Expression of nuclear receptor mRNA and liver X receptor-mediated regulation of ABC transporter A1 at rat blood-brain barrier

Neurochem Int. Mar-Apr 2008;52(4-5):669-74. doi: 10.1016/j.neuint.2007.08.012. Epub 2007 Aug 26.

Abstract

The aim of the present study was to investigate the expression of nuclear receptor mRNA and regulation of the expression of ATP-binding cassette (ABC) transporters by nuclear receptor agonists in rat brain capillary endothelial cells, which form the blood-brain barrier, by using rat brain capillary fraction from 8-week-old rats and a conditionally immortalized brain capillary endothelial cell line (TR-BBB13). RT-PCR analysis revealed that liver X receptor alpha and beta, retinoid X receptor alpha and beta and peroxisome proliferator-activating receptor alpha and beta mRNAs were expressed in the rat brain capillary endothelial cells and TR-BBB cells. In contrast, pregnane X receptor, farnesoid X receptor and constitutive androstane receptor were not detected. Furthermore, treatment with a liver X receptor agonist increased the ABCA1 mRNA level in TR-BBB13 cells, while ABCG2 mRNA expression was not affected. Treatment with a rat pregnane X receptor agonist did not affect the ABCB1 mRNA level in TR-BBB13 cells. These results demonstrate that the rat blood-brain barrier has an expressional regulation mechanism via sterol-related nuclear receptor, and indicate that the blood-brain barrier in 8-week-old rats lacks ABCB1 regulation via pregnane X receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / biosynthesis*
  • ATP-Binding Cassette Transporters / genetics
  • Animals
  • Blood-Brain Barrier / physiology*
  • Capillaries / metabolism
  • Cell Line
  • Endothelial Cells / metabolism
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology
  • Male
  • Pregnane X Receptor
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Receptors, Steroid / biosynthesis*
  • Receptors, Steroid / genetics
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Pregnane X Receptor
  • RNA, Messenger
  • Receptors, Steroid