Journal
JOURNAL OF NEUROCHEMISTRY
Volume 121, Issue 1, Pages 157-167Publisher
WILEY
DOI: 10.1111/j.1471-4159.2012.07661.x
Keywords
birth control pills; complex IV; cyclic-AMP response element-binding protein; mitochondrial complex activity; mitochondrial respiration; ROS
Categories
Funding
- American Heart Association [0730089N, 11GRNT7370069]
- James and Esther King Biomedical Research Program
- Florida Department of Health [07KN-10]
- Sex and Gender Influences on Addiction and Health: A Developmental Perspective [5 P50 DA024584-05]
- Stanley J. Glaser Foundation
- Drs Chantal and Peritz Scheinberg Research Fund
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Chronic nicotine and oral contraceptive (NOC) exposure caused significant loss of hippocampal membrane-bound estrogen receptor-beta (ER-beta) in female rats compared with exposure to nicotine alone. Mitochondrial ER-beta regulates estrogen-mediated mitochondrial structure and function; therefore, investigating the impact of NOC on mitochondrial ER-beta 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-beta 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-beta 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-beta 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-beta loss is responsible for mitochondrial malfunction after NOC.
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