PET-ESIPT-based fluorescent probes for revealing the fluctuation of peroxynitrite (ONOO-) in living cells, zebrafishes and brain tissues
PET-ESIPT-based fluorescent probes for revealing the fluctuation of peroxynitrite (ONOO-) in living cells, zebrafishes and brain tissues
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基于 PET-ESIPT 的荧光探针，用于揭示活细胞、斑马鱼和脑组织中过氧亚硝酸盐 (ONOO-) 的波动
DOI：
10.1016/j.snb.2021.131121
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Baoli Dong
中科院分区：
文献类型：
--
作者：
Yaru Sun;Xiaochan Tang;Xiaobing Li;Xiuqi Kong;Minggang Tian;Yue Wang;Baoli Dong
过氧亚硝酸盐（ONOO-）在生命系统的多种生理和病理过程中起着至关重要的作用，因此，ONOO-的实时原位成像对于深入研究其生物学作用具有重要意义。在此基础上，我们开发了基于PET-ESIPT的荧光探针（BCN和BCN-A），用于检测活细胞、斑马鱼和脑组织中的ONOO-，BCN是一种高灵敏的ONOO-探针，其中荧光团的荧光性质同时受PET和ESIPT机制控制，并通过乙酰化转化为BCN-A。BCN-A对ONOO-具有很高的Stokes位移，对ONOO-具有很高的选择性; BCN-A通过引入乙酸酯基团，阻断了荧光团的ESIPT过程，提高了膜的通透性。在活细胞中，BCN-A通过酯酶水解释放出ONOO-响应探针（BCN），然后检测ONOO-。生物成像表明，虽然二甲双胍和鱼藤酮都是线粒体复合物I抑制剂，但二甲双胍可以增加ONOO的产生，而鱼藤酮对活细胞和斑马鱼中ONOO的产生没有显着影响。此外，抑郁症小鼠脑内杏仁核和内嗅/外嗅皮质的荧光强度均较正常小鼠增强，提示LPS诱导的抑郁症可导致小鼠两个脑区ONOO-的产生。我们期望这两个探针（BCN和BCN-A）能广泛地作为研究ONOO生物学作用的有力分子工具，为药物作用机制和抑郁症的深入研究提供有力的工具。
Peroxynitrite (ONOO-) plays crucial roles in a variety of physiological and pathological processes in living systems, and therefore, real-time and in situ imaging of ONOO-is of great significance to in-depth study its biological roles. Herein, we have developed PET-ESIPT-based fluorescent probes (BCNandBCN-A) for the detection of ONOO-in living cells, zebrafishes and brain tissues.BCNwas a highly sensitive ONOO-probe in which the fluorescence property of the fluorophore was simultaneously controlled by PET and ESIPT mechanisms, and transformed toBCN-Avia acetylation. Especially,BCNshowed large Stokes shift in response to ONOO-, and displayed high selectivity to ONOO-.BCN-Aemployed the acetate group to switch off ESIPT process of the fluorophore and improve the membrane permeability. In living cells,BCN-Areleased an ONOO--responsive probe (BCN) by the hydrolysis of esterase, and then detected ONOO-. Biological imaging demonstrated that although both metformin and rotenone are mitochondrial complex I inhibitors, metformin can increase the generation of ONOO-while rotenone had no significant influence on the generation of ONOO-in living cells and zebrafishes. Moreover, the amygdala and perirhinal/entorhinal cortex in the brain of depressive mouse both showed increasing fluorescence intensity relative to those of normal mouse, which suggested that the LPS-induced depressive disorder could result in the generation of ONOO-in the two brain areas of mouse. We expect that the probes (BCNandBCN-A) could extensively serve as the powerful molecular tools to investigate the biological roles of ONOO-for the in-depth study of drug mechanism and depressive disorder.
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影响因子：
8.4
作者：
Cao J;An W;Reeves AG;Lippert AR
通讯作者：
Lippert AR
影响因子：
7.2
作者：
Choi, HR;Choi, JS;Chung, HY
通讯作者：
Chung, HY
DOI：
10.1073/pnas.92.16.7162
发表时间：
1995-08-01
影响因子：
11.1
作者：
BONFOCO, E;KRAINC, D;LIPTON, SA
通讯作者：
LIPTON, SA
影响因子：
7.4
作者：
Csaba Szabó
通讯作者：
Csaba Szabó
一种基于次膦酸盐的近红外荧光探针，用于体外和体内超氧自由基阴离子成像
影响因子：
4.9
作者：
Zhang Jianjian;Li Chuwen;Zhang Rui;Zhang Fengyuan;Liu Wei;Liu Xiaoyan;Lee Simon Ming-Yuen;Zhang Haixia
通讯作者：
Zhang Haixia