Enhanced glutathione depletion, protein adduct formation, and cytotoxicity following exposure to 4-hydroxy-2-nonenal (HNE) in cells expressing human multidrug resistance protein-1 (MRP1) together with human glutathione S-transferase-M1 (GSTM1)

► We asked whether MRP1 + GSTM1 protect against 4-hydroxy-2-nonenal toxicity (HNE). ► MRP1 + GSTM1 sensitized 2.3-fold, not protected, MCF7 cells against HNE. ► Glutathione was depleted in cells expressing MRP1 ± GSTM1 (faster with GSTM1). ► HNE-protein adducts were strongly enhanced when both MRP1 and GSTM1 are expressed.