Brain regional quantification of F-ring and D-/E-ring isoprostanes and neuroprostanes in Alzheimer's disease
Brain regional quantification of F-ring and D-/E-ring isoprostanes and neuroprostanes in Alzheimer's disease
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DOI：
10.1016/s0002-9440(10)63968-5
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发表时间：
2001-01-01
影响因子：
6
通讯作者：
Montine, TJ
中科院分区：
文献类型：
--
作者：
Reich, EE;Markesbery, WR;Montine, TJ
异前列腺素（IsoP）仅由花生四烯酸的自由基损伤产生，花生四烯酸是一种均匀分布在整个白色物质和灰质中的脂肪酸，而神经前列腺素（NP）类似地由二十二碳六烯酸（DHA）产生，二十二碳六烯酸是一种富集在灰质中的脂肪酸，其集中在神经元中。IsoP和NP衍生自异构化为D/E-环形式或还原为F-环化合物的内过氧化物中间体。我们定量F环和D/E环IsoP和NPs在颞叶和顶叶皮质，海马，小脑的9个明确的阿尔茨海默病（AD）患者和11个年龄匹配的对照。总NP水平（F环加D/E环），但总IsoP在AD中显著高于对照组（P < 0.0001）;只有AD患者的大脑区域的NPs大于对照组与对照组相比，AD患者的所有脑区中NP的F环与D/E环的比率均降低40 - 70这些数据扩展了原位技术的结果，原位技术通过量化AD患者大脑中含有DHA的室比对照组显著更大的自由基损伤，将脂质过氧化反应产物主要定位于神经元，并表明氧化应激增加的一种机制可能是含有DHA的室的还原能力降低。
Isoprostanes (IsoP) are produced exclusively from free radical damage to arachidonic acid, a fatty acid that is evenly distributed throughout white matter and gray matter, whereas neuroprostanes (NPs) are generated analogously from docosahexaenoic acid (DHA), a fatty acid enriched in gray matter where it is concentrated in neurons. IsoP and NPs derive from endoperoxide intermediates that isomerize to D/E-ring forms or that are reduced to F-ring compounds. We quantified F-ring and D/E-ring IsoP and NPs in temporal and parietal cortex, hippocampus, and cerebellum of nine definite Alzheimer's disease (AD) patients and 11 age-matched controls. Total NP levels (F-ring plus D/E-ring), but not total IsoP, were significantly greater in AD than controls (P < 0.0001); only cerebral regions in AD patients had NPs greater than controls (P < 0.05), The F-ring to D/E-ring ratio for NPs, but not IsoP, was 40 to 70% lower in all brain regions of AD patients compared to controls (P < 0.005), These data extend results from in situ techniques, that have localized reactive products of lipid peroxidation primarily to neurons, by quantifying significantly greater free radical damage to the DHA-containing compartments in cerebrum in AD patients than controls, and suggest that one mechanism of increased oxidative stress may be diminished reducing capacity in DHA-containing compartments.