ATP-binding cassette transporter G2 mediates the efflux of phototoxins on the luminal membrane of retinal capillary endothelial cells

Tomoko Asashima, Satoko Hori, Sumio Ohtsuki, Masanori Tachikawa, Masahiko Watanabe, Chisato Mukai, Shinji Kitagaki, Naoki Miyakoshi, Tetsuya Terasaki

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

Purpose. The purpose of this study was to clarify the localization and function of the ATP-binding cassette transporter G2 (ABCG2; BCRP/MXR/ABCP) in retinal capillary endothelial cells, which form the inner blood-retinal barrier, as an efflux transport system. Methods. The expression was determined by reverse transcriptase polymerase chain reaction and Western blotting. The localization was identified by immunostaining. The transport function of ABCG2 was measured by flow cytometry. Results. Western blotting indicated that ABCG2 was expressed as a glycosylated disulfide-linked complex in the mouse retina and in peripheral tissues, including liver, kidney, and small intestine. Double immunolabeling of ABCG2 and glucose transporter 1 suggested that ABCG2 was localized on the luminal membrane of mouse retinal capillary endothelial cells. ABCG2 mRNA and protein were found to be expressed in a conditionally immortalized rat retinal capillary endothelial cell line, TR-iBRB, and rat retina. Treatment with Ko143, an ABCG2 inhibitor, restored the accumulation of pheophorbide a and protoporphyrin IX in TR-iBRB cells. Conclusion. ABCG2 is expressed on the luminal membrane of retinal capillary endothelial cells, where ABCG2 acts as the efflux transporter for photosensitive toxins such as pheophorbide a and protoporphyrin IX. ABCG2 could play an important role at the inner blood-retinal barrier in restricting the distribution of phototoxins and xenobiotics in retinal tissue.

Original languageEnglish
Pages (from-to)1235-1242
Number of pages8
JournalPharmaceutical research
Volume23
Issue number6
DOIs
Publication statusPublished - 2006 Jun

Keywords

  • ABC half-transporter
  • ABCG2/BCRP/MXR/ABCP
  • Inner blood-retinal barrier
  • Pheophorbide a
  • Retinal capillary endothelial cell

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

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