Estradiol in vivo regulation of brain mitochondrial proteome

Jon Nilsen, Ronald W. Irwin, Timothy K. Gallaher, Roberta Diaz Brinton

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

Abstract

We used a combined proteomic and functional biochemical approach to determine the overall impact of 17β-estradiol (E2) on mitochondrial protein expression and function. To elucidate mitochondrial pathways activated by E2 in brain, two-dimensional (2D) gel electrophoresis was conducted to screen the mitoproteome. Ovariectomized adult female rats were treated with a single injection of E2. After 24 h of E2 exposure, mitochondria were purified from brain and 2D analysis and liquid chromatography-tandem mass spectrometry protein identification were conducted. Results of proteomic analyses indicated that of the 499 protein spots detected by image analysis, a total of 66 protein spots had a twofold or greater change in expression. Of these, 28 proteins were increased in expression after E2 treatment whereas 38 proteins were decreased in expression relative to control. E2 regulated key metabolic enzymes including pyruvate dehydrogenase, aconitase, and ATP-synthase. To confirm that E 2-inducible changes in protein expression translated into functional consequences, we determined the impact of E2 on the enzymatic activity of the mitochondrial electron transport chain. In vivo, E2 treatment enhanced brain mitochondrial efficiency as evidenced by increased respiratory control ratio, elevated cytochrome-c oxidase activity and expression while simultaneously reducing free radical generation in brain. Results of these analyses provide insights into E2 mechanisms of regulating brain mitochondria, which have the potential for sustaining neurological health and prevention of neurodegenerative diseases associated with mitochondrial dysfunction such as Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)14069-14077
Number of pages9
JournalJournal of Neuroscience
Volume27
Issue number51
DOIs
StatePublished - Dec 19 2007
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Biomarker
  • Estrogen receptor
  • Mitochondria
  • Proteomics
  • Therapeutic development

ASJC Scopus subject areas

  • Neuroscience(all)

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