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Fabrication of a Dual-Responsive Fluorescence Probe for Monitoring Cardiac Injury and Repairing by a Golgi-Targeting
Ao Li1, Zhe Chen1, Mengqi Wang1
1School of Pharmacy, Hunan Provincial Key Laboratory of Tumor Microenvironment Responsive Drug Research, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang Medical School, University of South China, Hengyang, 421001, P. R. China.
Abstract:
Doxorubicin (Dox) can cause delayed severe myocardial injury by promoting oxidative stress. The Golgi apparatus is involved in the occurrence and development of cardiovascular diseases. In this work, a dual-responsive fluorescent probe GHO, which can detect simultaneously both Golgi superoxide anion (O2 •-) and peroxynitrite anion (ONOO-) with two distinct emission bands, is developed for investigating the Golgi stress-mediated myocardial injury mechanism. Furthermore, a synthesized hydrogen sulfide (H2S) donor (GADT) with Golgi apparatus targeting ability is used for intervening the process of Dox-induced cardiac damage, which shows significant antioxidant capacity in the Golgi apparatus with the help of evaluation of the probe GHO. In detail, compound GADT inhibits Golgi apparatus stress by clearing reactive oxygen species (ROS), thus recover the myocardial damage caused by Dox in cardiomyocytes, zebrafish, and mice. Finally, GADT is proven to play an effective therapeutic role by promoting the degradation of the damaged Golgi apparatus into an autophagosome. Therefore, focusing on the Golgi apparatus, development of the small molecule fluorescent probe GHO and the Golgi-targeting H2S donor GADT provides a novel perspective for the diagnosis and treatment of Dox-induced myocardial injury mechanism.
Insights
A novel fluorescent probe (GHO) and hydrogen sulfide donor (GADT) target the Golgi apparatus to combat Doxorubicin-induced myocardial injury by reducing oxidative stress and promoting autophagy.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Molecular Biology
Background:
- Doxorubicin (Dox) induces delayed myocardial injury via oxidative stress.
- The Golgi apparatus plays a role in cardiovascular disease development.
- Investigating Golgi stress is crucial for understanding Dox-induced cardiotoxicity.
Purpose of the Study:
- Develop a dual-responsive fluorescent probe (GHO) for simultaneous detection of superoxide anion (O2•−) and peroxynitrite anion (ONOO−) in the Golgi apparatus.
- Synthesize a Golgi-targeting hydrogen sulfide (H2S) donor (GADT) to intervene in Dox-induced cardiac damage.
- Elucidate the mechanism of Golgi stress in Dox-induced myocardial injury.
Main Methods:
- Development of a dual-emission fluorescent probe (GHO) for Golgi superoxide anion and peroxynitrite anion detection.
- Synthesis of a Golgi-targeting hydrogen sulfide (H2S) donor (GADT).
- Evaluation of GADT's antioxidant capacity and therapeutic effect in cardiomyocytes, zebrafish, and mice using the GHO probe.
Main Results:
- The probe GHO successfully detected O2•− and ONOO− in the Golgi apparatus.
- GADT demonstrated significant antioxidant capacity within the Golgi apparatus, mitigating Dox-induced reactive oxygen species (ROS).
- GADT treatment recovered myocardial damage in various models and promoted the degradation of damaged Golgi apparatus via autophagy.
Conclusions:
- The developed fluorescent probe GHO and Golgi-targeting H2S donor GADT offer a novel approach for studying and treating Dox-induced myocardial injury.
- Targeting Golgi apparatus stress presents a promising therapeutic strategy for mitigating Doxorubicin cardiotoxicity.
- The findings highlight the potential of autophagy in managing Dox-induced cardiac damage.
