually formed in vivo during normal oxidative metabolism. We hypothesized that muscles of the patients with cardiomyopathy including AF are subjected to higher oxidative stress and are afflicted with more severe oxidative damage. Thus, we investigated GSH/GSSG ratio together with oxidative damage in the atrial muscle of patients with AF and other heart diseases. In the first part of this study, we found that the heart tissues from the patients with AF had significantly higher oxidative damage. The tissue levels of 8-OH-dG/dG ratio (0.91±0.11 x10-4) and lipid peroxides (0.32±0.03 pmol/mg protein) were significantly higher than those of the controls (8-OH-dG/dG, 0.63±0.05 x10-4; lipid peroxides, 0.24±0.05 pmol/mg protein)(p<0.05). The average GSH/GSSG ratio(56.14±9.71) of the patients with AF was lower that of the controls (74.66±12.50) although the difference did not reach the significant level. In the second part of the study, we identified 4,977-bp and 7,436-bp mtDNA deletions in the heart tissues of patients with AF and other diseases. We observed that the incidences of 4,977-bp deletion (15/16) and 7,436-bp (6/13) deletion in the heart tissues of patients with AF were higher than those of the control (22/37; 4/23). We also found that the proportion of mtDNA with the 4,977-bp deletion was well correlated with the degree of oxidative damage, as indicated by 8-OH-dG content in the heart tissues of patients with AF. These findings suggest that the heart tissues of patients with AF are exposed to higher oxidative stress and suffer from more frequent attack of free radicals attack, and are thus afflicted with more severe oxidative damage as compared to the heart tissues of normal controls.