Capsaicin protects cardiomyocytes against lipopolysaccharide-induced damage via 14-3-3γ-mediated autophagy augmentation
| العنوان: | Capsaicin protects cardiomyocytes against lipopolysaccharide-induced damage via 14-3-3γ-mediated autophagy augmentation |
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| المؤلفون: | Dong Yin, Yang Qiao, Liang Wang, Huan He, Ming He, Tianhong Hu |
| المصدر: | Frontiers in Pharmacology Frontiers in Pharmacology, Vol 12 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Inflammation, RM1-950, 14-3-3γ, 030204 cardiovascular system & hematology, Mitochondrion, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Autophagy, medicine, Pharmacology (medical), Protein kinase A, PI3K/AKT/mTOR pathway, Original Research, Pharmacology, chemistry.chemical_classification, Reactive oxygen species, lipopolysaccharide, Mitochondria, Cell biology, 030104 developmental biology, chemistry, Mitochondrial permeability transition pore, Cardiac dysfunction, Therapeutics. Pharmacology, Capsaicin, medicine.symptom, Oxidative stress |
| الوصف: | 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. |
| تدمد: | 1663-9812 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::aa24a6bdf2e795987d8c77a357a5d30e https://pubmed.ncbi.nlm.nih.gov/33986684 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....aa24a6bdf2e795987d8c77a357a5d30e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16639812 |
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