ABC transporters, cytochromes P450 and their main transcription factors: expression at the human blood-brain barrier

J Neurochem. 2008 Dec;107(6):1518-28. doi: 10.1111/j.1471-4159.2008.05720.x.

Abstract

We have established the expression patterns of the genes encoding ATP-binding cassette (ABC) transporters and cytochromes P450 (CYPs) at the adult human blood-brain barrier (BBB) using isolated brain microvessels and cortex biopsies from patients with epilepsia or glioma. Microves synaptophysin (neurons) and neuron-glial antigen 2 (NG2) (pericytes). ABCG2 [breast cancer resistance protein (BCRP)] and ABCB1 (MDR1) were the main ABC transporter genes expressed in microvessels, with 20 times more ABCG2 and 25 times more ABCB1 in microvessels than in the cortex. The CYP1B1 isoform represented over 80% of all the CYPs genes detected in microvessels. There were 14 times more CYP1B1 in microvessels than in the cortex, showing that CYP1B1 is mainly expressed at the BBB. p-glycoprotein (ABCB1), BCRP (ABCG2) and CYP1B1 proteins were found in microvessels by western blotting. The expression of genes encoding three transcription factors [pregnane xenobiotic receptor (PXR), constitutive androstane receptor (CAR), aryl hydrocarbon receptor (AhR)] was also investigated. The AhR gene, involved in the regulation of CYP1B1 expression, was highly expressed in brain microvessels, whereas PXR and CAR genes were almost undetected. This detailed pattern of ABC and CYPs gene expression at the human BBB provides useful information for understanding how their substrates enter the brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics*
  • ATP-Binding Cassette Transporters / metabolism*
  • Antigens / metabolism
  • Blood-Brain Barrier / metabolism*
  • Brain Neoplasms / pathology
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Gene Expression / physiology
  • Gene Expression Regulation, Neoplastic / physiology
  • Glial Fibrillary Acidic Protein / metabolism
  • Humans
  • Microvessels / metabolism
  • Neoplasm Proteins / metabolism
  • Proteoglycans / metabolism
  • RNA, Messenger / metabolism
  • Synaptophysin / metabolism

Substances

  • ABCG2 protein, human
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Antigens
  • Glial Fibrillary Acidic Protein
  • Neoplasm Proteins
  • Proteoglycans
  • RNA, Messenger
  • Synaptophysin
  • chondroitin sulfate proteoglycan 4
  • Cytochrome P-450 Enzyme System