Abstract:
Superoxide anion (O2·-) and peroxynitrite (ONOO-), two important oxidants under oxidative stress, coexist in complex cell and organism systems, playing crucial roles in various physiological and pathological processes, particularly in neurodegenerative diseases. Despite the absence of robust molecular tools capable of simultaneously visualizing O2·- and ONOO- in biosystems, the relationship between these two species remains understudied. Herein, we present sequentially activated fluorescent probe, DHX-SP, which exhibits exceptional selectivity and sensitivity toward O2·- and ONOO-. This probe enables precise imaging of these species in living PC12 cells under oxidative stress conditions using distinct fluorescence signal combinations. Furthermore, the probe DHX-SP has the ability to visualize changes in O2·- and ONOO- levels during ferroptosis of PC12 cells and in the Parkinson\'s disease model. These findings establish a connection between the crosstalk of the phosphorus group of O2·- and ONOO- in PC12 cells under oxidative stress.
摘要:
超氧阴离子(O2·-)和过氧亚硝酸盐(ONOO-),两种重要的氧化剂在氧化应激下,在复杂的细胞和生物体系统中共存,在各种生理和病理过程中发挥关键作用,特别是在神经退行性疾病中。尽管缺乏能够在生物系统中同时可视化O2·-和ONOO-的强大分子工具,这两个物种之间的关系仍未得到充分研究。在这里,我们提出了顺序激活的荧光探针,DHX-SP,对O2·-和ONOO-表现出优异的选择性和灵敏度。该探针能够使用不同的荧光信号组合在氧化应激条件下对活PC12细胞中的这些物种进行精确成像。此外,DHX-SP探针能够观察PC12细胞铁凋亡过程中和帕金森病模型中O2·-和ONOO-水平的变化。这些发现在氧化应激下PC12细胞中O2·-和ONOO-的磷基团的串扰之间建立了联系。