Oxidative DNA damage in the parkinsonian brain: An apparent selective increase in 8-hydroxyguanine levels in substantia nigra
Oxidative DNA damage in the parkinsonian brain: An apparent selective increase in 8-hydroxyguanine levels in substantia nigra
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DOI：
10.1046/j.1471-4159.1997.69031196.x
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发表时间：
1997-09-01
影响因子：
4.7
通讯作者：
Halliwell, B
中科院分区：
文献类型：
--
作者：
Alam, ZI;Jenner, A;Halliwell, B
氧化损伤与帕金森病（PD）的病理学有关，例如，已经报道了DNA损伤产物8-羟基-2 ′-脱氧鸟苷水平的升高。然而，许多其他产物是由氧化性DNA损伤引起的，并且产物的模式可以诊断氧化物质。气相色谱/质谱法用于检查对照和PD脑中所有四种DNA碱基的氧化和脱氨基产物。产物在所有检查的脑区域中检测到，包括正常和PD。分析显示，在PD中，8-羟基鸟嘌呤（8-OHG）水平趋于升高，2，6-二氨基-4-羟基-5-甲酰胺基嘧啶（FAP y鸟嘌呤）水平趋于降低。最显著的差异是Pa黑质中8-OHG的升高（p = 0.0002）;其他碱性氧化/脱氨产物的升高不明显，表明8-OHG的升高不太可能是由于过氧亚硝酸盐（ONOO-）或羟基自由基（OH.），然而，8-OHG的一些或全部升高可能是由于8-OHG/FAP γ鸟嘌呤比率的变化，而不是由于总氧化鸟嘌呤损伤的增加。
Oxidative damage has been implicated in the pathology of Parkinson's disease (PD), e.g., rises in the level of the DNA damage product, 8-hydroxy-2'-deoxyguanosine, have been reported. However, many other products result from oxidative DNA damage, and the pattern of products can be diagnostic of the oxidizing species. Gas chromatography/mass spectrometry was used to examine products of oxidation and deamination of all four DNA bases in control and PD brains. Products were detected in all brain regions examined, both normal and PD. Analysis showed that levels of 8-hydroxyguanine (8-OHG) tended to be elevated and levels of 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FAPy guanine) tended to be decreased in PD. The most striking difference was a rise in 8-OHG in Pa substantia nigra (p = 0.0002); rises in other base oxidation/deamination products were not evident, showing that elevation in 8-OHG is unlikely to be due to peroxynitrite (ONOO-) or hydroxyl radicals (OH.), or to be a prooxidant effect of treatment with L-Dopa, However, some or ail of the rise in 8-OHG could be due to a change in 8-OHG/FAPy guanine ratios rather than to an increase in total oxidative guanine damage.