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Thioredoxin-1 and geranylgeranylacetone Resist Neurotoxicity of Amyloid-β

神经药理学报 2019年第4期9卷 15-64页

作者： BAI Li-ping LI Ye ZHOU Xiao-shuang ZHANG Xian-wen SUN Bo YAN Chen DENG Ru-hua BAI Jie Faculty of Environmental Science and Engineering Kunming University of Science and TechnologyKunming 650500China Medical School Kunming University of Science and TechnologyKunming650500China

Objective:Alzheimer’s disease( AD) is the most common neurodegenerative disorder which is characterized by amyloid-β( Aβ) aggradation in the brain and impairment of cognitive function. Thioredoxin-1( Trx-1) is a redox regulating protein,and plays roles in resisting the oxidative stress and protecting neurons. Our previous study found that Trx-1 improved the cognitive function of Parkinson’s Disease( PD) mice. geranylgeranylacetone( GGA) is an antiulcer drug and induces the expression of Trx-1 in vivo and in vitro. However,whether Trx-1 improves cognitive functions in mice of APP/PS1 or GGA protects SH-SY5 Y cells from cytotoxicity induced by Aβ is still unknown. The objective of present is to investigate the roles of Trx-1 and GGA in inhibiting neurotoxicity of Aβ. Methods:We used MTT assay to test the cell viability induced by Aβ(25-35) and western blot to detect the expression of Trx-1 in SH-SY5 Y cells. Trx-1 overexpression transgenic mice were hybridized with APP/PS1 transgenic mice to get control,Trx-1,Tx-1/APP/PS1 and APP/PS1 mice. Then we used Morris water maze,high plus maze and object recognition test to detect the cognitive function of different kinds of mice. We also used RT-PCR and western blot to test the mRNA level and expression of Trx-1,APP,PS1 and Aβ. Results:In our present study,we demonstrated that Aβ(25-35) decreased the cell viability and the expression of Trx-1 in SH-SY5 Y cells. The cell viability and the expression of Trx-1 were reversed by GGA. Our results showed that the escape latency in APP/PS1 mice was longer when compared with the Trx-1/APP/PS1 mice in Morris water maze and high plus maze. Whereas navigational experiments in Morris water maze result showed that the total number of crossings and the percentage of time spent in the target quadrant were significantly decreased in APP/PS1 mice when compared to Trx-1/APP/PS1 mice. Object recognition test the discrimination index was significantly decreased in APP/PS1 mice when compared with

关键词： thioredoxin-1 Alzheimer’s disease geranylgeranylacetone amyloid-β APP/PS1 cognitive function

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Protective effects of heat shock protein70 induced by geranyl-geranylacetone in atrophic gastritis in rats

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Acta Pharmacologica Sinica 2007年第7期28卷 1001-1006页

作者： Wei-li LIU~2,Shu-jie CHEN~2,Yan CHEN~(2,3),Lei-min SUN~2,Wei ZHANG~2,Ya-min ZENG~2,Tian-hua ZHOU~(2,4),Jian-min SI~(2,5)~2 Department of Gastroenterology and Zhejiang Key laboratory of Traditional Chinese Medicine(TCM),Sir Run Run Shaw Hospital,ZhejiangUniversity School of Medicine,Hangzhou 310012,China ~3 Department of Gastroenterology,Second Affiliated Hospital and ~4 Center forDisease Modeling,Zhejiang University College of Medicine,Hangzhou 310058,China Department of Gastroenterology and Zhejiang Key laboratory of Traditional Chinese Medicine (TCM) Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou China Department of Gastroenterology Second Affiliated Hospital Zhejiang University College of Medicine Hangzhou China Center for Disease Modeling Zhejiang University College of Medicine Hangzhou China

Aim:To investigate the effect of geranylgeranylacetone (GGA) on the progres-sion of atrophic gastritis in rats and its potential ***:Atrophicgastritis was induced in Sprague-Dawley rats with 0.1% ammonia solution,60%ethanol,and 20 mmol/L deoxycholic acid for 24 *** by theinduction of atrophic gastritis,200 mg/kg GGA was administered by oral gavagefor 8 weeks (weeks 17-24).The histological changes in gastric mucosa werequantitated by the index of inflammation,the gastric mucosal thickness,and theamount of glands of 1 mm horizontal length in *** heat shockprotein (HSP)70 levels and distribution were determined by immunoblotting andimmunohistochemistry in gastric ***:GGA alleviated the pathologi-cal progression of atrophic gastritis with inflammation relief (inflammation index:1.40 in the GGA group and 1.65 in the atrophic gastritis group) and glandularrestoration (mucosal thickness and quantity of glands:194.3 μm and 38.7 mm inthe GGA group;123.3 μm and 32.7 mm in the atrophic gastritis group;P<0.05).GGA significantly induced HSP70 synthesis (P<0.05).Moreover,quercetin,aninhibitor of HSP70 expression,aggravated the infiltration of inflammatory cellsand glandular loss in the ***:GGA prevented the progression ofatrophic gastritis in rats via the induction of HSP70 expression.

关键词： geranylgeranylacetone heat shock protein70 atrophic gastritis quercetin

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