Is the glutathione conjugate of trans-4-hydroxy-2-nonenal transported by the multispecific organic anion transporting-ATPase of human erythrocytes?
Trans-4-hydroxy-2-nonenal (4-HNE), a cytotoxic end product of lipid peroxidation, is present in normal human blood plasma at concentrations of 0.1-1.0 microM. It can be, however, further metabolized within a cell, and one of the main products is 4-HNE glutathione conjugate (HNE-SG). In human erythrocyte membrane the system for active extrusion of glutathione (GSH) conjugates of various endo- and xenobiotics has been described; it exhibits either a low (Km at submillimolar concentration range) or a high (Km at low micromolar range) affinity for the transported substrates, such as for example S-(2,4-dinitrophenyl)glutathione (Dnp-SG). In the present study it has been shown that the high affinity transport system for Dnp-SG is competitively inhibited by HNE-SG with Ki of 0.2 microM, while 4-HNE inhibits non-competitively the activity of the transport system for Dnp-SG with Ki of 220microM. These observations point to the possibility that HNE-SG shares the same transport system with GSH conjugates of other endo- and xenobiotics in erythrocytes. This may be of importance for overall detoxification of the organism under oxidative stress.
Department of Cellular Biochemistry, M. Nencki Institute of Experimental Biology, Warsaw, Poland.
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Makowski
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Pikuła
D000251:Adenosine Triphosphatases / Q000097:blood*; D000447:Aldehydes / Q000737:chemistry* / Q000493:pharmacokinetics; D002384:Catalysis; D004912:Erythrocytes / Q000378:metabolism*; D005978:Glutathione / Q000737:chemistry*; D006801:Humans; D017136:Ion Transport; D015227:Lipid Peroxidation / Q000502:physiology; D013379:Substrate Specificity
D000447:Aldehydes; D000251:Adenosine Triphosphatases; D005978:Glutathione; C027576:4-hydroxy-2-nonenal