Reduced levels of DEAD-box proteins DBP-RB and p72 in fetal Down syndrome brains.
Down syndrome (DS) is characterized by abnormal brain morphology and neurological and behavioral functions. The pivotal role of helicases in brain development, growth, and differentiation made us evaluate three DEAD BOX proteins, DEAD-box protein 1 (DBP-RB), DEAD-box protein 3 (HLP2), DEAD-box protein 72 (P72), and the RuvB-like DNA helicase (TIP49b), in fetal brain of controls and DS subjects, using two-dimensional electrophoresis with subsequent mass spectroscopic (MALDI-MS) identification. HLP2 and TIP49b brain levels were comparable between DS and controls, and protein levels of p72 and DBP-RB were significantly reduced in DS fetal cortex (p72: 2.04+/-1.90 vs. 5.57+/-2.56 in controls, p < 0.01; DBP-RB: 0.58+/-0.94 vs. 1.90+/-0.97 in controls, p < 0.01). Impairment of the helicases p72 and DBP-RB may reflect or lead to deficient growth and differentiation of brain development early in life and can be considered pathogenetic factors along with the reported deficits of transcription, splicing, and elongation factors already described in fetal DS brains.
Kircher
Susanne G
SG
Institute of Medical Chemistry, University of Vienna, Austria.
Kim
Seong Hwan
SH
Fountoulakis
Michael
M
Lubec
Gert
G
D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D001921:Brain / Q000196:embryology*; D002352:Carrier Proteins / Q000378:metabolism; D053487:DEAD-box RNA Helicases; D004265:DNA Helicases / Q000378:metabolism; D004314:Down Syndrome / Q000196:embryology*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005333:Fetus / Q000378:metabolism; D006801:Humans; D008297:Male; D020365:RNA Helicases / Q000378:metabolism*; D012016:Reference Values; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D002352:Carrier Proteins; D000251:Adenosine Triphosphatases; C086252:DDX1 protein, human; C102004:DDX17 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C122079:RUVBL2 protein, human; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases