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Sphingomyelin synthase 2

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https://www.readbyqxmd.com/read/27836537/possible-roles-of-long-chain-sphingomyelines-and-sphingomyelin-synthase-2-in-mouse-macrophage-inflammatory-response
#1
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...
November 9, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27775668/role-of-intracellular-lipid-logistics-in-the-preferential-usage-of-very-long-chain-ceramides-in-glucosylceramide
#2
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
#3
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/27591968/regulation-of-glucose-homeostasis-and-insulin-action-by-ceramide-acyl-chain-length-a-beneficial-role-for-very-long-chain-sphingolipid-species
#4
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
#5
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
#6
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/27394416/sms-regulates-the-expression-and-function-of-p-gp-and-mrp2-in-caco-2-cells
#7
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/27244255/the-sensitivity-of-chronic-myeloid-leukemia-cd34-cells-to-bcr-abl-tyrosine-kinase-inhibitors-is-modulated-by-ceramide-levels
#8
Jiaqiao Wang, June Hu, Zhiliang Jin, Huihui Wan
Despite BCR-ABL tyrosine kinase inhibitors (TKIs) improved outcome of patients with chronic myeloid leukemia (CML), resistance still develops when progresses to blast phase (BP). The mechanisms underlying resistance to TKIs are not well understood. In this study, we analyzed ceramide levels in CD34 cells derived from BP-CML patients and healthy donor bone marrow (BM) using liquid chromatography mass spectrometry. We found that ceramide level was significantly lower in BP-CML CD34 compared with normal BM counterparts...
August 2016: Leukemia Research
https://www.readbyqxmd.com/read/27236378/genome-wide-association-study-for-sperm-membrane-integrity-in-frozen-thawed-semen-of-holstein-friesian-bulls
#9
Stanisław Kamiński, Dorota M Hering, Kamil Oleński, Marek Lecewicz, Władysław Kordan
The aim of the study was to screen the entire bull genome to identify SNP markers and propose candidate genes potentially involved in the variation of sperm membrane integrity in Holstein-Friesian bulls. Two hundred eighty eight bulls kept in one AI center were included in the study. Each bull was genotyped for 54.001 Single Nucleotide Polymorpisms (SNP) by the Illumina BovineSNP50 BeadChip. Commercial straws of frozen-thawed semen were used for the evaluation of sperm plasma membrane integrity (SYBR-14/PI staining) and sperm mitochondrial function (JC1/PI staining)...
July 2016: Animal Reproduction Science
https://www.readbyqxmd.com/read/27170180/psychosine-triggered-endomitosis-is-modulated-by-membrane-sphingolipids-through-regulation-of-phosphoinositide-4-5-bisphosphate-production-at-the-cleavage-furrow
#10
Hiroshi Watanabe, Kyohei Okahara, Yuko Naito-Matsui, Mitsuhiro Abe, Shinji Go, Jinichi Inokuchi, Toshiro Okazaki, Toshihide Kobayashi, Yasunori Kozutsumi, Shogo Oka, Hiromu Takematsu
Endomitosis is a special type of mitosis in which only cytokinesis-the final step of the cell division cycle-is defective, resulting in polyploid cells. Although endomitosis is biologically important, its regulatory aspects remain elusive. Psychosine, a lysogalactosylceramide, prevents proper cytokinesis when supplemented to proliferating cells. Cytokinetic inhibition by psychosine does not inhibit genome duplication. Consequently cells undergo multiple rounds of endomitotic cell cycles, resulting in the formation of giant multiploid cells...
July 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27151272/characterization-of-the-role-of-sphingomyelin-synthase-2-in-glucose-metabolism-in-whole-body-and-peripheral-tissues-in-mice
#11
Masayuki Sugimoto, Yoichi Shimizu, Songji Zhao, Naoyuki Ukon, Ken-ichi Nishijima, Masato Wakabayashi, Takeshi Yoshioka, Kenichi Higashino, Yoshito Numata, Tomohiko Okuda, Nagara Tamaki, Hisatoshi Hanamatsu, Yasuyuki Igarashi, Yuji Kuge
Sphingomyelin synthase 2 (SMS2) is a proposed potential therapeutic target for obesity and insulin resistance. However, the contributions of SMS2 to glucose metabolism in tissues and its possible therapeutic mechanisms remain unclear. Thus, to determine whole-body glucose utilization and the contributions of each insulin-targeted tissue to glucose uptake, we performed a glucose kinetics study, using the radiolabeled glucose analog (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG), in wild-type (WT) and SMS2 knockout (KO) mice...
August 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27010944/imaging-mass-spectrometry-reveals-acyl-chain-and-region-specific-sphingolipid-metabolism-in-the-kidneys-of-sphingomyelin-synthase-2-deficient-mice
#12
Masayuki Sugimoto, Masato Wakabayashi, Yoichi Shimizu, Takeshi Yoshioka, Kenichi Higashino, Yoshito Numata, Tomohiko Okuda, Songji Zhao, Shota Sakai, Yasuyuki Igarashi, Yuji Kuge
Obesity was reported to cause kidney injury by excessive accumulation of sphingolipids such as sphingomyelin and ceramide. Sphingomyelin synthase 2 (SMS2) is an important enzyme for hepatic sphingolipid homeostasis and its dysfunction is considered to result in fatty liver disease. The expression of SMS2 is also high in the kidneys. However, the contribution of SMS2 on renal sphingolipid metabolism remains unclear. Imaging mass spectrometry is a powerful tool to visualize the distribution and provide quantitative data on lipids in tissue sections...
2016: PloS One
https://www.readbyqxmd.com/read/26562048/prenatal-alcohol-exposure-inducing-the-apoptosis-of-mossy-cells-in-hippocampus-of-sms2-mice
#13
Lai Wang, Lin Wu, Xiaoqing Wang, Jiexin Deng, Zhanyou Ma, Wenjuan Fan, Weiya He, Jinbo Deng
In order to understand the mechanisms of alcohol-induced neuroapoptosis through the ceramide pathway, sphingomyelin synthase 2 knockout (SMS2-/-) mice were used to make the prenatal alcohol exposure model, and the role of ceramide regulation on alcohol-induced neuroapoptosis was studied in the offspring. Initially the levels of serum sphingomyelin (SM) were detected with enzymatic method in P0 pups after alcohol exposure in parents. Then the apoptosis of mossy cells in the offspring hippocampus was investigated after prenatal alcohol exposure with immunohistochemistry and TUNEL assay...
November 2015: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/26535077/vitamin-c-stimulates-epidermal-ceramide-production-by-regulating-its-metabolic-enzymes
#14
Kun Pyo Kim, Kyong-Oh Shin, Kyungho Park, Hye Jeong Yun, Shivtaj Mann, Yong Moon Lee, Yunhi Cho
Ceramide is the most abundant lipid in the epidermis and plays a critical role in maintaining epidermal barrier function. Overall ceramide content in keratinocyte increases in parallel with differentiation, which is initiated by supplementation of calcium and/or vitamin C. However, the role of metabolic enzymes responsible for ceramide generation in response to vitamin C is still unclear. Here, we investigated whether vitamin C alters epidermal ceramide content by regulating the expression and/or activity of its metabolic enzymes...
November 2015: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/26314925/discovery-synthesis-and-biological-evaluation-of-2-4-n-phenethylsulfamoyl-phenoxy-acetamides-sapas-as-novel-sphingomyelin-synthase-1-inhibitors
#15
Ya-Li Li, Xiang-Yu Qi, Hui Jiang, Xiao-Dong Deng, Yan-Ping Dong, Ting-Bo Ding, Lu Zhou, Peng Men, Yong Chu, Ren-Xiao Wang, Xian-Cheng Jiang, De-Yong Ye
Sphingomyelin synthase (SMS) has been proved to be a potential drug target for the treatment of atherosclerosis. However, few SMS inhibitors have been reported. In this paper, structure-based virtual screening was performed on hSMS1. SAPA 1a was discovered as a novel SMS1 inhibitor with an IC50 value of 5.2 μM in enzymatic assay. A series of 2-(4-(N-phenethylsulfamoyl)phenoxy)acetamides (SAPAs) were synthesized and their biological activities toward SMS1 were evaluated. Among them, SAPA 1j was found to be the most potent SMS1 inhibitor with an IC50 value of 2...
September 15, 2015: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/26232616/ceramide-generation-during-curcumin-induced-apoptosis-is-controlled-by-crosstalk-among-bcl-2-bcl-xl-caspases-and-glutathione
#16
Abo Bakr Abdel Shakor, Mona Atia, Ali Saleh Alshehri, Andrzej Sobota, Katarzyna Kwiatkowska
Curcumin exhibits anti-cancer properties manifested by activation of pro-apoptotic signaling. We have demonstrated earlier that apoptosis of HL-60 human leukemia cells induced by curcumin is controlled by ceramide generated by neutral sphingomyelinase (nSMase) which contributes to sphingomyelin synthase (SMS) inhibition favoring accumulation of ceramide in cells. Here we report that the activity of nSMase, ceramide accumulation and death of HL-60 cells are inhibited by overexpression of Bcl-xL or Bcl-2 proteins, while down-regulation of nSMase interferes with degradation of Bcl-2 but not Bcl-xL...
November 2015: Cellular Signalling
https://www.readbyqxmd.com/read/26116739/analysis-of-lipid-composition-changes-in-plasma-membrane-microdomains
#17
Hideo Ogiso, Makoto Taniguchi, Toshiro Okazaki
Sphingolipids accumulate in plasma membrane microdomain sites, such as caveolae or lipid rafts. Such microdomains are considered to be important nexuses for signal transduction, although changes in the microdomain lipid components brought about by signaling are poorly understood. Here, we applied a cationic colloidal silica bead method to analyze plasma membrane lipids from monolayer cells cultured in a 10 cm dish. The detergent-resistant fraction from the silica bead-coated membrane was analyzed by LC-MS/MS to evaluate the microdomain lipids...
August 2015: Journal of Lipid Research
https://www.readbyqxmd.com/read/26020299/physiology-and-endocrinology-symposium-cellular-and-molecular-mechanisms-of-heat-stress-related-to-bovine-ovarian-function
#18
Z Roth
In light of the intensive genetic selection for high milk production and the onset of global warming, it seems that the reduced fertility of lactating cows during the summer will worsen in coming years. Although not entirely clear, the mechanism appears to be multifactorial in nature. It includes alterations in follicular development, depression of follicular dominance, and impairment of steroidogenesis and gonadotropin secretion. Heat-induced perturbations in the physiology of the follicle-enclosed oocyte have also been documented, expressed by impaired cleavage rate and reduced developmental competence...
May 2015: Journal of Animal Science
https://www.readbyqxmd.com/read/25888510/pc-plc-sphingomyelin-synthase-activity-plays-a-central-role-in-the-development-of-myogenic-tone-in-murine-resistance-arteries
#19
Joseph R H Mauban, Joseph Zacharia, Seth Fairfax, Withrow Gil Wier
Myogenic tone is an intrinsic property of the vasculature that contributes to blood pressure control and tissue perfusion. Earlier investigations assigned a key role in myogenic tone to phospholipase C (PLC) and its products, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG). Here, we used the PLC inhibitor, U-73122, and two other, specific inhibitors of PLC subtypes (PI-PLC and PC-PLC) to delineate the role of PLC in myogenic tone of pressurized murine mesenteric arteries. U-73122 inhibited depolarization-induced contractions (high external K(+) concentration), thus confirming reports of nonspecific actions of U-73122 and its limited utility for studies of myogenic tone...
June 15, 2015: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/25839235/expression-of-ceramide-synthase-6-transcriptionally-activates-acid-ceramidase-in-a-c-jun-n-terminal-kinase-jnk-dependent-manner
#20
Tejas S Tirodkar, Ping Lu, Aiping Bai, Matthew J Scheffel, Salih Gencer, Elizabeth Garrett-Mayer, Alicja Bielawska, Besim Ogretmen, Christina Voelkel-Johnson
A family of six ceramide synthases with distinct but overlapping substrate specificities is responsible for generation of ceramides with acyl chains ranging from ∼14-26 carbons. Ceramide synthase 6 (CerS6) preferentially generates C14- and C16-ceramides, and we have previously shown that down-regulation of this enzyme decreases apoptotic susceptibility. In this study, we further evaluated how increased CerS6 expression impacts sphingolipid composition and metabolism. Overexpression of CerS6 in HT29 colon cancer cells resulted in increased apoptotic susceptibility and preferential generation of C16-ceramide, which occurred at the expense of very long chain, saturated ceramides...
May 22, 2015: Journal of Biological Chemistry
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