Protection of oxidative preconditioning against apoptosis induced by H2O2 in PC12 cells:: Mechanisms via MMP, ROS, and Bcl-2

The present study is designed to investigate the effects of preconditioning with different doses of hydrogen peroxide (H2O2) on oxidative stress-induced apoptosis and the changes in mitochondrial membrane potential (NIMP), intracellular reactive oxygen species (ROS) level, and expression of Bcl-2 during H2O2 preconditioning in rat pheochromocytoma (PC12) cells. It was shown that (1) H2O2 induced apoptosis in PC12 cells in a dose-dependent manner; (2) the preconditioning with 10 mu mol L-1 or 20 mu mol L-1 H2O2 can significantly protect PC12 cells against apoptosis induced by 50 or 100 mu mol L-1 H2O2, low (5 mu mol L-1) and higher (30 mu mol L-) concentrations of H2O2 had no cytoprotections; (3) high concentration (100 mu mol L-) of H202 reduced NIMP and expression of Bcl-2, and increased ROS level, but these effects were blocked by preconditioning with 10 mu mol L-1 H2O2; (4) the preconditioning with 10 mu mol L-1 H2O2 induced overexpression of Bcl-2. These results suggested that the preconditioning with low dose of H202 could protect the oxidative stress-induced PC 12 cells apoptosis not only by preventing the reduction of MNIP and expression of Bcl-2 as well as increase in ROS level, but also through overexpression of Bcl-2. It was indicated that overexpression of Bcl-2 may play a key role in the cytoprotection induced by preconditioning with low dose of H2O2 in PC12 cells. (c) 2005 Elsevier B.V. All rights reserved.