Hypochlorous acid inhibits glutathione S-conjugate export from human erythrocytes.
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.
Soszyński
Mirosław
M
Department of Molecular Biophysics, University of Lódź, Banacha 12/16, 90-237, Lódź, Poland. sosmirek@biol.uni.lodz.pl
Zavodnik
Ilya
I
Zavodnik
Leu
L
Zylinska
Ludmiła
L
Bartosz
Grzegorz
G
Bryszewska
Maria
M
D001693:Biological Transport, Active / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors; D004586:Electrophoresis; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000201:enzymology; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology*; D015151:Immunoblotting; D008564:Membrane Potentials; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D010084:Oxidation-Reduction; D013997:Time Factors
D001643:Bridged Bicyclo Compounds; D017301:Ca(2+) Mg(2+)-ATPase; D005978:Glutathione; D006997:Hypochlorous Acid; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C080120:glutathione-bimane