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

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<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>in vitro</jats:italic> 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.</jats:p>

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