Protective effect of edaravone against PrP106-126-induced PC12 cell death.
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.
Pan
Yong-Hui
YH
Department of Neurology, First Clinical Medical College of Harbin Medical University, Harbin 150001, People's Republic of China.
Wang
Yong-Chen
YC
Zhang
Li-Ming
LM
Duan
Shu-Rong
SR
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005978:Glutathione / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000378:metabolism; D016716:PC12 Cells; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism
D016166:Free Radical Scavengers; D018621:PrPC Proteins; D008315:Malondialdehyde; D013482:Superoxide Dismutase; C505410:Casp3 protein, rat; D053148:Caspase 3; D005978:Glutathione; D000077553:Edaravone; D000983:Antipyrine