博文
Visualizing peroxynitrite dynamics in an epilepsy model
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a
Key Laboratory of Haikou Trauma, Key Laboratory of Hainan Trauma and Disaster Rescue, Key Laboratory of Emergency and Trauma, Ministry of Education, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou 571199, China
b
College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, China
c
Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, College of Emergency and Trauma, Hainan Medical University, Haikou 571199, China
Received 15 April 2025, Revised 11 July 2025, Accepted 25 July 2025, Available online 26 July 2025, Version of Record 26 July 2025.
Highlights•An endoplasmic reticulum-targeted fluorescence sensor ER-EO was prepared.
•ER-EO has high selectivity, sensitivity and low detection limit toward peroxynitrite.
•ER-EO enables favorable imaging of peroxynitrite in biological models.
•ER-EO can serve as a molecular tool for diagnosing epilepsy.
Abstract
Epilepsy is a chronic neurodegenerative disorder that poses a significant threat to global health. Recent studies have shown a strong correlation between the onset of epilepsy and the highly reactive nitrogen species (RNS) peroxynitrite (ONOO−), with endoplasmic reticulum (ER) stress playing a critical role in its pathological process. However, the spatiotemporal dynamics of ONOO− levels under ER stress during epilepsy remain poorly understood. To address this, we developed a novel ER-targeting fluorescent probe, ER-EO, for real-time monitoring of ONOO− changes in epileptic conditions. The ER-EO probe exhibits high specificity, precisely targeting the ER and detecting ONOO− at concentrations as low as 4.5 nM, while enabling visualization of both exogenous and endogenous ONOO−. Experimental results demonstrated that ER-EO significantly detected elevated ONOO− levels in cells under tunicamycin-induced ER stress and simulated epileptic conditions. Furthermore, in kainic acid (KA)-induced epilepsy models, including cells, zebrafish, and mice, ER-EO successfully enabled real-time monitoring of ONOO− level fluctuations during both the onset and remission phases of epilepsy. This study not only provides a powerful tool for elucidating the pathological mechanisms of ONOO− in epilepsy but also reveals the dynamic interplay between ER stress and epilepsy progression, offering new insights into the pathological processes of epilepsy and laying a foundation for the development of potential therapeutic strategies.
https://wap.sciencenet.cn/blog-2438823-1496799.html
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