Oxidative damage to mitochondrial DNA and its relationship to diabetic complications

Diabetes Res Clin Pract. 1999 Sep;45(2-3):161-8. doi: 10.1016/s0168-8227(99)00046-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA Damage*
  • DNA, Mitochondrial / chemistry
  • DNA, Mitochondrial / genetics*
  • DNA, Mitochondrial / metabolism
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / analysis
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Humans
  • Muscle, Skeletal / metabolism
  • Polymerase Chain Reaction
  • Reference Values
  • Regression Analysis
  • Sequence Deletion

Substances

  • DNA, Mitochondrial
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine