Hydrogen peroxide preconditioning protects PC12 cells against apoptosis induced by dopamine

Dopamine (DA), one of the major sources of reactive oxygen species (ROS), is implicated in neuronal death associated with Parkinson's disease (PD). Preconditioning with oxidative stress has been shown to provide cytoprotection similar to ischemic Preconditioning (IPC), against cell apoptosis. In this study, using the model neurosecretory cell line, PC12, we investigated whether hydrogen peroxide (H2O2) at low concentration (10 mu M) can protect PC12 cells against apoptosis induced by DA. PC12 cells were preconditioned with 10 mu M H2O2 for 90 min, followed by 24-h recovery and subsequent exposures to different concentrations (20, 50 100 and 200 mu M) of DA for 24-h, respectively. DA induced apoptotic cell death with significant morphological nuclear changes and DNA fragmentation as well as the dysfunction of mitochondria. Preconditioning with H2O2 at 10 mu M significantly reduced the percentage of apoptotic cells and partly blocked the decreases in 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) reduction and mitochondrial membrane potential (MMP) induced by DA. These results suggest that preconditioning with low concentration of H2O2 protected PC12 cells against DAinduced apoptosis, the part restoration of the damaged mitochondrial functions might be one of the underlying mechanisms of this cytoprotection. (c) 2005 Elsevier Inc. All rights reserved.