17β-Estradiol increases expression of the oxidative stress response and DNA repair protein apurinic endonuclease (Ape1) in the cerebral cortex of female mice following hypoxia

Alicia K. Dietrich, Gwendolyn I. Humphreys, Ann M. Nardulli

Research output: Contribution to journalArticle

Abstract

While it is well established that 17β-estradiol (E2) protects the rodent brain from ischemia-induced damage, it has been unclear how this neuroprotective effect is mediated. Interestingly, convincing evidence has also demonstrated that maintaining or increasing the expression of the oxidative stress response and DNA repair protein apurinic endonuclease 1 (Ape1) is instrumental in reducing ischemia-induced damage in the brain. Since E 2 increases expression of the oxidative stress response proteins Cu/Zn superoxide dismutase and thioredoxin in the brain, we hypothesized that E2 may also increase Ape1 expression and that this E 2-induced expression of Ape1 may help to mediate the neuroprotective effects of E2 in the brain. To test this hypothesis, we utilized three model systems including primary cortical neurons, brain slice cultures, and whole animals. Although estrogen receptor α and Ape1 were expressed in primary cortical neurons, E2 did not alter Ape1 expression in these cells. However, immunofluorescent staining and quantitative Western blot analysis demonstrated that estrogen receptor α and Ape1 were expressed in the nuclei of cortical neurons in brain slice cultures and that E2 increased Ape1 expression in the cerebral cortex of these cultures. Furthermore, Ape1 expression was increased and oxidative DNA damage was decreased in the cerebral cortices of ovariectomized female C57Bl/6J mice that had been treated with E2 and exposed to hypoxia. Taken together, our studies demonstrate that the neuronal microenvironment may be required for increased Ape1 expression and that E2 enhances expression of Ape1 and reduces oxidative DNA damage, which may in turn help to reduce ischemia-induced damage in the cerebral cortex and mediate the neuroprotective effects of E2.

Original languageEnglish (US)
Pages (from-to)410-420
Number of pages11
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume138
DOIs
StatePublished - Oct 1 2013

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DNA-(Apurinic or Apyrimidinic Site) Lyase
Oxidative stress
DNA Repair
Cerebral Cortex
Estradiol
Oxidative Stress
Repair
DNA
Brain
Proteins
Neuroprotective Agents
Neurons
Estrogen Receptors
DNA Damage
Ischemia
Hypoxia
Thioredoxins
Heat-Shock Proteins
Brain Ischemia
Rodentia

Keywords

  • Apurinic endonuclease 1
  • Estrogen
  • Estrogen receptor
  • Hypoxia
  • Neuroprotection
  • Reactive oxygen species

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

17β-Estradiol increases expression of the oxidative stress response and DNA repair protein apurinic endonuclease (Ape1) in the cerebral cortex of female mice following hypoxia. / Dietrich, Alicia K.; Humphreys, Gwendolyn I.; Nardulli, Ann M.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 138, 01.10.2013, p. 410-420.

Research output: Contribution to journalArticle

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