Physiological substrates of glutathione S-transferases

Human glutathione S-transferases (GSTs) hGSTA1-1 and hGSTA2-2 catalyze glut athione-dependent reduction of phospholipid hydroperoxides (P-OOH) and 5-hy droperoxyeicosatetraenoic acid (5-HPETE). In human liver these isozymes con tribute to a major portion of glutathione peroxidase activity towards P-OOH . K562 cells transfected with hGSTA1-1, hGSTA2-2, or mGSTA4-4 acquire parti al resistance to H2O2 cytotoxicity. Transfection of K562 cells with mGSTA4- 4, which has selective substrate preference for 4-hydroxynonenal (4-HNE), a ttenuates 4-HNE induced apoptosis and differentiation of K562 cells. mGSTA4 -4 transfected cells grew at a rate about 1.4 fold higher than that of wild -type cells. These studies suggest that the ct-class GSTs play an important role in protection mechanisms against lipid peroxidation and regulate intr acellular concentrations of 4-HNE, which is involved in cellular signaling processes. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.