Synergistic inhibitory effect of nicotine plus oral contraceptive on mitochondrial complex-IV is mediated by estrogen receptor-β in female rats

Ami P. Raval, Kunjan R. Dave, Isabel Saul, Gabriel J. Gonzalez, Francisca Diaz

Research output: Contribution to journalArticle

8 Scopus citations


Chronic nicotine and oral contraceptive (NOC) exposure caused significant loss of hippocampal membrane-bound estrogen receptor-beta (ER-β) in female rats compared with exposure to nicotine alone. Mitochondrial ER-β regulates estrogen-mediated mitochondrial structure and function; therefore, investigating the impact of NOC on mitochondrial ER-β and its function could help delineate the harmful synergism between nicotine and OC. In this study, we tested the hypothesis that NOC-induced loss of mitochondrial ER-β alters the oxidative phosphorylation system protein levels and mitochondrial respiratory function. This hypothesis was tested in hippocampal mitochondria isolated from female rats exposed to saline, nicotine, OC or NOC for 16 days. NOC decreased the mitochondrial ER-β protein levels and reduced oxygen consumption and complex IV (CIV) activity by 34% and 26% compared with saline- or nicotine-administered groups, respectively. We also observed significantly low protein levels of all mitochondrial-encoded CIV subunits after NOC as compared with the nicotine or saline groups. Similarly, the silencing of ER-β reduced the phosphorylation of cyclic-AMP response element binding protein, and also reduced levels of CIV mitochondrial-encoded subunits after estrogen stimulation. Overall, these results suggest that mitochondrial ER-β loss is responsible for mitochondrial malfunction after NOC.

Original languageEnglish (US)
Pages (from-to)157-167
Number of pages11
JournalJournal of neurochemistry
Issue number1
StatePublished - Apr 1 2012



  • birth control pills
  • complex IV
  • cyclic-AMP response element-binding protein
  • mitochondrial complex activity
  • mitochondrial respiration
  • ROS

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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