Changes of voltage-dependent anion-selective channel proteins VDAC1 and VDAC2 brain levels in patients with Alzheimer's disease and Down Syndrome

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Abstract
Voltage‐dependent anion‐selective channel proteins (VDACs) are pore‐forming proteins found in the outher 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 pIs (pI 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 pI 10.0 was significantly reduced in temporal, frontal, and occipital cortex with the pI 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.