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在缺氧/再灌注应激条件下,通过近红外荧光成像在细胞、组织和体内可视化并评估线粒体半胱氨酸。

Visualizing and evaluating mitochondrial cysteine via near-infrared fluorescence imaging in cells, tissues and in vivo under hypoxia/reperfusion stress.

作者信息

Zhang Xia, Zhang Liangwei, Wang Xiaoyan, Han Xiaoyue, Huang Yan, Li Bowei, Chen Lingxin

机构信息

CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Shandong Key Laboratory of Coastal Environmental Processes, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China; University of Chinese Academy of Sciences, Beijing 100049, China.

CAS Key Laboratory of Coastal Environmental Processes and Ecological Remediation, Shandong Key Laboratory of Coastal Environmental Processes, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, China.

出版信息

J Hazard Mater. 2021 Oct 5;419:126476. doi: 10.1016/j.jhazmat.2021.126476. Epub 2021 Jun 25.

Abstract

Increasingly grim environmental pollutions are closely related with the occurrence and development of diseases. However, it's obscure how environmental stress disturbs the normal physiological process, and then how endogenous reactive species mend the cases. Hypoxia/reperfusion (H/R), a common and intractable injury in aquaculture and clinic, can induce oxidative stress and ultimately cause irreversible injury to organism. Cysteine (Cys) plays essential roles in maintaining transduction of numerous reactive species and redox homeostasis in subcellular structures, cells and organisms. A great deal of fluorescence research about Cys are focusing on development of selective probes but with poor exploration of the biofunction under environmental stress. Therefore, it is of great significance to examine the bio-effects of Cys against H/R stress. In the present work, we design a fluorescent probe BCy-AC for in situ detecting Cys, the unique Enol-Keto tautomerization of fluorophore BCy-Keto propels the reaction process which will improve the sensitivity and potential application performance of the probe. BCy-AC is conveniently applied to visualize Cys in HT-22 cells, zebrafish and mice tissues. Moreover, imaging results obtained from H/R models reveal that endogenous Cys changes with hypoxia and reperfusion time and Cys pretreatment effectively defend H/R injury in cells and in vivo.

摘要

日益严峻的环境污染与疾病的发生和发展密切相关。然而,环境应激如何扰乱正常生理过程,以及内源性活性物质如何修复这些情况尚不清楚。缺氧/再灌注(H/R)是水产养殖和临床中常见且棘手的损伤,可诱导氧化应激并最终对生物体造成不可逆损伤。半胱氨酸(Cys)在维持亚细胞结构、细胞和生物体中多种活性物质的转导和氧化还原稳态方面发挥着重要作用。大量关于Cys的荧光研究集中在选择性探针的开发上,但对环境应激下的生物功能探索较少。因此,研究Cys对H/R应激的生物效应具有重要意义。在本工作中,我们设计了一种用于原位检测Cys的荧光探针BCy-AC,荧光团BCy-Keto独特的烯醇-酮互变异构推动了反应过程,这将提高探针的灵敏度和潜在应用性能。BCy-AC可方便地用于可视化HT-22细胞、斑马鱼和小鼠组织中的Cys。此外,从H/R模型获得的成像结果表明,内源性Cys随缺氧和再灌注时间而变化,Cys预处理可有效保护细胞和体内的H/R损伤。

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