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Updated: Dec 25, 2025
A Flow Cytometry-based Assay for Measuring Mitochondrial Membrane Potential in Cardiac Myocytes After Hypoxia/Reoxygenation
Published on: July 13, 2018
Inhibition of GPR35 Preserves Mitochondrial Function After Myocardial Infarction by Targeting Calpain 1/2
Ken Chen1,2, Lei He1, Yong Li3
1Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, Sichuan, P.R. China.
Abstract:
Ischemia and anoxia-induced mitochondrial impairment may be a key factor leading to heart injury during myocardial infarction (MI). Calpain 1 and 2 are involved in the MI-induced mitochondria injury. G protein-coupled receptor 35 (GPR35) could be triggered by hypoxia. Whether or not GPR35 regulates calpain 1/2 in the pathogenesis of MI is still unclear. In this study, we determined that MI increases GPR35 expression in myocardial tissue. Suppression of GPR35 protects heart from MI injury in mice through reduction of reactive oxygen species activity and mitochondria-dependent apoptosis. Further studies show that GPR35 regulates calpain 1/2. Suppression of GPR35 reduces the expression and activity of calpain 1/2, and alleviates calpain 1/2-associated mitochondrial injury to preserve cardiac function. Based on these data, we conclude that a functional inhibition of GPR35 downregulates calpain 1/2 and contributes to maintenance of cardiac function under pathologic conditions with mitochondrial disorder. In conclusion, our study showed that the identified regulation by GPR35 of calpain 1/2 has important implications for the pathogenesis of MI. Targeting the action of GPR35 and calpain 1/2 in mitochondria presents a potential therapeutic intervention for MI.
Insights
In myocardial infarction, G protein-coupled receptor 35 (GPR35) exacerbates heart injury by activating calpain 1/2. Inhibiting GPR35 protects the heart by reducing calpain activity and mitochondrial damage.
Area of Science:
- Cardiovascular Biology
- Mitochondrial Medicine
- Molecular Cardiology
Background:
- Myocardial infarction (MI) involves ischemia and anoxia, leading to mitochondrial dysfunction and heart injury.
- Calpain 1 and 2 are implicated in MI-induced mitochondrial damage.
- Hypoxia can activate G protein-coupled receptor 35 (GPR35), but its role in MI pathogenesis is unknown.
Purpose of the Study:
- To investigate the role of GPR35 in myocardial infarction.
- To determine if GPR35 regulates calpain 1/2 activity in the context of MI.
- To explore GPR35 as a potential therapeutic target for MI.
Main Methods:
- Assessed GPR35 expression in myocardial tissue post-MI.
- Utilized mouse models to evaluate the effects of GPR35 suppression on MI injury.
- Measured reactive oxygen species (ROS) activity and apoptosis.
- Investigated the impact of GPR35 on calpain 1/2 expression and activity.
- Examined mitochondrial function and cardiac performance.
Main Results:
- MI significantly increased GPR35 expression in myocardial tissue.
- GPR35 suppression conferred protection against MI injury in mice.
- Inhibition of GPR35 reduced ROS production and mitochondria-dependent apoptosis.
- GPR35 was found to regulate calpain 1/2, with suppression decreasing their expression and activity.
- Alleviation of calpain 1/2-associated mitochondrial injury preserved cardiac function.
Conclusions:
- GPR35 plays a critical role in MI pathogenesis by regulating calpain 1/2 and promoting mitochondrial injury.
- Functional inhibition of GPR35 downregulates calpain 1/2, preserving cardiac function under pathological conditions.
- Targeting GPR35 and calpain 1/2 within mitochondria offers a promising therapeutic strategy for MI.
