http://dx.doi.org/10.1111/cns.12286">
 

Document Type

Journal Article

Authors

Xiao-Juan Chao, Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University
Zi-Wei Chen, Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University
An-Min Liu, Department of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
Xi-Xin He, Department of Traditional Chinese Medicine Chemistry, College of Chinese Materia Madica, Guangzhou University of Chinese Medicine
Shao-Gui Wang, Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University
Yu-Ting Wang, Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University
Pei-Qing Liu, Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University
Charles Ramassamy, INRS-Institut Armand Frappier
Shing-Hung Mak, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University
Wei Cui, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University
Ah-Ng Kong, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey
Zhi-Ling Yu, Research and Development Division, School of Chinese Medicine, Hong Kong Baptist UniversityFollow
Yi-Fan Han, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University
Rong-Biao Pi, Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University

Department/Unit

School of Chinese Medicine

Title

Effect of tacrine-3-caffeic acid, a novel multifunctional anti-Alzheimer's dimer, against oxidative-stress-induced cell death in HT22 hippocampal neurons: Involvement of Nrf2/HO-1 pathway

Language

English

Abstract

Aims: Oxidative stress (OS) plays an important role in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). This study was designed to uncover the cellular and biochemical mechanisms underlying the neuroprotective effects of tacrine-3-caffeic acid (T3CA), a novel promising multifunctional anti-Alzheimer's dimer, against OS-induced neuronal death. Methods and Results: T3CA protected HT22 cells against high-concentration-glutamate-induced cell death in time- and concentration-dependent manners and potently attenuated glutamate-induced intracellular reactive oxygen species (ROS) production as well as mitochondrial membrane-potential (ΔΨ) disruption. Besides, T3CA significantly induced nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation and increased its transcriptional activity, which were demonstrated by Western blotting, immunofluorescence, and antioxidant response element (ARE)-luciferase reporter gene assay. Further studies showed that T3CA potently up-regulated heme oxygenase-1 (HO-1), an endogenous antioxidative enzyme and a downstream effector of Nrf2, at both mRNA and protein levels. The neuroprotective effects of T3CA were partially reversed by brusatol, which reduced protein level of Nrf2, or by inhibiting HO-1 with siRNA or ZnPP-IX, a specific inhibitor of HO-1. Conclusions: Taken together, these results clearly demonstrate that T3CA protects neurons against OS-induced cell death partially through Nrf2/ARE/HO-1 signaling pathway, which further supports that T3CA might be a promising novel therapeutic agent for OS-associated diseases. © 2014 John Wiley & Sons Ltd.

Keywords

Cell death, HO-1, Nrf2, Oxidative stress, T3CA

Publication Date

2014

Source Publication Title

CNS Neuroscience and Therapeutics

Volume

20

Issue

9

Start Page

840

End Page

850

Publisher

Wiley

ISSN (print)

17555930

ISSN (electronic)

17555949

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