A Newly Synthesized Rhamnoside Derivative Alleviates Alzheimer's Amyloid- &beta; -Induced Oxidative Stress, Mitochondrial Dysfunction, and Cell Senescence through Upregulating SIRT3

doi:10.1155/2020/7698560

	A Newly Synthesized Rhamnoside Derivative Alleviates Alzheimer's Amyloid- β -Induced Oxidative Stress, Mitochondrial Dysfunction, and Cell Senescence through Upregulating SIRT3
	Li, Yi1,2 ; Lu, Jing 1; Cao, Xin 3; Zhao, Hongwei 4; Gao, Longfei 1; Xia, Peng 5; Pei, Gang1,6,7
	2020-02-13
发表期刊	OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
ISSN	19420994
卷号	2020
发表状态	已发表
DOI	10.1155/2020/7698560
摘要	Oxidative stress-induced mitochondrial dysfunction and cell senescence are considered critical contributors to Alzheimer's disease (AD), and oxidant/antioxidant imbalance has been a therapeutic target in AD. SIRT3 is a mitochondrial protein regulating metabolic enzyme activity by deacetylation and its downregulation is associated with AD pathology. In the present study, we showed that a newly synthesized rhamnoside derivative PL171 inhibited the generation of reactive oxidant species (ROS) induced by amyloid-β42 oligomers (Aβ42O), major AD pathological proteins. Moreover, the reduction of mitochondrial membrane potential (MMP) and the impairment of mitochondrial oxygen consumption triggered by Aβ42O were also prevented by PL171. Further experiments demonstrated that PL171 reduced the acetylation of mitochondrial proteins, and particularly the acetylation of manganese superoxide dismutase (MnSOD) and oligomycin-sensitivity-conferring protein (OSCP), two mitochondrial SIRT3 substrates, was suppressed by PL171. Mechanism studies revealed that PL171 upregulated SIRT3 and its upstream peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) under basal and Aβ42O-treated conditions. The inhibition of SIRT3 activity could eliminate the protective effects of PL171. Further, long-term treatment with Aβ42O increased the number of senescent neuronal cell, which was also alleviated by PL171 in a SIRT3-dependent manner. Taken together, our results indicated that PL171 rescued Aβ42O-induced oxidative stress, mitochondrial dysfunction, and cell senescence via upregulating SIRT3 and might be a potential drug candidate against AD. © 2020 Yi Li et al.
URL	查看原文
收录类别	EI ; SCIE
资助项目	[31701240]
出版者	Hindawi Limited, 410 Park Avenue, 15th Floor, 287 pmb, New York, NY 10022, United States
EI入藏号	20201008265390
EI主题词	Acetylation ; Biosynthesis ; Cytology ; Enzyme activity ; Glycoproteins ; Manganese compounds ; Neurodegenerative diseases ; Oxidants ; Oxidative stress
EI分类号	Bioengineering and Biology:461 ; Chemical Reactions:802.2 ; Chemical Agents and Basic Industrial Chemicals:803
原始文献类型	Journal article (JA)
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/120827
专题	生命科学与技术学院_特聘教授组_裴钢组生命科学与技术学院_博士生
通讯作者	Pei, Gang
作者单位	1.State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China 2.School of Life Science and Technology, ShanghaiTech University, Shanghai, China 3.Zhongshan Institute of Clinical Science, Fudan University, China 4.Chemical Biology Core Facility, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai; 200031, China 5.Shanghai EW Medicine Co. Ltd., China 6.Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology, Tongji University, Shanghai, China 7.Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China
第一作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Li, Yi,Lu, Jing,Cao, Xin,et al. A Newly Synthesized Rhamnoside Derivative Alleviates Alzheimer's Amyloid- β -Induced Oxidative Stress, Mitochondrial Dysfunction, and Cell Senescence through Upregulating SIRT3[J]. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY,2020,2020.
APA	Li, Yi.,Lu, Jing.,Cao, Xin.,Zhao, Hongwei.,Gao, Longfei.,...&Pei, Gang.(2020).A Newly Synthesized Rhamnoside Derivative Alleviates Alzheimer's Amyloid- β -Induced Oxidative Stress, Mitochondrial Dysfunction, and Cell Senescence through Upregulating SIRT3.OXIDATIVE MEDICINE AND CELLULAR LONGEVITY,2020.
MLA	Li, Yi,et al."A Newly Synthesized Rhamnoside Derivative Alleviates Alzheimer's Amyloid- β -Induced Oxidative Stress, Mitochondrial Dysfunction, and Cell Senescence through Upregulating SIRT3".OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020(2020).