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一种用于检测粘度和 HS 的双重响应荧光探针及其在研究它们在线粒体中相互作用影响的应用。

A Dual-Response Fluorescent Probe for the Detection of Viscosity and HS and Its Application in Studying Their Cross-Talk Influence in Mitochondria.

机构信息

Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Key Laboratory of Environmentally Friendly Chemistry and Applications of Ministry of Education, College of Chemistry , Xiangtan University , Xiangtan , 411105 , PR China.

College of Chemical Engineering , Xiangtan University , Xiangtan , 411105 , PR China.

出版信息

Anal Chem. 2018 Aug 7;90(15):9418-9425. doi: 10.1021/acs.analchem.8b02068. Epub 2018 Jul 13.

Abstract

Intracellular viscosity is an essential microenvironmental parameter and HS is a critical gaseous signaling molecule, which are both related to various physiological processes. It is reported that the change of viscosity and an imbalance of HS production in the mitochondria are both associated with overexpression of amyloid betapeptide (Aβ), which is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, to our best knowledge, no fluorescent probe is found for dual detection of mitochondrial viscosity and HS. Herein, a dual-response fluorescent probe (Mito-VS) is designed and synthesized to monitor the level of viscosity and HS, respectively. Mito-VS itself is nonfluorescent due to a free intramolecular rotation between dimethylaniline and pyridine. After the increase of viscosity, the rotation is prohibited and an intense red fluorescence is released. Upon the addition of HS, the probe can react with HS to form compound 3 and a strong green fluorescence can be observed. Moreover, the probe possesses a good mitochondrion-targeting ability and is applied for imaging the change of viscosity on the red channel and visualizing the variation of exogenous and endogenous HS concentration on the green channel in mitochondria. Most importantly, the probe is capable of studying the cross-talk influence of viscosity and HS in mitochondria, which is very beneficial for knowing the pathogenesis of AD.

摘要

细胞内黏度是一个重要的微观环境参数,HS 是一种关键的气态信号分子,它们都与各种生理过程有关。有报道称,线粒体中黏度的变化和 HS 产生的失衡都与淀粉样肽β(Aβ)的过表达有关,Aβ被认为在阿尔茨海默病(AD)的发病机制中起核心作用。然而,据我们所知,目前还没有用于同时检测线粒体黏度和 HS 的荧光探针。在此,设计并合成了一种双响应荧光探针(Mito-VS),分别用于监测黏度和 HS 的水平。由于二甲基苯胺和吡啶之间的自由分子内旋转,Mito-VS 本身没有荧光。当黏度增加时,旋转受到限制,会释放出强烈的红色荧光。当加入 HS 时,探针可以与 HS 反应生成化合物 3,并观察到强烈的绿色荧光。此外,该探针具有良好的线粒体靶向能力,可用于成像红色通道中黏度的变化,以及可视化线粒体中外源性和内源性 HS 浓度的变化。最重要的是,该探针能够研究线粒体中黏度和 HS 的相互影响,这对于了解 AD 的发病机制非常有益。

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