Visualizing Peroxynitrite Fluxes in Endothelial Cells Reveals the Dynamic Progression of Brain Vascular Injury
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- 作者：Xin Li ; Rong-Rong Tao ; Ling-Juan Hong ; Juan Cheng ; Quan Jiang ; Ying-Mei Lu ; Mei-Hua Liao ; Wei-Feng Ye ; Nan-Nan Lu ; Feng Han ; Yong-Zhou Hu ; You-Hong Hu
- 刊名：Journal of the American Chemical Society
- 出版年：2015
- 出版时间：September 30, 2015
- 年：2015
- 卷：137
- 期：38
- 页码：12296-12303
- 全文大小：706K
- ISSN：1520-5126
文摘
Accumulating evidence suggests that formation of peroxynitrite (ONOO鈥?/sup>) in the cerebral vasculature contributes to the progression of ischemic damage, while the underlying molecular mechanisms remain elusive. To fully understand ONOO鈥?/sup> biology, efficient tools that can realize the real-time tracing of endogenous ONOO鈥?/sup> fluxes are indispensable. While a few ONOO鈥?/sup> fluorescent probes have been reported, direct visualization of ONOO鈥?/sup> fluxes in the cerebral vasculature of live mice remains a challenge. Herein, we present a fluorescent switch-on probe (NP3) for ONOO鈥?/sup> imaging. NP3 exhibits good specificity, fast response, and high sensitivity toward ONOO鈥?/sup> both in vitro and in vivo. Moreover, NP3 is two-photon excitable and readily blood鈥揵rain barrier penetrable. These desired photophysical and pharmacokinetic properties endow NP3 with the capability to monitor brain vascular ONOO鈥?/sup> generation after injury with excellent temporal and spatial resolution. As a proof of concept, NP3 has enabled the direct visualization of neurovascular ONOO鈥?/sup> formation in ischemia progression in live mouse brain by use of two-photon laser scanning microscopy. Due to these favorable properties, NP3 holds great promise for visualizing endogenous peroxynitrite fluxes in a variety of pathophysiological progressions in vitro and in vivo.