title: Effect of estrogens on base excision repair in brain and liver mitochondria of aged female rats.
abstract: Changes in the endocrine system have been suggested to act as signaling factors in the regulation of age-related events. Among the different hormones that have been linked to the aging process, estrogens have been widely investigated. They have been associated with inflammatory and oxidative processes and several investigations have established a relationship between the protective effects of estrogens and the mitochondrial function. Mitochondrial DNA is subjected to continuous oxidative attack by free radicals, and the base excision repair (BER) pathway is the main DNA repair route present in mitochondria. We have investigated the effect of estrogen levels on some of the key enzymes of BER in brain and liver mitochondria. In both tissues, depletion of estrogens led to an increased mitochondrial AP endonuclease (mtAPE1) activity, while restoration of estrogen levels by exogenous supplementation resulted in restitution of control APE1 activity only in liver. Moreover, in hepatic mitochondria, changes in estrogen levels affected the processing of oxidative lesions but not deaminations. Our results suggest that changes in mtAPE1 activity are related to specific translocation of the enzyme from the cytosol into the mitochondria probably due to oxidative stress changes as a consequence of changes in estrogen levels.
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Leclère
authors.forename: R
authors.initials: R
authors.lastname: Torregrosa-Muñumer
authors.forename: R
authors.initials: R
authors.lastname: Kireev
authors.forename: C
authors.initials: C
authors.lastname: García
authors.forename: E
authors.initials: E
authors.lastname: Vara
authors.forename: J A F
authors.initials: JA
authors.lastname: Tresguerres
authors.forename: R
authors.initials: R
authors.lastname: Gredilla
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D004967:Estrogens / Q000502:physiology*; D005260:Female; D008928:Mitochondria / Q000502:physiology*; D008930:Mitochondria, Liver / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004967:Estrogens