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Beiqing Wu, Jianhui Liu, Runze Zhao, Yuju Li, Justin Peer, Alexander L Braun, Lixia Zhao, Yi Wang, Zenghan Tong, Yunlong Huang, Jialin C Zheng
BACKGROUND: Extracellular vesicles (EVs) are important in the intercellular communication of the central nervous system, and their release is increased during neuroinflammation. Our previous data demonstrated an increased release of EVs during HIV-1 infection and immune activation in glial cells. However, the molecular mechanism by which infection and inflammation increase EV release remains unknown. In the current study, we investigated the role of glutaminase 1 (GLS1)-mediated glutaminolysis and the production of a key metabolic intermediate α-ketoglutarate on EV release...
March 14, 2018: Journal of Neuroinflammation
Daniel Alejandro Peñalva, Silvia Antollini, Ernesto Ambroggio, Marta I Aveldaño, Maria Laura Fanani
In rat sperm head, sphingomyelin (SM) species that contain very long chain PUFA (V-SM) become ceramides (V-Cer) after inducing in vitro the acrosomal reaction. The reason for such a specific location of this conversion, catalysed by a sphingomyelinase (SMase), has received little investigation so far. Here, the effects of SMase were compared in unilamellar vesicles (LUVs, GUVs) containing phosphatidylcholine and either V-SM or a palmitate-rich SM (P-SM). In uniformly sized LUVs at 37 °C, more V-Cer was generated, and more rapidly, than P-Cer...
March 15, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Christian L Wennberg, Ali Narangifard, Magnus Lundborg, Lars Norlén, Erik Lindahl
The stratum corneum is the outermost layer of human skin and the primary barrier toward the environment. The barrier function is maintained by stacked layers of saturated long-chain ceramides, free fatty acids, and cholesterol. This structure is formed through a reorganization of glycosylceramide-based bilayers with cubic-like symmetry into ceramide-based bilayers with stacked lamellar symmetry. The process is accompanied by deglycosylation of glycosylceramides and dehydration of the skin barrier lipid structure...
March 13, 2018: Biophysical Journal
Cynthia Kanagaratham, Victoria Chiwara, Bianca Ho, Sanny Moussette, Mina Youssef, David Venuto, Lucie Jeannotte, Guillaume Bourque, Juan Bautista de Sanctis, Danuta Radzioch, Anna K Naumova
The human chromosomal region 17q12-q21 is one of the best replicated genome-wide association study loci for childhood asthma. The associated SNPs span a large genomic interval that includes several protein-coding genes. Here, we tested the hypothesis that the zona pellucida-binding protein 2 (ZPBP2) gene residing in this region contributes to asthma pathogenesis using a mouse model. We tested the lung phenotypes of knock-out (KO) mice that carry a deletion of the Zpbp2 gene. The deletion attenuated airway hypersensitivity (AHR) in female, but not male, mice in the absence of allergic sensitization...
March 13, 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
Natalia Pascuali, Leopoldina Scotti, Mariana Di Pietro, Gonzalo Oubiña, Diana Bas, María May, Antonio Gómez Muñoz, Patricia S Cuasnicú, Débora J Cohen, Marta Tesone, Dalhia Abramovich, Fernanda Parborell
STUDY QUESTION: Is ceramide-1-phosphate (C1P) an ovarian protective agent during alkylating chemotherapy? SUMMARY ANSWER: Local administration of C1P drastically reduces ovarian damage induced by cyclophosphamide (Cy) via protection of follicular reserve, restoration of hormone levels, inhibition of apoptosis and improvement of stromal vasculature, while protecting fertility, oocyte quality and uterine morphology. WHAT IS KNOWN ALREADY: Cancer-directed therapies cause accelerated loss of ovarian reserve and lead to premature ovarian failure (POF)...
March 9, 2018: Human Reproduction
Victoria M Pak, Feng Dai, Brendan T Keenan, Nalaka S Gooneratne, Allan I Pack
Sleepiness and cardiovascular disease share common molecular pathways; thus, metabolic risk factors for sleepiness may also predict cardiovascular disease risk. Daytime sleepiness predicts mortality and cardiovascular disease, although the mechanism is unidentified. This study explored the associations between subjective sleepiness and metabolite concentrations in human blood plasma within the oxidative and inflammatory pathways, in order to identify mechanisms that may contribute to sleepiness and cardiovascular disease risk...
April 2018: Sleep Medicine
Yeji Sung, Konstantina Spagou, Marina Kafeza, Michael Kyriakides, Brahman Dharmarajah, Joseph Shalhoub, Jose A Diaz, Thomas W Wakefield, Elaine Holmes, Alun H Davies
OBJECTIVES: Deep vein thrombosis (DVT) is a major health problem, responsible for significant morbidity and mortality. The identification of a simple and effective diagnostic biomarker of DVT remains a challenge. Metabolomics have recently emerged as a new powerful scientific tool to characterise metabolic phenotypes of complex diseases and investigate small molecules in biofluids. The aim of the study was to identify the blood and vein wall metabolomic signature of DVT in a murine experimental model...
March 8, 2018: European Journal of Vascular and Endovascular Surgery
Jie-Qiong Ma, Chan-Min Liu, Wei Yang
Rutin, a natural flavonoid, possess beneficial health effects. However, its renoprotective effect against carbon tetrachloride (CCl4 ) induced injury and the underlying mechanism is not clarified. The current study aims is to identify the therapeutic effects of rutin on oxidative stress, inflammation and apoptosis in mouse kidney exposed to CCl4 . ICR mice received CCl4 with or without rutin co-administration for one week. Compared with the control group, mice receiving CCl4 alone showed kidney injury as evidenced by elevation in serum biochemical markers, inflammation, caspase-3 activity and apoptosis in kidney, while rutin administration significantly attenuated these pathophysiological changes...
March 6, 2018: Chemico-biological Interactions
Lisa Repsold, Anna Margaretha Joubert
Erythrocytes play an important role in oxygen and carbon dioxide transport. Although erythrocytes possess no nucleus or mitochondria, they fulfil several metabolic activities namely, the Embden-Meyerhof pathway, as well as the hexose monophosphate shunt. Metabolic processes within the erythrocyte contribute to the morphology/shape of the cell and important constituents are being kept in an active, reduced form. Erythrocytes undergo a form of suicidal cell death called eryptosis. Eryptosis results from a wide variety of contributors including hyperosmolarity, oxidative stress, and exposure to xenobiotics...
2018: BioMed Research International
Stanley M Walls, Anthony Cammarato, Dale A Chatfield, Karen Ocorr, Greg L Harris, Rolf Bodmer
Lipotoxic cardiomyopathy (LCM) is characterized by abnormal myocardial accumulation of lipids, including ceramide; however, the contribution of ceramide to the etiology of LCM is unclear. Here, we investigated the association of ceramide metabolism and ceramide-interacting proteins (CIPs) in LCM in the Drosophila heart model. We find that ceramide feeding or ceramide-elevating genetic manipulations are strongly associated with cardiac dilation and defects in contractility. High ceramide-associated LCM is prevented by inhibiting ceramide synthesis, establishing a robust model of direct ceramide-associated LCM, corroborating previous indirect evidence in mammals...
March 6, 2018: Cell Reports
Ying Chen, Olga Berejnaia, Jinqi Liu, Sheng-Ping Wang, Natalie A Daurio, Wu Yin, Rafael Mayoral, Aleksandr Petrov, Takhar Kasumov, Guo-Fang Zhang, Stephen F Previs, David E Kelley, David G McLaren
Numerous studies have implicated dyslipidemia as a key factor in mediating insulin resistance. Ceramides have received special attention since their levels are inversely associated with normal insulin signaling and positively associated with factors that are involved in cardiometabolic disease. Despite the growing literature surrounding ceramide biology, there are limited data regarding the activity of ceramide synthesis and turnover in vivo. Herein, we demonstrate the ability to measure ceramide kinetics by coupling the administration of [2 H]water with LC-MS/MS analyses...
March 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
Feng Wang, Hongyan Li, Ela Markovsky, Ryan Glass, Elisa de Stanchina, Simon N Powell, Gary K Schwartz, Adriana Haimovitz-Friedman
Recent data in our laboratory indicate that engagement of host-derived microenvironmental elements impact tumor response to single high dose radiation therapy (SDRT). In these studies we showed that microvascular endothelial damage plays a critical role in tumor response as regulator of direct lethal damage of SDRT. Using a genetic model of Acid Sphingomyelinase (ASMase)-deficient mice we showed that activation of this enzyme by SDRT-induced damage in the endothelium is mandatory for tumor cure. ASMase activation triggers ceramide-mediated apoptosis, and therein microvascular dysfunction, which increased the vulnerability of tumor cells to lethal damage by radiation...
February 6, 2018: Oncotarget
M Carmen Crespo, Joao Tomé-Carneiro, Diego Gómez-Coronado, Emma Burgos-Ramos, Alba García-Serrano, Roberto Martín-Hernández, Shishir Baliyan, Javier Fontecha, César Venero, Alberto Dávalos, Francesco Visioli
The increasing incidence of age-induced cognitive decline justifies the search for complementary ways of prevention or delay. We studied the effects of concentrates of phospholipids, sphingolipids, and/or 3-n fatty acids on the expression of genes or miRNAs related to synaptic activity and/or neurodegeneration, in the hippocampus of aged Wistar rats following a 3-month supplementation. The combination of two phospholipidic concentrates of krill oil (KOC) and buttermilk (BMFC) origin modulated the hippocampal expression of 119 miRNAs (11 were common to both BMFC and BMFC + KOC groups)...
March 5, 2018: Scientific Reports
Ahmed El Kaffas, Azza Al-Mahrouki, Amr Hashim, Niki Law, Anoja Giles, Gregory J Czarnota
Background: High-dose radiotherapy (>8-10 Gy) causes rapid endothelial cell death via acid sphingomyelinase (ASMase)-induced ceramide production, resulting in biologically significant enhancement of tumor responses. To further augment or solicit similar effects at low radiation doses, we used genetic and chemical approaches to evaluate mechano-acoustic activation of the ASMase-ceramide pathway by ultrasound-stimulated microbubbles (USMB). Methods: Experiments were carried out in wild-type and acid sphingomyelinase (asmase) knockout mice implanted with fibrosarcoma xenografts...
February 28, 2018: Journal of the National Cancer Institute
Efrem N Tessema, Tsige Gebre-Mariam, Getahun Paulos, Johannes Wohlrab, Reinhard H H Neubert
Deficiency or altered composition of stratum corneum (SC) lipids such as ceramides (CERs), causing skin barrier dysfunction and skin dryness, have been associated with skin diseases such as atopic dermatitis and psoriasis, and ageing. Replenishing the depleted native CERs with exogenous CERs has also been shown to have beneficial effects in restoring the skin barrier. Phyto-derived CERs such as oat CERs were shown to be potential for skin barrier reinforcement. To effect this, however, the oat CERs should overcome the SC barrier and delivered deep into the lipid matrix using the various novel formulations...
February 28, 2018: European Journal of Pharmaceutics and Biopharmaceutics
G S Gooris, M Kamran, A Kros, D J Moore, J A Bouwstra
The outermost layer of the skin, the stratum corneum (SC), acts as the natural physical barrier. The SC consists of corneocytes embedded in a crystalline lipid matrix consisting of ceramides, free fatty acids and cholesterol. Although phospholipids are frequently present in topical formulations, no detailed information is reported on the interactions between phospholipids and SC lipids. The aim of this study was to examine the interactions between a model phospholipid, dipalmitoylphosphatidylcholine (DPPC) and synthetic ceramide-based mixtures (referred to as SC lipids)...
February 27, 2018: Biochimica et Biophysica Acta
Amanda Migotto, Vanessa F M Carvalho, Giovanna C Salata, Fernanda W M da Silva, Chao Yun Irene Yan, Kelly Ishida, Leticia V Costa-Lotufo, Alexandre A Steiner, Luciana B Lopes
Considering that breast cancer usually begins in the lining of the ducts, local drug administration into the ducts could target cancers and pre-tumor lesions locally while reducing systemic adverse effects. In this study, a cationic bioadhesive nanoemulsion was developed for intraductal administration of C6 ceramide, a sphingolipid that mediates apoptotic and non-apoptotic cell death. Bioadhesive properties were obtained by surface modification with chitosan. The optimized nanoemulsion displayed size of 46...
November 2018: Drug Delivery
Huihui Sun, Marina Resmini, Ali Zarbakhsh
Understanding the interaction of nanoparticles (NP) with ceramide lipids is important in developing strategies to overcome the formidable obstacle that is skin. This paper presents studies of interactions between N-isopropylacrylamide nanogels, crosslinked with 30% N,N'-methylenebisacrylamide, and model ceramide lipid monolayers at the air-water interface as a function of temperature. In the case of the mixed ceramide/cholesterol/behenic acid monolayer, the interaction of nanogels with the ceramide was strongly mediated by the fatty acids...
February 17, 2018: Journal of Colloid and Interface Science
Nejc Kozar, Kristi Kruusmaa, Marko Bitenc, Rosa Argamasilla, Antonio Adsuar, Nandu Goswami, Darja Arko, Iztok Takač
INTRODUCTION: Epithelial ovarian cancer (EOC) is a disease with a poor survival rate mostly due to its discovery in late stages. The aim of this study was to investigate the metabolomic profile of ovarian cancer with the intention of identifying and describing novel biomarkers with diagnostic potential. MATERIAL AND METHODS: Targeted serum metabolomic profiling was performed on 15 patients with ovarian cancer, 21 healthy controls and 21 patients with benign ovarian conditions, using HPLC-TQ/MS...
February 23, 2018: Clinica Chimica Acta; International Journal of Clinical Chemistry
Lisa Rein-Fischboeck, Elisabeth M Haberl, Rebekka Pohl, Verena Schmid, Susanne Feder, Sabrina Krautbauer, Gerhard Liebisch, Christa Buechler
Adipose tissue dysfunction contributes to the pathogenesis of non-alcoholic steatohepatitis (NASH). The adapter protein alpha-syntrophin (SNTA) is expressed in adipocytes. Knock-down of SNTA increases preadipocyte proliferation and formation of small lipid droplets, which are both characteristics of healthy adipose tissue. To elucidate a potential protective role of SNTA in NASH, SNTA null mice were fed a methionine-choline-deficient (MCD) diet or an atherogenic diet which are widely used as preclinical NASH models...
February 20, 2018: Biochimica et Biophysica Acta
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