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基于D-A-D型的近红外荧光探针用于监测铁死亡过程中胰腺癌细胞内的半胱氨酸水平。

D-A-D type based NIR fluorescence probe for monitoring the cysteine levels in pancreatic cancer cell during ferroptosis.

作者信息

Qin Jingcan, Wang Jing, Bian Yun, Shao Chengwei

机构信息

Department of Radiology, Changhai Hospital, Naval Medical University, Changhai Road 168, Shanghai 200433, China.

Shanghai East Hospital, The Institute for Biomedical Engineering & Nano Science, Tongji University School of Medicine, Shanghai, China.

出版信息

Bioorg Chem. 2024 May;146:107260. doi: 10.1016/j.bioorg.2024.107260. Epub 2024 Mar 4.

Abstract

Cysteine (Cys) as a crucial precursor for intracellular glutathione (GSH) synthesis, plays an important role in the redox regulation in ferroptosis, Therefore, evaluating intracellular Cys levels is worthy to better understand ferroptosis-related physiological process. In this work, we constructed a novel NIR coumarin-derived fluorescent probe (NCDFP-Cys) based on a dual-ICT system, the NCDFP-Cys can show fluorescence turn-on response at 717 nm toward Cys over other amino acids, and possess large Stokes shift (Δλ = 167 nm), low detection limit, hypotoxicity. More significantly, NCDFP-Cys has been utilized to monitor the intracellular Cys fluctuation in pancreatic cancer cells during ferroptosis induced by Erastin and RSL3 respectively, and revealing the difference of Cys levels changes in different activator-triggered ferroptosis pathways.

摘要

半胱氨酸(Cys)作为细胞内谷胱甘肽(GSH)合成的关键前体,在铁死亡的氧化还原调节中起重要作用。因此,评估细胞内Cys水平对于更好地理解铁死亡相关的生理过程具有重要意义。在本研究中,我们构建了一种基于双分子内电荷转移(ICT)体系的新型近红外香豆素衍生荧光探针(NCDFP-Cys),该探针在717nm处对Cys呈现荧光开启响应,对其他氨基酸无此响应,且具有大斯托克斯位移(Δλ = 167nm)、低检测限和低细胞毒性。更重要的是,NCDFP-Cys已被用于分别监测由埃拉斯汀(Erastin)和RSL3诱导的铁死亡过程中胰腺癌细胞内Cys的波动情况,并揭示不同激活剂触发的铁死亡途径中Cys水平变化的差异。

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