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Updated: Sep 24, 2025
Improved Rodent Model of Myocardial Ischemia and Reperfusion Injury
Published on: March 7, 2022
GSK3β Exacerbates Myocardial Ischemia/Reperfusion Injury by Inhibiting Myc
Cong Wen1,2, Meide Lan1,2, Xin Tan1,2
1Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China.
Abstract:
Myocardial ischemia/reperfusion (MI/R) injury is a life-threatening disease with high morbidity and mortality. Herein, the present study is conducted to explore the regulatory mechanism of GSK3β in MI/R injury regarding cardiomyocyte apoptosis and oxidative stress. The MI/R injury mouse model and hypoxic reoxygenation (H/R) cell model were established. The expression pattern of GSK3β, FTO, KLF5, and Myc was determined followed by their relation validation. Next, loss-of-function experiments were implemented to verify the effect of GSK3β/FTO/KLF5/Myc on cardiomyocyte apoptosis and oxidative stress in the MI/R injury mouse model and H/R cell model. High expression of GSK3β and low expression of FTO, KLF5, and Myc were observed in the MI/R injury mouse model and H/R cell model. GSK3β promoted phosphorylation of FTO and KLF5, thus increasing the ubiquitination degradation of FTO and KLF5. A decrease of FTO and KLF5 was able to downregulate Myc expression, resulting in enhanced cardiomyocyte apoptosis and oxidative stress. These data together supported the crucial role that GSK3β played in facilitating cardiomyocyte apoptosis and oxidative stress so as to accelerate MI/R injury, which highlights a promising therapeutic strategy against MI/R injury.
Insights
Glycogen synthase kinase 3 beta (GSK3β) promotes heart cell death and oxidative stress in myocardial ischemia/reperfusion (MI/R) injury. Inhibiting GSK3β may offer a new therapeutic strategy for treating MI/R injury.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Myocardial ischemia/reperfusion (MI/R) injury poses significant health risks due to high morbidity and mortality.
- Understanding the molecular mechanisms underlying MI/R injury is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the regulatory role of GSK3β in MI/R injury.
- To elucidate the mechanism involving GSK3β, FTO, KLF5, and Myc in cardiomyocyte apoptosis and oxidative stress.
Main Methods:
- Established MI/R mouse and hypoxic reoxygenation (H/R) cell models.
- Assessed expression levels of GSK3β, FTO, KLF5, and Myc.
- Performed loss-of-function experiments to validate the pathway's role.
Main Results:
- Observed high GSK3β expression and low FTO, KLF5, and Myc expression in MI/R and H/R models.
- Demonstrated that GSK3β promotes FTO and KLF5 phosphorylation, leading to their degradation.
- Showed that reduced FTO and KLF5 downregulate Myc, enhancing cardiomyocyte apoptosis and oxidative stress.
Conclusions:
- GSK3β significantly contributes to cardiomyocyte apoptosis and oxidative stress in MI/R injury.
- The GSK3β/FTO/KLF5/Myc pathway is a key regulator of MI/R injury.
- Targeting GSK3β presents a potential therapeutic strategy for MI/R injury.
