Zinc suppresses apoptosis of U937 cells induced by hydrogen peroxide through an increase of the Bcl-2/Bax ratio

Treatment of human premonocytic U937 cells with 500 mu M H2O2 for 1h followed by 4h incubation in fresh medium to allow the cells to execute apoptotic processes caused DNA fragmentation. However, in the presence of 1mM ZnSO4 throughout the incubation, DNA ladder formation was markedly inhibited. Hydrogen peroxide treatment for 1h with or without zinc increased both Bcl-2 and Bax proteins. However, only Bax protein decreased to basal levels in the presence of zinc during the following 4h incubation, resulting in an increase of the Bcl-2/Bax ratio and prevention of apoptosis. Treatment of U937 cells with 1mM ZnSO4 alone also decreased the levels of Bax protein. Furthermore, we observed that zinc completely inhibited the activation of CPP32 by H2O2, while no significant changes of ICE activities occurred with either H2O2 and/or zinc. These results indicate that the suppression of H2O2-induced apoptosis by zinc is mediated through an increase of the Bcl-2/Bax ratio, which occurs upstream from the activation of CPP32. (C) 1998 Academic Press.