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Ceramide inflammation

Kinga Czubowicz, Sylwia Wójtowicz, Przemysław Leonard Wencel, Robert Piotr Strosznajder
Alzheimer's disease (AD) is characterized by alterations of amyloid precursor protein (APP) metabolism, accumulation of amyloid  peptides (A), hyperphosphorylation of Tau proteins and also by sphingolipids disturbances. These changes lead to oxidative stress, mitochondria dysfunction, synaptic loss and neuro-inflammation. It is known that A may promote ceramides formation and reversely, ceramides could stimulate A peptides release. However, the effect of ceramide and sphingosine-1-phosphate (S1P) on APP metabolism has not been fully elucidated...
2018: Folia Neuropathologica
Teresa De Vita, Clara Albani, Natalia Realini, Marco Migliore, Abdul Basit, Giuliana Ottonello, Andrea Cavalli
Alzheimer's disease (AD) is a slow-progressing disease of the brain characterized by symptoms such as impairment of memory and other cognitive functions. AD is associated with an inflammatory process that involves astrocytes and microglial cells, among other components. Astrocytes are the most abundant type of glial cells in the central nervous system (CNS). They are involved in inducing neuroinflammation. The present study uses astrocyte-neuron co-cultures to investigate how ARN14494, a serine palmitoyltransferase (SPT) inhibitor, affects the CNS in terms of anti-inflammation and neuroprotection...
November 27, 2018: ACS Chemical Neuroscience
Fabian Ps Yu, Ben Sajdak, Jakub Sikora, Alexander E Salmon, Murtaza S Nagree, Jiří Gurka, Iris S Kassem, Daniel M Lipinski, Joseph Carroll, Jeffrey A Medin
Farber Disease (FD) is a debilitating lysosomal storage disorder characterized by severe inflammation and neurodegeneration. FD is caused by mutations in the ASAH1 gene resulting in deficient acid ceramidase (ACDase) activity. Patients with ACDase deficiency exhibit a broad clinical spectrum. In classical cases, patients develop hepatosplenomegaly, nervous system involvement, and childhood mortality. Ocular manifestations include decreased vision, a grayish appearance to the retina with a cherry red spot, and nystagmus...
November 22, 2018: American Journal of Pathology
Prashant Chauhan, Bhaskar Saha
Immunometabolic framework provides a way to understand the immune regulation via cell intrinsic metabolic fluxes and metabolites during infections, tumors, and inflammatory disorders. During these diseases, the immune cells are activated requiring more energy and moderating their metabolic functions. The two categories of metabolic alterations are therefore causally associated with energy derivation and cellular functions. Pathogens, tumors and inflammation target energy metabolism, primarily glucose uptake, glucose catabolism, gluconeogenesis for continuing lipid metabolism through mainstream pathways such as glycolysis, tricarboxylic acid cycle, mitochondrial respiration and pentose phosphate pathway...
November 21, 2018: Cytokine
Chao Yang, Qing Jiang
Nuclear factor-κB (NF-κB) regulates inflammation and cell survival, and is considered a potential target for anti-inflammatory and anti-cancer therapy. δ-Tocotrienol (δTE), a vitamin E form, has been shown to inhibit NF-κB, but the mechanism underlying this action is not clear. In the present study, we show that δTE inhibited TNF-α-induced activation of NF-κB and LPS-stimulated IL-6 in a dose- and time-dependent manner in Raw 264.7 macrophages. δTE potently inhibited TNF-α-induced phosphorylation of transforming growth factor β-activated kinase 1 (TAK1), an upstream kinase essential for the activation of NF-κB...
November 3, 2018: Journal of Nutritional Biochemistry
Janine Schulte-Zweckel, Tabea Schneidewind, Jose Luis Abad, Andreas Brockmeyer, Petra Janning, Gemma Triola
Ceramide plays key roles in autophagy, inflammation and apoptosis. However, little is known about the molecular mechanisms regulating its function and only a handful of cellular effectors are known for this lipid. Here we show that azide-tagged sphingolipids are powerful tools to identify ceramide targets. The combination of a protein array analysis and a mass spectrometry-based proteomic profiling successfully detects known ceramide-binding proteins and identifies others not yet reported, several of which we validated using a variety of techniques...
November 20, 2018: Chemical Communications: Chem Comm
Mariana Nikolova-Karakashian
Sphingolipids are class of metabolically distinct lipids that play structural and signaling functions in all organisms. Sphingolipid metabolism is deregulated during various diseases such as cancer, neurological and immune disorders, and metabolic syndrome. With the advancement of sphingo-lipidomics and sphingo-genomics, an understanding of the specific roles of ceramide, the quintessential bioactive sphingolipid, in fatty liver disease has taken shape. Two major pathways for ceramide generation, the de novo pathway and the sphingomyelinase pathway are activated in the course of both, the non-alcoholic and the alcoholic, forms of fatty liver disease...
December 2018: Advances in Biological Regulation
Svenja Plöhn, Bärbel Edelmann, Lukasz Japtok, Xingxuan He, Matthias Hose, Wiebke Hansen, Edward H Schuchman, Anja Eckstein, Utta Berchner-Pfannschmidt
Purpose: Graves' orbitopathy (GO) is an autoimmune orbital disorder associated with Graves' disease caused by thyrotropin receptor autoantibodies. Orbital fibroblasts (OFs) and CD40 play a key role in disease pathogenesis. The bioactive lipid sphingosine-1-phosphate (S1P) has been implicated in promoting adipogenesis, fibrosis, and inflammation in OFs. We investigated the role of CD40 signaling in inducing S1P activity in orbital inflammation. Methods: OFs and T cells were derived from GO patients and healthy control (Ctl) persons...
November 1, 2018: Investigative Ophthalmology & Visual Science
Madeline Fink, Abdulla Al Mamun Bhuyan, Nefeli Zacharopoulou, Florian Lang
BACKGROUND/AIMS: The sesquiterpene lactone Costunolide is effective against various disorders including inflammation and malignancy. The substance is effective in part by triggering suicidal death or apoptosis of tumor cells. Mechanisms involved include altered function of transcription factors and mitochondria. Erythrocytes lack nuclei and mitochondria but are - in analogy to apoptosis of nucleated cells - able to enter suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface...
2018: Cellular Physiology and Biochemistry
Lu-Min Shih, Hsiang-Yu Tang, Ke-Shiuan Lynn, Cheng-Yu Huang, Hung-Yao Ho, Mei-Ling Cheng
Non-alcoholic fatty liver disease (NAFLD) as a global health problem has clinical manifestations ranging from simple non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), cirrhosis, and cancer. The role of different types of fatty acids in driving the early progression of NAFL to NASH is not understood. Lipid overload causing lipotoxicity and inflammation has been considered as an essential pathogenic factor. To correlate the lipid profiles with cellular lipotoxicity, we utilized palmitic acid (C16:0)- and especially unprecedented palmitoleic acid (C16:1)-induced lipid overload HepG2 cell models coupled with lipidomic technology involving labeling with stable isotopes...
November 2, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
K E Mercer, C F Pulliam, L Hennings, M A Cleves, E E Jones, R R Drake, M J J Ronis
Diethylnitrosamine-treated male mice were assigned to 4 groups: a casein-based 35% high fat ethanol liquid diet (EtOH), an EtOH diet made with soy protein isolate protein (EtOH/SOY), an EtOH liquid diet supplemented with genistein (EtOH/GEN) and a chow group. EtOH feeding, final concentration 5% (v/v), continued for 16 wks. EtOH increased incidence and multiplicity of basophilic lesions and adenomas compared to the chow group, (p < 0.05). The EtOH/SOY group had reduced adenoma progression when compared to the EtOH and EtOH/GEN group, (p < 0...
2018: Advances in Experimental Medicine and Biology
Fodé Diop, Thomas Vial, Pauline Ferraris, Sineewanlaya Wichit, Michèle Bengue, Rodolphe Hamel, Loïc Talignani, Florian Liegeois, Julien Pompon, Hans Yssel, Guillaume Marti, Dorothée Missé
Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family. Although infection with ZIKV generally leads to mild disease, its recent emergence in the Americas has been associated with an increase in the development of the Guillain-Barré syndrome in adults, as well as with neurological complications, in particular congenital microcephaly, in new-borns. To date, little information is available on neuroinflammation induced by ZIKV, notably in microglial cells in the context of their metabolic activity, a series of chemical transformations that are essential for their growth, reproduction, structural maintenance and environmental responses...
2018: PloS One
Youming Zhang, Saffron A G Willis-Owen, Sarah Spiegel, Clare M Lloyd, Miriam F Moffatt, William O C M Cookson
RATIONALE: Polymorphisms on chromosome 17q21 confer the major genetic susceptibility to childhood-onset asthma. Risk alleles positively correlate with ORMDL3 expression. The locus influences disease severity and the frequency of human rhinovirus (HRV) initiated exacerbations. ORMDL3 is known to regulate sphingolipid synthesis by binding serine palmitoyltransferase (SPT), but its role in inflammation is incompletely understood. OBJECTIVES: To investigate the role of ORMDL3 in cellular inflammation...
October 19, 2018: American Journal of Respiratory and Critical Care Medicine
Tetsuya Okuda
The data presented here pertain to a research article entitled "Structural characterization and dynamics of globotetraosylceramide in vascular endothelial cells under TNF-α stimulation" (Okuda et al., 2010). The present article provides additional structural and gene expression data for the characterization of a TNF-α-inducible glycosphingolipid, globotetraosylceramide (Gb4), in vascular endothelial cells. (i) Structural details of Gb4 in lipid raft-enriched cell membranes were determined by MALDI-TOF MS...
December 2018: Data in Brief
Natalia Presa, Robin D Clugston, Susanne Lingrell, Samuel E Kelly, Alfred H Merrill, Sayantan Jana, Zamaneh Kassiri, Antonio Gómez-Muñoz, Dennis E Vance, Rene L Jacobs, Jelske N van der Veen
Phosphatidylethanolamine N-methyltransferase (PEMT) converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC), mainly in the liver. Pemt-/- mice are protected from high-fat diet (HFD)-induced obesity and insulin resistance, but develop severe non-alcoholic fatty liver disease (NAFLD) when fed a HFD, mostly due to impaired VLDL secretion. Oxidative stress is thought to be an essential factor in the progression from simple steatosis to steatohepatitis. Vitamin E is an antioxidant that has been clinically used to improve NAFLD pathology...
October 6, 2018: Biochimica et biophysica acta. Molecular basis of disease
Marta Ordoñez, Natalia Presa, Asier Dominguez-Herrera, Miguel Trueba, Antonio Gomez-Muñoz
We showed previously that ceramide kinase (CerK) expression increases during adipogenesis pointing to a relevant role of intracellular C1P in this process. In the present work we demonstrate that administration of exogenous C1P inhibits the differentiation of 3T3-L1 pre-adipocytes into mature adipocytes through a mechanism involving activation of extracellularly regulated kinases (ERK) 1-2. Exogenous C1P reduced the accumulation of lipid droplets and the content of triacylglycerol in these cells, and potently inhibited the expression of the early and late adipogenic markers C/EBPβ and PPARγ, respectively...
September 27, 2018: Experimental Cell Research
Paul T Reidy, Alec I McKenzie, Ziad Mahmassani, Vincent R Morrow, Nikol M Yonemura, Paul N Hopkins, Robin L Marcus, Matthew T Rondina, Yu Kuei Lin, Micah J Drummond
KEY POINTS: Insulin sensitivity (as determined by a hyperinsulinaemic-euglyceamic clamp) decreased 15% after reduced activity. Despite not fully returning to baseline physical activity levels, insulin sensitivity unexpectedly, rebounded above that recorded before 2 weeks of reduced physical activity by 14% after the recovery period. Changes in insulin sensitivity in response to reduced activity were primarily driven by men but, not women. There were modest changes in ceramides (nuclear/myofibrillar fraction and serum) following reduced activity and recovery but, in the absence of major changes to body composition (i...
November 2018: Journal of Physiology
Victor García-González, José Fernando Díaz-Villanueva, Octavio Galindo-Hernández, Israel Martínez-Navarro, Gustavo Hurtado-Ureta, Abril Alicia Pérez-Arias
Ceramides are key lipids in energetic-metabolic pathways and signaling cascades, modulating critical physiological functions in cells. While synthesis of ceramides is performed in endoplasmic reticulum (ER), which is altered under overnutrition conditions, proteins associated with ceramide metabolism are located on membrane arrangement of mitochondria and ER (MAMs). However, ceramide accumulation in meta-inflammation, condition that associates obesity with a chronic low-grade inflammatory state, favors the deregulation of pathways such as insulin signaling, and induces structural rearrangements on mitochondrial membrane, modifying its permeability and altering the flux of ions and other molecules...
August 26, 2018: International Journal of Molecular Sciences
Guangbi Li, Qinghua Zhang, Jinni Hong, Joseph K Ritter, Pin-Lan Li
The pannexin-1 (Panx1) channel has been reported to mediate the release of ATP that is involved in local tissue inflammation, obesity, and many chronic degenerative diseases. It remains unknown whether Panx1 is present in podocytes and whether this channel in podocytes mediates ATP release leading to glomerular inflammation or fibrosis. To answer these questions, we first characterized the expression of Panx channels in podocytes. Among the three known pannexins, Panx1 was the most enriched in podocytes, either cultured or native in mouse glomeruli...
October 2018: Biochimica et biophysica acta. Molecular and cell biology of lipids
Djahida Bedja, Wenwen Yan, Viren Lad, Domenica Iocco, Nickash Sivakumar, Veera Venkata Ratnam Bandaru, Subroto Chatterjee
Sphingolipids have been accorded numerous biological functions however, the effects of feeding a western diet (diet rich in cholesterol and fat) on skin phenotypes, and color is not known. Here, we observed that chronic high-fat and high-cholesterol diet intake in a mouse model of atherosclerosis (ApoE-/-) decreases the level of ceramides and glucosylceramide. At the expense of increased levels of lactosylceramide due to an increase in the expression of lactosylceramide synthase (GalT-V). This is accompanied with neutrophil infiltration into dermis, and enrichment of tumor necrosis factor-stimulated gene-6 (TSG-6) protein...
July 30, 2018: Scientific Reports
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