An increase in S-glutathionylated proteins in the Alzheimer's disease inferior parietal lobule, a proteomics approach.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neurofibrillary tangles, senile plaques, and loss of synapses. Many studies support the notion that oxidative stress plays an important role in AD pathogenesis. Previous studies from our laboratory employed redox proteomics to identify oxidatively modified proteins in the AD inferior parietal lobule (IPL) and hippocampus. The proteins were consistent with biochemical or pathological alterations in AD and have been central to further investigations of the disease. The present study focused on the identification of specific targets of protein S-glutathionylation in AD and control IPL by using a redox proteomics approach. For AD IPL, we identified deoxyhemoglobin, alpha-crystallin B, glyceraldehyde phosphate dehydrogenase (GAPDH), and alpha-enolase as significantly S-glutathionylated relative to these brain proteins in control IPL. GAPDH and alpha-enolase were also shown to have reduced activity in the AD IPL. This study demonstrates that specific proteins are sensitive to S-glutathionylation, which most likely is due to their sensitivity to cysteine oxidation initiated by the increase in oxidative stress in the AD brain.
Newman
Shelley F
SF
Department of Chemistry, University of Kentucky, Lexington, Kentucky 40506, USA.
Sultana
Rukhsana
R
Perluigi
Marzia
M
Coccia
Rafella
R
Cai
Jian
J
Pierce
William M
WM
Klein
Jon B
JB
Turner
Delano M
DM
Butterfield
D Allan
DA
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D016022:Case-Control Studies; D003545:Cysteine / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D010296:Parietal Lobe / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D040901:Proteomics; D038203:alpha-Crystallin B Chain / Q000378:metabolism*
D006454:Hemoglobins; D038203:alpha-Crystallin B Chain; C100003:deoxyhemoglobin; C055686:glyceraldehyde 3-phosphate phosphatase; D010744:Phosphoric Monoester Hydrolases; D010751:Phosphopyruvate Hydratase; D005978:Glutathione; D003545:Cysteine