title: Decreased protein levels of complex I 30-kDa subunit in fetal Down syndrome brains.
abstract: Defects of mitochondrial electron transport enzymes have been implicated in the pathogenesis of several neurodegenerative diseases. In previous work, we reported decreased protein levels of mitochondrial electron transport enzyme subunits in adult brain with Down syndrome (DS). However it is not clear whether cellular damage due to mitochondrial defects in brain of DS fetus begins in utero. Here we investigated the protein levels of mitochondrial electron transport enzymes in fetal DS brain using the proteomic technologies. Two-dimensional (2-D) gel electrophoresis, matrix-assisted laser desorption ionization mass spectroscopy (MALDI-MS) and specific software for quantification were used. The protein levels of complex I 30-kDa subunit were significantly decreased in cerebral cortex of fetal DS brain. We conclude that decreased mitochondrial electron transport enzyme subunits in fetal DS brains could contribute to the impaired energy and free radical metabolism affecting brain development in DS fetus. Furthermore, the defects of mitochondrial electron enzymes shown in adult DS brains could begin in utero and continue during the life span of the individual with DS.
authors.affiliation: Department of Pediatrics, University of Vienna, Austria.
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: M
authors.initials: M
authors.lastname: Fountoulakis
authors.forename: M
authors.initials: M
authors.lastname: Dierssen
authors.forename: G
authors.initials: G
authors.lastname: Lubec
mesh_terms: D000251:Adenosine Triphosphatases / Q000032:analysis; D001921:Brain / Q000002:abnormalities / Q000201:enzymology*; D002352:Carrier Proteins; D004314:Down Syndrome / Q000378:metabolism*; D004579:Electron Transport; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III / Q000032:analysis; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005333:Fetus / Q000201:enzymology; D005649:Fumarate Hydratase / Q000032:analysis; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000032:analysis; D008297:Male; D008565:Membrane Proteins / Q000032:analysis; D008928:Mitochondria / Q000201:enzymology; D025261:Mitochondrial Proton-Translocating ATPases; D009247:NADH, NADPH Oxidoreductases / Q000032:analysis / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D007521:Isocitrate Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; D000251:Adenosine Triphosphatases; D025261:Mitochondrial Proton-Translocating ATPases; D005649:Fumarate Hydratase; D042967:Electron Transport Complex I; D014450:Electron Transport Complex III; C020439:oligomycin sensitivity-conferring protein