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一种新型“双响应”和“双靶向”多功能荧光探针监测细胞焦亡过程中线粒体中过氧亚硝酸盐(ONOO)的水平变化。

A Novel "Double-Responsive" and "Dual-Targeted" Multifunctional Fluorescent Probe Monitors the Level Changes of ONOO in Mitochondria during Cell Pyroptosis.

作者信息

Wei Di, Dai Yingshu, Yan Xixian, Lan Daoguo, Liao Jiayang, Qin Zhengbang, Fu Nanyan

机构信息

Ministry of Education Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection for Food Safety, College of Chemistry, Fuzhou University, Fuzhou 350108, P. R. China.

出版信息

ACS Sens. 2025 Apr 25;10(4):2542-2553. doi: 10.1021/acssensors.4c02841. Epub 2025 Apr 12.

Abstract

Pyroptosis, often referred to as inflammatory necrosis, is a type of programmed cell death, characterized by the swelling of cells until the cell membranes rupture, resulting in the release of intracellular substances and a strong inflammatory response. Lipid droplets and mitochondria play important roles in cellular activities. A strong correlation exists between pyroptosis and mitochondrial dysfunction, which can be reflected through physiological functions and involves changes in the mitochondrial microenvironment and morphology. In this work, a "double-responsive" and "dual-targeted" fluorescent probe named was constructed. It has excellent response performance to viscosity and ONOO, and can simultaneously monitor the relevant levels in lipid droplets and mitochondria. Its remarkable targeting ability toward mitochondria and lipid droplets has been verified through colocalization experiments. In cell imaging experiments, the interaction between mitochondria and lipid droplets during nutritional stress was preliminarily studied. With the help of doxorubicin hydrochloride, the changes in the level of ONOO in mitochondria during pyroptosis were explored, providing a new perspective for understanding the mechanism of this process.

摘要

细胞焦亡,常被称为炎性坏死,是一种程序性细胞死亡,其特征是细胞肿胀直至细胞膜破裂,导致细胞内物质释放并引发强烈的炎症反应。脂滴和线粒体在细胞活动中发挥重要作用。细胞焦亡与线粒体功能障碍之间存在密切关联,这可通过生理功能体现出来,且涉及线粒体微环境和形态的变化。在这项工作中,构建了一种名为 的“双响应”和“双靶向”荧光探针。它对粘度和过氧亚硝酸盐具有出色的响应性能,并且能够同时监测脂滴和线粒体中的相关水平。通过共定位实验验证了其对线粒体和脂滴的显著靶向能力。在细胞成像实验中,初步研究了营养应激期间线粒体与脂滴之间的相互作用。借助盐酸多柔比星,探索了细胞焦亡过程中线粒体中过氧亚硝酸盐水平的变化,为理解这一过程的机制提供了新的视角。

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