Document Detail

Oxidative damage to mitochondrial DNA in atrial muscle of patients with atrial fibrillation.
MedLine Citation:
PMID:  14607530     Owner:  NLM     Status:  MEDLINE    
Atrial fibrillation (AF) is the most common cause of arrhythmia and is an aging-related disease encountered in clinical practice. The electrophysiological remolding with Ca(2+) overloading and cellular structure changes were found in cardiomyocytes of AF patients. In previous studies, increased oxidative stress and oxidative damage was found in cardiomyocytes during the ischemia/reperfusion injury. Besides, mitochondrial DNA (mtDNA) deletion and mtDNA proliferation occur frequently in affected tissues of patients with certain degenerative diseases and during aging of the human. However, it remains unclear whether high oxidative stress and alteration of mtDNA play a role in the pathophysiology of AF. In this study, we first screened for large-scale deletions of mtDNA in the atrial muscle of AF patients by long-range polymerase chain reaction (PCR). The results showed that large-scale deletions between nucleotide positions 7900 and 16500 of mtDNA occurred at a high frequency. Among them, the 4977 bp deletion was the most frequent and abundant one, and the mean proportion of mtDNA with the 4977 bp deletion in the atrial muscle of the patients with AF was 3.75-fold higher than that of the patients without AF (p <.005). Furthermore, quantitative PCR was performed to evaluate lesions in mtDNA caused by oxidative damage. We found that the degree of mtDNA damage in the patients with AF was greater than that of the patients without AF (3.29 vs.1.60 per 10 kb, p <.0005). The 8-OHdG, which is one of the most common products of oxidative damage to DNA, was also found at a higher frequency in mtDNA of patients with AF as compared with those without AF. In addition, the mtDNA content was found to increase significantly in the patients with AF (p =.0051). The level of mtDNA lesion and the mtDNA content was positively correlated (r = 0.44). These results suggest that oxidative injury and deletion of mtDNA in cardiac muscle are increased in the patients with AF, which may contribute to the impairment of bioenergetic function of mitochondria and induction of the oxidative vicious cycle involved in the pathogenesis of atrial myopathy in AF.
Po Han Lin; Shih Huang Lee; Chia Ping Su; Yau Huei Wei
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Free radical biology & medicine     Volume:  35     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-11-10     Completed Date:  2004-07-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1310-8     Citation Subset:  IM    
Department of Biochemistry and Center for Cellular and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan, Republic of China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Atrial Fibrillation / genetics*
DNA Damage*
DNA, Mitochondrial / genetics*
Deoxyguanosine / analogs & derivatives*,  metabolism
Heart Atria / pathology*
Mitochondria, Heart / genetics,  metabolism
Muscle Fibers, Skeletal / pathology*
Oxidative Stress*
Polymerase Chain Reaction
Sequence Deletion / genetics
Reg. No./Substance:
0/8-hydroxy-2'-deoxyguanosine; 0/DNA, Mitochondrial; 961-07-9/Deoxyguanosine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Urinary excretion of three nucleic acid oxidation adducts and isoprostane F(2)alpha measured by liqu...
Next Document:  Cooperation of antioxidants in protection against photosensitized oxidation.