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构建用于区分溶酶体和线粒体功能障碍的双发射探针。

Construction of a Dual-Emissive Probe for Discriminative Visualization of Lysosomal and Mitochondrial Dysfunction.

机构信息

School of Chemistry and Chemical Engineering, University of Jinan, Jinan, Shandong 250022, China.

School of Medical Technology, Institute of Engineering Medicine, School of Life Science, Beijing Key Laboratory for Separation and Analysis in Biomedicine and Pharmaceuticals, Beijing Institute of Technology, Beijing 100081, China.

出版信息

Anal Chem. 2023 Oct 3;95(39):14787-14796. doi: 10.1021/acs.analchem.3c03024. Epub 2023 Sep 19.

DOI:10.1021/acs.analchem.3c03024
PMID:37726214
Abstract

Discriminatively visualizing mitochondrial and lysosomal dysfunction is crucial for an in-depth understanding of cell apoptosis regulation and relative biology. However, fluorescent probes for the separate visualization of lysosomal and mitochondria damages have not been reported yet. Herein, we have constructed a fluorescent probe [2-(4-hydroxystyryl)-1,3,3-trimethyl-3-indol-1-ium iodide (HBSI)] for labeling mitochondria and lysosomes in dual emission colors and discriminatively imaging mitochondrial and lysosomal damage in two different sets of fluorescent signals. In living cells, HBSI targeted both lysosomes and mitochondria to give green and red emission, respectively. During mitochondrial damages, HBSI immigrated into lysosomes, and the red emission decreased. During lysosomal damage, HBSI immigrated into mitochondria, and the green emission decreased. With the robust probe, the different damaging sequences of mitochondria and lysosomes under different amounts of HO and chloral hydrate have been revealed. The sequential damage of lysosomes and mitochondria during cell apoptosis induced by rotenone, paclitaxel, and colchicine has been discovered. Furthermore, the regulation of mitochondria, lysosome, and their interplay during autophagy was also observed with the probe.

摘要

区分可视化线粒体和溶酶体功能障碍对于深入了解细胞凋亡调控和相关生物学至关重要。然而,目前还没有用于分别可视化溶酶体和线粒体损伤的荧光探针。在此,我们构建了一种荧光探针[2-(4-羟基苯乙烯基)-1,3,3-三甲基-3-吲哚-1-碘化物(HBSI)],用于在双发射颜色中标记线粒体和溶酶体,并以两组不同的荧光信号区分成像线粒体和溶酶体损伤。在活细胞中,HBSI 分别靶向溶酶体和线粒体,产生绿色和红色发射。在线粒体损伤时,HBSI 迁移到溶酶体中,红色发射减弱。在线粒体损伤时,HBSI 迁移到线粒体中,绿色发射减弱。使用这种强大的探针,我们揭示了不同浓度的 HO 和水合氯醛作用下线粒体和溶酶体的不同损伤序列。发现了鱼藤酮、紫杉醇和秋水仙碱诱导细胞凋亡过程中溶酶体和线粒体的顺序损伤。此外,还可以用该探针观察自噬过程中线粒体、溶酶体及其相互作用的调节。

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