Hypochlorous acid inhibits glutathione S-conjugate export from human erythrocytes

Biochim Biophys Acta. 2002 Aug 31;1564(2):479-86. doi: 10.1016/s0005-2736(02)00500-x.

Abstract

It was found that the hypochlorous acid (HOCl) inhibits the active efflux of glutathione S-conjugates, 2,4-dinitrophenyl-S-glutathione (DNP-SG, c(50%)=258+/-24 microM HOCl) and bimane-S-glutathione (B-SG, c(50%)=125+/-16 microM HOCl) from human erythrocytes, oxidises intracellular reduced glutathione (the ratio [HOCl]/[GSH](oxidized)=4) and inhibits basal as well as 2,4-dinitrophenol- (DNP) and 2,4-dinitrophenyl-S-glutathione (DNP-SG)-stimulated Mg(2+)-ATPase activities of erythrocyte membranes. Multidrug resistance-associated protein (MRP1) mediates the active export of glutathione S-conjugates in mammalian cells, including human erythrocytes. A direct impairment of erythrocyte membrane MRP by hypochlorous acid was shown by electrophoresis and immunoblotting (c(50%)=478+/-36 microM HOCl). The stoichiometry of the MRP/HOCl reaction was 1:1. These results demonstrate that MRP can be one of the cellular targets for the inflammatory mediator hypochlorous acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport, Active / drug effects
  • Bridged Bicyclo Compounds / metabolism
  • Ca(2+) Mg(2+)-ATPase / antagonists & inhibitors
  • Electrophoresis
  • Erythrocyte Membrane / drug effects
  • Erythrocyte Membrane / enzymology
  • Erythrocytes / drug effects*
  • Erythrocytes / metabolism
  • Glutathione / analogs & derivatives*
  • Glutathione / chemistry
  • Glutathione / metabolism
  • Humans
  • Hypochlorous Acid / pharmacology*
  • Immunoblotting
  • Membrane Potentials
  • Multidrug Resistance-Associated Proteins / metabolism
  • Oxidation-Reduction
  • Time Factors

Substances

  • Bridged Bicyclo Compounds
  • Multidrug Resistance-Associated Proteins
  • glutathione-bimane
  • Hypochlorous Acid
  • Ca(2+) Mg(2+)-ATPase
  • Glutathione