Changes of voltage-dependent anion-selective channel proteins VDAC1 and VDAC2 brain levels in patients with Alzheimer's disease and Down syndrome.
Voltage-dependent anion-selective channel proteins (VDACs) are pore-forming proteins found in the other mitochondrial membrane of all eukaryotes and in brain postsynaptic membranes. VDACs regulate anion fluxes of a series of metabolites including ATP, thus regulating mitochondrial metabolic functions. We determined protein levels of VDACs in individual post-mortem brain regions of patients with Down Syndrome (DS) and Alzheimer's disease (AD) using two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-mass spectroscopy (MALDI-MS). VDAC1 (SWISS-PROT accession number P21796) and VDAC2 (P45880) were unambiguously identified and quantified, but VDAC3 was not found. The spots representing VDAC1 were separated with different p/s (p/7.5, 8.5, and 10.0) probably caused by post-translational modifications as, e.g., phosphorylation. In DS cerebellum, total VDAC1 protein was elevated significantly whereas VDAC2 did not show any significant alterations. In AD brains, VDAC1 p/10.0 was significantly reduced in temporal, frontal, and occipital cortex with the p/7.5 form elevated in occipital cortex. Total VDAC1 was significantly decreased in frontal cortex and thalamus. VDAC2 was significantly elevated in temporal cortex only. The biological meaning of our results may be derangement of voltage-dependent anion-selective channel function and reflecting impaired glucose, energy, and intermediary metabolism as well as apoptotic mechanisms.
Yoo
B C
BC
Department of Pediatrics, University of Vienna, Vienna, Austria.
Fountoulakis
M
M
Cairns
N
N
Lubec
G
G
D000367:Age Factors; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D000838:Anions; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D004314:Down Syndrome / Q000378:metabolism* / Q000473:pathology; D004553:Electric Conductivity; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D033681:Mitochondrial Membrane Transport Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018272:Porins / Q000378:metabolism*; D011180:Postmortem Changes; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013997:Time Factors; D050995:Voltage-Dependent Anion Channel 1; D050996:Voltage-Dependent Anion Channel 2; D050994:Voltage-Dependent Anion Channels
D000838:Anions; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018272:Porins; C494762:VDAC1 protein, human; C494765:VDAC2 protein, human; C494768:VDAC3 protein, human; D050996:Voltage-Dependent Anion Channel 2; D050994:Voltage-Dependent Anion Channels; D050995:Voltage-Dependent Anion Channel 1