Elevated oxidative stress in patients with ataxia telangiectasia

Antioxid Redox Signal. 2002 Jun;4(3):465-9. doi: 10.1089/15230860260196254.

Abstract

Ataxia telangiectasia (AT) is a pleiotropic genetic disorder characterized by progressive neurodegeneration, especially of cerebellar Purkinje cells, immunodeficiency, increased incidence of cancer, and premature aging. The disease is caused by functional inactivation of the ATM (AT-mutated) gene product, which is thought to act as a sensor of reactive oxygen species and oxidative damage of cellular macromolecules and DNA. The compound phenotype of AT might thus be linked to a continuous state of oxidative stress leading to an increase of programmed cell death (apoptosis). To assess this hypothesis, we analyzed lipid peroxidation products and the oxidative stress associated DNA base damage 8-hydroxy-2-deoxyguanosine in patients with AT. Oxidative damage to lipids and DNA was found to be markedly increased in AT patients. These results indicate that ATM might play an important role in the maintenance of cell homeostasis in response to oxidative damage. In this context, a better control of levels of reactive oxygen species could be a rational foundation of therapeutic intervention to help alleviate some of the symptoms associated with AT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adolescent
  • Adult
  • Apoptosis / physiology*
  • Ataxia Telangiectasia / metabolism*
  • Ataxia Telangiectasia / therapy
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • Child
  • Child, Preschool
  • DNA Damage
  • DNA-Binding Proteins
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / metabolism
  • Female
  • Homeostasis
  • Humans
  • Lipid Peroxidation
  • Lymphocytes / metabolism
  • Male
  • Oxidative Stress*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Tumor Suppressor Proteins

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • 8-Hydroxy-2'-Deoxyguanosine
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases
  • Deoxyguanosine