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通过含硒近红外荧光探针成像观察缺氧应激下细胞内硫烷硫表达的变化

Imaging of intracellular sulfane sulfur expression changes under hypoxic stress via a selenium-containing near-infrared fluorescent probe.

作者信息

Gao Min, Wang Rui, Yu Fabiao, Li Bowei, Chen Lingxin

机构信息

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

出版信息

J Mater Chem B. 2018 Nov 7;6(41):6637-6645. doi: 10.1039/c8tb01794h. Epub 2018 Oct 4.

DOI:10.1039/c8tb01794h
PMID:32254872
Abstract

Hypoxia is a significant global issue affecting the health of organisms. Oxygen homeostasis is critical for mammalian cell survival and cellular activities. Hypoxic stress can lead to cell injury and death, which contributes to many diseases. Sulfane sulfur is involved in crucial roles in physiological processes of maintaining intracellular redox state and ameliorating oxidative damage. Therefore, real-time imaging of changes in sulfane sulfur levels is important for understanding their biofunctions in cells. In this study, we develop a new near-infrared (NIR) fluorescent probe BD-diSeH for imaging of sulfane sulfur changes in cells and in vivo under hypoxic stress. The probe includes two moieties: an NIR azo-BODIPY fluorophore equipped with a strong nucleophilic phenylselenol group (-SeH). The probe is capable of tracing dynamic changes of endogenous sulfane sulfur based on a fast and spontaneous intramolecular cyclization reaction. The probe has been successfully used for imaging sulfane sulfur in 3D-multicellular spheroid and mouse hippocampus under hypoxic stress. The overall levels of sulfane sulfur are affected by the degree and length of hypoxic stress. The results reveal a close relationship between sulfane sulfur and hypoxia in living cells and in vivo, allowing better understanding of physiological and pathological processes involving sulfane sulfur. Moreover, to investigate the effects of environmental hypoxia on aquatic animals, this probe has been applied for sulfane sulfur detection in hypoxic zebrafish.

摘要

缺氧是一个影响生物体健康的重大全球性问题。氧稳态对于哺乳动物细胞的存活和细胞活动至关重要。缺氧应激可导致细胞损伤和死亡,这会引发多种疾病。硫烷硫在维持细胞内氧化还原状态和减轻氧化损伤的生理过程中发挥着关键作用。因此,实时成像硫烷硫水平的变化对于理解其在细胞中的生物功能很重要。在本研究中,我们开发了一种新的近红外(NIR)荧光探针BD-diSeH,用于在缺氧应激下对细胞和体内硫烷硫变化进行成像。该探针包括两个部分:一个配备有强亲核苯硒醇基团(-SeH)的近红外偶氮硼二吡咯荧光团。该探针能够基于快速且自发的分子内环化反应追踪内源性硫烷硫的动态变化。该探针已成功用于在缺氧应激下对三维多细胞球体和小鼠海马体中的硫烷硫进行成像。硫烷硫的总体水平受缺氧应激的程度和持续时间影响。结果揭示了活细胞和体内硫烷硫与缺氧之间的密切关系,有助于更好地理解涉及硫烷硫的生理和病理过程。此外,为了研究环境缺氧对水生动物的影响,该探针已应用于缺氧斑马鱼中硫烷硫的检测。

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