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Advances in Brief

ATP-dependent Transport of Glutathione S-Conjugates by the Multidrug Resistance-associated Protein

Gabriele Jedlitschky, Inka Leier, Ulrike Buchholz, Melvin Center and Dietrich Keppler
Gabriele Jedlitschky
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Inka Leier
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Ulrike Buchholz
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Melvin Center
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Dietrich Keppler
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DOI:  Published September 1994
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Abstract

The ATP-dependent transport of the endogenous glutathione conjugate leukotriene C4 (LTC4) was more than 25-fold higher in membrane vesicles prepared from human leukemia cells (HL60/ADR) overexpressing the multidrug resistance-associated protein than from drug-sensitive parental HL60 cells or revertant cells. Similar results were obtained with S-(2,4-dinitrophenyl)glutathione as substrate. Photoaffinity labeling detected preferentially in the HL60/ADR membranes a 190-kilodalton protein binding [3H]LTC4 and 8-azido[α-32P]ATP. The [3H]LTC4-labeled 190-kilodalton protein was immunoprecipitated by an antiserum against the COOH-terminal sequence of multidrug resistance-associated protein. Our results indicate that multidrug resistance-associated protein mediates the ATP-dependent transport of LTC4 and structurally related anionic amphiphilic conjugates.

Footnotes

  • ↵1 This work was supported in part by the Deutsche Forschungsgemeinschaft through SFB 352, Heidelberg (D. K.), and by USPHS Grant CA-37585 from the National Cancer Institute (M. C.).

  • ↵2 To whom requests for reprints should be addressed.

  • Received July 8, 1994.
  • Accepted August 3, 1994.
  • ©1994 American Association for Cancer Research.
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September 1994
Volume 54, Issue 18
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ATP-dependent Transport of Glutathione S-Conjugates by the Multidrug Resistance-associated Protein
Gabriele Jedlitschky, Inka Leier, Ulrike Buchholz, Melvin Center and Dietrich Keppler
Cancer Res September 15 1994 (54) (18) 4833-4836;

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ATP-dependent Transport of Glutathione S-Conjugates by the Multidrug Resistance-associated Protein
Gabriele Jedlitschky, Inka Leier, Ulrike Buchholz, Melvin Center and Dietrich Keppler
Cancer Res September 15 1994 (54) (18) 4833-4836;
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