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
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
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通过新型 Au-Se 荧光纳米探针实时原位监测 Lon 和 Caspase-3，评估缺氧条件下心肌细胞的状态
DOI：
10.1016/j.bios.2021.112965
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发表时间：
2021
影响因子：
12.6
通讯作者：
Tang Bo
中科院分区：
文献类型：
--
作者：
Zhan Renhui;Guo Wenfei;Gao Xiaonan;Liu Xiaojun;Xu Kehua;Tang Bo
缺血和缺氧条件下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。目前对心肌功能障碍的诊断仍集中在症状阶段，通常是在发生不可逆重构和功能损害之后。因此，早期识别缺氧诱导的心肌细胞凋亡对于预防心肌功能障碍的发生和延缓心肌功能障碍的进展具有重要意义。本研究开发了一种具有强抗干扰能力的新型Au-Se纳米探针，用于同时实时监测活心肌细胞中Lon蛋白酶（Lon）和Caspase-3的高保真表达。由于Lon上调在缺氧诱导的细胞凋亡启动中起主要作用，而Caspase-3是细胞凋亡的标记蛋白，纳米探针已成功应用于成像Lon-Caspase-3凋亡信号通路的激活和评估缺氧条件下心肌细胞的状态。此外，我们还结合线粒体h2o2探针- mitopy1，证实了Lon和ROS在缺氧诱导心肌细胞凋亡中的协同作用，并评价了ROS清除剂对心肌细胞凋亡的抑制作用。本研究为缺氧缺血性心肌功能障碍的早期诊断、预防和治疗提供了一种有前景的策略。
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-timein situmonitoring 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 H2O2probe-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.