Electrochemical analysis of protein nitrotyrosine and dityrosine in the Alzheimer brain indicates region-specific accumulation.
HPLC with electrochemical array detection (HPLC-ECD) was used to quantify 3,3'-dityrosine (diTyr) and 3-nitrotyrosine (3-NO2-Tyr) in four regions of the human brain that are differentially affected in Alzheimer's disease (AD). DiTyr and 3-NO2-Tyr levels were elevated consistently in the hippocampus and neocortical regions of the AD brain and in ventricular cerebrospinal fluid (VF), reaching quantities five- to eightfold greater than mean concentrations in brain and VF of cognitively normal subjects. Uric acid, a proposed peroxynitrite scavenger, was decreased globally in the AD brain and VF. The results suggest that AD pathogenesis may involve the activation of oxidant-producing inflammatory enzyme systems, including nitric oxide synthase.
Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
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Hensley
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Maidt
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Yu
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Sang
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Markesbery
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Floyd
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000276:immunology / Q000378:metabolism*; D001921:Brain / Q000276:immunology / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D008297:Male; D009566:Nitrates / Q000032:analysis; D009573:Nitrites / Q000032:analysis; D010084:Oxidation-Reduction; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis; D014527:Uric Acid / Q000032:analysis
D016166:Free Radical Scavengers; D009566:Nitrates; D009573:Nitrites; D014527:Uric Acid; C002744:3-nitrotyrosine; D014443:Tyrosine; C007543:dityrosine