Thiffault C, Aumont N, Quirion R, Poirier J
Department of Pharmacology and Therapeutics, McGill Center for Studies in Aging, Montreal, Quebec, Canada.
J Neurochem. 1995 Dec;65(6):2725-33. doi: 10.1046/j.1471-4159.1995.65062725.x.
Excessive free radical formation or antioxidant enzyme deficiency can result in oxidative stress, a mechanism proposed in the toxicity of MPTP and in the etiology of Parkinson's disease (PD). However, it is unclear if altered antioxidant enzyme activity is sufficient to increase lipid peroxidation in PD. We therefore investigated if MPTP can alter the activity of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) and the level of lipid peroxidation. L-Deprenyl, prior to MPTP administration, is used to inhibit MPP+ formation and its subsequent effect on antioxidant enzymes. MPTP induced a threefold increase in SOD activity in the striatum of C57BL/6 mice. No parallel increase in GSH-PX or CAT activities was observed, while striatal lipid peroxidation decreased. At the level of the substantia nigra (SN), even though increases in CAT activity and reduction in SOD and GSH-PX activities were detected, lipid peroxidation was not altered. Interestingly, L-deprenyl induced similar changes in antioxidant enzymes and lipid peroxidation levels, as did MPTP. Taken together, these results suggest that an alteration in SOD activity, without compensatory increases in CAT or GSH-PX activities, is not sufficient to induce lipid peroxidation.
过量的自由基形成或抗氧化酶缺乏会导致氧化应激，这是一种在MPTP毒性及帕金森病（PD）病因学中被提出的机制。然而，抗氧化酶活性的改变是否足以增加PD中的脂质过氧化尚不清楚。因此，我们研究了MPTP是否会改变抗氧化酶超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-PX）的活性以及脂质过氧化水平。在给予MPTP之前，使用L-司来吉兰抑制MPP+的形成及其对抗氧化酶的后续影响。MPTP使C57BL/6小鼠纹状体中的SOD活性增加了三倍。未观察到GSH-PX或CAT活性的相应增加，而纹状体脂质过氧化减少。在黑质（SN）水平，尽管检测到CAT活性增加以及SOD和GSH-PX活性降低，但脂质过氧化未发生改变。有趣的是，L-司来吉兰诱导的抗氧化酶和脂质过氧化水平变化与MPTP相似。综上所述，这些结果表明，SOD活性改变而无CAT或GSH-PX活性的代偿性增加不足以诱导脂质过氧化。
