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A Flow Cytometry-based Assay for Measuring Mitochondrial Membrane Potential in Cardiac Myocytes After Hypoxia/Reoxygenation
Published on: July 13, 2018
The protective effect of the mitochondrial-derived peptide MOTS-c on LPS-induced septic cardiomyopathy
Abstract:
Septic cardiomyopathy is associated with mechanisms such as excessive inflammation, oxidative stress, regulation of calcium homeostasis, endothelial dysfunction, mitochondrial dysfunction, and cardiomyocyte death, and there is no effective treatment at present. MOTS-c is a mitochondria-derived peptide (MDP) encoded by mitochondrial DNA (mtDNA) that protects cells from stresses in an AMPK-dependent manner. In the present study, we aim to explore the protective effect of MOTS-c on lipopolysaccharide (LPS)-induced septic cardiomyopathy. LPS is used to establish a model of septic cardiomyopathy. Our results demonstrate that MOTS-c treatment reduces the mRNA levels of inflammatory cytokines ( IL-1β, IL-4, IL-6, and TNFα) in cardiomyocytes and the levels of circulating myocardial injury markers, such as CK-MB and TnT, alleviates cardiomyocyte mitochondrial dysfunction and oxidative stress, reduces cardiomyocyte apoptosis, activates cardioprotection-related signaling pathways, including AMPK, AKT, and ERK, and inhibits the inflammation-related signaling pathways JNK and STAT3. However, treatment with the AMPK pathway inhibitor compound C (CC) abolishes the positive effect of MOTS-c on LPS stress. Collectively, our research suggests that MOTS-c may attenuate myocardial injury in septic cardiomyopathy by activating AMPK and provides a new idea for therapeutic strategies in septic cardiomyopathy.
Insights
Mitochondria-derived peptide MOTS-c shows protective effects against septic cardiomyopathy by reducing inflammation and cell damage. This peptide activates the AMPK pathway, offering a potential new therapeutic strategy for this condition.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Septic cardiomyopathy, a severe complication of sepsis, involves inflammation, oxidative stress, and cardiomyocyte death.
- Current treatments for septic cardiomyopathy are limited, highlighting the need for novel therapeutic approaches.
Purpose of the Study:
- To investigate the protective effects of MOTS-c (mitochondria-derived peptide) against lipopolysaccharide (LPS)-induced septic cardiomyopathy.
- To elucidate the underlying molecular mechanisms, particularly the role of the AMPK pathway.
Main Methods:
- Establishment of a septic cardiomyopathy model using LPS in cardiomyocytes.
- Assessment of inflammatory cytokine mRNA levels, myocardial injury markers (CK-MB, TnT), mitochondrial function, and oxidative stress.
- Analysis of key signaling pathways including AMPK, AKT, ERK, JNK, and STAT3.
- Evaluation of MOTS-c's effects with and without the AMPK inhibitor Compound C (CC).
Main Results:
- MOTS-c treatment significantly reduced inflammatory cytokine mRNA levels (IL-1β, IL-4, IL-6, TNFα) and circulating myocardial injury markers (CK-MB, TnT).
- MOTS-c alleviated cardiomyocyte mitochondrial dysfunction, oxidative stress, and apoptosis.
- MOTS-c activated cardioprotective pathways (AMPK, AKT, ERK) and inhibited inflammation-related pathways (JNK, STAT3).
- The protective effects of MOTS-c were abolished by the AMPK inhibitor CC, confirming the pathway's crucial role.
Conclusions:
- MOTS-c demonstrates significant cardioprotective effects in a model of septic cardiomyopathy.
- Activation of the AMPK pathway is essential for MOTS-c's therapeutic action.
- MOTS-c represents a promising therapeutic candidate for treating septic cardiomyopathy.
