Transport of eicosapentaenoic acid-derived PGE3, PGF, and TXB3 by ABCC4

Nobuaki Tanaka, Hiroaki Yamaguchi, Nariyasu Mano

研究成果: Article査読

11 被引用数 (Scopus)

抄録

Background: Eicosapentaenoic acid-derived prostaglandin (PG) E3, PGF, and thromboxane (TX) B3 are bioactive lipid mediators which have anti-cancer and anti-inflammatory effects. To exert their effects, PGE3, PGF, and TXB3 must be released to the extracellular space from cells, but the release mechanism has been unclear. We therefore investigated the contribution of ATP-binding cassette transporter C4 (ABCC4), which has been known as a prostanoids efflux transporter, to the release of PGE3, PGF, and TXB3.

Materials and Methods: ATP-dependent transport of PGE3, PGF, and TXB3 via ABCC4 was investigated by using inside-out membrane vesicles prepared from ABCC4-overexpressing HEK293 cells. To evaluate the contribution of ABCC4 to the release of PGE3, PGF, and TXB3, we measured the extracellular and intracellular levels of PGE3, PGF, and TXB3 in A549 cells when we used ABCC4 inhibitors (dipyridamole, MK571, and probenecid) or ABCC4 siRNAs. The quantification of PGE3, PGF, and TXB3 was performed by using liquid chromatography-tandem mass spectrometry.

Results: The apparent Km values for ABCC4-mediated transport were 2.960.1 mM for PGE3, 12.161.3 mM for PGF, and 11.961.4 mM for TXB3 and the ATP-dependent accumulation of PGE3, PGF, and TXB3 into vesicles was decreased by using typical substrates and inhibitors of ABCC4. ABCC4 inhibitors and ABCC4 knockdown showed the reduction of extracellular/ intracellular ratio of PGE3 (40-60% of control) and PGF (60-80% of control) in A549 cells.

Conclusions: Our results suggest that PGE3, PGF, and TXB3 are substrates of ABCC4 and ABCC4 partially contributes to the release of PGE3 and PGF.

本文言語English
論文番号e109270
ジャーナルPloS one
9
10
DOI
出版ステータスPublished - 2014 10月 2

ASJC Scopus subject areas

  • 生化学、遺伝学、分子生物学(全般)
  • 農業および生物科学(全般)
  • 一般

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