keyword
MENU ▼
Read by QxMD icon Read
search

Sphingomyelin synthase 2

keyword
https://www.readbyqxmd.com/read/29872506/preclinical-evaluation-of-novel-fatty-acid-synthase-inhibitors-in-primary-colorectal-cancer-cells-and-a-patient-derived-xenograft-model-of-colorectal-cancer
#1
Yekaterina Y Zaytseva, Piotr G Rychahou, Anh-Thu Le, Timothy L Scott, Robert M Flight, Ji Tae Kim, Jennifer Harris, Jinpeng Liu, Chi Wang, Andrew J Morris, Theru A Sivakumaran, Teresa Fan, Hunter Moseley, Tianyan Gao, Eun Y Lee, Heidi L Weiss, Timothy S Heuer, George Kemble, Mark Evers
Fatty Acid Synthase (FASN), a key enzyme of de novo lipogenesis, is upregulated in many cancers including colorectal cancer (CRC); increased FASN expression is associated with poor prognosis. Potent FASN inhibitors (TVBs) developed by 3-V Biosciences demonstrate anti-tumor activity in vitro and in vivo and a favorable tolerability profile in a Phase I clinical trial. However, CRC characteristics associated with responsiveness to FASN inhibition are not fully understood. We evaluated the effect of TVB-3664 on tumor growth in nine CRC patient-derived xenografts (PDXs) and investigated molecular and metabolic changes associated with CRC responsiveness to FASN inhibition...
May 15, 2018: Oncotarget
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
#2
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
#3
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
#4
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/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 Wang, Xue Jiang, Mariana Nikolova-Karakashian, Guanghu Wang, Erhard Bieberich
Sphingolipids are key signaling lipids in cancer. Genome-wide studies have identified neutral SMase-2 (nSMase2), an enzyme generating ceramide from SM, as a potential repressor for hepatocellular 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 a marked increase of SM in the tumor. Unexpectedly, tumor tissues presented with more than a 7-fold increase of C16 -ceramide, concurrent with upregulation of ceramide synthase 5...
May 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/29375716/sphingomyelin-synthase-2-overexpression-promotes-cisplatin-induced-apoptosis-of-hepg2-cells
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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/28619536/discovery-of-the-selective-sphingomyelin-synthase-2-inhibitors-with-the-novel-structure-of-oxazolopyridine
#14
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/28522594/sphingomyelin-synthase-2-deficiency-inhibits-the-induction-of-murine-colitis-associated-colon-cancer
#15
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/28505533/discovery-and-characterization-of-selective-human-sphingomyelin-synthase-2-inhibitors
#16
Ryutaro Adachi, Kazumasa Ogawa, Shin-Ichi Matsumoto, Takuya Satou, Yukiya Tanaka, Jyunichi Sakamoto, Takashi Nakahata, Rei Okamoto, Masahiro Kamaura, Tomohiro Kawamoto
Sphingomyelin synthase (SMS) is a membrane enzyme that catalyzes the synthesis of sphingomyelin, is required for the maintenance of plasma membrane microdomain fluidity, and has two isoforms: SMS1 and SMS2. Although these isoforms exhibit the same SMS activity, they are different enzymes with distinguishable subcellular localizations. It was reported that SMS2 KO mice displayed lower inflammatory responses and anti-atherosclerotic effects, suggesting that inhibition of SMS2 would be a potential therapeutic approach for controlling inflammatory responses and atherosclerosis...
August 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28087695/novel-interconnections-in-lipid-metabolism-revealed-by-overexpression-of-sphingomyelin-synthase-1
#17
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 fewer triacylglycerols than controls but similar diacylglycerol acyltransferase activity, triacylglycerol secretion, and mitochondrial function...
March 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28078595/method-to-measure-sphingomyelin-synthase-activity-changes-in-response-to-cd95l
#18
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
#19
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...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27991764/high-throughput-lipidomic-and-transcriptomic-analysis-to-compare-sp2-0-cho-and-hek-293-mammalian-cell-lines
#20
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 that phosphatidylethanolamine (PE) and phosphatidylcholine (PC) were the major lipid components in all cell lines with lower amounts of sphingomyelin (SM) in SP2/0 compared to CHO and HEK, which was subsequently confirmed and expanded upon following mass spectrometry (MS) analysis...
February 7, 2017: Analytical Chemistry
keyword
keyword
7225
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"