Combination of melatonin and irisin ameliorates lipopolysaccharide‐induced cardiac dysfunction through suppressing the Mst1–JNK pathways
| Autor: | Fengfan Xia, Jiankai Zhong, Yuanyan Deng, Qian Li, Sulin Zheng, Jianhua Lu, Yunzhao Hu, Haichun Ouyang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharides
0301 basic medicine MST1 Lipopolysaccharide MAP Kinase Signaling System Physiology Clinical Biochemistry Apoptosis Mice Transgenic Mitochondrion Pharmacology medicine.disease_cause Melatonin Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine In vivo Proto-Oncogene Proteins Sepsis medicine Animals Myocytes Cardiac Cells Cultured Hepatocyte Growth Factor Kinase business.industry Heart Cell Biology Fibronectins Mitochondria Metabolism disorder Mice Inbred C57BL Oxidative Stress 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cardiomyopathies business Oxidative stress Signal Transduction medicine.drug |
| Zdroj: | Journal of Cellular Physiology. 235:6647-6659 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.29561 |
| Popis: | Despite significant advances in therapies in past decades, the mortality rate of septic cardiomyopathy remains high. The aim of this study is to explore the therapeutic effects of combined treatment using melatonin and irisin in a mouse model of lipopolysaccharide (LPS)-mediated septic cardiomyopathy. Our data found that melatonin and irisin could further attenuate LPS-induced myocardial depression. Molecular investigation illustrated that melatonin and irisin cotreatment sustained cardiomyocyte viability and improved mitochondrial function under LPS stress. Pathway analysis demonstrated that macrophage-stimulating 1 (Mst1), which was significantly activated by LPS, was drastically inhibited by melatonin/irisin cotreatment. Mechanically, Mst1 activated c-Jun N-terminal kinase (JNK) pathway and the latter induced oxidative stress, adenosine triphosphate metabolism disorder, mitochondrial membrane potential reduction, and cardiomyocyte death activation. Melatonin and irisin cotreatment effectively inhibited the Mst1-JNK pathway and, thus, promoted cardiomyocyte survival and mitochondrial homeostasis. Interestingly, Mst1 overexpression abolished the beneficial effects of melatonin and irisin in vivo and in vitro. Altogether, our results confirmed that melatonin and irisin combination treatment could protect heart against sepsis-induced myocardial depression via modulating the Mst1-JNK pathways. |
| Databáze: | OpenAIRE |
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