Simultaneous visualization of lipid droplets and tracking of the endogenous hypochlorous acid in psoriatic mice models with a novel fluorescent probe in a wash-free fashion.

Autor: Zhao X; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China., Hu X; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China., Li L; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China., Liu Y; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China., Song B; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China., Li Y; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address: liyuzhi@cdutcm.edu.cn., Cao Z; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China., Zhou H; Sichuan New Green Pharmaceutical Technology Development Co. Ltd., Chengdu 611930, China., Peng C; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China., Deng Y; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. Electronic address: dengyun@cdutcm.edu.cn., Fang Y; State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China; Sichuan New Green Pharmaceutical Technology Development Co. Ltd., Chengdu 611930, China. Electronic address: yyfang@cdutcm.edu.cn.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2024 Dec; Vol. 153, pp. 107967. Date of Electronic Publication: 2024 Nov 16.
DOI: 10.1016/j.bioorg.2024.107967
Abstrakt: Psoriasis is an autoimmune inflammation-related disease accompanied by a variety of complications. Reactive oxygen species (ROS) are modulators of inflammation, and their excessive production caused by oxidative/anti-oxidative imbalance has been observed in psoriatic patients. Hypochlorous acid (HOCl) is a ROS produced by myeloperoxidase (MPO) from chloride ions (Cl - ) and hydrogen peroxide (H 2 O 2 ). Endogenous HOCl has recently been studied as a potential biomarker of psoriasis underlying the necessity for the development of efficient analytical tools for its detection and real time monitoring. Herein, we designed a novel highly sensitive and selective coumarin-based fluorescent probe for HOCl detection, named CN 2 -CF 3 -S. The probe itself featured negligible fluorescence because of the heavy atom effect of the thiocarbonyl group. However, upon responding to HOCl a conversion to sulfur-free derivative CN 2 -CF 3 -O occurs, resulting in a dramatical fluorescent enhancement setting the detection limit for HOCl of 3.2 nM. The HOCl-recognition mechanism could be ascribed to the HOCl-triggered oxidative desulfurization process that agrees with liquid chromatography-mass spectrometry (LC-MS) analysis and density functional theory (DFT) computations. The probe's design incorporated a synergistic combination of two structural features for efficient lipid droplets (LDs)-targeting imaging. An efficient push-pull system reinforced by the presence of two strongly electron-donating dimethylamino groups equipped CN 2 -CF 3 -O with pronounced solvatochromism realized through the enhanced blue-shifted emission in non-polar media. Meanwhile, the presence of trifluormethylphenyl moiety at the acceptor side led to an increased lipophilicity. The CN 2 -CF 3 -S probe has been successfully utilized to track the endogenous HOCl in cells and on skin of the psoriatic mice in a wash-free manner. As a result, we have demonstrated that the concentration of HOCl in skin might correlate positively with the degree of inflammation in psoriasis. Thus, CN 2 -CF 3 -S constitutes the first example of LDs-imaging fluorescent probe for detecting the psoriasis-linked HOCl, offering a convenient tool for further in-depth investigation of psoriasis pathophysiology.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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