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Real-time in situ monitoring of Lon and Caspase-3 for assessing the state of cardiomyocytes under hypoxic conditions via a novel Au–Se fluorescent nanoprobe
Biosensors and Bioelectronics ( IF 12.6 ) Pub Date : 2021-01-05 , DOI: 10.1016/j.bios.2021.112965
Renhui Zhan , Wenfei Guo , Xiaonan Gao , Xiaojun Liu , Kehua Xu , Bo Tang

Myocardial dysfunction caused by cardiomyocyte apoptosis under ischemic and hypoxic conditions is the pathological basis of most cardiovascular diseases. Current diagnosis of myocardial dysfunction still focuses on the symptomatic stage, usually after the occurrence of the irreversible remodelling and functional impairment. Thus, early stage identification of the apoptotic cardiomyocytes induced by hypoxia is highly significant for preventing the onset and delaying the progression of myocardial dysfunction. Herein, a novel Au–Se nanoprobe with strong anti-interference capability was developed for simultaneous real-time in situ monitoring the expression of Lon protease (Lon) and Caspase-3 with high-fidelity in living cardiomyocytes. As Lon upregulation plays a major role in the initiation of hypoxia-induced apoptosis and Caspase-3 is a marker protein for apoptosis, the nanoprobe has been successfully applied for imaging the activation of Lon-Caspase-3 apoptotic signalling pathway and assessing the state of cardiomyocytes under hypoxic conditions. Furthermore, combining with mitochondrial H2O2 probe-MitoPY1, the nanoprobe was also used to confirm the synergistic effect of Lon and ROS on hypoxia-induced apoptosis of cardiomyocytes and evaluate the function of ROS scavenger on attenuating such apoptosis. This work proposed a promising strategy for early diagnosis, prevention and treatment of hypoxic-ischemic myocardial dysfunction.



中文翻译:

通过新型Au-Se荧光纳米探针对Lon和Caspase-3进行实时原位监测,以评估缺氧条件下的心肌细胞状态

在缺血和缺氧条件下由心肌细胞凋亡引起的心肌功能障碍是大多数心血管疾病的病理基础。当前对心肌功能障碍的诊断通常集中在症状期,通常是在发生不可逆的重塑和功能障碍之后。因此,由缺氧引起的凋亡性心肌细胞的早期鉴定对于预防心肌功能障碍的发作和延迟其进展非常重要。在此,开发了一种具有强大抗干扰能力的新型Au-Se纳米探针,可同时进行原位实时高保真度监测活的心肌细胞中Lon蛋白酶(Lon)和Caspase-3的表达。由于Lon上调在缺氧诱导的细胞凋亡的启动中起主要作用,而Caspase-3是细胞凋亡的标记蛋白,因此纳米探针已成功应用于成像Lon-Caspase-3凋亡信号通路并评估其状态。低氧条件下的心肌细胞。此外,与线粒体H 2 O 2结合探针-MitoPY1,该纳米探针还用于证实Lon和ROS对缺氧诱导的心肌细胞凋亡的协同作用,并评估ROS清除剂减弱这种凋亡的功能。这项工作为低氧缺血性心肌功能障碍的早期诊断,预防和治疗提出了一种有希望的策略。

更新日期:2021-01-06
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