Journal article

Publication year: 2007

Pages: 47-52

Journal: Neuroscience Letters

Volume number: 423

Issue number: 1

ISSN: 0304-3940

DOI Link: https://doi.org/10.1016/j.neulet.2007.05.063

Publisher: Elsevier

Abstract: 
The nuclear oxysterol receptors known as liver X receptors (LXR) are responsible for regulating genes involved in cholesterol homeostasis. Two subtypes exist, LXR-alpha and LXR-beta, both of which are expressed in the central nervous system (CNS). Activation of LXR causes an increase in mechanisms involved in cholesterol efflux, including ATP-binding cassette transporters (ABC)-A1 and ABC-G1. Although LXR agonists have been found to induce gene expression for ABC-A1 and ABC-G1 in the CNS, no functional response has been recorded. In this study, we show that an LXR agonist (TO-901317) increases protein levels of the cholesterol transporters ABC-A1 and ABC-G1 as well as the cholesterol chaperone protein apolipoprotein E (apoE). These changes are associated with a decrease in cholesterol levels from isolated cortical synaptosomal plasma membranes. LXR activation occurs in response to increased cholesterol levels in cells. However, while data exists on how LXR alter cholesterol efflux, there is no data on whether these receptors alter production of cholesterol. We found that TO-901317 increases HMG-CoA reductase activity, the rate-limiting step of cholesterol production in vivo. This finding was duplicated in an in vitro system. Although high concentrations (>1 mu M) of TO-901317 were required to induce HMG-CoA reductase activity, these changes only occurred in the presence of apolipoprotein A1, suggesting that cholesterol efflux is required for this effect to occur. These data show that the LXR agonist TO-901317 is capable of reducing cholesterol in neurons of the CNS. (C)07 Elsevier Ireland Ltd. All rights reserved.

Harvard Citation style: Eckert, G., Vardanian, L., Rebeck, G. and Burns, M. (2007) Regulation of central nervous system cholesterol homeostasis by the liver X receptor agonist TO-901317, Neuroscience Letters, 423(1), pp. 47-52. https://doi.org/10.1016/j.neulet.2007.05.063

APA Citation style: Eckert, G., Vardanian, L., Rebeck, G., & Burns, M. (2007). Regulation of central nervous system cholesterol homeostasis by the liver X receptor agonist TO-901317. Neuroscience Letters. 423(1), 47-52. https://doi.org/10.1016/j.neulet.2007.05.063