In vitro transport of methotrexate by Drosophila Multidrug Resistance-associated Protein

Agnes Karasik, A. Váradi, Flóra Szeri

Research output: Contribution to journalArticle

Abstract

Methotrexate (MTX) is a widely used chemotherapeutic agent, immune suppressant and antimalarial drug. It is a substrate of several human ABC proteins that confer multidrug resistance to cancer cells and determine compartmentalization of a wide range of physiological metabolites and endo or xenobiotics, by their primary active transport across biological membranes. The substrate specificity and tissue distribution of these promiscuous human ABC transporters show a high degree of redundancy, providing robustness to these key physiological and pharmacological processes, such as the elimination of toxins, e.g. methotrexate from the body. A similar network of proteins capable of transporting methotrexate has been recently suggested to exist in Drosophila melanogaster. One of the key players of this putative network is Drosophila Multidrug-resistance Associated Protein (DMRP). DMRP has been shown to be a highly active and promiscuous ABC transporter, capable of transporting various organic anions. Here we provide the first direct evidence that DMRP, expressed alone in a heterologous system lacking other, potentially functionally overlapping D. melanogaster organic anion transporters, is indeed able to transport methotrexate. Our in vitro results support the hypothesized but debated role of DMRP in in vivo methotrexate excretion.

Original languageEnglish
Article numbere0205657
JournalPLoS One
Volume13
Issue number10
DOIs
Publication statusPublished - Oct 1 2018

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Multidrug Resistance-Associated Proteins
methotrexate
Drosophila Proteins
multiple drug resistance
Methotrexate
Drosophila
ATP-Binding Cassette Transporters
ABC transporters
Drosophila melanogaster
proteins
anions
Organic Anion Transporters
Physiological Phenomena
P-Glycoproteins
Biological membranes
Active Biological Transport
Antimalarials
Xenobiotics
Tissue Distribution
Substrates

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

In vitro transport of methotrexate by Drosophila Multidrug Resistance-associated Protein. / Karasik, Agnes; Váradi, A.; Szeri, Flóra.

In: PLoS One, Vol. 13, No. 10, e0205657, 01.10.2018.

Research output: Contribution to journalArticle

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