Pentavalent methylated arsenicals are substrates of human AQP9

Joseph R. McDermott, Xuan Jiang, Lauren C. Beene, Barry P. Rosen, Zijuan Liu

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Liver aquaglyceroporin AQP9 facilitates movement of trivalent inorganic arsenite (AsIII) and organic monomethylarsonous acid (MAs III). However, the transport pathway for the two major pentavalent arsenic cellular metabolites, MAsV and DMAsV, remains unknown in mammals. These products of arsenic metabolism, in particular DMAsV, are the major arsenicals excreted in the urine of mammals. In this study, we examined the uptake of the two pentavalent organic arsenicals by human AQP9 in Xenopus laevis oocytes. Xenopus laevis oocytes microinjected with AQP9 cRNA exhibited uptake of both MAsV and DMAsV in a pH-dependent manner. The rate of transport was much higher at acidic pH (pH5.5) than at neutral pH. Hg(II), an aquaporin inhibitor, inhibited transport of AsIII, MAsIII, MAsV and DMAsV via AQP9. However, phloretin, which inhibits water and glycerol permeation via AQP9, can only inhibit transport of pentavalent MAsV and DMAsV but not trivalent AsIII and MAsIII, indicating the translocation mechanisms of these arsenic species are not exactly the same. Reagents such as FCCP, valinomycin and nigericin that dissipate transmembrane proton potential or change the transmemebrane pH gradient did not significantly inhibit all arsenic transport via AQP9, suggesting the transport of pentavalent arsenic is not proton coupled. The results suggest that in addition to the initial uptake of trivalent inorganic AsIII inside cells, AQP9 plays a dual role in the detoxification of arsenic metabolites by facilitating efflux from cells.

Original languageEnglish (US)
Pages (from-to)119-127
Number of pages9
JournalBioMetals
Volume23
Issue number1
DOIs
StatePublished - Feb 2010
Externally publishedYes

Keywords

  • AQP9
  • Arsenate
  • Arsenite
  • Dimethylarsinate
  • Liver
  • Methylation
  • Monomethylarsonate
  • Monomethylarsonous acid
  • Urine

ASJC Scopus subject areas

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

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