Therapeutic contribution of melatonin to the treatment of septic cardiomyopathy: A novel mechanism linking Ripk3-modified mitochondrial performance and endoplasmic reticulum function

Publication date: Available online 27 July 2019Source: Redox BiologyAuthor(s): Jiankai Zhong, Ying Tan, Jianhua Lu, Jichen Liu, Xiaochan Xiao, Pinji Zhu, Sainan Chen, Sulin Zheng, Yuying Chen, Yunzhao Hu, Zhigang GuoAbstractThe basic pathophysiological mechanisms underlying septic cardiomyopathy have not yet been completely clarified. Disease-specific treatments are lacking, and care is still based on supportive modalities. The aim of our study was to assess the protective effects of melatonin on septic cardiomyopathy, with a focus on the interactions between receptor-interacting protein kinase 3 (Ripk3), the mitochondria, endoplasmic reticulum (ER) and cytoskeletal degradation in cardiomyocytes. Ripk3 expression was increased in heart samples challenged with LPS, followed by myocardial inflammation, cardiac dysfunction, myocardial breakdown and cardiomyocyte death. The melatonin treatment attenuated septic myocardial injury in a comparable manner to the genetic depletion of Ripk3. Molecular investigations revealed that Ripk3 intimately regulated mitochondrial function, ER stress, cytoskeletal homeostasis and cardioprotective signaling pathways. Melatonin-mediated inhibition of Ripk3 improved mitochondrial bioenergetics, reduced mitochondria-initiated oxidative damage, sustained mitochondrial dynamics, ameliorated ER stress, normalized calcium recycling, and activated cardioprotective signaling pathways (including AKT, ERK and AMPK) in cardiomyocytes. Interestingly, Ripk3 ove...
Source: Redox Biology - Category: Biology Source Type: research

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Publication date: Available online 30 September 2020Source: Journal of Hazardous MaterialsAuthor(s): Anthony Beauvois, Delphine Vantelon, Jacques Jestin, Martine Bouhnik-Le Coz, Charlotte Catrouillet, Valérie Briois, Thomas Bizien, Mélanie Davranche
Source: Journal of Hazardous Materials - Category: Environmental Health Source Type: research
Authors: Saavedra J, Reyes JG, Salinas DG Abstract Cytosolic Ca2+ concentration ([Ca2+ ]) has an important role in spermatozoa and hence it regulates fertilization. In male germinal cells, there are indirect evidences that this ion could regulate physiological processes in spermatogenesis. Since little is known about Ca 2+ homeostasis in spermatogenic cells, in this work we propose a mathematical model that accounts for experimental [Ca2+ ] dynamics triggered by blockade of the SERCA transport ATPase with thapsigargin in round rat spermatids, without external Ca2+ and with different extracellular lactate concentrat...
Source: Channels - Category: Molecular Biology Tags: Channels (Austin) Source Type: research
In conclusion, the presence of anti-SOX1 abs alone is a potential predictor of an uncommon paraneoplastic neurological disorder, usually occurring in the setting of LEMS, PCD, and SCLC. The detection of anti-SOX1 abs contributes to an early diagnosis of underlying tumors, given the diversity of clinical symptoms and the absence of characteristic neuroimaging features. PMID: 33029958 [PubMed]
Source: Journal of Clinical Neurology - Category: Neurology Tags: J Clin Neurol Source Type: research
In conclusion, leucocytes, leucocyte fractions, CRP, LDH, and electrolytes are useful indicators for COVID-19 diagnosis. PMID: 33028754 [PubMed - in process]
Source: The Tohoku Journal of Experimental Medicine - Category: Research Authors: Tags: Tohoku J Exp Med Source Type: research
Conclusion: SLT induces relaxation of rat isolated tail artery through endothelium-independent mechanisms. The SLT-induced vasodilatation appeared to be jointly meditated by blockages of extracellular Ca2+ influx via receptor-gated and voltage-gated Ca2+ channels and inhibition of the release of Ca2+ from the sarcoplasmic reticulum. PMID: 33029174 [PubMed]
Source: Evidence-based Complementary and Alternative Medicine - Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research
Conclusions: ELS-induced visceral pain and visceral hypersensitivity are associated with the underfunction of SK2 channels in the spinal DH. PMID: 33029124 [PubMed - in process]
Source: Neural Plasticity - Category: Neurology Authors: Tags: Neural Plast Source Type: research
Authors: Gau JT, Ebersbacher C, Kao TC Abstract Context: Subclinical features of zinc deficiency can be challenging to recognize. The prevalence of zinc deficiency based on blood zinc concentration in an adult outpatient clinic setting has not been well-studied. Objective: To estimate the prevalence of low serum zinc concentrations among community-dwelling adults, and to characterize clinical features and risk factors associated with zinc deficiency. Methods: This retrospective pilot prevalence study took place from 2014 to 2017 at an outpatient clinic in southeast Ohio. Patients aged 50 years or older with...
Source: Journal of the American Osteopathic Association - Category: Complementary Medicine Tags: J Am Osteopath Assoc Source Type: research
Conclusion: Mitofusin 2 promotes Parkin translocation and phosphorylation, leading to mitophagy to clear damaged mitochondria. However, the beneficial effects of MFN2 were reversed by autophagy inhibitors. Additionally, MFN2 participates in mitochondrial fusion to maintain mitochondrial quality. Thus, MFN2 participated in mitophagy and mitochondrial fusion against Ang II-induced cardiomyocyte injury. Introduction Ventricular remodeling is the core foundation for the development of heart failure (Hill and Olson, 2008). Pathological remodeling is typically due to a number of causes that result in increased pressure o...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
Discussion Barth syndrome is characterized by a dilated cardiomyopathy, proximal skeletal muscle weakness, neutropenia and short stature that usually presents at birth or soon after. It is a rare X-linked recessive disease process caused by mutations in the TAZ gene. The TAZ gene codes for tafazzin which alters cardiolipin in mitochondria. Characteristic facies can be seen especially in infancy including a tall and broad forehead, prominent chin and full cheeks, larger ears, and deep-set eyes. Most patients present at birth or soon afterwards but some may not until later in life. Life expectancy is reduced with many childr...
Source: - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Discussion With new developments in computational power and data availability, a growing amount of research is using a systems biology approach to understand pathogenesis and progression of disease. Effective and integrated in vitro and in silico models could inform biological phenomena, even without the need of a living subject. For instance, over the last few decades, collagen hydrogel with muscle derived cells (CHMDCs) have promised to revolutionize in vitro experiments and tissue engineering. For CHMDCs to reach the envisioned use, verification by use of mathematical simulations are needed. Recently while examining sha...
Source: PLOS Currents Muscular Dystrophy - Category: Neurology Authors: Source Type: research
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