Huang Yundi, Song Bo, Chen Kaiwen, Tang Zhixin, Ma Hua, Kong Deshu, Liu Qi, Yuan Jingli
State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China.
School of Bioengineering, Dalian University of Technology, Dalian 116024, China.
Anal Chem. 2023 Feb 28;95(8):4024-4032. doi: 10.1021/acs.analchem.2c04409. Epub 2023 Feb 17.
Liver injury can result from various risk factors including diabetes, virus, alcohol, drugs, and other toxins, which is mainly responsible for global mortality and morbidity. Selenocysteine (Sec), as the main undertaker of selenium function in the life system, features prominently in a series of hepatic injuries and has close association with the pathological progression of liver injuries. Here, we report a mitochondria-targetable lanthanide complex-based probe, , that can be used for accurately determining Sec in live cells and laboratory animals via the ratiometric time-gated luminescence (TGL) technique. This probe is composed of 2,2':6',2″-terpyridine-Tb/Eu mixed complexes as the luminophore, 2,4-dinitrophenyl (DNP) as the responsive moiety and a lipophilic triphenylphosphonium cation (PPh) as the mitochondria-targeting moiety. Upon reaction with Sec, accompanied by the cleavage of DNP from the probe molecule, the / ratio of the probe increased by 55 times, which enabled Sec to be detected with the ratiometric TGL method. After being incubated with living cells, the probe molecules were selectively accumulated in mitochondria to allow the mitochondrial Sec to be successfully imaged under the ratiometric TGL mode. Importantly, using this probe coupled with the ratiometric TGL imaging technique, the fluctuations of liver Sec in various liver injuries of model mice induced by diabetes, drug, toxin, and alcohol were precisely monitored, revealing that Sec plays an important antioxidant role during the oxidative stress process in liver injury, and the Sec levels have a close interrelationship with the degree of liver injury. All the results suggest that the new probe could be a potential tool for the accurate diagnosis of liver injury.
肝损伤可由多种风险因素引起，包括糖尿病、病毒、酒精、药物和其他毒素，这些因素是全球死亡率和发病率的主要原因。硒代半胱氨酸（Sec）作为生命系统中硒功能的主要承担者，在一系列肝损伤中表现突出，并且与肝损伤的病理进展密切相关。在此，我们报道了一种基于线粒体靶向镧系配合物的探针，该探针可通过比率时间分辨发光（TGL）技术用于准确测定活细胞和实验动物中的Sec。该探针由作为发光体的2,2':6',2″-三联吡啶-Tb/Eu混合配合物、作为响应部分的2,4-二硝基苯基（DNP）和作为线粒体靶向部分的亲脂性三苯基鏻阳离子（PPh）组成。与Sec反应后，伴随着DNP从探针分子上的裂解，探针的/比率增加了55倍，这使得能够通过比率TGL方法检测Sec。与活细胞孵育后，探针分子选择性地积聚在线粒体中，从而能够在比率TGL模式下成功成像线粒体Sec。重要的是，使用该探针结合比率TGL成像技术，精确监测了糖尿病、药物、毒素和酒精诱导的模型小鼠各种肝损伤中肝脏Sec的波动，揭示了Sec在肝损伤氧化应激过程中发挥重要的抗氧化作用，并且Sec水平与肝损伤程度密切相关。所有结果表明，新探针可能是准确诊断肝损伤的潜在工具。
