Protective effect of edaravone against PrP106-126–induced PC12 cell death

✍ Scribed by Yong-Hui Pan; Yong-Chen Wang; Li-Ming Zhang; Shu-Rong Duan

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 257 KB
• Volume: 24
• Category: Article
• ISSN: 1095-6670
• DOI: 10.1002/jbt.20330

✦ Synopsis

Abstract

The prion protein peptide PrP106‐126 induces cell apoptosis through mechanisms involving production of intracellular reactive oxygen species. The present study investigated the effects of edaravone, a potent free radical scavenger in clinical use, on cell cytotoxicity induced by PrP106‐126. Results showed that PrP106‐126 decreased PC12 cell viability in a dose‐ and time‐dependent manner. Edaravone significantly antagonized the cytotoxic effects of PrP106‐126. Mechanistically, PrP106‐126 decreased PC 12 intracellular glutathione (GSH) concentrations, decreased superoxide dismutase (SOD) enzyme activity, increased concentrations of the oxidation end product malondialdehyde (MDA), depolarized the mitochondrial membrane, and increased caspase‐3 activity. Edaravone alone did not affect GSH, SOD, or MDA but did effectively reverse all of the intracellular prooxidant effects induced by PrP106‐126 and inhibit induced apoptosis in PC12 cells. In conclusion, edaravone may be a viable candidate for the treatment of oxidative stress‐induced neurodegenerative disease. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 24:235–241, 2010; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20330