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Updated: May 25, 2025
Fast and Specific Assessment of the Halogenating Peroxidase Activity in Leukocyte-enriched Blood Samples
Published on: July 28, 2016
Novel Hypochlorous Acid-Activated Near-Infrared Probe Monitors the Dynamic Changes of Myeloperoxidase Activity in
Meiling Sun1, Yuting Wang2, Huijun Xu2
1School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China.
Abstract:
Myeloperoxidase (MPO) contributes to the progression of ischemic damage. To fully understand MPO biology, highly sensitive and specific probes that can trace the activity of endogenous MPO fluxes are indispensable. Here, we developed two hypochlorous acid (HClO)-activated near-infrared probes to image MPO activity in a noninvasive manner. The probe MPO-NIR-II could track MPO-induced HClO in real time and in situ upon various stimuli with high sensitivity and specificity. Furthermore, MPO-NIR-II could monitor the MPO activity by in vivo fluorescence imaging and confocal laser scanning microscopy in mice with ischemic stroke. Moreover, a high-content screening system for MPO inhibitors was established by combining MPO-NIR-II with MPO-overexpressed cells and mouse brain slices with ischemic stroke, and the candidate compound AZD5904 was found to effectively attenuate ischemic brain injury. Overall, this work provides a versatile fluorescence tool that holds great promise for visualizing endogenous MPO fluxes of brain ischemia.
Insights
Researchers developed a new near-infrared probe, MPO-NIR-II, to track myeloperoxidase (MPO) activity in real-time. This tool aids in understanding ischemic damage and screening for MPO inhibitors to treat brain ischemia.
Area of Science:
- Biochemistry
- Medical Imaging
- Neuroscience
Background:
- Myeloperoxidase (MPO) is implicated in ischemic damage progression.
- Sensitive and specific probes are needed to study endogenous MPO activity.
- Hypochlorous acid (HClO) is a reactive species produced by MPO.
Purpose of the Study:
- To develop novel near-infrared (NIR) fluorescent probes for noninvasive imaging of MPO activity.
- To utilize these probes for real-time monitoring of MPO-induced HClO.
- To establish a high-content screening system for MPO inhibitors.
Main Methods:
- Development of two HClO-activated NIR probes, including MPO-NIR-II.
- In situ and real-time tracking of MPO-induced HClO.
- In vivo fluorescence imaging and confocal microscopy in a mouse model of ischemic stroke.
- High-content screening using MPO-overexpressed cells and ischemic mouse brain slices.
Main Results:
- MPO-NIR-II demonstrated high sensitivity and specificity in tracking MPO activity and HClO production.
- The probe successfully monitored MPO activity in mice with ischemic stroke.
- A candidate MPO inhibitor, AZD5904, was identified and shown to attenuate ischemic brain injury.
Conclusions:
- The developed MPO-NIR-II probe is a versatile tool for visualizing endogenous MPO fluxes in brain ischemia.
- This technology facilitates real-time monitoring of MPO activity and inhibitor screening.
- The findings hold promise for advancing the study and treatment of ischemic conditions.
