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Published on: May 26, 2023
Capsaicin protects cardiomyocytes against lipopolysaccharide-induced damage via 14-3-3γ-mediated autophagy
Yang Qiao1, Liang Wang2, Tianhong Hu3
1Institute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Insights
Capsaicin protects heart cells from sepsis-induced damage by enhancing autophagy via 14-3-3γ signaling. This treatment reduces inflammation, oxidative stress, and improves mitochondrial function, mitigating cardiac dysfunction in sepsis.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Biology
Background:
- Sepsis-induced cardiac dysfunction is a major cause of mortality.
- Lipopolysaccharide (LPS) damages the myocardium, but cardiomyocyte autophagy changes are unclear.
- Capsaicin's protective effects and mechanisms in sepsis-induced cardiac injury require elucidation.
Purpose of the Study:
- To investigate the role of 14-3-3γ-dependent autophagy in LPS-induced cardiomyocyte injury.
- To determine the protective effects and underlying mechanisms of capsaicin (Cap) in this model.
Main Methods:
- Primary neonatal rat cardiomyocytes were subjected to LPS-induced injury.
- The effects of capsaicin pretreatment were assessed on cell viability, autophagy markers, and inflammatory responses.
- Molecular pathways involving 14-3-3γ, AMPK, ULK1, and mTOR were analyzed.
- Oxidative stress, mitochondrial function, and inflammatory cytokine levels were quantified.
Main Results:
- LPS downregulated 14-3-3γ and inhibited autophagy, leading to cardiomyocyte damage.
- Capsaicin upregulated 14-3-3γ, activated AMPK/ULK1, suppressed mTOR, and augmented autophagy.
- Capsaicin alleviated LPS-induced cardiac dysfunction, inflammation, oxidative stress, and improved mitochondrial function.
- Silencing 14-3-3γ abolished the protective effects of capsaicin.
Conclusions:
- Capsaicin protects cardiomyocytes against LPS-induced injury by modulating 14-3-3γ-dependent autophagy.
- Capsaicin mitigates sepsis-related cardiac damage by inhibiting oxidative stress and inflammation.
- Capsaicin enhances cardiomyocyte survival and function through improved mitochondrial integrity.
Abstract:
Background: The myocardium is susceptible to lipopolysaccharide (LPS)-induced damage in sepsis, and cardiac dysfunction is a leading cause of mortality in patients with sepsis. The changes in cardiomyocyte autophagy in sepsis and the effects and mechanism of action of capsaicin (Cap) remain unclear. Methods and Results: The potential pathway of 14-3-3γ-dependent autophagy and the effects and mechanisms of Cap were studied in LPS-induced injury to primary cultured neonatal rat cardiomyocytes. The results showed that cardiomyocyte viability decreased, lactate dehydrogenase and creatine kinase activities increased, 14-3-3γ expression was downregulated, and autophagy was inhibited after LPS challenge. Cap pretreatment augmented autophagy by upregulating 14-3-3γ expression and activating AMP-activated protein kinase (AMPK) and unc-51 like autophagy-activating kinase 1 (ULK1), suppressing mammalian target of rapamycin (mTOR), alleviating cardiac dysfunction and improving the inflammation response, whereas pAD/14-3-3γ-shRNA nullified the above effects. Cap pretreatment also decreased the levels of IL-1β, TNF-α, IL-6, and IL-10; suppressed intracellular oxidative stress; reduced the intracellular/mitochondrial reactive oxygen species (ROS); balanced GSH/GSSG; increased GSH-Px, catalase, and SOD activities; and decreased MDA contents. It also increased ATP content, activated complex Ⅰ and complex Ⅲ, stabilized the mitochondrial membrane potential, and decreased the mitochondrial permeability transition pore opening, thereby improving mitochondrial function. Conclusion: Pretreatment with Cap can regulate autophagy by upregulating 14-3-3γ expression, inhibiting oxidative stress and inflammation, maintaining mitochondrial function, and protecting cardiomyocytes against LPS-induced injury.
