Cholesterol Research Today is a free monthly online journal that collates and summarizes the latest research about Cholesterol, including details on high cholesterol, hdl, ldl, diet, risks.

Neuronal apoptosis mediated by inhibition of intracellular cholesterol transport: microarray and proteomics analyses in cultured murine cortical neurons.

Koh CH, Peng ZF, Ou K, Melendez A, Manikandan J, Qi RZ, Cheung NS

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Studies suggest that cholesterol imbalance in the brain might be related to the development of neurological disorders. U18666A is a well-known amphiphile which inhibits intracellular cholesterol transport in treated cells. We have previously shown that U18666A leads to apoptosis and cholesterol accumulation in primary cortical neurons, which is associated with activation of caspases and calpains, hyperphosphorylation of tau, and increased oxidative stress markers. However, the mechanisms involved in U18666A-mediated apoptosis remain unknown. In this report, we sought to gain an insight into the molecular processes contributing to the neuronal apoptosis induced by U18666A. The microarray approach was used in conjunction with proteomics techniques to identify specific proteins which may serve as signature biomarkers during U18666A treatment. Eleven differentially expressed proteins were correlated at the gene expression level in a time-dependent manner. These proteins have been shown to play a role in lipid metabolism and transport, responses to cell death, protein folding and trafficking, and regulation of transcription. The identification of these differentially expressed proteins might provide a clue to decipher the intracellular biochemical changes during U18666A-mediated neuronal apoptosis. Our results provide, for the first time, a combined microarray and proteomics analysis of neuronal apoptosis mediated by inhibition of intracellular cholesterol transport. This new insight may greatly facilitate the study of neurodegenerative diseases.

Published 5 February 2007 in J Cell Physiol, 211(1): 63-87.
Full-text of this article is available online (may require subscription).

© 2004-2008 Cholesterol Research Today. All Rights Reserved.