Activatable Proximity-Labeled Fluorogenic Probe for Visualizing the Role of Estrogen in Regulating Liver...

Area of Science:

• Biochemistry
• Pharmacology
• Molecular Biology

Background:

• Estradiol (E2), a key estrogen, influences physiological functions and disease states.
• Carboxylesterases (CEs) are vital drug-metabolizing enzymes affected by estrogen levels.
• Understanding E2-CEs interplay is crucial for drug therapy in women.

Purpose of the Study:

• To develop a probe for detecting carboxylesterases (CEs) activity.
• To investigate the effect of estradiol (E2) on CEs expression and activity.
• To provide tools for understanding estrogen regulation of CEs.

Main Methods:

• Development of a proximity-labeled fluorogenic probe (DCI2F-MC) for CEs detection.
• In vitro studies using LO2 cells to assess E2's effect on CEs.
• In vivo studies in an ovariectomized mouse model using fluorescence imaging and Western blot.

Main Results:

• DCI2F-MC probe enabled selective detection and imaging of CEs activity.
• E2 dose-dependently decreased CEs expression in LO2 cells.
• E2 supplementation reduced hepatic CEs activity in ovariectomized mice.

Conclusions:

• E2 modulates CEs expression and activity, potentially via transcriptional regulation or the AP-1 pathway.
• The developed probe serves as a valuable tool for studying estrogen-CEs interactions.
• Findings support a scientific basis for personalized drug therapy in women.