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Ergothioneine rescues PC12 cells from β-amyloid-induced apoptotic death

Cited 71 time in Web of Science Cited 73 time in Scopus
Authors
Jang, Jung-Hee; Aruoma, Okezie I.; Jen, Ling-Sun; Chung, Hae Young; Surh, Young-Joon
Issue Date
2004-02
Citation
Free Radical Biology and Medicine, Vol.36 No.3, pp.288-299
Keywords
Alzheimer's diseaseapoptosisbeta-amyloidergothioneineoxidative and/or nitrosative stressperoxynitritefree radicals
Abstract
Amyloid (Abeta) peptide is the major component of senile plaques and considered to have a causal role in the development and progression of Alzheimer's disease. There has been compelling evidence that Abeta-induced cytotoxicity is mediated through oxidative and/or nitrosative stress. Recently, considerable attention has been focused on dietary manipulation of oxidative and/or nitrosative damage. L-Ergothioneine (EGT; 2-mereaptohistidine trimethylbetaine) is a low-molecular-weight naturally occurring thiol compound of dietary origin that exists in the brain, liver, kidney, erythrocytes, ocular tissues, and seminal fluids of mammals. This water-soluble antioxidant has the ability to scavenge hydroxyl and peroxynitrite radicals as well as activated oxygen species, such as singlet oxygen. In this study, we investigated the effects of EGT on Abeta-induced oxidative and/or nitrosative cell death. Rat pheochromocytorna (PC12) cells treated with Abeta underwent apoptotic death as determined by positive in situ terminal end-labeling (TUNEL staining), decreased mitochondrial transmembrane potential, increased ratio of proapoptotic Bax to antiapoptotic BCl-X-L, elevated caspase-3 activity, and cleavage of poly(ADP-ribose) polymerase. EGT pretreatment attenuated Abeta-induced apoptosis in PC12 cells. Compared to N-acetyl-L-cysteine, which mainly scavenges reactive oxygen species, EGT effectively inhibited Abeta-induced cell death by suppressing peroxynitrite formation and subsequent nitration of protein tyrosine residues. The effects of EGT on the cytotoxicity induced by the nitric oxide donor sodium nitroprusside (SNP) and the peroxynitrite-generating 3-morpholinosydnonimine chlorhydrate (SIN-1) were compared. Whereas EGT significantly protected against SIN-1-mediated cell death, it barely affected the cytotoxicity induced by SNP. Thus EGT may attenuate apoptosis caused by Abeta, preferentially by eliminating peroxynitrite derived from the neurotoxic peptide. The importance of diet-derived antioxidants in the management of Alzheimer's disease and other neurodegenerative disorders is discussed. (C) 2003 Elsevier Inc. All rights reserved.
ISSN
0891-5849
URI
https://hdl.handle.net/10371/172722
DOI
https://doi.org/10.1016/j.freeradbiomed.2003.11.005
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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