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Visualization of Acrolein Upregulation during Ferroptosis by a Ratiometric Fluorescent Probe.

Qingxia Duan¹, Yunpeng Wang¹, Xiaoli Zhang²

¹Key Laboratory of Medical Molecule Science and Pharmaceutics Engineering, Ministry of Industry and Information Technology, Key Laboratory of Cluster Science of Ministry of Education, Beijing Key Laboratory of Photo-Electronic/Electrophotonic Conversion Materials, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China.

Analytical Chemistry

|June 7, 2024

Summary

Researchers developed a novel fluorescent probe, HBT-SH, to visualize acrolein (ACR) during ferroptosis. This tool helps detect ACR, a key molecule in ferroptosis, offering insights into disease mechanisms and potential biomarkers.

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Area of Science:

Biochemistry
Cell Biology
Chemical Biology

Background:

Ferroptosis is an iron-dependent cell death pathway linked to various diseases.
Acrolein (ACR), a toxic lipid peroxidation metabolite, plays a role in ferroptosis.
Detecting ACR is crucial for understanding ferroptosis mechanisms and related diseases.

Purpose of the Study:

To develop the first ratiometric fluorescent probe for visualizing endogenous acrolein (ACR) during ferroptosis.
To investigate the role and potential as a biomarker of ACR in ferroptosis progression.

Main Methods:

Design and synthesis of a novel ratiometric fluorescent probe (HBT-SH) utilizing a 2-(2'-hydroxyphenyl) benzothiazole (HBT) core.
Development of a regiospecific intramolecular cyclization strategy for ACR detection using 2-aminoethanethiol.
Application of the probe in HeLa cells and zebrafish to monitor ACR levels during ferroptosis.

Main Results:

The HBT-SH probe demonstrated excellent selectivity, high sensitivity (LOD = 0.26 μM), and good biocompatibility.
Upregulation of ACR levels was successfully observed during ferroptosis in both cellular and in vivo models.
ACR was identified as a potential specific active molecule or biomarker in ferroptosis.

Conclusions:

The developed HBT-SH probe enables effective visualization and detection of endogenous ACR during ferroptosis.
ACR upregulation during ferroptosis suggests its essential biological role and potential as a ferroptosis marker.
This work provides a valuable tool for studying ferroptosis-related diseases and developing therapeutic strategies.