Evaluating the Protective Effects of Mitochondrial Glutathione on Cerebral Ischemia/Reperfusion Injury via Near-Infrared Fluorescence Imaging

doi:10.1021/acs.analchem.9b04082

	Evaluating the Protective Effects of Mitochondrial Glutathione on Cerebral Ischemia/Reperfusion Injury via Near-Infrared Fluorescence Imaging
	Xia Zhang; Lingxin Chen; Xiaoyue Han; Yue Wang; Zhang LW(张良伟)
发表期刊	Analytical Chemistry
ISSN	0003-2700
	2019
卷号	91 期号:22 页码:10.1021/acs.analchem.9b04082
关键词	LIVING CELLS SUPEROXIDE ANION OXIDATIVE STRESS GENE-EXPRESSION IN-VIVO PROBE REDOX ISCHEMIA MECHANISMS ACTIVATION
研究领域	Chemistry, Analytical
DOI	10.1021/acs.analchem.9b04082
产权排序	[Zhang, Xia; Huang, Yan; Han, Xiaoyue; Wang, Yue; Zhang, Liangwei; Chen, Lingxin] Chinese Acad Sci, Yantai Inst Coastal Zone Res, Res Ctr Coastal Environm Engn & Technol, CAS Key Lab Coastal Environm Proc & Ecol Remediat, Yantai 264003, Peoples R China; [Huang, Yan; Chen, Lingxin] Binzhou Med Univ, Sch Pharm, Yantai 264003, Peoples R China; [Chen, Lingxin] Chinese Acad Sci, Ctr Ocean Mega Sci, Qingdao 266071, Peoples R China; [Zhang, Xia; Han, Xiaoyue; Wang, Yue] Univ Chinese Acad Sci, Beijing 100049, Peoples R China
通讯作者	Zhang, Liangwei(liangweizhang@yic.ac.cn) ; Chen, Lingxin(lxchen@yic.ac.cn)
作者部门	海岸带环境工程技术研究与发展中心
英文摘要	Cerebral ischemia/reperfusion (I/R) is common and intractable in the clinic, associated with the outburst of reactive oxygen species (ROS) in mitochondria. Although numerous research studies have been conducted to prove the protective-effect roles of glutathione (GSH) in this event, the changes in GSH concentrations in living cells remain largely unexplained, and there is scarce evidence by fluorescence imaging for its roles. Herein we have designed and synthesized two distinctive "off-on" near-infrared (NIR) fluorescent probes BCy-SeSe and BCy-SS based on a new fluorophore BCy-Keto for specific response to mitochondrial GSH changes during the cerebral I/R process. Both of them exhibit powerful targeting capability in mitochondria and excellent photophysical properties toward endogenous GSH with high selectivity and sensitivity. In contrast to BCy-SS, BCy-SeSe was screened for biological application on account of its faster response rate. We have utilized BCy-SeSe to real-time image GSH during the cerebral I/R process in living cells and the mice focal cerebral ischemia model (middle cerebral artery occlusion, MCAO), and these intensive studies revealed that low GSH levels were associated with aggravation of apoptosis and cerebral infarction. Pretreatment with GSH synthase inhibitor aggravates damage while GSH-ester alleviates damage, confirming that GSH is effective on the cerebrum for protection from I/R. All the results demonstrated that the probes were powerful tools for investigating mitochondrial GSH during the I/R process in living cells and in vivo.
文章类型	Article
资助机构	National Nature Science Foundation of ChinaNational Natural Science Foundation of China [21976209, 21575159, 21778026] ; program of Youth Innovation Pro-motion Association, CAS [2019217] ; Taishan Scholar Project Special Funding
收录类别	SCI
语种	英语
关键词[WOS]	LIVING CELLS ; SUPEROXIDE ANION ; OXIDATIVE STRESS ; GENE-EXPRESSION ; IN-VIVO ; PROBE ; REDOX ; ISCHEMIA ; MECHANISMS ; ACTIVATION
研究领域[WOS]	Chemistry, Analytical
WOS记录号	WOS:000498280100076
引用统计	被引频次：40[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.yic.ac.cn/handle/133337/24174
专题	中国科学院海岸带环境过程与生态修复重点实验室
通讯作者	Xia Zhang
推荐引用方式 GB/T 7714	Xia Zhang,Lingxin Chen,Xiaoyue Han,et al. Evaluating the Protective Effects of Mitochondrial Glutathione on Cerebral Ischemia/Reperfusion Injury via Near-Infrared Fluorescence Imaging[J]. Analytical Chemistry,2019,91(22):10.1021/acs.analchem.9b04082.
APA	Xia Zhang,Lingxin Chen,Xiaoyue Han,Yue Wang,&Zhang LW.(2019).Evaluating the Protective Effects of Mitochondrial Glutathione on Cerebral Ischemia/Reperfusion Injury via Near-Infrared Fluorescence Imaging.Analytical Chemistry,91(22),10.1021/acs.analchem.9b04082.
MLA	Xia Zhang,et al."Evaluating the Protective Effects of Mitochondrial Glutathione on Cerebral Ischemia/Reperfusion Injury via Near-Infrared Fluorescence Imaging".Analytical Chemistry 91.22(2019):10.1021/acs.analchem.9b04082.