Amyloid-β-peptide reduces the expression level of mitochondrial cytochrome oxidase subunits

Mitochondrial dysfunction is an important cause of neurological disorder including Alzheimer's disease (AD). Mitochondria play a key role in the generation of reactive oxygen species (ROS), resulting in oxidative damage to neuronal cell and cellular compartments in the AD brain. Cytotoxicity induced by amyloid-beta (A beta), a protein fragment of 25-35 amino acids in amyloid plaques has been shown to have neuro-toxic properties. They seem to involve mitochondrial dysfunction, but the underlying mechanisms are not clearly understood. The purpose of this study was to assess whether A beta induced mitochondrial dysfunction involves changes in cytochrome c oxidase (COX) expression. We measured the activities of COX after expose of SK-N-SH cells (a human neuroblastoma cell line) to A beta. We found that levels of mRNAs expressing mitochondrial COX subunits decreased significantly in A beta-treated SK-N-SH cells in a dose-dependent manner. Human mitochondrial transcription factor-1 (TFAM) mRNA level also decreased after A beta-treatment. These results suggest that A beta modulates the mitochondrial gene expression through a decrease in TFAM.