Characterization of the cellular localization, expression level, and function of SNP variants of MRP2/ABCC2

Masakazu Hirouchi, Hiroshi Suzuki, Masaya Itoda, Shogo Ozawa, Jun Ichi Sawada, Ichiro Ieiri, Kenji Ohtsubo, Yuichi Sugiyama

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97 Citations (Scopus)

Abstract

Purpose. The presence of single nucleotide polymorphisms (SNPs) has been reported for multidrug resistance-associated protein 2 (MRP2/ABCC2). The purpose of the current study was to characterize the localization, expression level, and function of MRP2 variants. Methods. The expression and cellular localization of the wild-type and three kinds of reported SNP variants of MRP2 molecules were analyzed in LLC-PK1 cells after infection with the recombinant Tetoff adenoviruses. Their function was determined by using the isolated membrane vesicles from the infected LLC-PK1 cells. Results. The transport activity for E217βG, LTC4, and DNP-SG, normalized by the expression level of MRP2, was similar between the wild-type, V417I, and A1450T MRP2s. The transport activity of S789F MRP2 was slightly higher than that of wild-type MRP2. However, the expression level of S789F and A1450T MRP2 proteins was significantly lower compared with the wild-type and V417I MRP2. In addition, although the wild-type and V417I MRP2 were exclusively localized in the apical membrane, S789F and A1450T MRP2 were located in the apical membrane and also in the intracellular compartment. Conclusions. These results suggest that the most frequently observed V417I substitution may not affect the in vivo function of MRP2, whereas the much less frequently observed S789F and A1450T may be associated with the reduced in vivo function.

Original languageEnglish
Pages (from-to)742-748
Number of pages7
JournalPharmaceutical Research
Volume21
Issue number5
DOIs
Publication statusPublished - May 1 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

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

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