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

研究成果: Article査読

60 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1235-1242
ページ数8
ジャーナルPharmaceutical research
23
6
DOI
出版ステータスPublished - 2006 6月
外部発表はい

ASJC Scopus subject areas

  • バイオテクノロジー
  • 分子医療
  • 薬理学
  • 薬科学
  • 有機化学
  • 薬理学(医学)

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