Low dose nicotine attenuates Aβ neurotoxicity through activation early growth response gene 1 pathway

Maoqiang Xue; Liuwei Zhu; Jie Zhang; Jinhua Qiu; Guicheng Du; Zhiliang Qiao; Guanghui Jin; Fengguang Gao; Qiqing Zhang

doi:10.1371/journal.pone.0120267

Low dose nicotine attenuates Aβ neurotoxicity through activation early growth response gene 1 pathway

PLoS One. 2015 Mar 27;10(3):e0120267. doi: 10.1371/journal.pone.0120267. eCollection 2015.

Authors

Maoqiang Xue¹, Liuwei Zhu², Jie Zhang², Jinhua Qiu², Guicheng Du², Zhiliang Qiao², Guanghui Jin², Fengguang Gao², Qiqing Zhang³

Affiliations

¹ College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, P.R.China; Institute of Biomedical Engineering, Department of Biomaterials, College of Materials, Xiamen University, Xiamen, Fujian, 361005, P.R.China; Department of Basic Medical Science, Medical College, Xiamen University, Xiamen, Fujian, 361005, P.R.China.
² Department of Basic Medical Science, Medical College, Xiamen University, Xiamen, Fujian, 361005, P.R.China.
³ College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian, 361005, P.R.China; Institute of Biomedical Engineering, Department of Biomaterials, College of Materials, Xiamen University, Xiamen, Fujian, 361005, P.R.China; Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, The Key Laboratory of Biomedical Material of Tianjin, Tianjin, 300192, P.R.China.

Abstract

Epidemiological studies indicate that smoking is negatively correlated with the incidence and development of Alzheimer's disease (AD). Nicotine was reported to be the active factor. However, the detailed mechanisms still remain to be fully elucidated. Early growth response gene 1 (EGR-1) plays important roles in several important biological processes such as promoting cell growth, differentiation, anti oxidative stress, and apoptosis, but few in the pathogenesis of AD. In the present study, we show that nicotine can activate the MAPK/ERK/EGR-1 signaling pathway partially through α7 nAChR. In addition, the up-regulation of EGR-1 by nicotine can also increase the phosphorylation of CyclinD1 which contributes to the attenuation of amyloid-β (Aβ(25-35)) -induced neurotoxicity. Although nicotine and Aβ(25-35) can activate EGR-1, the expression of EGR-1 is down-regulated following treatment with nicotine and Aβ(25-35). This study demonstrates that low dose nicotine attenuates Aβ(25-35)-induced neurotoxicity in vitro and in vivo through activating EGR-1 pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / metabolism
Alzheimer Disease / prevention & control*
Amyloid beta-Peptides / metabolism*
Animals
Apoptosis / drug effects
Blotting, Western
Cell Proliferation / drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Early Growth Response Protein 1 / genetics
Early Growth Response Protein 1 / metabolism*
Fluorescent Antibody Technique
Gene Expression Regulation / drug effects*
Hippocampus / cytology
Hippocampus / drug effects*
Hippocampus / metabolism
Humans
Immunoenzyme Techniques
Male
Mice, Inbred C57BL
Neuroblastoma / metabolism
Neuroblastoma / pathology
Neuroblastoma / prevention & control*
Neurons / cytology
Neurons / drug effects
Neurons / metabolism
Nicotine / pharmacology*
PC12 Cells
RNA, Messenger / genetics
Rats
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects

Substances

Amyloid beta-Peptides
EGR1 protein, human
Early Growth Response Protein 1
RNA, Messenger
Nicotine

Grants and funding

This work was supported by National Science Foundation in China (2014J01375; 81271421). The Natural Science Foundation of Fujian Province of China (Grant: 2013J01147; and 2014J06019). This work was also supported by Program for New Century Excellent Talents in University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.