Glutathione transport is a unique function of the ATP-binding cassette protein ABCG2

Heather M. Brechbuhl, Neal Gould, Remy Kachadourian, Wayne R. Riekhof, Dennis R. Voelkerand, Brian J. Day

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Glutathione (GSH) transport is vital for maintenance of intracellular and extracellular redox balance. Only a few human proteins have been identified as transporters of GSH, glutathione disulfide (GSSG) and/or GSH conjugates (GS-X). Human epithelial MDA1586, A549, H1975, H460, HN4, and H157 cell lines were exposed to 2′,5′-dihydroxychalcone, which induces a GSH efflux response. A real-time gene superarray for 84 proteins found in families that have a known role in GSH, GSSG, and/or GS-X transport was employed to help identify potential GSH transporters. ABCG2 was identified as the only gene in the array that closely corresponded with the magnitude of 2′,5′- dihydroxychalcone (2′,5′-DHC)-induced GSH efflux. The role of human ABCG2 as a novel GSH transporter was verified in a Saccharomyces cerevisiae galactose-inducible gene expression system. Yeast expressing human ABCG2 had 2.5-fold more extracellular GSH compared with those not expressing ABCG2. GSH efflux in ABCG2-expressing yeast was abolished by the ABCG2 substrate methotrexate (10 μM), indicating competitive inhibition. In contrast, 2′,5′-DHC treatment of ABCG2-expressing yeast increased extracellular GSH levels in a dose-dependent manner with a maximum 3.5-fold increase in GSH after 24 h. In addition, suppression of ABCG2 with short hairpin RNA or ABCG2 overexpression in human epithelial cells decreased or increased extracellular GSH levels, respectively. Our data indicate that ABCG2 is a novel GSH transporter.

Original languageEnglish (US)
Pages (from-to)16582-16587
Number of pages6
JournalJournal of Biological Chemistry
Volume285
Issue number22
DOIs
StatePublished - May 28 2010

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Yeast
Glutathione
Glutathione Disulfide
Carrier Proteins
Adenosine Triphosphate
Yeasts
Proteins
Genes
Galactose
Gene expression
Methotrexate
Small Interfering RNA
Cells
Oxidation-Reduction
Saccharomyces cerevisiae
Epithelial Cells
Maintenance
glutathione transporter
Substrates
Gene Expression

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Glutathione transport is a unique function of the ATP-binding cassette protein ABCG2. / Brechbuhl, Heather M.; Gould, Neal; Kachadourian, Remy; Riekhof, Wayne R.; Voelkerand, Dennis R.; Day, Brian J.

In: Journal of Biological Chemistry, Vol. 285, No. 22, 28.05.2010, p. 16582-16587.

Research output: Contribution to journalArticle

Brechbuhl, HM, Gould, N, Kachadourian, R, Riekhof, WR, Voelkerand, DR & Day, BJ 2010, 'Glutathione transport is a unique function of the ATP-binding cassette protein ABCG2', Journal of Biological Chemistry, vol. 285, no. 22, pp. 16582-16587. https://doi.org/10.1074/jbc.M109.090506
Brechbuhl, Heather M. ; Gould, Neal ; Kachadourian, Remy ; Riekhof, Wayne R. ; Voelkerand, Dennis R. ; Day, Brian J. / Glutathione transport is a unique function of the ATP-binding cassette protein ABCG2. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 22. pp. 16582-16587.
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