Amyloid-beta down-regulates XIAP expression in human SH-SY5Y neuroblastoma cells.
Recent observations suggest that amyloid-beta (Abeta), a major constituent of senile plaques, induces apoptosis in cultured neuronal cells. However, the concentration of Abeta that leads to neuronal cell death is much higher (10-25 microM) than that in the cerebrospinal fluid of normal controls or AD patients (nM order). As reported here, we found that subtoxic concentrations (100-500 nM) of Abeta(1-42) can down-regulate the expression of the X-linked inhibitor of apoptosis (XIAP) in human SH-SY5Y neuroblastoma cells, and that vulnerability to oxidative stress caused by Abeta(1-42) is attenuated by over-expression of XIAP. These results suggest that down-regulation of XIAP expression in response to subtoxic, more physiological concentrations (100-500 nM) of Abeta(1-42) increases vulnerability to oxidative stress.
Yamamori
Hidenaga
H
Division of Psychiatry and Behavioral Proteomics, Department of Post-Genomics and Diseases, Course of Advanced Medicine, Osaka University, Graduate School of Medicine. D-3, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tanaka
Toshihisa
T
Kudo
Takashi
T
Takeda
Masatoshi
M
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D009447:Neuroblastoma; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D051636:X-Linked Inhibitor of Apoptosis Protein
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011506:Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; C075222:amyloid beta-protein (1-42); D006861:Hydrogen Peroxide; D020169:Caspases