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 mu M. 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 (K-m at submillimolar concentration range) or a high (K-m 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 far Dnp-SG is competitively inhibited by HNE-SG with K-i of 0.2 mu M, while 4-HNE inhibits non-competitively the activity of the transport system for Dnp-SG with K-i of 220 mu M. 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.