Oxygen-induced changes in mitochondrial DNA and DNA repair enzymes in aging rat lens

Mech Ageing Dev. 2010 Nov-Dec;131(11-12):666-73. doi: 10.1016/j.mad.2010.09.003. Epub 2010 Sep 18.

Abstract

The treatment of patients with hyperbaric oxygen (HBO), vitrectomy and loss of vitreous gel during aging is associated with a high risk of subsequent development of nuclear cataract. Many studies proved that oxidation is the key reason of nuclear cataract. Reactive oxygen species (ROS) are formed in mitochondria as a by-product of normal metabolism and as a consequence of exposure to environmental compounds. Therefore, mitochondrial DNA (mtDNA) is at particularly high risk of ROS-induced damage. Oxidative damage to mtDNA has been implicated as a causative factor in a wide variety of degenerative diseases and aging. However, the effect of mtDNA damage to the lens has not been studied. The goals of the study were to identify if there was increased mtDNA damage in lens when the eye were exposed to hyperoxic or hypoxic conditions and also to evaluate the changes in gene expression of mtDNA base excision repair (mtBER) enzymes. Our data have shown that the damage of mtDNA, the expression of mtBER enzymes and the level of 8-OHdG in lens increased after inspired hyperoxia, which is likely associated with oxidative stress. However, there was no effect to mtDNA and mtBER enzymes in lens after inspired hypoxia. Nuclear cataract appeared rapidly at 14 month old rats in hyperoxia group, and lens kept transparency in other groups.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Aging / drug effects*
  • Aging / genetics
  • Aging / pathology*
  • Animals
  • Cataract / chemically induced*
  • Cataract / enzymology
  • Cataract / pathology
  • DNA Glycosylases / metabolism
  • DNA Repair Enzymes / metabolism*
  • DNA Repair*
  • DNA, Mitochondrial / drug effects*
  • DNA-Directed DNA Polymerase / metabolism
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / analysis
  • Deoxyguanosine / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression / drug effects
  • Lens, Crystalline / drug effects*
  • Lens, Crystalline / enzymology
  • Lens, Crystalline / pathology
  • Male
  • Oxidative Stress / genetics
  • Oxygen / toxicity*
  • Polymerase Chain Reaction
  • Rats
  • Rats, Wistar

Substances

  • DNA, Mitochondrial
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA-Directed DNA Polymerase
  • DNA Glycosylases
  • OGG1 protein, rat
  • DNA Repair Enzymes
  • Deoxyguanosine
  • Oxygen