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Lipid droplet-targeting fluorescent probes for monitoring hydrogen sulfide in ferroptosis.

作者信息

Wang Chen, Wang Zhaomin, Li Bingyan, Yang Ziye, Yang Ruo, Zhu Keming, Liu Yong

机构信息

State Key Laboratory for Vegetation Structure, Functions and Construction, Ministry of Education Key Laboratory for Transboundary Ecosecurity of Southwest China, Yunnan Key Laboratory of Ecological Protection and Resource Utilization of River-lake Networks, Yunnan University, Kunming, 650500, China; Microcystins Pollution Control Engineering Research Center of Yunnan Education Department, Yunnan Key Laboratory of Soil Erosion Prevention and Green Development, Yunnan University, Kunming, 650500, China.

State Key Laboratory for Vegetation Structure, Functions and Construction, Ministry of Education Key Laboratory for Transboundary Ecosecurity of Southwest China, Yunnan Key Laboratory of Ecological Protection and Resource Utilization of River-lake Networks, Yunnan University, Kunming, 650500, China.

出版信息

Anal Chim Acta. 2025 Aug 8;1362:344156. doi: 10.1016/j.aca.2025.344156. Epub 2025 May 10.

DOI:10.1016/j.aca.2025.344156
PMID:40447398
Abstract

BACKGROUND

Ferroptosis represents a unique form of regulated cell death that is distinct from apoptosis, necroptosis, and other modalities. It is characterized by iron-dependent lipid peroxidation and the depletion of glutathione (GSH). Hydrogen sulfide (HS), a key endogenous gaseous signaling molecule, plays an essential role in various biological and physiological processes. However, owing to the lack of advanced monitoring techniques, elucidating the dynamic fluctuations of HS during ferroptosis has posed significant challenges for researchers.

RESULTS

In this study, we designed and synthesized two lipid droplet-targeting fluorescent probes (Pr-SERA and Pr-SERB) to investigate the dynamic changes of HS during ferroptosis. The results indicated that these probes possess high specificity, enabling effective monitoring of HS concentration fluctuations. Specifically, in the Erastin-induced cell model, a gradual decrease in fluorescence intensity was observed; in contrast, Fer-1-treated cells exhibited a significant increase in fluorescence intensity. This observation aligns with the mechanism by which Erastin suppresses HS production via the depletion of intracellular GSH, thereby further validating the progressive decline of HS levels during ferroptosis. Moreover, these probes demonstrated excellent detection performance in zebrafish in vivo models, confirming their suitability and reliability for biological applications. Overall, the fluorescent probes developed in this study serve as valuable tools for elucidating the mechanisms of active molecules involved in ferroptosis.

SIGNIFICANCE

It is anticipated that the methodology developed in this investigation will provide a comprehensive and robust analytical tool for the accurate, in-situ quantification of HS. This approach holds significant promise for advancing the understanding of ferroptosis and its associated disorders.

摘要

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