title: Oxidative damage to mitochondrial DNA and its relationship to diabetic complications.
abstract: Increased oxidative stress induced by hyperglycemia may contribute to the pathogenesis of diabetic complications. Oxidative stress is known to increase the conversion of deoxyguanosine (dG) to 8-hydroxydeoxyguanosine (8-OHdG) in DNA, which is linked to increased mitochondrial DNA (mtDNA) deletions. We investigated mtDNA deletions and 8-OHdG in the muscle DNA of non-insulin-dependent diabetes mellitus (NIDDM) patients. mtDNA deletion of 4977 bp (delta mtDNA4977) and the content of 8-OHdG in the muscle DNA of the NIDDM patients were much higher than those of the control subjects. There was a significant correlation between delta mtDNA4977 and the 8-OHdG content (P < 0.0001). Both delta mtDNA4977 and the 8-OHdG content were also correlated with the duration of diabetes. Delta mtDNA4977 and the 8-OHdG content in muscle DNA increased in proportion to the severity of diabetic nephropathy and retinopathy. This is the first report that an increase in delta mtDNA4977 and 8-OHdG is proportional to the severity of diabetic complications. Oxidative mtDNA damage is speculated to contribute to the pathogenesis of diabetic complications though a defect in mitochondrial oxidative phosphorylation or other mechanisms. 8-OHdG and delta mtDNA4977 are useful markers to evaluate oxidative mtDNA damage in the diabetic patients.
authors.affiliation: The Third Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan. ssuzuki@int3.med.tohoku.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Hinokio
authors.forename: K
authors.initials: K
authors.lastname: Komatu
authors.forename: M
authors.initials: M
authors.lastname: Ohtomo
authors.forename: M
authors.initials: M
authors.lastname: Onoda
authors.forename: S
authors.initials: S
authors.lastname: Hirai
authors.forename: M
authors.initials: M
authors.lastname: Hirai
authors.forename: A
authors.initials: A
authors.lastname: Hirai
authors.forename: M
authors.initials: M
authors.lastname: Chiba
authors.forename: S
authors.initials: S
authors.lastname: Kasuga
authors.forename: H
authors.initials: H
authors.lastname: Akai
authors.forename: T
authors.initials: T
authors.lastname: Toyota
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012016:Reference Values; D012044:Regression Analysis; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine