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 (H(2)O(2)) at low concentration (10 microM) can protect PC12 cells against apoptosis induced by DA. PC12 cells were preconditioned with 10 microM H(2)O(2) for 90 min, followed by 24-h recovery and subsequent exposures to different concentrations (20, 50, 100 and 200 microM) 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 H(2)O(2) at 10 microM 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 H(2)O(2) protected PC12 cells against DA-induced apoptosis, the part restoration of the damaged mitochondrial functions might be one of the underlying mechanisms of this cytoprotection.
Xiao-Qing
Tang
T
Department of Physiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou 510080, P.R. China.
Jun-Li
Zhi
Z
Yu
Cui
C
Jian-Qiang
Feng
F
Pei-Xi
Chen
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000648:ultrastructure; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists; D005434:Flow Cytometry; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats
D018492:Dopamine Antagonists; D016877:Oxidants; D006861:Hydrogen Peroxide; D004298:Dopamine