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 (MMP), 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 micromol L(-1) or 20 micromol L(-1) H2O2 can significantly protect PC12 cells against apoptosis induced by 50 or 100 micromol L(-1) H2O2, low (5 micromol L(-1)) and higher (30 micromol L(-1)) concentrations of H2O2 had no cytoprotections; (3) high concentration (100 micromol L(-1)) of H2O2 reduced MMP and expression of Bcl-2, and increased ROS level, but these effects were blocked by preconditioning with 10 micromol L(-1) H2O2; (4) the preconditioning with 10 micromol L(-1) H2O2 induced overexpression of Bcl-2. These results suggested that the preconditioning with low dose of H2O2 could protect the oxidative stress-induced PC12 cells apoptosis not only by preventing the reduction of MMP 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.
Tang
Xiao-Qing
XQ
Department of Physiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou 510080, PR China.
Feng
Jian-Qiang
JQ
Chen
Jin
J
Chen
Pei-Xi
PX
Zhi
Jun-Li
JL
Cui
Yu
Y
Guo
Rui-Xian
RX
Yu
Hui-Min
HM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western / Q000379:methods; D002452:Cell Count / Q000379:methods; D016923:Cell Death; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007150:Immunohistochemistry / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013997:Time Factors
D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide