Cerebral Vascular Disease Research Laboratories, Leonard M. Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
J Neurochem. 2012 Apr;121(1):157-67. doi: 10.1111/j.1471-4159.2012.07661.x. Epub 2012 Feb 6.
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.
慢性尼古丁和口服避孕药（NOC）暴露导致雌性大鼠海马膜结合雌激素受体-β（ER-β）的显著损失，与单独暴露于尼古丁相比。线粒体 ER-β 调节雌激素介导的线粒体结构和功能；因此，研究 NOC 对线粒体 ER-β 及其功能的影响有助于阐明尼古丁和 OC 之间的有害协同作用。在这项研究中，我们检验了这样一个假设，即 NOC 诱导的线粒体 ER-β 丧失改变了氧化磷酸化系统蛋白水平和线粒体呼吸功能。该假设在接受盐水、尼古丁、OC 或 NOC 处理 16 天的雌性大鼠海马线粒体中进行了测试。与盐水或尼古丁处理组相比，NOC 使线粒体 ER-β 蛋白水平降低，并使耗氧量和复合物 IV（CIV）活性分别降低 34%和 26%。与尼古丁或盐水组相比，我们还观察到 NOC 后所有线粒体编码的 CIV 亚基的蛋白水平显著降低。同样，ER-β 的沉默降低了环磷腺苷反应元件结合蛋白的磷酸化，并且在雌激素刺激后也降低了 CIV 线粒体编码亚基的水平。总体而言，这些结果表明，NOC 后线粒体 ER-β 的丧失是线粒体功能障碍的原因。
