期刊
NEUROCHEMISTRY INTERNATIONAL
卷 97, 期 -, 页码 8-14出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2016.04.014
关键词
Honokiol; Beta-amyloid; Apoptosis; Oxidative stress; GSK-3 beta; PC12 cells
资金
- Direct Grant for Research from the Faculty of Medicine, The Chinese University of Hong Kong [2015.1.081]
Beta-amyloid (A beta) accumulation, one of the most important pathogenic traits of Alzheimer's disease (AD), has been reported to induce neurotoxicity in vitro as well as in vivo. Honokiol, isolated from the bark of Magnolia officinalis, has neuroprotective effects in different models of AD in vivo and in vitro. However, the exact mechanism for its neuroprotective effect is not well understood. The present study aimed to investigate the molecular mechanisms underlying the protective action of honokiol against A beta(1-42)-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. The results revealed that honokiol protected PC12 cells from A beta(1-42) induced cytotoxicity with increases in cell viability, GSH production and Bcl-2 expression, but decreases in the release of lactate dehydrogenase and cytochrome c, the amount of DNA fragmentation and MDA level, as well as Bax expression. Mechanistic study showed that honokiol could inhibit the activation of glycogen synthase kinase (GSK)-3 beta, attenuate the nuclear accumulation of beta-catenin and suppress the phosphorylation of 13-catenin (Ser33/Ser37/Thr41 site) in the A beta(1-42)-treated PC12 cells. These results indicate that the anti-oxidative and anti-apoptotic effects of honokiol in A beta(1-42)-treated PC12 cells may be mediated, at least in part, by regulation the GSK-3 beta and beta-catenin signaling pathways. (C) 2016 Elsevier Ltd. All rights reserved.
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