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

Abstract Treatment of human premonocytic U937 cells with 500μM H 2 O 2 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 ZnSO 4 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 ZnSO 4 alone also decreased the levels of Bax protein. Furthermore, we observed that zinc completely inhibited the activation of CPP32 by H 2 O 2 , while no significant changes of ICE activities occurred with either H 2 O 2 and/or zinc. These results indicate that the suppression of H 2 O 2 -induced apoptosis by zinc is mediated through an increase of the Bcl-2/Bax ratio, which occurs upstream from the activation of CPP32.