Fluorescence Dynamics Imaging Reveals Inflammation Driven by Ferroptosis through a MAO/ONOO^- Dual-Responsive Probe

Area of Science:

• Biomedical Imaging
• Molecular Biology
• Inflammation Research

Background:

• Uncontrolled inflammation drives tissue damage via oxidative stress.
• Monoamine oxidase A (MAO-A) and peroxynitrite (ONOO⁻) are key mediators of oxidative damage.
• Existing dual-probe methods for monitoring these mediators lack consistency.

Purpose of the Study:

• To develop a mitochondria-targeted, dual-responsive fluorescent probe for real-time visualization of MAO-A and ONOO⁻.
• To investigate the molecular mechanisms underlying inflammation-associated oxidative stress.
• To explore potential therapeutic interventions targeting identified pathways.

Main Methods:

• Development of a novel mitochondria-targeted dual-responsive fluorescent probe (KMO).
• In situ real-time imaging of MAO-A and ONOO⁻ in inflammatory cells and an acute hepatitis mouse model.
• Analysis of the inflammatory self-amplifying cycle involving MAO-A, ONOO⁻, and ferroptosis.

Main Results:

• Achieved the first in situ real-time visualization of MAO-A and ONOO⁻ dynamics.
• Revealed a self-amplifying inflammatory cycle: MAO-A activation → ONOO⁻ burst → ferroptosis → inflammation exacerbation.
• Demonstrated that inhibiting ferroptosis disrupts this inflammatory pathway.

Conclusions:

• The KMO probe offers a reliable tool for dynamic monitoring of MAO-A and ONOO⁻ in inflammatory processes.
• Identified a novel self-amplifying inflammatory mechanism involving MAO-A, ONOO⁻, and ferroptosis.
• Inhibiting ferroptosis presents a potential therapeutic strategy for acute inflammation.