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Bcl-2 protects against Aβ(25-35)-induced oxidative PC12 cell death by potentiation of antioxidant capacity

Cited 28 time in Web of Science Cited 28 time in Scopus
Authors
Jang, Jung-Hee; Surh, Young-Joon
Issue Date
2004-07
Citation
Biochemical and Biophysical Research Communications, Vol.320 No.3, pp.880-886
Keywords
apoptosisakt/protein kinase Bbcl-2beta-amyloidcatalaseNF-kappa Boxidative stressPC12 cells
Abstract
A substantial body of data indicates that reactive oxygen intermediates (ROIs) are implicated in pathogenesis of diverse human diseases. Oxidative stress induced by ROIs often causes cell death via apoptosis that is regulated by a plenty of functional genes and their protein products. Bcl-2 is one such protein that blocks apoptosis induced by various death stimuli. In spite of extensive research, the molecular mechanisms underlying antiapoptotic function of Bcl-2 are not fully clarified. In the present work, we have investigated the role of bcl-2 in protecting against beta-amyloid (Abeta)-induced oxidative death in rat pheochromocytoma (PC12) cells. Transfection with the antiapoptotic bcl-2 gene rescued PC12 cells from apoptotic death induced by Abeta. Addition of an NF-kappaB inhibitor, such as pyrrolidine dithiocarbamate or N-tosyl-L-phenylalanine chloromethyl ketone, to the media aggravated Abeta-induced PC12 cell death. PC12 cells overexpressing bcl-2 exhibited higher levels of constitutively activated NF-kappaB compared with vector-transfected controls, which appear to be mediated by the elevated activation of Akt/protein kinase B. The ectopic expression of bcl-2 enhanced both the expression and the activity of catalase, which were attenuated by NF-kappaB blockers. These results suggest that NF-kappaB plays a role in bcl-2-mediated protection against Abeta-induced apoptosis in PC12 cells through augmentation of cellular antioxidant capacity. (C) 2004 Elsevier Inc. All rights reserved.
ISSN
0006-291X
URI
https://hdl.handle.net/10371/172838
DOI
https://doi.org/10.1016/j.bbrc.2004.06.035
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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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