Document Detail


Potential roles of PI3K/Akt and Nrf2-Keap1 pathways in regulating hormesis of Z-ligustilide in PC12 cells against oxygen and glucose deprivation.
MedLine Citation:
PMID:  22146407     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Many phytochemicals may ameliorate neurological disorders through a hormetic mechanism. The aim of this study was to characterize the hormetic role of Z-ligustilide in PC12 cells against oxygen glucose deprivation (OGD) induced cell death. We examined the interactions of Z-ligustilide with the pro-survival signals mediated by phosphatidylinositol 3-kinase (PI3K) and transcription factor nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathways. We also investigated the effect of Z-ligustilide on the intracellular redox signaling system involving reactive oxygen species (ROS) and glutathione (GSH). Z-ligustilide not only triggered stress response by causing ROS formation and transient GSH depletion, but also activated survival-promoting signals via cross-talking of PI3K and Nrf2 pathways. A key finding was that Z-ligustilide preconditioning protected PC12 cells from OGD-induced injury either at a low concentration for a prolonged period of time or at a high concentration for a short period of time. Presumably, mild preconditioning stimulated moderate ROS production, but effectively activated hormetic signals and induced stress responsive genes. In contrast, higher concentrations of Z-ligustilide could be toxic over a prolonged period of time due to massive ROS production. These results suggest that the effect of Z-ligustilide may be regulated by a biphasic hormetic mechanism involving initial induction of oxidative stress and subsequent activation of stress response gene expression.
Authors:
Hongyi Qi; Yifan Han; Jianhui Rong
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-29
Journal Detail:
Title:  Neuropharmacology     Volume:  -     ISSN:  1873-7064     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-12-7     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0236217     Medline TA:  Neuropharmacology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier Ltd. All rights reserved.
Affiliation:
School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 10 Sassoon Road, Pokfulam, Hong Kong, China.
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