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The Journal of Neuroscience, October 15, 1998, 18(20):8126-8132
Electrochemical Analysis of Protein Nitrotyrosine and Dityrosine in the Alzheimer Brain Indicates Region-Specific Accumulation
Kenneth Hensley1, Michael L. Maidt1, Zhenqiang Yu1, Hong Sang1, William R. Markesbery2, and Robert A. Floyd1 1 Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, and 2 Department of Neurology and Anatomy and Sanders Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40528
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.
Key words: HPLC; nitrotyrosine; dityrosine; Alzheimer's disease; protein oxidation; inflammation
Copyright © 1998 Society for Neuroscience 0270-6474/98/18208126-07$05.00/0
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