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Sphingosine-1-phosphate

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https://www.readbyqxmd.com/read/29673590/the-cross-roles-of-sphingosine-kinase-1-2-and-ceramide-glucosyltransferase-in-cell-growth-and-death
#1
Jingdong Qin, John P Kilkus, Glyn Dawson
Sphingosine-1-phosphate is synthesized by two sphingosine kinases, cytosolic SK1 and nuclear SK2 but SK2 expression was much higher than SK1in mouse skin fibroblasts. However, in SK2-/- cells, SK1 expression was markedly increased to SK2 levels whereas in SK1-/- cells, SK2 expression was unaffected. Ceramide, glucosylceramide and sphingosine levels were all increased in SK1-/- but less so in SK2-/- cells and S1P levels were not significantly reduced in either SK1-/- or SK2-/- cells. Greatly increased Ceramide glucosyltransferase expression was observed in SK1-/- cells but less so in SK2-/- cells suggested a role in drug resistance...
April 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29673037/sphingosine-1-phosphate-selectively-activates-vagal-afferent-c-fiber-subtype-in-guinea-pig-esophagus
#2
X Yu, M J Patil, M Yu, Y Liu, J Wang, B J Undem, S Yu
BACKGROUND: Activation and sensitization of visceral afferent nerves by inflammatory mediators play important roles in visceral nociception. Sphingosine-1-phosphate (S1P) is a lipid with intracellular and extracellular functions. Extracellularly, it can act as an autacoid via interactions with S1P receptors. The present study aims to determine the effect of S1P on esophageal vagal afferent nerve functions. METHODS: Extracellular single-unit recordings were performed in ex vivo guinea pig esophageal-vagal preparations...
April 19, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29669385/apolipoprotein-m-protects-lipopolysaccharide-treated-mice-from-death-and-organ-injury
#3
Makoto Kurano, Koichi Tsuneyama, Yuki Morimoto, Tomo Shimizu, Masahiro Jona, Hidetoshi Kassai, Kazuki Nakao, Atsu Aiba, Yutaka Yatomi
OBJECTIVE:  High-density lipoprotein (HDL) has been epidemiologically shown to be associated with the outcome of sepsis. One potential mechanism is that HDL possesses pleiotropic effects, such as anti-apoptosis, some of which can be ascribed to sphingosine 1-phosphate (S1P) carried on HDL via apolipoprotein M (apoM). Therefore, the aim of this study was to elucidate the roles of apoM/S1P in the consequent lethal conditions of sepsis, such as multiple organ failure caused by severe inflammation and/or disseminated intravascular coagulation...
April 18, 2018: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29663386/decreased-serum-levels-of-sphingomyelins-and-ceramides-in-sickle-cell-disease-patients
#4
Mutay Aslan, Ebru Kıraç, Sabriye Kaya, Filiz Özcan, Ozan Salim, Osman Alphan Küpesiz
Limited data are available on the serum levels of different sphingomyelin (CerPCho) and ceramide (CER) species in sickle-cell disease (SCD). This study was aimed at identifying the levels of C16-C24 CerPCho and C16-C24 CER in serum obtained from SCD patients and controls. Circulating levels of neutral sphingomyelinase (N-SMase) activity, ceramide-1-phosphate (C1P), and sphingosine-1-phosphate (S1P) were also determined. Blood was collected from 35 hemoglobin (Hb)A volunteers and 45 homozygous HbSS patients...
April 16, 2018: Lipids
https://www.readbyqxmd.com/read/29662200/targeting-sphingosine-1-phosphate-lyase-as-an-anabolic-therapy-for-bone-loss
#5
Sarah Weske, Mithila Vaidya, Alina Reese, Karin von Wnuck Lipinski, Petra Keul, Julia K Bayer, Jens W Fischer, Ulrich Flögel, Jens Nelsen, Matthias Epple, Marta Scatena, Edzard Schwedhelm, Marcus Dörr, Henry Völzke, Eileen Moritz, Anke Hannemann, Bernhard H Rauch, Markus H Gräler, Gerd Heusch, Bodo Levkau
Sphingosine-1-phosphate (S1P) signaling influences bone metabolism, but its therapeutic potential in bone disorders has remained unexplored. We show that raising S1P levels in adult mice through conditionally deleting or pharmacologically inhibiting S1P lyase, the sole enzyme responsible for irreversibly degrading S1P, markedly increased bone formation, mass and strength and substantially decreased white adipose tissue. S1P signaling through S1P2 potently stimulated osteoblastogenesis at the expense of adipogenesis by inversely regulating osterix and PPAR-γ, and it simultaneously inhibited osteoclastogenesis by inducing osteoprotegerin through newly discovered p38-GSK3β-β-catenin and WNT5A-LRP5 pathways...
April 16, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29662189/akt-as-a-key-target-for-growth-promoting-functions-of-neutral-ceramidase-in-colon-cancer-cells
#6
Nicolas Coant, Mónica García-Barros, Qifeng Zhang, Lina M Obeid, Yusuf A Hannun
Despite advances in the field, colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Research into bioactive sphingolipids over the past two decades has played an important role in increasing our understanding of the pathogenesis and therapeutics of CRC. In the complex metabolic network of sphingolipids, ceramidases (CDases) have a key function. These enzymes hydrolyze ceramides into sphingosine (SPH) which in turn is phosphorylated by sphingosine kinases (SK) 1 and 2 to generate sphingosine-1 phosphate (S1P)...
April 17, 2018: Oncogene
https://www.readbyqxmd.com/read/29660940/age-dependent-changes-to-sphingolipid-balance-in-the-human-hippocampus-are-gender-specific-and-may-sensitize-to-neurodegeneration
#7
Timothy A Couttas, Nupur Kain, Collin Tran, Zac Chatterton, John B Kwok, Anthony S Don
The greatest risk factor for developing Alzheimer's disease (AD) is aging. The major genetic risk factor for AD is the ɛ4 allele of the APOE gene, encoding the brain's major lipid transport protein, apolipoprotein E (ApoE). The research community is yet to decipher why the ApoE4 variant pre-disposes to AD, and how aging causes the disease. Studies have shown deregulated levels of sphingolipids, including decreased levels of the neuroprotective signaling lipid sphingosine 1-phosphate (S1P), and increased ceramide content, in brain tissue and serum of people with pre-clinical or very early AD...
April 11, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29658313/metabonomic-analysis-of-toxic-action-of-long-term-low-level-exposure-to-acrylamide-in-rat-serum
#8
C Cao, H Shi, M Zhang, L Bo, L Hu, S Li, S Chen, S Jia, Y J Liu, Y L Liu, X Zhao, L Zhang
This study assessed the effects of long-term, low-dose acrylamide (AA) administration in rats using ultra-performance liquid chromatography-mass spectrometry. Forty male Wistar rats were randomly divided into the following four groups: control, low-dose AA (0.2 mg/kg BW), middle-dose AA (1 mg/kg BW), and high-dose AA (5 mg/kg BW). AA was administered to rats via drinking water ad libitum. After 16-week treatment, rat serum was collected for metabonomic analysis. Biochemical tests were further conducted to verify metabolic alterations...
January 1, 2018: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29658075/induced-pluripotent-stem-cell-derived-hematopoietic-embryoid-bodies-secrete-sphingosine-1-phosphate-and-revert-endothelial-injury
#9
S Kasuda, R Kudo, K Yuui, Y Sakurai, K Hatake
The possibility of sphingosine-1-phosphate production by induced pluripotent stem cells is examined to assess their potential in treatment of sepsis. The hematopoietic embryoid bodies were derived from the culture of 6-day-old differentiated induced pluripotent stem cells. These embryoid bodies secreted sphingosine-1-phosphate, an important bioactive lipid that regulates integrity of the pulmonary endothelial barrier, prevents elevation of its permeability, and impedes the formation of stress fibers in human endotheliocytes derived from umbilical vein...
April 16, 2018: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29656444/predicting-therapeutic-response-to-fingolimod-treatment-in-multiple-sclerosis-patients
#10
Bibiana Quirant-Sánchez, José V Hervás-García, Aina Teniente-Serra, Luis Brieva, Ester Moral-Torres, Antonio Cano, Elvira Munteis, María J Mansilla, Silvia Presas-Rodriguez, Juan Navarro-Barriuso, Cristina Ramo-Tello, Eva M Martínez-Cáceres
AIMS: Fingolimod, an orally active immunomodulatory drug for relapsing-remitting multiple sclerosis (RRMS), sequesters T cells in lymph nodes through functional antagonism of the sphingosine-1-phosphate receptor, reducing the number of potential autoreactive cells that migrate to the central nervous system. However, not all RRMS patients respond to this therapy. Our aim was to test the hypothesis that by immune-monitoring RRMS patient's leukocyte subpopulations it is possible to find biomarkers associated with clinical response to fingolimod...
April 15, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29643998/deletion-of-sphingosine-kinase-1-inhibits-liver-tumorigenesis-in-diethylnitrosamine-treated-mice
#11
Jinbiao Chen, Yanfei Qi, Yang Zhao, Dominik Kaczorowski, Timothy A Couttas, Paul R Coleman, Anthony S Don, Patrick Bertolino, Jennifer R Gamble, Mathew A Vadas, Pu Xia, Geoffrey W McCaughan
Primary liver cancer is the 3rd leading cause of cancer deaths worldwide with very few effective treatments. Sphingosine kinase 1 (SphK1), a key regulator of sphingolipid metabolites, is over-expressed in human hepatocellular carcinoma (HCC) and our previous studies have shown that SphK1 is important in liver injury. We aimed to explore the role of SphK1 specifically in liver tumorigenesis using the SphK1 knockout ( SphK1 -/- ) mouse. SphK1 deletion significantly reduced the number and the size of DEN-induced liver cancers in mice...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29643855/targeting-sphingosine-kinase-isoforms-effectively-reduces-growth-and-survival-of-neoplastic-mast-cells-with-d816v-kit
#12
Geethani Bandara, Rosa Muñoz-Cano, Araceli Tobío, Yuzhi Yin, Hirsh D Komarow, Avanti Desai, Dean D Metcalfe, Ana Olivera
Mastocytosis is a disorder resulting from an abnormal mast cell (MC) accumulation in tissues that is often associated with the D816V mutation in KIT, the tyrosine kinase receptor for stem cell factor. Therapies available to treat aggressive presentations of mastocytosis are limited, thus exploration of novel pharmacological targets that reduce MC burden is desirable. Since increased generation of the lipid mediator sphingosine-1-phosphate (S1P) by sphingosine kinase (SPHK) has been linked to oncogenesis, we studied the involvement of the two SPHK isoforms (SPHK1 and SPHK2) in the regulation of neoplastic human MC growth...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29627873/disease-modifying-treatment-in-progressive-multiple-sclerosis
#13
REVIEW
John Robert Ciotti, Anne Haney Cross
PURPOSE OF REVIEW: Multiple sclerosis (MS) is an immune-mediated disorder that affects the central nervous system (CNS), often first affecting people in early adulthood. Although most MS patients have a relapsing-remitting course (RRMS) at disease onset, a substantial proportion later develop chronic progression, termed secondary progressive MS (SPMS). Approximately 10% of MS patients experience chronic progression from disease onset, termed primary progressive multiple sclerosis (PPMS)...
April 7, 2018: Current Treatment Options in Neurology
https://www.readbyqxmd.com/read/29624923/neutrophil-elastase-correlates-with-increased-sphingolipid-content-in-cystic-fibrosis-sputum
#14
Sophia Karandashova, Apparao Kummarapurugu, Shuo Zheng, Le Kang, Shumei Sun, Bruce K Rubin, Judith A Voynow
INTRODUCTION: Sphingolipids are associated with the regulation of pulmonary inflammation. Although sphingolipids have been investigated in the context of cystic fibrosis (CF), the focus has been on loss of CF transmembrane conductance regulator (CFTR) function in mice, and in CF human lung epithelial cell lines. The sphingolipid content of CF sputum and the potential link between ceramide and airway inflammation in CF remain relatively unexplored. METHODS: Fifteen patients with CF provided two spontaneously expectorated sputum samples, one collected during a hospitalization for an acute pulmonary exacerbation and one from an outpatient visit at a time of clinical stability...
April 6, 2018: Pediatric Pulmonology
https://www.readbyqxmd.com/read/29624476/immunotherapy-in-inflammatory-bowel-disease-novel-and-emerging-treatments
#15
Ignacio Catalan-Serra, Øystein Brenna
Inflammatory bowel disease (IBD) is a chronic disabling inflammatory process that affects young individuals, with growing incidence. The etiopathogenesis of IBD remains poorly understood. A combination of genetic and environmental factors triggers an inadequate immune response against the commensal intestinal flora in IBD patients. Thus, a better understanding of the immunological mechanisms involved in IBD pathogenesis is central to the development of new therapeutic options. Current pharmacological treatments used in clinical practice like thiopurines or anti-TNF are effective but can produce significant side effects and their efficacy may diminish over time...
April 6, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29623953/erratum-extracellular-%C3%AE-synuclein-induces-sphingosine-1-phosphate-receptor-subtype-1-uncoupled-from-inhibitory-g-protein-leaving-%C3%AE-arrestin-signal-intact
#16
Lifang Zhang, Taro Okada, Shaymaa Mohamed Mohamed Badawy, Chihoko Hirai, Taketoshi Kajimoto, Shun-Ichi Nakamura
This corrects the article DOI: 10.1038/srep44248.
April 6, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29623068/nuclear-insulin-like-growth-factor-binding-protein-3-as-a-biomarker-in-triple-negative-breast-cancer-xenograft-tumors-effect-of-targeted-therapy-and-comparison-with-chemotherapy
#17
Sohel M Julovi, Janet L Martin, Robert C Baxter
Triple-negative breast cancer (TNBC) typically has a worse outcome than other breast cancer subtypes, in part owing to a lack of approved therapeutic targets or prognostic markers. We have previously described an oncogenic pathway in basal-like TNBC cells, initiated by insulin-like growth factor binding protein-3 (IGFBP-3), in which the epidermal growth factor receptor (EGFR) is transactivated by sphingosine-1-phosphate (S1P) resulting from sphingosine kinase (SphK)-1 activation. Oncogenic IGFBP-3 signaling can be targeted by combination treatment with the S1P receptor modulator and SphK inhibitor, fingolimod, and the EGFR kinase inhibitor, gefitinib (F + G)...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29620575/sphingosine-1-phosphate-receptor-2-signaling-promotes-caspase-11-dependent-macrophage-pyroptosis-and-worsens-escherichia-coli-sepsis-outcome
#18
Fang Song, Jinchao Hou, Zhecong Chen, Baoli Cheng, Ruyi Lei, Ping Cui, Yaqi Sun, Haihong Wang, Xiangming Fang
BACKGROUND: Pyroptosis, a type of proinflammatory programmed cell death, drives cytokine storm. Caspase-11-dependent macrophage pyroptosis contributes to mortality during sepsis. Sphingosine-1-phosphate receptor 2 (S1PR2) signaling can amplify interleukin-1β secretion in endotoxin-induced inflammation. Here, we hypothesized that S1PR2 signaling increases caspase-11-dependent macrophage pyroptosis and worsens Gram-negative sepsis outcome. METHODS: A Gram-negative sepsis model was induced through intraperitoneal injection of Escherichia coli...
April 3, 2018: Anesthesiology
https://www.readbyqxmd.com/read/29618748/fingolimod-therapy-is-not-effective-in-a-mouse-model-of-spontaneous-autoimmune-peripheral-polyneuropathy
#19
Petra Huehnchen, Wolfgang Boehmerle, Matthias Endres
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disorder, which causes progressive sensory and motor deficits and often results in severe disability. Knockout of the co-stimulatory protein CD86 in mice of the non-obese diabetic background (NoD.129S4-Cd86tm1Shr /JbsJ) results in the development of a spontaneous autoimmune peripheral polyneuropathy (SAPP). We used this previously described transgenic model to study the effects of the sphingosine-1-phosphate receptor agonist fingolimod on SAPP symptoms, functional and electrophysiological characteristics...
April 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29615404/the-tumor-suppressive-tgf-%C3%AE-smad1-s1pr2-signaling-axis-is-recurrently-inactivated-in-diffuse-large-b-cell-lymphoma
#20
Anna Stelling, Hind Hashwah, Katrin Bertram, Markus G Manz, Alexandar Tzankov, Anne Müller
The sphingosine-1-phosphate receptor S1PR2 and its downstream signaling pathway is commonly silenced in diffuse large B-cell lymphoma (DLBCL), either by mutational inactivation or through negative regulation by the oncogenic transcription factor FOXP1. In this study, we have examined the upstream regulators of S1PR2 expression and have newly identified the TGF-β/TGF-βR2/SMAD1 axis as critically involved in S1PR2 transcriptional activation. Phosphorylated SMAD1 directly binds to regulatory elements in the S1PR2 locus as assessed by chromatin immunoprecipitation, and the CRISPR-mediated genomic editing of S1PR2 , SMAD1 or TGFBR2 in DLBCL cell lines renders cells unresponsive to TGF-β-induced apoptosis...
April 3, 2018: Blood
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