Molecular fluorescent probes for imaging and evaluation of peroxynitrite fluctuations in living cells and in vivo under hypoxic stress
Molecular fluorescent probes for imaging and evaluation of peroxynitrite fluctuations in living cells and in vivo under hypoxic stress
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DOI：
10.1016/j.snb.2022.132410
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发表时间：
2022-07-21
影响因子：
8.4
通讯作者：
Chen, Lingxin
中科院分区：
文献类型：
--
作者：
Huang, Yan;Yu, Lei;Chen, Lingxin
缺氧应激通过产生过量的活性氧（ROS）导致细胞损伤和凋亡，这是生物学和医学界普遍关注的问题。过氧亚硝酸盐（ONOO-）在许多疾病的致病机制中，在组织蛋白的氧化损伤中发挥着至关重要的作用，它是ROS的一种。因此，ONOO-的过量产生可能是导致缺氧应激损伤的关键因素之一。但由于ONOO-化学性质不稳定、反应活性强，现有检测手段大多无法实时成像检测其含量。在此，为了在活细胞和体内选择性地成像和检测ONOO-，我们合成了荧光探针Cy-CF3（我们用于检测ONOO-的荧光探针）。 Cy-CF3 能够以优异的灵敏度和选择性监测 ONOO-。使用 Cy-CF3 评估缺氧应激与 ONOO- 之间的关系。该探针还用于检测缺氧条件下斑马鱼ONOO-的变化以及测定急性肝缺血活体小鼠ONOO-的变化。总而言之，所提出的探针可能是研究 ONOO- 生物机制的强大化学工具。
Hypoxia stress causes cell damage and apoptosis by producing excessive reactive oxygen species (ROS), which is a universal concern in biology and medicine. Peroxynitrite (ONOO-) plays a vital part in the oxidative injury of tissue proteins in the pathogenic mechanism of many disorders, which is a one of ROS. Thus, excessive pro-duction of ONOO- may be one of the crucial factors leading to hypoxia stress injury. However, due to the unstable chemical property and strong reactivity of ONOO-, most of the existing detection ways cannot image and detect its level in real time. Herein, in order to selectively imaging and detecting ONOO- in living cells and in vivo, we synthesized a fluorescent probe Cy-CF3 (our fluorescent probe for detection of ONOO-). Cy-CF3 was capable of monitoring ONOO- with excellent sensitivity and selectivity. Using Cy-CF3, the relationship between hypoxia stress and ONOO- was evaluated. The probe was also employed to sense the change of ONOO- in zebrafish under hypoxia conditions as well as determine ONOO- in living mice with acute liver ischemia. Taken together, the proposed probe maybe a powerful chemical tool for the study of ONOO- in biological mechanisms.