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sphingomyelin synthase

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https://www.readbyqxmd.com/read/28087695/novel-interconnections-in-lipid-metabolism-revealed-by-overexpression-of-sphingomyelin-synthase-1
#1
Gergana M Deevska, Patrick P Dotson, Alexander A Karakashian, Giorgis Isaac, Mark Wrona, Samuel B Kelly, Alfred H Merrill, Mariana N Nikolova-Karakashian
This study investigates the consequences of elevating sphingomyelin synthase 1 (SMS1) activity, which generates the main mammalian sphingolipid, sphingomyelin. HepG2 cells stably transfected with SMS1 (HepG2-SMS1), exhibit elevated enzyme activity in vitro and increased sphingomyelin content (mainly C22:0- and C24:0-sphingomyelin), but lower hexosylceramide (Hex-Cer) levels. HepG2-SMS1 cells have less triacylglycerols than controls but similar diacylglycerol acyltransferase activity, triacylglycerol secretion, and mitochondrial function...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28078595/method-to-measure-sphingomyelin-synthase-activity-changes-in-response-to-cd95l
#2
Fatima Bilal, Michaël Pérès, Nathalie Andrieu-Abadie, Thierry Levade, Bassam Badran, Ahmad Daher, Bruno Ségui
Sphingomyelin synthases 1 and 2 convert the anti-oncometabolite ceramide to sphingomyelin, the most abundant sphingolipid in plasma membrane. CD95L-induced ceramide increase is associated with the caspase-dependent inhibition of sphingomyelin synthesis, which enhances the mitochondrial route to apoptosis. Knocking down sphingomyelin synthase 1 or inhibiting sphingomyelin synthesis facilitates ceramide accumulation, cytochrome c release from mitochondria, and caspase-9 activation in cancer cell upon CD95L treatment...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28035360/hepatic-inflammatory-cytokine-production-can-be-regulated-by-modulating-sphingomyelinase-and-ceramide-synthase-6
#3
Min Hee Kim, Hee Kyung Ahn, Eun-Ji Lee, Su-Jeong Kim, Ye-Ryung Kim, Joo-Won Park, Woo-Jae Park
Chronic inflammation is associated with the pathogenesis of type 2 diabetes and diabetic complications, and palmitate has been nominated as a candidate for the molecular link between these disorders. Recently, a crucial role of ceramide in inflammation and metabolic diseases has been reported. Therefore, in this study, we investigated whether ceramide formation is involved in palmitate‑induced hepatic inflammation in vitro and in vivo. Ceramide can be generated either by the de novo pathway or by sphingomyelin degradation, and six different ceramide synthases (CerS) determine the specific acyl chain length of ceramide in mammals...
December 22, 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27991764/high-troughput-lipidomic-and-transcriptomic-analysis-to-compare-sp2-0-cho-and-hek-293-mammalian-cell-lines
#4
Yue Zhang, Deniz Baycin Hizal, Amit Kumar, Joseph Priola, Michelle Bahri, Kelley M Heffner, Miao Wang, Xianlin Han, Michael A Bowen, Michael J Betenbaugh
A combined lipidomics and transcriptomics analysis was performed on mouse myeloma SP2/0, Chinese Hamster Ovary (CHO) and Human Embryonic Kidney (HEK) cells in order to compare widely used mammalian expression systems. Initial thin layer chromatography (TLC) analysis indicated phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were the major lipid components with lower amounts of sphingomyelin (SM) in SP2/0 compared to CHO and HEK, which was subsequently confirmed and expounded upon following mass spectrometry (MS) analysis...
December 19, 2016: Analytical Chemistry
https://www.readbyqxmd.com/read/27941971/plasma-metabolomics-biosignature-according-to-hiv-stage-of-infection-pace-of-disease-progression-viremia-level-and-immunological-response-to-treatment
#5
Bruno Scarpelini, Michelle Zanoni, Maria Cecilia Araripe Sucupira, Hong-Ha M Truong, Luiz Mario Ramos Janini, Ismael Dale Cotrin Segurado, Ricardo Sobhie Diaz
BACKGROUND: We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment...
2016: PloS One
https://www.readbyqxmd.com/read/27927984/carboxyl-terminal-tail-mediated-homodimerizations-of-sphingomyelin-synthases-are-responsible-for-efficient-export-from-the-endoplasmic-reticulum
#6
Yasuhiro Hayashi, Yoko Nemoto-Sasaki, Naoki Matsumoto, Takashi Tanikawa, Saori Oka, Yusuke Tanaka, Seisuke Arai, Ikuo Wada, Takayuki Sugiura, Atsushi Yamashita
Sphingomyelin synthase (SMS) is the key enzyme for cross-talk between bioactive sphingolipids and glycerolipids. In mammals, SMS consists of two isoforms: SMS1 is localized in the Golgi apparatus, whereas SMS2 is localized in both the Golgi and plasma membranes. SMS2 seems to exert cellular functions through protein-protein interactions; however, the existence and functions of quaternary structures of SMS1 and SMS2 remain unclear. Here, we demonstrate that both SMS1 and SMS2 form homodimers. The SMSs have six membrane-spanning domains, and the N- and C-termini of both proteins face the cytosolic side of the Golgi apparatus...
December 7, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27892528/sphingomyelin-generated-by-sphingomyelin-synthase-1-is-involved-in-attachment-and-infection-with-japanese-encephalitis-virus
#7
Makoto Taniguchi, Takafumi Tasaki, Hideaki Ninomiya, Yoshibumi Ueda, Koh-Ichi Kuremoto, Susumu Mitsutake, Yasuyuki Igarashi, Toshiro Okazaki, Tsutomu Takegami
Japanese encephalitis virus (JEV) is a mosquito-borne RNA virus which infects target cells via the envelope protein JEV-E. However, its cellular targets are largely unknown. To investigate the role of sphingomyelin (SM) in JEV infection, we utilized SM-deficient immortalized mouse embryonic fibroblasts (tMEF) established from SM synthase 1 (SMS1)/SMS2 double knockout mice. SMS deficiency significantly reduced both intracellular and extracellular JEV levels at 48 h after infection. Furthermore, after 15 min treatment with JEV, the early steps of JEV infection such as attachment and cell entry were also diminished in SMS-deficient tMEFs...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27836537/possible-roles-of-long-chain-sphingomyelines-and-sphingomyelin-synthase-2-in-mouse-macrophage-inflammatory-response
#8
Hideaki Sakamoto, Tetsuya Yoshida, Takao Sanaki, Shuhei Shigaki, Hirotoshi Morita, Miki Oyama, Masaru Mitsui, Yoshikazu Tanaka, Toru Nakano, Susumu Mitsutake, Yasuyuki Igarashi, Hiroshi Takemoto
To evaluate the precise role of sphingomyelin synthase 2 (SMS2) in sphingomyelin (SM) metabolism and their anti-inflammatory properties, we analyzed species of major SM and ceramide (Cer) (18:1, 18:0 sphingoid backbone, C14 - C26 N-acyl part) in SMS2 knockout and wild-type mouse plasma and liver using HPLC-MS. SMS2 deficiency significantly decreased very long chain SM (SM (d18:1/22:0) and SM (d18:1/24:0 or d18:0/24:1)) and increased very long chain Cer (Cer (d18:1/24:0 or d18:0/24:1) and Cer (d18:1/24:1)), but not long chain SM (SM (d18:1/16:0), SM (d18:1/18:0 or d18:0/18:1) and SM (d18:1/18:1)) in plasma...
January 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27788151/sphingomyelin-synthase-1-is-essential-for-male-fertility-in-mice
#9
Anke Wittmann, Marcus O W Grimm, Harry Scherthan, Marion Horsch, Johannes Beckers, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabě de Angelis, Steven J Ford, Neal C Burton, Daniel Razansky, Dietrich Trümbach, Michaela Aichler, Axel Karl Walch, Julia Calzada-Wack, Frauke Neff, Wolfgang Wurst, Tobias Hartmann, Thomas Floss
Sphingolipids and the derived gangliosides have critical functions in spermatogenesis, thus mutations in genes involved in sphingolipid biogenesis are often associated with male infertility. We have generated a transgenic mouse line carrying an insertion in the sphingomyelin synthase gene Sms1, the enzyme which generates sphingomyelin species in the Golgi apparatus. We describe the spermatogenesis defect of Sms1-/- mice, which is characterized by sloughing of spermatocytes and spermatids, causing progressive infertility of male homozygotes...
2016: PloS One
https://www.readbyqxmd.com/read/27775668/role-of-intracellular-lipid-logistics-in-the-preferential-usage-of-very-long-chain-ceramides-in-glucosylceramide
#10
Toshiyuki Yamaji, Aya Horie, Yuriko Tachida, Chisato Sakuma, Yusuke Suzuki, Yasunori Kushi, Kentaro Hanada
Ceramide is a common precursor of sphingomyelin (SM) and glycosphingolipids (GSLs) in mammalian cells. Ceramide synthase 2 (CERS2), one of the six ceramide synthase isoforms, is responsible for the synthesis of very long chain fatty acid (C20-26 fatty acids) (VLC)-containing ceramides (VLC-Cer). It is known that the proportion of VLC species in GSLs is higher than that in SM. To address the mechanism of the VLC-preference of GSLs, we used genome editing to establish three HeLa cell mutants that expressed different amounts of CERS2 and compared the acyl chain lengths of SM and GSLs by metabolic labeling experiments...
October 21, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27756324/acid-sphingomyelinase-as-target-of-lycium-chinense-promising-new-action-for-cell-health
#11
Maria Rachele Ceccarini, Michela Codini, Samuela Cataldi, Samuele Vannini, Andrea Lazzarini, Alessandro Floridi, Massimo Moretti, Milena Villarini, Bernard Fioretti, Tommaso Beccari, Elisabetta Albi
BACKGROUND: Sphingomyelin plays very important roles in cell function under physiological and pathological conditions. Physical and chemical stimuli produce reactive oxygen species that stimulate acid sphingomyelinase to induce apoptosis. Antioxidant plants of the traditional Chinese Pharmacopoeia, such as Lycium Barbarum and Lycium Chinense, have become increasingly popular in Western countries. We investigated the effects of Lycium Chinense on acid sphingomyelinase and sphingomyelin species in relation to gene expression...
October 19, 2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27711049/clozapine-modulates-glucosylceramide-clears-aggregated-proteins-and-enhances-atg8-lc3-in-caenorhabditis-elegans
#12
Limin Hao, Oshrit Ben-David, Suzann M Babb, Anthony H Futerman, Bruce M Cohen, Edgar A Buttner
Defining the mechanisms of action of the antipsychotic drug (APD), clozapine, is of great importance, as clozapine is more effective and has therapeutic benefits in a broader range of psychiatric disorders compared with other APDs. Its range of actions have not been fully characterized. Exposure to APDs early in development causes dose-dependent developmental delay and lethality in Caenorhabditis elegans. A previous genome-wide RNAi screen for suppressors of clozapine-induced developmental delay and lethality revealed 40 candidate genes, including sms-1, which encodes a sphingomyelin synthase...
October 26, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27703011/a-role-for-ceramides-but-not-sphingomyelins-as-antagonists-of-insulin-signaling-and-mitochondrial-metabolism-in-c2c12-myotubes
#13
Min Park, Vincent Kaddai, Jianhong Ching, Kevin T Fridianto, Ryan J Sieli, Shigeki Sugii, Scott A Summers
The accumulation of sphingolipids in obesity leads to impairments in insulin sensitivity and mitochondrial metabolism, but the precise species driving these defects is unclear. We have modeled these obesity-induced effects in cultured C2C12 myotubes, using BSA-conjugated palmitate to increase synthesis of endogenous sphingolipids and to inhibit insulin signaling and oxidative phosphorylation. Palmitate (a) induced the accumulation of sphingomyelin (SM) precursors such as sphinganine, dihydroceramide, and ceramide; (b) inhibited insulin stimulation of a central modulator of anabolic metabolism, Akt/PKB; (c) inhibited insulin-stimulated glycogen synthesis; and (d) decreased oxygen consumption and ATP synthesis...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27591968/regulation-of-glucose-homeostasis-and-insulin-action-by-ceramide-acyl-chain-length-a-beneficial-role-for-very-long-chain-sphingolipid-species
#14
Magdalene K Montgomery, Simon H J Brown, Xin Y Lim, Corrine E Fiveash, Brenna Osborne, Nicholas L Bentley, Jeremy P Braude, Todd W Mitchell, Adelle C F Coster, Anthony S Don, Gregory J Cooney, Carsten Schmitz-Peiffer, Nigel Turner
In a recent study, we showed that in response to high fat feeding C57BL/6, 129X1, DBA/2 and FVB/N mice all developed glucose intolerance, while BALB/c mice displayed minimal deterioration in glucose tolerance and insulin action. Lipidomic analysis of livers across these five strains has revealed marked strain-specific differences in ceramide (Cer) and sphingomyelin (SM) species with high-fat feeding; with increases in C16-C22 (long-chain) and reductions in C>22 (very long-chain) Cer and SM species observed in the four strains that developed HFD-induced glucose intolerance...
November 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27539961/cholesterol-dependent-increases-in-glucosylceramide-synthase-activity-in-niemann-pick-disease-type-c-model-cells-abnormal-trafficking-of-endogenously-formed-ceramide-metabolites-by-inhibition-of-the-enzyme
#15
Naohiro Hashimoto, Ikiru Matsumoto, Hiromasa Takahashi, Hitomi Ashikawa, Hiroyuki Nakamura, Toshihiko Murayama
Sphingolipids such as sphingomyelin and glycosphingolipids (GSLs) derived from glucosylceramide (GlcCer), in addition to cholesterol, accumulate in cells/neurons in Niemann-Pick disease type C (NPC). The activities of acid sphingomyelinase and lysosomal glucocerebrosidase (GCase), which degrade sphingomyelin and GlcCer, respectively, are down-regulated in NPC cells, however, changes in GlcCer synthase activity have not yet been elucidated. We herein demonstrated for the first time that GlcCer synthase activity for the fluorescent ceramide, 4-nitrobenzo-2-oxa-1,3-diazole-labeled C6-ceramide (NBD-ceramide) increased in intact NPC1((-/-)) cells and cell lysates without affecting the protein levels...
November 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27510408/sphingomyelin-synthase%C3%A2-2-affects-cd14%C3%A2-associated-induction-of-nf%C3%A2-%C3%AE%C2%BAb-by-lipopolysaccharides-in-acute-lung-injury-in-mice
#16
Shidong Hu, Yi Ding, Jie Gong, Nianlong Yan
Lipopolysaccharide (LPS) is the predominant component of the outer membrane of Gram-negative bacteria, which can cause severe inflammation in the body. The acute lung injury (ALI) induced by LPS can cause extensive damage to the lung tissue, the severe stage of which is termed acute respiratory distress syndrome, when multiple organ dysfunction syndrome may appear. There are no effective clinical treatment measures at present. The involvement of cluster of differentiation (CD)14 assists LPS in causing inflammatory reactions, and CD14 and sphingomyelin (SM), located in lipid rafts areas, are closely associated...
October 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27449796/circular-rnas-one-of-the-enigmas-of-the-brain
#17
Ivan B Filippenkov, Eugene O Kalinichenko, Svetlana A Limborska, Lyudmila V Dergunova
Circular RNAs (circRNAs) provide a new and relatively unexplored class of noncoding RNAs that are predominantly found in mammalian cells. In this review, we present the latest data regarding the structural organization, possible mechanisms of synthesis, and functions of circRNAs. These transcripts were isolated as an RNA fraction that was resistant to RNase R treatment, which selectively destroys the linear forms of RNA molecules. circRNAs are encoded by orthologous genes in different organisms and show tissue- and organ-specific expression...
July 23, 2016: Neurogenetics
https://www.readbyqxmd.com/read/27430385/effects-of-asterias-amurensis-derived-sphingoid-bases-on-the-de-novo-ceramide-synthesis-in-cultured-normal-human-epidermal-keratinocytes
#18
Daisuke Mikami, Shota Sakai, Shigefumi Sasaki, Yasuyuki Igarashi
Asterias amurensis starfish provide several bioactive species in addition to being fishery waste. Glucosyl ceramides (GlcCers) were extracted from the viscera of these starfish and were isolated by silica gel column chromatography. Degraded GlcCers generated A. amurensis sphingoid bases (ASBs) that mainly consisted of the triene-type bases d18:3 and 9-methyl-d18:3. The effect of these bases on ceramide synthesis and content were analyzed using normal human epidermal keratinocytes (NHEKs). The bases significantly enhanced the de novo ceramide synthesis and gene expression in NHEKs for proteins, such as serine-palmitoyltransferase and ceramide synthase...
August 1, 2016: Journal of Oleo Science
https://www.readbyqxmd.com/read/27394416/sms-regulates-the-expression-and-function-of-p-gp-and-mrp2-in-caco-2-cells
#19
Guiying Jin, Yang Li, Yuwen Zhu, Lisha Du, Junkai Yan, Qing Yang
Sphingomyelin synthase (SMS) has two isoforms of SMS1 and SMS2, the last enzyme involved in the biosynthesis of sphingomyelin (SM), and has impact on the expression of membrane proteins. In the present study, we explored the potential effects of SMS on drug transporters, a special family of membrane proteins in human intestinal epithelial Caco-2 cells. The specific knockdown of SMS1 or SMS2 with siRNA in Caco-2 cells substantially decreased the expression and function of P-glycoprotein (P-gp) and multidrug resistance protein 2 (MRP2) rather than other drug transporters MRP1, MRP3, PEPT1, OATP2B1, and BCRP...
July 9, 2016: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27391427/inhibition-of-sphingomyelin-synthase-1-affects-ceramide-accumulation-and-hydrogen-peroxide-induced-apoptosis-in-neuro-2a-cells
#20
Ranran Tu, Wei Yang, Zhiping Hu
Oxidative stress plays a key role in brain injury after cerebral ischemia-reperfusion, which contributes toward excessive apoptosis of nerve cells. Therefore, it would be beneficial to identify a therapy that could interfere with the progression of apoptosis and protect the brain from ischemia-reperfusion injury. As ceramide, a well-known second messenger of apoptosis, can be metabolized by sphingomyelin synthase 1 (SMS1), recent research has focused on the link between SMS1 and apoptosis in different cells...
September 7, 2016: Neuroreport
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