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Woojin Scott Kim, Eve Jary, Russell Pickford, Ying He, Rebekah M Ahmed, Olivier Piguet, John R Hodges, Glenda M Halliday
Behavioral variant frontotemporal dementia (bvFTD) is the most prevalent form of FTD syndromes. bvFTD is characterized clinically by changes in behavior and cognition and pathologically by focal brain atrophy and concomitant loss of lipids. bvFTD is further characterized by eating abnormalities that result in dyslipidemia. Although dyslipidemia is apparent in bvFTD, very little is known about global lipid changes in bvFTD and lipid dysregulation underlying bvFTD. Here, we undertook a comprehensive lipidomics analysis of blood plasma from patients with bvFTD, patients with Alzheimer's disease (AD) and controls, using liquid chromatography-tandem mass spectrometry, with the aim of understanding lipid dysregulation in bvFTD...
2018: Frontiers in Neurology
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
Majid Vahed, Saburo Neya, Katsumi Matsuzaki, Tyuji Hoshino
The interaction of amyloid beta (Aβ) peptide with cell membrane is one of the factors enhancing Aβ aggregation, which is closely related to neuro-disturbance disease. In this work, we performed molecular dynamics (MD) simulation to investigate the initial stage of adhesion of Aβ40 to a GM1 ganglioside-containing membrane. Conformational change of Aβ40 due to interaction with the membrane was monitored and compared with that of Aβ42 observed in the previous study. Multiple computational trials were executed to analyze the probability of Aβ binding using a calculation model consisting of a GM1-containing mixed lipid membrane, water layer, ions, and Aβ40...
March 14, 2018: Journal of Physical Chemistry. B
Sitapriya Moorthi, Tara Ann Burns, Gui-Qin Yu, Chiara Luberto
Bcr-Abl (break-point cluster region-abelson), the oncogenic trigger of chronic myelogenous leukemia (CML), has previously been shown to up-regulate the expression and activity of sphingomyelin synthase 1 (SMS1), which contributes to the proliferation of CML cells; however, the mechanism by which this increased expression of SMS1 is mediated remains unknown. In the current study, we show that Bcr-Abl enhances the expression of SMS1 via a 30-fold up-regulation of its transcription. Of most interest, the Bcr-Abl-regulated transcription of SMS1 is initiated from a novel transcription start site (TSS) that is just upstream of the open reading frame...
March 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Cher-Pheng Ooi, Terry K Smith, Eva Gluenz, Nadina Vasileva Wand, Sue Vaughan, Gloria Rudenko
The predominant secretory cargo of bloodstream form Trypanosoma brucei is Variant Surface Glycoprotein (VSG), comprising ~10% total protein and forming a dense protective layer. Blocking VSG translation using Morpholino oligonucleotides triggered a precise pre-cytokinesis arrest. We investigated the effect of blocking VSG synthesis on the secretory pathway. The number of Golgi decreased, particularly in post-mitotic cells, from 3.5 ± 0.6 to 2.0 ± 0.04 per cell. Similarly, the number of ER exit sites (ERES) in post-mitotic cells dropped from (3...
March 13, 2018: Traffic
Rui-Dong Duan
Alkaline sphingomyelinase cleaves phosphocholine from sphingomyelin, platelet-activating factor, lysophosphatidylcholine, and less effectively phosphatidylcholine. The enzyme shares no structure similarities with acid or neutral sphingomyelinase but belongs to ecto-nucleotide pyrophosphatase/phosphodiesterase (NPP) family and therefore is also called NPP7 nowadays. The enzyme is expressed in the intestinal mucosa in many species and additionally in human liver. The enzyme in the intestinal tract has been extensively studied but not that in human liver...
February 27, 2018: World Journal of Hepatology
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
Giuseppe Corona, Renato Cannizzaro, Gianmaria Miolo, Laura Caggiari, Mariangela De Zorzi, Ombretta Repetto, Agostino Steffan, Valli De Re
A positive family history is a strong and consistently reported risk factor for gastric cancer (GC). So far, it has been demonstrated that serum pepsinogens (PGs), and gastrin 17 (G17) are useful for screening individuals at elevated risk to develop atrophic gastritis but they are suboptimal biomarkers to screen individuals for GC. The main purpose of this study was to investigate serum metabolomic profiles to find additional biomarkers that could be integrated with serum PGs and G17 to improve the diagnosis of GC and the selection of first-degree relatives (FDR) at higher risk of GC development...
March 7, 2018: International Journal of Molecular Sciences
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
H-M Burger, S Abel, W C A Gelderblom
Fumonisin B1 (FB1 ), a group 2B natural occurring carcinogenic mycotoxin, modulated lipid and fatty acid (FA) constituents of lipid rafts isolated from primary hepatocytes following exposure to a cytotoxic concentration of FB1 (250 μM). The major effects observed in rafts, included a significant (p < 0.05) increase in raft cholesterol (CHOL) and glycerophospholipid such as phosphatidylethanolamine (PE), whereas sphingomyelin (SM) decreased (p < 0.05). Changes in lipid constituents resulted in the disruption of important membrane fluidity parameters represented as a decreased (p < 0...
March 3, 2018: Food and Chemical Toxicology
Tamara A Piñero, Malena Landoni, Vilma G Duschak, Alejandro M Katzin, Alicia S Couto
Parasites of the genus Plasmodium responsible for Malaria are obligate intracellular pathogens residing in mammalian red blood cells, hepatocytes, or mosquito midgut epithelial cells. Regarding that detailed knowledge on the sphingolipid biosynthetic pathway of the apicomplexan protozoan parasites is scarce, different stages of Plasmodium falciparum were treated with tamoxifen in order to evaluate the effects of this drug on the glycosphingolipid biosynthesis. Thin layer chromatography, High performance reverse phase chromatography and UV-MALDI-TOF mass spectrometry were the tools used for the analysis...
February 26, 2018: Biochemical and Biophysical Research Communications
Kalle Kilk, Argo Aug, Aigar Ottas, Ursel Soomets, Siiri Altraja, Alan Altraja
Apart from the refined management-oriented clinical stratification of chronic obstructive pulmonary disease (COPD), the molecular pathologies behind this highly prevalent disease have remained obscure. The aim of this study was the characterization of patients with COPD, based on the metabolomic profiling of peripheral blood and exhaled breath condensate (EBC) within the context of defined clinical and demographic variables. Mass-spectrometry-based targeted analysis of serum metabolites (mainly amino acids and lipid species), untargeted profiles of serum and EBC of patients with COPD of different clinical characteristics ( n = 25) and control individuals ( n = 21) were performed...
February 27, 2018: International Journal of Molecular Sciences
Anna Wojakowska, Laura M Cole, Mykola Chekan, Katarzyna Bednarczyk, Magdalena Maksymiak, Małgorzata Oczko-Wojciechowska, Barbara Jarząb, Malcolm R Clench, Joanna Polańska, Monika Pietrowska, Piotr Widlak
INTRODUCTION: The distinction of papillary thyroid carcinomas from benign thyroid lesions has important implication for clinical man-agement. Classification based on histopathological features can be supported by molecular biomarkers, including lipidomic signatures, identified with the use of high-throughput mass spectrometry techniques. Formalin fixation is a standard procedure for stabilization and preservation of tissue samples, therefore this type of samples constitute highly valuable source of clinical material for retrospective molecular studies...
2018: Endokrynologia Polska
Fiona Henderson, Philippa J Hart, Jesus M Pradillo, Michael Kassiou, Lidan Christie, Kaye J Williams, Herve Boutin, Adam McMahon
RATIONALE: Stroke is a leading cause of disability worldwide. Understanding the recovery process post-stroke is essential; however, longer-term recovery studies are lacking. In-vivo Positron emission tomography (PET) can image biological recovery processes, but is limited by spatial resolution and its targeted nature. Untargeted mass spectrometry imaging offers high spatial resolution, providing an ideal ex-vivo tool for brain recovery imaging. METHODS: Magnetic resonance imaging (MRI) was used to image a rat brain 48 hours after ischaemic stroke to locate the infarcted regions of the brain...
February 27, 2018: Rapid Communications in Mass Spectrometry: RCM
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
Junfei Jin, Zhongyang Lu, Yanchun Li, L Ashley Cowart, Maria F Lopes-Virella, Yan Huang
It is well known that saturated fatty acids (SFAs) and unsaturated fatty acid, in particular omega-3 polyunsaturated fatty acids (n-3 PUFAs), have different effects on inflammatory signaling: SFAs are pro-inflammatory but n-3 PUFAs have strong anti-inflammatory properties. We have reported that palmitic acid (PA), a saturated fatty acid, robustly amplifies lipopolysaccharide (LPS) signaling to upregulate proinflammatory gene expression in macrophages. We also reported that the increased production of ceramide (CER) via sphingomyelin (SM) hydrolysis and CER de novo synthesis plays a key role in the synergistic effect of LPS and PA on proinflammatory gene expression...
2018: PloS One
Paul L Wood, Margaret Steinman, Erdal Erol, Craig Carter, Undine Christmann, Ashutosh Verma
Currently available diagnostic assays for leptospirosis cannot differentiate vaccine from infection serum antibody. Several leptospiral proteins that are upregulated during infection have been described, but their utility as a diagnostic marker is still unclear. In this study, we undertook a lipidomics approach to determine if there are any differences in the serum lipid profiles of horses naturally infected with pathogenic Leptospira spp. and horses vaccinated against a commercially available bacterin. Utilizing a high-resolution mass spectrometry serum lipidomics analytical platform, we demonstrate that cyclic phosphatidic acids, diacylglycerols, and hydroperoxide oxidation products of choline plasmalogens are elevated in the serum of naturally infected as well as vaccinated horses...
2018: PloS One
Kotaro Hama, Yuko Fujiwara, Masashi Morita, Fumiyoshi Yamazaki, Yuko Nakashima, Shiro Takei, Shigeo Takashima, Mitsutoshi Setou, Nobuyuki Shimozawa, Tsuneo Imanaka, Kazuaki Yokoyama
ABCD1 is a gene responsible for X-linked adrenoleukodystrophy (X-ALD), and is critical for the transport of very long-chain fatty acids (VLCFA) into peroxisomes and subsequent β-oxidation. VLCFA-containing lipids accumulate in X-ALD patients, although the effect of ABCD1-deficiency on each lipid species in the central nervous system has not been fully characterized. In this study, each phospholipid and lysophospholipid species in Abcd1-deficient mice brains were profiled by liquid chromatography-mass spectrometry...
February 22, 2018: Lipids
Evgeny Berdyshev, Elena Goleva, Irina Bronova, Nathan Dyjack, Cydney Rios, John Jung, Patricia Taylor, Mingeum Jeong, Clifton F Hall, Brittany N Richers, Kathryn A Norquest, Tao Zheng, Max A Seibold, Donald Ym Leung
Lipids in the stratum corneum of atopic dermatitis (AD) patients differ substantially in composition from healthy subjects. We hypothesized that hyperactivated type 2 immune response alters AD skin lipid metabolism. We have analyzed stratum corneum lipids from nonlesional and lesional skin of AD subjects and IL-13 skin-specific Tg mice. We also directly examined the effects of IL-4/IL-13 on human keratinocytes in vitro. Mass spectrometric analysis of lesional stratum corneum from AD subjects and IL-13 Tg mice revealed an increased proportion of short-chain (N-14:0 to N-24:0) NS ceramides, sphingomyelins, and 14:0-22:0 lysophosphatidylcholines (14:0-22:0 LPC) with a simultaneous decline in the proportion of corresponding long-chain species (N-26:0 to N-32:0 sphingolipids and 24:0-30:0 LPC) when compared with healthy controls...
February 22, 2018: JCI Insight
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