Chronic exposure to U18666A is associated with oxidative stress in cultured murine cortical neurons.
Findings that antioxidant treatment may be beneficial in Alzheimer's disease indicate that oxidative stress is an important factor in its pathogenesis. Studies have also suggested that cholesterol imbalance in the brain might be related to the development of neurological disorders. Previously, we have reported that U18666A, a cholesterol transport-inhibiting agent, leads to apoptosis and intracellular cholesterol accumulation in primary cortical neurons. In this study, we found that neuronal apoptosis mediated by U18666A is associated with oxidative stress in the treated cortical neurons. Cortical neurons treated with U18666A also showed decreased secretion and increased intraneuronal accumulation of beta-amyloid. The association of neuronal apoptosis with oxidative stress and Abeta accumulation may provide clues to the pathogenesis of Alzheimer's disease, as well as the role oxidative stress plays in other neurodegenerative diseases.
Koh
Chor Hui Vivien
CH
Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore.
Whiteman
Matthew
M
Li
Qiao-Xin
QX
Halliwell
Barry
B
Jenner
Andrew M
AM
Wong
Boon Seng
BS
Laughton
Katrina M
KM
Wenk
Markus
M
Masters
Colin L
CL
Beart
Philip M
PM
Bernard
Ora
O
Cheung
Nam Sang
NS
D000255:Adenosine Triphosphate / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000502:physiology; D000736:Androstenes / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D019636:Neurodegenerative Diseases / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D046988:Proteasome Endopeptidase Complex; D013778:Tetrazolium Salts; D013844:Thiazoles
D016229:Amyloid beta-Peptides; D000736:Androstenes; D013778:Tetrazolium Salts; D013844:Thiazoles; C006261:3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one; D000255:Adenosine Triphosphate; D002784:Cholesterol; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D046988:Proteasome Endopeptidase Complex; C022616:thiazolyl blue; D005978:Glutathione