Increased brain protein levels of carbonyl reductase and alcohol dehydrogenase in Down syndrome and Alzheimer's disease.
Oxidative stress is considered to be crucial in the pathogenesis of Alzheimer's disease-like neurodegeneration. An elevation of carbonyl compounds that are biomarkers of and leading to oxidative stress has been demonstrated in Down Syndrome (DS) and Alzheimer's Disease (AD) brains and seems to be the result of a multifactorial process. Carbonyls, which are cytotoxic metabolic intermediates, are detoxified by either oxidation catalyzed by aldehyde dehydrogenase (ALDH), or by reduction to their corresponding alcohols by carbonyl reductase (CBR) and/or alcohol dehydrogenase (ADH). We quantified protein levels of CBR and its agonist/antagonist ADH using 2D gel electrophoresis with subsequent MALDI-identification and specific software in several brain regions of DS as well as AD patients and compared them to levels of CBR and ADH in brains of controls. Protein levels of both enzymes were increased in several brain regions because of enzyme induction by elevated carbonyls in DS and AD. Increased CBR in DS (trisomy 21) may be due to a gene dosage effect as the gene encoding CBR has been mapped to chromosome 21. These findings may confirm the proposed increase of reactive carbonyls in the brain thus supporting the involvement of oxidative stress and contribute to the understanding of carbonyl handling in brain of both neurodegenerative disorders.
Balcz
B
B
Department of Pediatrics, University of Vienna, Austria.
Kirchner
L
L
Cairns
N
N
Fountoulakis
M
M
Lubec
G
G
D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000032:analysis / Q000378:metabolism*; D000429:Alcohol Oxidoreductases / Q000032:analysis / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000201:enzymology*; D004314:Down Syndrome / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase