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Chronic exposure to UI8666A induces apoptosis in cultured murine cortical neurons

Citation

Cheung, NS and Koh, CH and Bay, BH and Qi, RZ and Choy, MS and Li, QT and Wong, KP and Whiteman, M, Chronic exposure to UI8666A induces apoptosis in cultured murine cortical neurons, Biochemical and Biophysical Research Communications, 315, (2) pp. 408-417. ISSN 0006-291X (2004) [Refereed Article]

DOI: doi:10.1016/j.bbrc.2004.01.066

Abstract

Niemann-Pick disease type C (NPC) is a juvenile neurodegenerative disorder characterized by premature neuronal loss and altered cholesterol metabolism. Previous reports applying an 8-h exposure of U18666A, a cholesterol transport-inhibiting agent, demonstrated a dose-dependent reduction in -amyloid (A) deposition and secretion in cortical neurons, with no significant cell injury. In the current study, we examined the chronic effect of 24-72h of U18666A treatment on primary cortical neurons and several cell lines. Our results showed caspase-3 activation and cellular injury in U18666A-treated cortical neurons but not in the cell lines, suggesting cell death by apoptosis only occurred in cortical neurons after chronic exposure to U18666A. We also demonstrated through filipin staining the accumulation of intracellular cholesterol in cortical neurons treated with U18666A, indicating the phenotypic mimic of NPC by U18666A. However, additions of 10 and 25M pravastatin with 0.5g/ml U18666A significantly attenuated toxicity. Taken together, these data showed for the first time that U18666A induces cell death by apoptosis and suggested an important in vitro model system to study NPC.

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Cheung, NS (Dr Nam Cheung)
ID Code:61532
Year Published:2004
Web of Science® Times Cited:32
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-03-04
Last Modified:2010-05-03
Downloads:0

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