Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, C1113AAD Buenos Aires, Argentina.
Mol Cell Biochem. 2010 Aug;341(1-2):251-7. doi: 10.1007/s11010-010-0456-z. Epub 2010 Apr 8.
Dopamine is a neurotransmitter that has been related to mitochondrial dysfunction. In this study, striatal intact mitochondria and submitochondrial membranes were incubated with different dopamine concentrations, and changes on mitochondrial function, hydrogen peroxide, and nitric oxide production were evaluated. A 35% decrease in state 3 oxygen uptake (active respiration state) was found after 1 mM dopamine incubation. In addition, mitochondrial respiratory control significantly decreased, indicating mitochondrial dysfunction. High dopamine concentrations induced mitochondrial depolarization. Also, evaluation of hydrogen peroxide production by intact striatal mitochondria showed a significant increase after 0.5 and 1 mM dopamine incubation. Incubation with 0.5 and 1 mM dopamine increased nitric oxide production in submitochondrial membranes by 28 and 49%, respectively, as compared with control values. This study provides evidence that high dopamine concentrations induce striatal mitochondrial dysfunction through a decrease in mitochondrial respiratory control and loss of membrane potential, probably mediated by free radical production.
多巴胺是一种与线粒体功能障碍有关的神经递质。在这项研究中,纹状体完整的线粒体和亚线粒体膜与不同浓度的多巴胺孵育,并评估线粒体功能、过氧化氢和一氧化氮的产生的变化。孵育 1mM 多巴胺后,发现状态 3 耗氧量(活性呼吸状态)下降了 35%。此外,线粒体呼吸控制显著降低,表明线粒体功能障碍。高多巴胺浓度诱导线粒体去极化。此外,完整纹状体线粒体产生的过氧化氢的评估显示,孵育 0.5 和 1mM 多巴胺后分别显著增加了 50%和 49%。与对照值相比,0.5 和 1mM 多巴胺孵育分别使亚线粒体膜中一氧化氮的产生增加了 28%和 49%。这项研究提供了证据表明,高多巴胺浓度通过降低线粒体呼吸控制和膜电位的丧失来诱导纹状体线粒体功能障碍,这可能是由自由基产生介导的。