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 17 October 2019Source: Materials Science and Engineering: CAuthor(s): Yuriko Takayama, Norihiro KatoAbstractProdigiosin production in the model opportunistic human pathogen, Serratia marcescens AS-1, depends on quorum sensing (QS), the activation of which is induced by an increase in N-hexanoyl homoserine lactone (C6HSL) concentration. When mixed with C6HSL in the broth culture of S. marcescens immobilized cyclodextrin (CD) effectively formed an inclusion complex resulting in suppression of the QS-mediated prodigiosin production. Thousands of parallel gel filament bundles could be fabrica...
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research
This study simulated the high-phosphorus (Pi) environment in patients with chronic kidney disease. Nano-hydroxyapatite (HAP) crystals were used to damage rat aortic smooth muscle cells (A7R5) pre-damaged with different concentrations of Pi solution to compare the differences in HAP-induced calcification in A7R5 cells before and after injury by high-Pi condition. After the A7R5 cells were damaged by high-Pi environment, the following were observed. HAP resulted in declined cell viability and lysosomal integrity, release of lactate dehydrogenase, and increased reactive oxygen species production. The ability of high-Pi damage...
Source: Materials Science and Engineering: C - Category: Materials Science Source Type: research
Publication date: Available online 20 October 2019Source: Molecular and Cellular NeuroscienceAuthor(s): Navneet Ammal Kaidery, Manuj Ahuja, Bobby ThomasAbstractSearch for a definitive cure for neurodegenerative disorders like Parkinson's disease (PD) has met with little success. Mitochondrial dysfunction and elevated oxidative stress precede characteristic loss of dopamine-producing neurons from the midbrain in PD. The majority of PD cases are classified as sporadic (sPD) with an unknown etiology, whereas mutations in a handful of genes cause monogenic form called familial (fPD). Both sPD and fPD is characterized by protei...
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research
Publication date: Available online 20 October 2019Source: Innovative Food Science &Emerging TechnologiesAuthor(s): Alline Artigiani Lima Tribst, Luiza Toledo Piza Falcade, Nathália Silva Carvalho, Marcelo Cristianini, Bruno Ricardo de Castro Leite Júnior, Miguel Meirelles de OliveiraAbstractWe assessed the impact of stirring (ST), high shear dispersing (HSD) and low (LPH, 3.5 MPa) and high pressure homogenization (HPH, 50 MPa) on physicochemical and structural characteristics of whole and skimmed sheep milk fresh or previously frozen and thawed (FT). Freezing affected the size of the fat globules, the...
Source: Innovative Food Science and Emerging Technologies - Category: Food Science Source Type: research
ConclusionsGrowth differentiation factor-15 can be used not only for the diagnosis of mitochondrial disease, but as an indicator of its acute exacerbation. A stroke-like episode of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes reflects a drastic derangement of multiple amino acids. The involvement of aspartic acid in the episodes should be explored in future studies.
Source: Journal of Medical Case Reports - Category: General Medicine Source Type: research
In this study, we exposed wild-type (WT) and AMPKα2−/− mice to PM2.5 every other day via intratracheal instillation for 4 weeks. After PM2.5 exposure, the AMPKα2−/− mice developed more severe lung injury and cardiac dysfunction than were developed in the WT mice; however the administration of metformin was effective in attenuating PM2.5-induced lung injury and cardiac dysfunction in both the WT and AMPKα2−/− mice. In the PM2.5-exposed mice, metformin treatment resulted in reduced systemic and pulmonary inflammation, preserved left ventricular ejection fraction, suppress...
Source: Redox Biology - Category: Biology Source Type: research
We report the case of two members of the same family with a novel mitochondrial DNA (mtDNA) gene variant in the MTND5 gene associated with MELAS syndrome and discuss limitations of genetics studies. The m.13045A>G mutation was detected at very low load in the daughter’s urine cells (5%) and at different levels in the skeletal muscle of both mother (50%) and daughter (84%), being absent in blood, hair and saliva.Our findings suggest that non-invasive genetic assessment in urine cells may not be a sensitive diagnostic method neither a good predictor of disease development in relatives of some families with mtDNA-ass...
Source: Mitochondrion - Category: Biochemistry 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: PediatricEducation.org - 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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