Bharat S, Cochran B C, Hsu M, Liu J, Ames B N, Andersen J K
Buck Institute for Age Research, Novato, CA 94945, USA.
Neurotoxicology. 2002 Oct;23(4-5):479-86. doi: 10.1016/s0161-813x(02)00035-9.
Oxidative stress is believed to play a key role in the degeneration of dopaminergic neurons in the substantia nigra (SN) of Parkinson's disease (PD) patients. An important biochemical feature of PD is a significant early depletion in levels of the thiol antioxidant compound glutathione (GSH) which may lead to the generation of reactive oxygen species (ROS), mitochondrial dysfunction, and ultimately to subsequent neuronal cell death. In earlier work from our laboratory, we demonstrated that depletion of GSH in dopaminergic PC12 cells affects mitochondrial integrity and specifically impairs the activity of mitochondrial complex I. Here we report that pre-treatment of PC12 cells with R-lipoic acid acts to prevent depletion of GSH content and preserves the mitochondrial complex I activity which normally is impaired as a consequence of GSH loss.
氧化应激被认为在帕金森病（PD）患者黑质（SN）中多巴胺能神经元的退化过程中起关键作用。PD的一个重要生化特征是硫醇抗氧化化合物谷胱甘肽（GSH）水平在早期显著降低，这可能导致活性氧（ROS）的产生、线粒体功能障碍，并最终导致随后的神经元细胞死亡。在我们实验室早期的研究中，我们证明多巴胺能PC12细胞中GSH的消耗会影响线粒体的完整性，并特别损害线粒体复合体I的活性。在此我们报告，用R-硫辛酸预处理PC12细胞可防止GSH含量的消耗，并保留线粒体复合体I的活性，而该活性通常会因GSH的损失而受损。
