Amyloid-beta-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 (Abeta), 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 Abeta 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 Abeta. We found that levels of mRNAs expressing mitochondrial COX subunits decreased significantly in Abeta-treated SK-N-SH cells in a dose-dependent manner. Human mitochondrial transcription factor-1 (TFAM) mRNA level also decreased after Abeta-treatment. These results suggest that Abeta modulates the mitochondrial gene expression through a decrease in TFAM.
Hong
Won Kyung
WK
Biobank for Health Sciences, Center for Genome Sciences, National Institute of Health, Korea Center for Disease Control and Prevention (KCDC), 194, Tongil-Ro, Eunpyung-Ku, Seoul 122-701, Korea.
Han
Eun Hae
EH
Kim
Dae Ghon
DG
Ahn
Jung Yup
JY
Park
Jeong Soon
JS
Han
Bok Ghee
BG
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D003576:Electron Transport Complex IV / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009447:Neuroblastoma; D010446:Peptide Fragments / Q000494:pharmacology*; D021122:Protein Subunits / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D021122:Protein Subunits; D012333:RNA, Messenger; C074636:amyloid beta-protein (25-35); D003576:Electron Transport Complex IV