Abstract
The involvement of the blood-cerebrospinal fluid (CSF) barrier in sterol transport and its regulation has important implication for sterol homeostasis in CNS. The purpose of this study was to clarify functional expression of LXRs, which are sterol-related nuclear receptors, and their target ATP-binding cassette (ABC) transporters at the blood-CSF barrier using a conditionally immortalized rat choroid plexus epithelial cell line (TR-CSFB3). The mRNA expression of LXRα, LXRβ and their target genes, ABCA1 and ABCG1, were detected in isolated rat choroid plexus and TR-CSFB3 cells. Following the treatment with 24S-hydroxycholesterol (24S-OH), an endogenous LXR ligand, the mRNA and protein levels of ABCA1 and ABCG1 were enhanced in TR-CSFB3 cells. Moreover, apoA-I and HDL-mediated cholesterol efflux to the apical side of TR-CSFB3 cells was facilitated by this treatment, whereas that to the basal side was unchanged. Investigating the effects of apoE isoforms on cholesterol release from TR-CSFB3 cells, 24S-OH increased cholesterol efflux mediated by apoE3 to a greater extent than that by apoE4. Apolipoproteins and HDL are reported to be involved in ABCA1- and ABCG1-mediated cholesterol efflux, respectively. The both transporter proteins were detected in the plasma membrane fraction of TR-CSFB3 cells by western blot analysis. Therefore, these results suggest that LXR activation facilitated cholesterol efflux to the CSF from choroid plexus epithelial cells through induction of ABCA1 and ABCG1 at the apical membrane. [Jpn J Physiol 55 Suppl:S31 (2005)]
