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sphingomyelin synthase

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https://www.readbyqxmd.com/read/29769046/%C3%AE-tocotrienol-induces-apoptosis-in-pancreatic-cancer-cells-by-upregulation-of-ceramide-synthesis-and-modulation-of-sphingolipid-transport
#1
Victoria E Palau, Kanishka Chakraborty, Daniel Wann, Janet Lightner, Keely Hilton, Marianne Brannon, William Stone, Koyamangalath Krishnan
BACKGROUND: Ceramide synthesis and metabolism is a promising target in cancer drug development. γ-tocotrienol (GT3), a member of the vitamin E family, orchestrates multiple effects that ensure the induction of apoptosis in both, wild-type and RAS-mutated pancreatic cancer cells. Here, we investigated whether these effects involve changes in ceramide synthesis and transport. METHODS: The effects of GT3 on the synthesis of ceramide via the de novo pathway, and the hydrolysis of sphingomyelin were analyzed by the expression levels of the enzymes serine palmitoyl transferase, ceramide synthase-6, and dihydroceramide desaturase, and acid sphingomyelinase in wild-type RAS BxPC3, and RAS-mutated MIA PaCa-2 and Panc 1 pancreatic cancer cells...
May 16, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29738550/genome-wide-association-meta-analysis-of-circulating-odd-numbered-chain-saturated-fatty-acids-results-from-the-charge-consortium
#2
Marcia C de Oliveira Otto, Rozenn N Lemaitre, Qi Sun, Irena B King, Jason H Y Wu, Ani Manichaikul, Stephen S Rich, Michael Y Tsai, Y D Chen, Myriam Fornage, Guan Weihua, Stella Aslibekyan, Marguerite R Irvin, Edmond K Kabagambe, Donna K Arnett, Majken K Jensen, Barbara McKnight, Bruce M Psaty, Lyn M Steffen, Caren E Smith, Ulf Risérus, Lars Lind, Frank B Hu, Eric B Rimm, David S Siscovick, Dariush Mozaffarian
BACKGROUND: Odd-numbered chain saturated fatty acids (OCSFA) have been associated with potential health benefits. Although some OCSFA (e.g., C15:0 and C17:0) are found in meats and dairy products, sources and metabolism of C19:0 and C23:0 are relatively unknown, and the influence of non-dietary determinants, including genetic factors, on circulating levels of OCSFA is not established. OBJECTIVE: To elucidate the biological processes that influence circulating levels of OCSFA by investigating associations between genetic variation and OCSFA...
2018: PloS One
https://www.readbyqxmd.com/read/29720183/disrupted-sphingolipid-metabolism-following-acute-clozapine-and-olanzapine-administration
#3
Katrina Weston-Green, Ilijana Babic, Michael de Santis, Bo Pan, Magdalene K Montgomery, Todd Mitchell, Xu-Feng Huang, Jessica Nealon
BACKGROUND: Second generation antipsychotics (SGAs) induce glucometabolic side-effects, such as hyperglycemia and insulin resistance, which pose a therapeutic challenge for mental illness. Sphingolipids play a role in glycaemic balance and insulin resistance. Endoplasmic reticulum (ER) stress contributes to impaired insulin signalling and whole-body glucose intolerance. Diabetogenic SGA effects on ER stress and sphingolipids, such as ceramide and sphingomyelin, in peripheral metabolic tissues are unknown...
May 2, 2018: Journal of Biomedical Science
https://www.readbyqxmd.com/read/29627573/regulation-of-glucosylceramide-synthesis-by-golgi-localized-phosphoinositide
#4
Yohei Ishibashi, Makoto Ito, Yoshio Hirabayashi
Phosphoinositides mediate a large number of signaling processes in mammalian cells. Here, we report that phophatidylinositol-4-phosphate (PtdIns(4)P) downregulates the cellular glucosylceramide (GlcCer) level by inhibiting the interaction between GlcCer synthase (UGCG) and UDP-glucose in the Golgi apparatus. In this study, we used two PH domain probes to bind phosphoinositides; one derived from FAPP1 for targeting to the Golgi PtdIns(4)P and the other from PLC δ for targeting to the plasma membrane PtdIns(4,5)P2 ...
April 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29567647/increased-liver-tumor-formation-in-neutral-sphingomyelinase-2-deficient-mice
#5
Liansheng Zhong, Ji Na Kong, Michael B Dinkins, Silvia Leanhart, Zhihui Zhu, Stefka D Spassieva, Haiyan Qin, Hsuan-Pei Lin, Ahmed Elsherbini, Rebecca R Wang, Xue Jiang, Mariana Nikolova-Karakashian, Guanghu Wang, Erhard Bieberich
Sphingolipids are key signaling lipids in cancer. Genome-wide studies have identified neutral sphingomyelinase-2 (nSMase2), an enzyme generating ceramide from sphingomyelin (SM), as a potential repressor for heptocellular carcinoma. However, little is known about the sphingolipids regulated by nSMase2 and their roles in liver tumor development. We discovered growth of spontaneous liver tumors in 27.3% (9 of 33) of aged male nSMase2-deficient (fro/fro) mice. Lipidomics analysis showed marked increase of SM in the tumor...
March 22, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29533737/bcr-abl-regulation-of-sphingomyelin-synthase-1-reveals-a-novel-oncogenic-driven-mechanism-of-protein-up-regulation
#6
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
https://www.readbyqxmd.com/read/29496449/effect-of-tamoxifen-on-the-sphingolipid-biosynthetic-pathway-in-the-different-intraerythrocytic-stages-of-the-apicomplexa-plasmodium-falciparum
#7
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...
March 18, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29454087/multi-step-splicing-of-sphingomyelin-synthase-linear-and-circular-rnas
#8
Ivan B Filippenkov, Olga Yu Sudarkina, Svetlana A Limborska, Lyudmila V Dergunova
The SGMS1 gene encodes the enzyme sphingomyelin synthase 1 (SMS1), which is involved in the regulation of lipid metabolism, apoptosis, intracellular vesicular transport and other significant processes. The SGMS1 gene is located on chromosome 10 and has a size of 320 kb. Previously, we showed that dozens of alternative transcripts of the SGMS1 gene are present in various human tissues. In addition to mRNAs that provide synthesis of the SMS1 protein, this gene participates in the synthesis of non-coding transcripts, including circular RNAs (circRNAs), which include exons of the 5'-untranslated region (5'-UTR) and are highly represented in the brain...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29375716/sphingomyelin-synthase-2-overexpression-promotes-cisplatin-induced-apoptosis-of-hepg2-cells
#9
Si Luo, Zhen Pan, Shuang Liu, Shujing Yuan, Nianlong Yan
Hepatoblastoma (HB) is the most type of common pediatric liver cancer. The primary chemotherapy drug for HB is cisplatin (DDP). However, patients readily develop intrinsic and acquired resistance, and severe side effects to treatment. Sphingomyelin synthase 2 (SMS2) is a key enzyme involved in the generation of sphingomyelin (SM), which is able to regulate cell proliferation, apoptosis and differentiation. The death receptors (DRs) have important functions in DDP-induced apoptosis. However, whether SMS2 is able to modulate cell apoptosis through the DR signaling pathway remains unknown...
January 2018: Oncology Letters
https://www.readbyqxmd.com/read/29345004/epidermal-permeability-barrier-function-and-sphingolipid-content-in-the-skin-of-sphingomyelin-synthase-2-deficient-mice
#10
Koji Nomoto, Yurina Itaya, Ken Watanabe, Tadashi Yamashita, Toshiro Okazaki, Yoshihiro Tokudome
BACKGROUND: Sphingomyelin synthase (SMS) is an enzyme that generates sphingomyelin (SM) from ceramide (CER) and phosphatidylcholine. SM in the epidermis is a precursor of CER, an important lipid for epidermal permeability barrier function. However, the physiological role of SMS in skin is unclear. OBJECTIVES: To uncover the function of SMS in skin, we investigated sphingolipid metabolism enzyme activity in skin, SM content in the epidermis, CER content in the stratum corneum (SC) and transepidermal water loss (TEWL) as an indicator of barrier function in SMS2-knockout (KO) mice...
January 17, 2018: Experimental Dermatology
https://www.readbyqxmd.com/read/29329781/dopamine-transporter-trafficking-is-regulated-by-neutral-sphingomyelinase-2-ceramide-kinase
#11
Jong Hoon Won, Seok Kyun Kim, In Chul Shin, Hae Chan Ha, Ji Min Jang, Moon Jung Back, Dae Kyong Kim
Dopamine (DA) reuptake is the primary mechanism to terminate dopaminergic transmission in the synaptic cleft. The dopamine transporter (DAT) has an important role in the regulation of DA reuptake. This study provides anatomical and physiological evidence that DAT recycling is regulated by ceramide kinase via the sphingomyelin pathway. First, the results show that DAT and neutral sphingomyelinase 2 (nSMase2) were successfully co-precipitated from striatal samples and were colocalized in the mouse striatum or PC12 cells...
April 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29285103/effects-of-sepsis-on-the-metabolism-of-sphingomyelin-and-cholesterol-in-mice-with-liver-dysfunction
#12
Jiaqi Li, Kun Xia, Mingdi Xiong, Xi Wang, Nianlong Yan
Sepsis is characterized by a severe inflammatory response to infection. With the spread of sepsis, various tissues, including the lungs, liver and kidney, may be damaged. This may finally develop into multiple organ dysfunction syndrome. Sphingomyelin and cholesterol are two main lipids involved in sepsis. The metabolism of sphingomyelin and cholesterol in the livers of mice with sepsis needs to be clarified. To achieve this, the present study intraperitoneally injected mice with PBS, lipopolysaccharide (LPS; 10 mg/kg) and LPS + pyrrolidine dithiocarbamate (PDTC; 30 mg/kg)...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29128370/the-inhibition-of-sphingomyelin-synthase-1-activity-induces-collecting-duct-cells-to-lose-their-epithelial-phenotype
#13
Yamila Romina Brandán, Edith Del Valle Guaytima, Nicolás Octavio Favale, Lucila Gisele Pescio, Norma B Sterin-Speziale, María Gabriela Márquez
Epithelial tissue requires that cells attach to each other and to the extracellular matrix by the assembly of adherens junctions (AJ) and focal adhesions (FA) respectively. We have previously shown that, in renal papillary collecting duct (CD) cells, both AJ and FA are located in sphingomyelin (SM)-enriched plasma membrane microdomains. In the present work, we investigated the involvement of SM metabolism in the preservation of the epithelial cell phenotype and tissue organization. To this end, primary cultures of renal papillary CD cells were performed...
February 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28988346/lipid-environment-induces-er-stress-txnip-expression-and-inflammation-in-immune-cells-of-individuals-with-type-2-diabetes
#14
Anaïs Szpigel, Isabelle Hainault, Aurélie Carlier, Nicolas Venteclef, Anne-Françoise Batto, Eric Hajduch, Catherine Bernard, Alain Ktorza, Jean-François Gautier, Pascal Ferré, Olivier Bourron, Fabienne Foufelle
AIMS/HYPOTHESIS: Obesity and type 2 diabetes are concomitant with low-grade inflammation affecting insulin sensitivity and insulin secretion. Recently, the thioredoxin interacting protein (TXNIP) has been implicated in the activation process of the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. In this study, we aim to determine whether the expression of TXNIP is altered in the circulating immune cells of individuals with type 2 vs type 1 diabetes and whether this can be related to specific causes and consequences of inflammation...
February 2018: Diabetologia
https://www.readbyqxmd.com/read/28864659/a-novel-role-for-ceramide-synthase-6-in-mouse-and-human-alcoholic-steatosis
#15
Bianca Williams, Jason Correnti, Amanke Oranu, Annie Lin, Victoria Scott, Maxine Annoh, James Beck, Emma Furth, Victoria Mitchell, Can E Senkal, Lina Obeid, Rotonya M Carr
Perilipin 2 (PLIN2) is a lipid-droplet protein that is up-regulated in alcoholic steatosis and associated with hepatic accumulation of ceramides, bioactive lipids implicated in alcoholic liver disease pathogenesis. The specific role of ceramide synthetic enzymes in the regulation of PLIN2 and promotion of hepatocellular lipid accumulation is not well understood. We examined the effects of pharmacologic ceramide synthesis inhibition on hepatic PLIN2 expression, steatosis, and glucose and lipid homeostasis in mice with alcoholic steatosis and in ethanol-incubated human hepatoma VL17A cells...
January 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28742512/the-sphingomyelin-synthase-family-proteins-diseases-and-inhibitors
#16
REVIEW
Yang Chen, Yu Cao
Sphingomyelin (SM) is among the most important biomolecules in eukaryotes and acts as both constructive components and signal carrier in physiological processes. SM is catalyzed by a membrane protein family, sphingomyelin synthases (SMSs), consisting of three members, SMS1, SMS2 and SMSr. SMSs modulate sphingomyelin and other sphingolipids levels, thereby regulating membrane mobility, ceramide-dependent apoptosis and DAG-dependent signaling pathways. SMSs was found associated with various diseases. Downregulation of SMS2 activity results in protective effects against obesity, atherosclerosis and diabetes and makes SMS2 inhibitors potential medicines...
November 27, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28619536/discovery-of-the-selective-sphingomyelin-synthase-2-inhibitors-with-the-novel-structure-of-oxazolopyridine
#17
Xiang-Yu Qi, Yang Cao, Ya-Li Li, Ming-Guang Mo, Lu Zhou, De-Yong Ye
Sphingomyelin synthase (SMS) is a key enzyme in sphingomyelin biosynthetic pathway, whose activity is highly related to the atherosclerosis progression. SMS2 could serve as a promising therapeutic target for atherosclerosis. Based on the structure of lead compound D2, a series of oxazolopyridine derivatives were designed, synthesized, and their inhibitory activities against purified SMS1 and SMS2 enzymes were evaluated respectively. The representative molecules QY4 and QY16 possess micromolar inhibitory activities against SMS2 and excellent isoform preferences over SMS1, qualified to be selected as potential molecules in further discovery of specific SMS2 inhibitors...
August 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28586047/identification-and-functional-analysis-of-the-risk-micrornas-associated-with-cerebral-low-grade-glioma-prognosis
#18
Xinrui Liu, Bin Song, Shanji Li, Nan Wang, Hongfa Yang
Low-grade gliomas (LGGs) are associated with neurological disability. The present study used microRNA (miRNA) expression profiles to identify risk miRNAs for potential prognosis of cerebral LGGs. miRNA expression profiles and clinical data from 408 patients with cerebral LGGs were obtained from the Cancer Genome Atlas database. Risk miRNAs were identified by plotting Kaplan‑Meier curves and Cox proportional hazard regression analysis with the survival and KMsurv packages in R. A regulatory network of miRNA‑targets was constructed, followed by gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using the Database for Annotation, Visualization and Integrated Discovery...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28522594/sphingomyelin-synthase-2-deficiency-inhibits-the-induction-of-murine-colitis-associated-colon-cancer
#19
Toshio Ohnishi, Chieko Hashizume, Makoto Taniguchi, Hidehiro Furumoto, Jia Han, Rongfen Gao, Shinichi Kinami, Takeo Kosaka, Toshiro Okazaki
Sphingomyelin synthase 2 (SMS2) is the synthetic enzyme of sphingomyelin (SM), which regulates membrane fluidity and microdomain structure. SMS2 plays a role in LPS-induced lung injury and inflammation; however, its role in inflammation-mediated tumorigenesis is unclear. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)-induced murine colitis and found inhibition of DSS-induced inflammation in SMS2-deficient (SMS2-/- ) mice. DSS treatment induced a significant increase in ceramide levels, with a decrease of SM levels in SMS2-/- colon tissue, and demonstrated attenuation of the elevation of both inflammation-related gene expression and proinflammatory cytokines and chemokines, leukocyte infiltration, and MAPK and signal transducer and activator of transcription 3 activation...
September 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28515139/changes-in-ceramide-metabolism-are-essential-in-madin-darby-canine-kidney-cell-differentiation
#20
Lucila Gisele Pescio, Bruno Jaime Santacreu, Vanina Gisela Lopez, Carlos Humberto Paván, Daniela Judith Romero, Nicolás Octavio Favale, Norma Beatriz Sterin-Speziale
Ceramides (Cers) and complex sphingolipids with defined acyl chain lengths play important roles in numerous cell processes. Six Cer synthase (CerS) isoenzymes (CerS1-6) are the key enzymes responsible for the production of the diversity of molecular species. In this study, we investigated the changes in sphingolipid metabolism during the differentiation of Madin-Darby canine kidney (MDCK) cells. By MALDI TOF TOF MS, we analyzed the molecular species of Cer, glucosylceramide (GlcCer), lactosylceramide (LacCer), and SM in nondifferentiated and differentiated cells (cultured under hypertonicity)...
July 2017: Journal of Lipid Research
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