Functional expression of rat ABCG2 on the luminal side of brain capillaries and its enhancement by astrocyte-derived soluble factor(s)

Satoko Hori, Sumio Ohtsuki, Masanori Tachikawa, Norihisa Kimura, Tetsu Kondo, Masahiko Watanabe, Emi Nakashima, Tetsuya Terasaki

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

The purpose of the present study was to clarify the expression, transport properties and regulation of ATP-binding cassette G2 (ABCG2) transporter at the rat blood-brain barrier (BBB). The rat homologue of ABCG2 (rABCG2) was cloned from rat brain capillary fraction. In rABCG2-transfected HEK293 cells, rABCG2 was detected as a glycoprotein complex bridged by disulfide bonds, possibly a homodimer. The protein transported mitoxantrone and BODIPY-prazosin. In rat brain capillary fraction, rABCG2 protein was also detected as a glycosylated and disulfide-linked complex. Immunohistochemical analysis revealed that rABCG2 was localized mainly on the luminal side of rat brain capillaries, suggesting that rABCG2 is involved in brain-to-blood efflux transport. For the regulation study, conditionally immortalized rat brain capillary endothelial (TR-BBB13), astrocyte (TR-AST4) and pericyte (TR-PCT1) cell lines were used as an in vitro BBB model. Following treatment of TR-BBB13 cells with conditioned medium of TR-AST4 cells, the Ko143 (an ABCG2-specific inhibitor)-sensitive transport activity and rABCG2 mRNA level were significantly increased, whereas conditioned medium of TR-PCT1 cells had no effect. These results suggest that rat brain capillaries express functional rABCG2 protein and that the transport activity of the protein is up-regulated by astrocyte-derived soluble factor(s) concomitantly with the induction of rABCG2 mRNA.

Original languageEnglish
Pages (from-to)526-536
Number of pages11
JournalJournal of Neurochemistry
Volume90
Issue number3
DOIs
Publication statusPublished - 2004 Aug

Keywords

  • ABCG2
  • Astrocyte
  • Blood-brain barrier
  • In vitro BBB model

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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