Isofurans, but not F2-isoprostanes, are increased in the substantia nigra of patients with Parkinson's disease and with dementia with Lewy body disease
Isofurans, but not F2-isoprostanes, are increased in the substantia nigra of patients with Parkinson's disease and with dementia with Lewy body disease
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DOI：
10.1046/j.1471-4159.2003.01709.x
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发表时间：
2003-05-01
影响因子：
4.7
通讯作者：
Zhang, J
中科院分区：
文献类型：
--
作者：
Fessel, JP;Hulette, C;Zhang, J
F-2-异前列烷（F-2-IsoPs）是体内氧化应激的公认的敏感和特异性标志物。异呋喃（Isofurans）也是脂质过氧化的产物，但与F-2-IsoPs相反，当体外或体内氧张力增加时，它们的形成是有利的。帕金森病（PD）中的线粒体功能障碍不仅可能导致脑组织的氧化损伤，而且可能导致细胞内氧张力增加，从而影响F-2-IsoPs和IsoFs的相对浓度。在这项研究中，我们试图比较F-2-IsoPs和IsoFs酯化的黑质（SN）中的磷脂水平，从PD患者的年龄匹配的控制，以及与其他神经退行性疾病，包括路易体病痴呆症（DLB），多系统萎缩（MSA），阿尔茨海默病（AD）的患者。结果表明，PD和DLB患者SN中的IsoF显著高于对照组，而F-2-IsoPs则无显著性差异。MSA和AD患者SN中的IsoF和F-2-IsoPs水平与年龄匹配的对照组无明显区别。PD或DLB患者SN中IsoF的优先增加不仅表明这两种疾病中氧化损伤的独特模式，而且表明PD和DLB中多巴胺能神经变性的潜在机制与MSA不同。
F-2-isoprostanes (F-2-IsoPs) are well-established sensitive and specific markers of oxidative stress in vivo. Isofurans (IsoFs) are also products of lipid peroxidation, but in contrast to F-2-IsoPs, their formation is favored when oxygen tension is increased in vitro or in vivo. Mitochondrial dysfunction in Parkinson's disease (PD) may not only lead to oxidative damage to brain tissue but also potentially result in increased intracellular oxygen tension, thereby influencing relative concentrations of F-2-IsoPs and IsoFs. In this study, we attempted to compare the levels of F-2-IsoPs and IsoFs esterified in phospholipids in the substantia nigra (SN) from patients with PD to those of age-matched controls as well as patients with other neurodegenerative diseases, including dementia with Lewy body disease (DLB), multiple system atrophy (MSA), and Alzheimer's disease (AD). The results demonstrated that IsoFs but not F-2-IsoPs in the SN of patients with PD and DLB were significantly higher than those of controls. Levels of IsoFs and F-2-IsoPs in the SN of patients with MSA and AD were indistinguishable from those of age-matched controls. This preferential increase in IsoFs in the SN of patients with PD or DLB not only indicates a unique mode of oxidant injury in these two diseases but also suggests different underlying mechanisms of dopaminergic neurodegeneration in PD and DLB from those of MSA.