Imaging of the mutual regulation between zinc cation and nitrosyl via two-photon fluorescent probes in cells and in vivo
Imaging of the mutual regulation between zinc cation and nitrosyl via two-photon fluorescent probes in cells and in vivo
复制标题
通过双光子荧光探针在细胞和体内对锌阳离子和亚硝酰之间的相互调节进行成像
DOI：
10.1016/j.snb.2020.127772
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发表时间：
2020-04-15
影响因子：
8.4
通讯作者：
Yu, Fabiao
中科院分区：
文献类型：
--
作者：
Li, Mingshun;Xing, Yanlong;Yu, Fabiao
细胞内锌离子池的动态平衡紊乱与严重疾病密切相关。已有研究表明，缺血再灌注(I/R)过程中高水平的游离锌离子可导致神经细胞氧化应激损伤。鉴于亚硝基(HNO)可加重脑I/R过程中的神经损伤，我们推测在一定的生理条件下，锌离子和HNO之间可能存在相互调节。为了揭示这种潜在的小信号分子串扰，我们合成了双光子荧光探针CHP-H和CHP-CH3来监测细胞和小鼠海马区I/R模型中的细胞内锌离子。该探针由两部分组成：香豆素衍生物作为双光子荧光传感器，2-肼基吡啶作为荧光调制剂和锌离子螯合剂。这两种探针在模拟生理体系中都表现出了良好的分析性能，用于检测锌离子。利用CHP-H和HNO探针Cyto-JN，我们对细胞I/R模型进行了荧光成像。结果证实，HNO能刺激不稳定的锌离子库释放锌离子，而细胞内锌离子浓度的增加不能上调HNO的水平。结合小鼠海马组织的深层组织成像，我们的探针可能为临床脑I/R相关疾病中HNO对锌离子释放的调节作用的医学诊断评估提供潜在的途径。
The homeostatic disorder of intracellular Zn2+ pool is closely associated with severe diseases. It has been reported that the high level of free Zn2+ during ischemia/reperfusion (I/R) process can result in oxidative stress damage on nerve cells. Given that nitrosyl (HNO) can aggravate the nerve injury during cerebral I/R process, we assume that there may exist a mutual regulation between Zn2+ and HNO under certain physiological conditions. To reveal this potential small-signaling-molecule crosstalk, we synthesized two-photon fluorescent probes CHP-H and CHP-CH3 to monitor intracellular Zn2+ in cell and mice hippocampus I/R models. The probes consist of two moieties: coumarin derivative as the two-photon fluorescence transducer, 2-hydrazino pyridine as the fluorescence modulator and Zn2+ chelator. Both probes exhibit excellent analytical properties for Zn2+ detection in simulated physiological systems. Utilizing CHP-H and an HNO probe Cyto-JN, we perform fluorescent imaging of cell I/R models. The results confirm that HNO can stimulate Zn2+ release from labile Zn2+ pool, whereas, the increase of intracellular Zn2+ cannot upregulate the level of HNO. Combining with the deep tissue imaging of mice hippocampus tissues, our probes may provide potential approaches for the medical diagnostic assessment of HNO regulation effect on Zn2+ release in clinical cerebral I/R-related diseases.