TY - JOUR
T1 - Proteomic identification of nitrated proteins in Alzheimer's disease brain
AU - Castegna, Alessandra
AU - Thongboonkerd, Visith
AU - Klein, Jon B.
AU - Lynn, Bert
AU - Markesberyl, William R.
AU - Butterfield, D. Allan
PY - 2003/6
Y1 - 2003/6
N2 - Nitration of tyrosine in biological conditions represents a pathological event that is associated with several neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease (AD). Increased levels of nitrated proteins have been reported in AD brain and CSF, demonstrating the potential involvement of reactive nitrogen species (RNS) in neurodegeneration associated with this disease. Reaction of NO with O2-. leads to formation of peroxynitrite ONOO-, which following protonation, generates cytotoxic species that oxidize and nitrate proteins. Several findings suggest an important role of protein nitration in modulating the activity of key enzymes in neurodegenerative disorders, although extensive studies on specific targets of protein nitration in disease are still missing. The present investigation represents a further step in understanding the relationship between oxidative modification of protein and neuronal death in AD. We previously applied a proteomics approach to determine specific targets of protein oxidation in AD brain, by successfully coupling immunochemical detection of protein carbonyls with two-dimensional polyacrylamide gel electrophoresis and mass spectrometry analysis. In the present study, we extend our investigation of protein oxidative modification in AD brain to targets of protein nitration. The identification of six targets of protein nitration in AD brain provides evidence to the importance of oxidative stress in the progression of this dementing disease and potentially establishes a link between RNS-related protein modification and neurodegeneration.
AB - Nitration of tyrosine in biological conditions represents a pathological event that is associated with several neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease (AD). Increased levels of nitrated proteins have been reported in AD brain and CSF, demonstrating the potential involvement of reactive nitrogen species (RNS) in neurodegeneration associated with this disease. Reaction of NO with O2-. leads to formation of peroxynitrite ONOO-, which following protonation, generates cytotoxic species that oxidize and nitrate proteins. Several findings suggest an important role of protein nitration in modulating the activity of key enzymes in neurodegenerative disorders, although extensive studies on specific targets of protein nitration in disease are still missing. The present investigation represents a further step in understanding the relationship between oxidative modification of protein and neuronal death in AD. We previously applied a proteomics approach to determine specific targets of protein oxidation in AD brain, by successfully coupling immunochemical detection of protein carbonyls with two-dimensional polyacrylamide gel electrophoresis and mass spectrometry analysis. In the present study, we extend our investigation of protein oxidative modification in AD brain to targets of protein nitration. The identification of six targets of protein nitration in AD brain provides evidence to the importance of oxidative stress in the progression of this dementing disease and potentially establishes a link between RNS-related protein modification and neurodegeneration.
KW - 3-Nitrotyrosine
KW - Alzheimer's disease
KW - Neurodegeneration
KW - Proteomics
KW - Reactive nitrogen species
UR - http://www.scopus.com/inward/record.url?scp=0038472495&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038472495&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.2003.01786.x
DO - 10.1046/j.1471-4159.2003.01786.x
M3 - Article
C2 - 12787059
AN - SCOPUS:0038472495
SN - 0022-3042
VL - 85
SP - 1394
EP - 1401
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 6
ER -