Superoxide dismutase SOD1, encoded on chromosome 21, but not SOD2 is overexpressed in brains of patients with Down syndrome.
BACKGROUND
The antioxidant enzyme Cu/Zn-superoxide dismutase-1 (SOD1) gene is localized to chromosome 21q22.1 and catalyzes the dismutation of superoxide anions to hydrogen peroxide, which may lead to the increased production of active oxygen species in Down Syndrome (DS), trisomy 21. Although a number of studies have addressed this question, proposing the overexpression hypothesis, no specific protein-chemical data on SOD protein levels in the brains of patients with DS are available.


METHODS
We therefore determined the protein SOD-1 and SOD-2 levels in the brains of controls (n = 9) and adult patients with DS (n = 9) and Alzheimer disease (AD; n = 9). Two-dimensional electrophoresis followed by matrix-assisted laser desorption/ionization-mass spectroscopy detection and identification was used for the analyses.


RESULTS
We found significantly increased SOD-1 levels in DS temporal, parietal, and occipital cortex, whereas SOD-1 was decreased in the AD temporal cortex and SOD-2 was comparable between all groups.


CONCLUSIONS
Increased SOD-1 levels in patients with DS may reflect the overexpression by the trisomic state, as a response to the oxidative stress, as has been proposed in DS by several authors. However, it well may be that glial proliferation, which is markedly increased in DS brain, may underlie the increased brain levels of this ubiquitous protein. The decrease of SOD1 in the temporal cortex of patients with AD may reflect an antiapoptotic mechanism or simply cell loss in the brain.
Gulesserian
T
T
Department of Pediatrics, University of Vienna, Austria.
Seidl
R
R
Hardmeier
R
R
Cairns
N
N
Lubec
G
G
D000368:Aged; D000544:Alzheimer Disease / Q000201:enzymology; D001921:Brain / Q000201:enzymology; D016022:Case-Control Studies; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D004314:Down Syndrome / Q000201:enzymology* / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1
C000606290:SOD1 protein, human; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1