Czerniczyniec A, Bustamante J, Lores-Arnaiz S
Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina.
Neuroscience. 2007 Jan 19;144(2):685-93. doi: 10.1016/j.neuroscience.2006.09.050. Epub 2006 Nov 3.
Deprenyl is a selective monoamine oxidase (MAO) B inhibitor, widely used for treatment of Parkinson's disease. The present study shows that deprenyl treatment was able to improve mitochondrial function. Fourteen month old mice were injected i.p. with deprenyl (20 mg/kg) and killed 1.5 h after the administration. Different brain subcellular fractions were isolated from control and deprenyl-treated animals to evaluate the effect of deprenyl on nitric oxide synthase (NOS) activity. Oxygen consumption, hydrogen peroxide (H(2)O(2)) production, mitochondrial membrane potential and calcium-induced permeability transition (MPT) were studied in intact mitochondria. In addition, the effect of deprenyl on respiratory complexes and MAO activities were evaluated in submitochondrial particles (SMP). Monoamine oxidase activity was found to be decreased by 55% in mitochondria from deprenyl-treated animals and as a consequence, H(2)O(2) production was significantly decreased. Deprenyl inhibited NOS activity in cytosolic fractions and SMP by 40% and 55%, respectively. In similar conditions, SMP from deprenyl-treated animals showed increased cytochrome oxidase activity. A 51% increase in the oxygen uptake in state 3 (active respiration state) was found after deprenyl treatment, but no significant changes were observed in state 4 (resting respiration state). Deprenyl treatment protected against calcium-induced depolarization and was able to inhibit calcium-induced MPT. This work provides evidence that deprenyl treatment exerts an improvement of brain mitochondrial function, through a reduction of free radical production, prevention of calcium-induced MPT and maintaining a mitochondrial transmembrane potential.
司来吉兰是一种选择性单胺氧化酶（MAO）B抑制剂，广泛用于治疗帕金森病。本研究表明，司来吉兰治疗能够改善线粒体功能。给14月龄小鼠腹腔注射司来吉兰（20mg/kg），给药后1.5小时处死。从对照动物和经司来吉兰治疗的动物中分离出不同的脑亚细胞组分，以评估司来吉兰对一氧化氮合酶（NOS）活性的影响。在完整的线粒体中研究了氧气消耗、过氧化氢（H₂O₂）产生、线粒体膜电位和钙诱导的通透性转换（MPT）。此外，在亚线粒体颗粒（SMP）中评估了司来吉兰对呼吸复合体和MAO活性的影响。发现经司来吉兰治疗的动物线粒体中的单胺氧化酶活性降低了55%，因此，H₂O₂的产生显著减少。司来吉兰分别抑制细胞溶质组分和SMP中的NOS活性40%和55%。在类似条件下，经司来吉兰治疗的动物的SMP显示细胞色素氧化酶活性增加。司来吉兰治疗后，状态3（活跃呼吸状态）的氧气摄取增加了51%，但在状态4（静息呼吸状态）未观察到显著变化。司来吉兰治疗可防止钙诱导的去极化，并能够抑制钙诱导的MPT。这项工作提供了证据，表明司来吉兰治疗通过减少自由基产生、预防钙诱导的MPT和维持线粒体跨膜电位来改善脑线粒体功能。
