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https://www.readbyqxmd.com/read/28315304/sphingosine-1-phosphate-a-double-edged-sword-in-the-brain
#1
REVIEW
Indulekha Karunakaran, Gerhild van Echten-Deckert
The physiological functions of sphingosine 1-phosphate (S1P) and its pathological roles in various diseases are increasingly being elucidated. Particularly, a growing body of literature has implicated S1P in the pathogenesis of brain related disorders. With the deciphering of more intricate aspects of S1P signalling, there is also a need to reconsider the notion of S1P only as a determinant of cell survival and proliferation. Further the concept of 'S1P-ceramide' balance as the controlling switch of cellular fate and functions needs to be refined...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28302566/mechanisms-of-sphingosine-1-phosphate-receptor-signalling-in-cancer
#2
REVIEW
Sathya Narayanan Patmanathan, Wei Wang, Lee Fah Yap, Deron R Herr, Ian C Paterson
S1P is a small bioactive lipid which exerts its effects following binding to a family of five G protein-coupled receptors, known as S1P1-5. Following receptor activation, multiple signalling cascades are activated, allowing S1P to regulate a range of cellular processes, such as proliferation, apoptosis, migration and angiogenesis. There is strong evidence implicating the involvement of S1P receptors (S1PRs) in cancer progression and the oncogenic effects of S1P can result from alterations in the expression of one or more of the S1PRs and/or the enzymes that regulate the levels of S1P...
March 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28302479/mir-126-impairs-the-intestinal-barrier-function-via-inhibiting-s1pr2-mediated-activation-of-pi3k-akt-signaling-pathway
#3
Tanzhou Chen, Haibo Xue, Ruoyang Lin, Zhiming Huang
BACKGROUND: Aberrant expression of miRNAs was a critical element in the pathogenesis of inflammatory bowel disease (IBD). This study aimed to explore the involvement and mechanism of miR-126 in IBD. METHODS: In this study, the endogenous expressions of miR-126, S1PR2 and S1P in the pathological tissues of patients with IBD were detected using qRT-PCR and western blot assay, respectively. The luciferase reporter gene assay was performed to confirm the targeting regulatory relation between miR-126 and S1PR2...
March 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28300788/protective-effect-of-protocatechuic-acid-on-tnbs-induced-colitis-in-mice-is-associated-with-modulation-of-the-sphk-s1p-signaling-pathway
#4
Irene Crespo, Beatriz San-Miguel, José Luis Mauriz, Juan José Ortiz de Urbina, Mar Almar, María Jesús Tuñón, Javier González-Gallego
(1) Background: The present study aimed to investigate whether beneficial effects of protocatechuic acid (PCA) are associated with inhibition of the SphK/S1P axis and related signaling pathways in a 2,4,6-trinitrobenzenesulfonic acid (TNBS) model of inflammatory bowel disease; (2) Methods: Colitis was induced in male Balb/c mice by intracolonic administration of 2 mg of TNBS. PCA (30 or 60 mg/kg body wt) was given intraperitoneally daily for five days; (3) Results: Administration of PCA prevented the macroscopic and microscopic damage to the colonic mucosa, the decrease in body weight gain and the increase in myeloperoxidase activity induced by TNBS...
March 16, 2017: Nutrients
https://www.readbyqxmd.com/read/28300348/sphingosine-1-phosphate-induces-ca-2-signaling-and-cxcl1-release-via-trpc6-channel-in-astrocytes
#5
Hisashi Shirakawa, Rumi Katsumoto, Shota Iida, Takahito Miyake, Takuya Higuchi, Takuya Nagashima, Kazuki Nagayasu, Takayuki Nakagawa, Shuji Kaneko
A biologically active lipid, sphingosine-1-phosphate (S1P) is highly abundant in blood, and plays an important role in regulating the growth, survival, and migration of many cells. Binding of the endogenous ligand S1P results in activation of various signaling pathways via G protein-coupled receptors, some of which generates Ca(2+) mobilization. In astrocytes, S1P is reported to evoke Ca(2+) signaling, proliferation, and migration; however, the precise mechanisms underlying such responses in astrocytes remain to be elucidated...
March 16, 2017: Glia
https://www.readbyqxmd.com/read/28300069/extracellular-%C3%AE-synuclein-induces-sphingosine-1-phosphate-receptor-subtype-1-uncoupled-from-inhibitory-g-protein-leaving-%C3%AE-arrestin-signal-intact
#6
Lifang Zhang, Taro Okada, Shaymaa Mohamed Mohamed Badawy, Chihoko Hirai, Taketoshi Kajimoto, Shun-Ichi Nakamura
Parkinson's disease (PD) is the second most common neurodegenerative disorder. The presence of α-synuclein (α-Syn)-positive intracytoplasmic inclusions, known as Lewy bodies, is the cytopathological hallmark of PD. Increasing bodies of evidence suggest that cell-to-cell transmission of α-Syn plays a role in the progression of PD. Although extracellular α-Syn is known to cause abnormal cell motility, the precise mechanism remains elusive. Here we show that impairment of platelet-derived growth factor-induced cell motility caused by extracellular α-Syn is mainly attributed to selective inhibition of sphingosine 1-phosphate (S1P) signalling...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28297574/bioactive-lipids-and-circulating-progenitor-cells-in-patients-with-cardiovascular-disease
#7
Salim S Hayek, Yuri Klyachkin, Ahmed Asfour, Nima Ghasemzadeh, Mosaab Awad, Iraj Hesaroieh, Hina Ahmed, Brandon Gray, Jinhee Kim, Edmund K Waller, Arshed A Quyyumi, Ahmed K Abdel-Latif
Bone marrow-derived progenitor cells are mobilized into the peripheral blood after acute myocardial injury and in chronic ischemic heart disease. However, the mechanisms responsible for this mobilization are poorly understood. We examined the relationship between plasma levels of bioactive lipids and number of circulating progenitor cells (CPCs) in patients (N = 437) undergoing elective or emergent cardiac catheterization. Plasma levels of sphingosine-1 phosphate (S1P) and ceramide-1 phosphate (C1P) were quantified using mass spectrometry...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28284343/sphk1-mediates-neuroinflammation-and-neuronal-injury-via-traf2-nf-%C3%AE%C2%BAb-pathways-in-activated-microglia-in-cerebral-ischemia-reperfusion
#8
Danying Su, Yuefeng Cheng, Shi Li, Dawei Dai, Wei Zhang, Manhua Lv
Sphingosine kinase 1 (Sphk1), a key enzyme responsible for phosphorylating sphingosine into sphingosine1-phosphate (S1P), plays an important role in mediating post-stroke neuroinflammation. However, the pathway and mechanism of the Sphk1-mediated inflammatory response remains unknown. In this study, we found that suppression of Sphk1 decreased IL17 production and relieved neuronal damage induced by microglia in cerebral ischemia reperfusion (IR) or in an in vitro oxygen-glucose deprivation reperfusion (OGDR) system...
April 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28284213/mathematical-modelling-and-a-systems-science-approach-to-describe-the-role-of-cytokines-in-the-evolution-of-severe-dengue
#9
S D Pavithra Jayasundara, S S N Perera, Gathsaurie Neelika Malavige, Saroj Jayasinghe
BACKGROUND: Dengue causes considerable morbidity and mortality in Sri Lanka. Inflammatory mediators such as cytokines, contribute to its evolution from an asymptotic infection to severe forms of dengue. The majority of previous studies have analysed the association of individual cytokines with clinical disease severity. In contrast, we view evolution to Dengue Haemorrhagic Fever as the behaviour of a complex dynamic system. We therefore, analyse the combined effect of multiple cytokines that interact dynamically with each other in order to generate a mathematical model to predict occurrence of Dengue Haemorrhagic Fever...
March 11, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28283249/sphingosine-1-phosphate-signaling-in-inflammatory-bowel-disease
#10
REVIEW
Ole Haagen Nielsen, Yuan Li, Bengt Johansson-Lindbom, Mehmet Coskun
An unmet medical need exists for the development of targeted therapies for the treatment of inflammatory bowel disease (IBD) with easily administered and stable oral drugs, particularly as most patients on biologics [i.e., tumor necrosis factor (TNF) inhibitors and anti-integrins] are either primary non-responders or lose responsiveness during maintenance treatment. A new class of small molecules, sphingosine-1-phosphate (S1P) receptor modulators, has recently shown efficacy in IBD. Here we provide an overview of the mechanism of action of this novel treatment principle in the context of intestinal inflammation...
March 7, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28283111/is-multiple-sclerosis-a-length-dependent-central-axonopathy-the-case-for-therapeutic-lag-and-the-asynchronous-progressive-ms-hypotheses
#11
REVIEW
Gavin Giovannoni, Gary Cutter, Maria Pia-Sormani, Shibeshih Belachew, Robert Hyde, Harold Koendgen, Volker Knappertz, Davorka Tomic, David Leppert, Robert Herndon, Claudia A M Wheeler-Kingshott, Olga Ciccarelli, David Selwood, Elisabetta Verdun di Cantogno, Ali-Frederic Ben-Amor, Paul Matthews, Daniele Carassiti, David Baker, Klaus Schmierer
Trials of anti-inflammatory therapies in non-relapsing progressive multiple sclerosis (MS) have been stubbornly negative except recently for an anti-CD20 therapy in primary progressive MS and a S1P modulator siponimod in secondary progressive MS. We argue that this might be because trials have been too short and have focused on assessing neuronal pathways, with insufficient reserve capacity, as the core component of the primary outcome. Delayed neuroaxonal degeneration primed by prior inflammation is not expected to respond to disease-modifying therapies targeting MS-specific mechanisms...
February 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28279838/modulation-of-sphingosine-1-phosphate-in-inflammatory-bowel-disease
#12
REVIEW
Laurent Peyrin-Biroulet, Ronald Christopher, Dominic Behan, Cheryl Lassen
Inflammatory bowel diseases (IBD), including ulcerative colitis and Crohn's disease, involve an inappropriate immune reaction in the digestive tract, causing a variety of disabling symptoms. The advent of monoclonal antibodies (anti-tumor necrosis factor, anti-integrin, anti-interleukin -23) has revolutionized IBD management. Nevertheless, these agents, with potential for immunogenicity, are associated with high rates of response loss and disease relapse over time. They are also associated with high production costs...
March 6, 2017: Autoimmunity Reviews
https://www.readbyqxmd.com/read/28277139/sphingosine-1-phosphate-activates-the-akt-pathway-to-inhibit-chemotherapy-induced-human-granulosa-cell-apoptosis
#13
Shuyi Li, Jianling Chen, Xiaoling Fang, Xiaomeng Xia
To investigate whether sphingosine-1-phosphate (S1P), an apoptosis-inhibitor would be able to inhibit chemotherapy induced human granulosa cell apoptosis. Cultures of primary granulosa cells were isolated from women undergoing in vitro fertilization (IVF). MTT assay was used to measure the optimum concentration of CTX and S1P acts on human granulosa cells. Granulosa cells were added with pertussis toxin (PTX), the PI3K inhibitor LY294002. Western blot analysis was used to analyze the signaling pathway of proteins and cell apoptosis...
February 21, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28276483/vascular-transcriptome-profiling-identifies-sphingosine-kinase-1-as-a-modulator-of-angiotensin-ii-induced-vascular-dysfunction
#14
Mateusz Siedlinski, Ryszard Nosalski, Piotr Szczepaniak, Agnieszka H Ludwig-Gałęzowska, Tomasz Mikołajczyk, Magdalena Filip, Grzegorz Osmenda, Grzegorz Wilk, Michał Nowak, Paweł Wołkow, Tomasz J Guzik
Vascular dysfunction is an important phenomenon in hypertension. We hypothesized that angiotensin II (AngII) affects transcriptome in the vasculature in a region-specific manner, which may help to identify genes related to vascular dysfunction in AngII-induced hypertension. Mesenteric artery and aortic transcriptome was profiled using Illumina WG-6v2.0 chip in control and AngII infused (490 ng/kg/min) hypertensive mice. Gene set enrichment and leading edge analyses identified Sphingosine kinase 1 (Sphk1) in the highest number of pathways affected by AngII...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28275141/cutting-edge-targeting-epithelial-ormdl3-increases-rather-than-reduces-airway-responsiveness-and-is-associated-with-increased-sphingosine-1-phosphate
#15
Marina Miller, Arvin B Tam, James L Mueller, Peter Rosenthal, Andrew Beppu, Ruth Gordillo, Matthew D McGeough, Christine Vuong, Taylor A Doherty, Hal M Hoffman, Maho Niwa, David H Broide
In this study, we used cre-lox techniques to generate mice selectively deficient in ORMDL3 in airway epithelium (Ormdl3(Δ2-3/Δ2-3)/CC10) to simulate an inhaled therapy that effectively inhibited ORMDL3 expression in the airway. In contrast to the anticipated reduction in airway hyperresponsiveness (AHR), OVA allergen-challenged Ormdl3(Δ2-3/Δ2-3)/CC10 mice had a significant increase in AHR compared with wild-type mice. Levels of airway inflammation, mucus, fibrosis, and airway smooth muscle were no different in Ormdl3(Δ2-3/Δ2-3)/CC10 and wild-type mice...
March 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28270699/fty720-attenuates-angiotensin-ii-induced-podocyte-damage-via-inhibiting-inflammatory-cytokines
#16
Ke Su, Ping Zeng, Wei Liang, Zhengyu Luo, Yiman Wang, Xifeng Lv, Qi Han, Miao Yan, Cheng Chen
FTY720, a new chemical substance derived from the ascomycete Isaria sinclairii, is used for treating multiple sclerosis, renal cancer, and asthma. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite and exists in red blood cells. FTY720 is a synthetic S1P analog which can block S1P evoking physiological effects. Recently studies show that S1P was participating in activated inflammation cells induced renal injury. The objective of this study was to assess the protective effect of FTY720 on kidney damage and the potential mechanism of FTY720 which alleviate podocyte injury in chronic kidney disease...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28270071/inhibitory-effects-of-novel-sphk2-inhibitors-on-migration-of-cancer-cells
#17
Deokho Jung, Junghyun Jung, Euiyeon Lee, Chang Soo Mok, Hyunjin Jeon, Chang Seo Park, Wonhee Jang, Youngeun Kwon
Cell migration is an essential process for survival and differentiation of mammalian cells. Numerous diseases are induced or influenced by inappropriate regulation of cell migration, which plays a key role in cancer cell metastasis. In fact, very few anti-metastasis drugs are available on the market. SphKs are enzymes that convert sphingosine to sphingosine-1- phosphate (S1P) and are known to control various cellular functions, including migration of cells. Among two human isozymes of SphK2, SphK2 is known to promote apoptosis, suppresses cell growth, and controls cell migration; in addition, the specific ablation of SphK2 activity was reported to inhibit cancer cell metastasis...
February 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28262793/characterization-of-cholesterol-homeostasis-in-sphingosine-1-phosphate-lyase-deficient-fibroblasts-reveals-a-niemann-pick-disease-type-c-like-phenotype-with-enhanced-lysosomal-ca-2-storage
#18
Hans Vienken, Nathalie Mabrouki, Katja Grabau, Ralf Frederik Claas, Agnes Rudowski, Nina Schömel, Josef Pfeilschifter, Dieter Lütjohann, Gerhild van Echten-Deckert, Dagmar Meyer Zu Heringdorf
Sphingosine-1-phosphate (S1P) lyase irreversibly cleaves S1P, thereby catalysing the ultimate step of sphingolipid degradation. We show here that embryonic fibroblasts from S1P lyase-deficient mice (Sgpl1(-/-)-MEFs), in which S1P and sphingosine accumulate, have features of Niemann-Pick disease type C (NPC) cells. In the presence of serum, overall cholesterol content was elevated in Sgpl1(-/-)-MEFs, due to upregulation of the LDL receptor and enhanced cholesterol uptake. Despite this, activation of sterol regulatory element-binding protein-2 was increased in Sgpl1(-/-)-MEFs, indicating a local lack of cholesterol at the ER...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28250108/the-sphingosine-rheostat-is-involved-in-the-cnidarian-heat-stress-response-but-not-necessarily-in-bleaching
#19
Sheila A Kitchen, Virginia M Weis
Sphingolipids play important roles in mitigating cellular heat and oxidative stress by altering membrane fluidity, receptor clustering and gene expression. Accumulation of signaling sphingolipids that comprise the sphingosine rheostat, pro-apoptotic sphingosine (Sph) and pro-survival sphingosine-1-phosphate (S1P), is key to determining cell fate. Reef-building corals and other symbiotic cnidarians living in shallow tropical waters can experience elevated seawater temperature and high UV irradiance, two stressors that are increasing in frequency and severity with climate change...
February 22, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28248965/pancreas-lineage-allocation-and-specification-are-regulated-by-sphingosine-1-phosphate-signalling
#20
Ioannis Serafimidis, Eva Rodriguez-Aznar, Mathias Lesche, Kazuaki Yoshioka, Yoh Takuwa, Andreas Dahl, Duojia Pan, Anthony Gavalas
During development, progenitor expansion, lineage allocation, and implementation of differentiation programs need to be tightly coordinated so that different cell types are generated in the correct numbers for appropriate tissue size and function. Pancreatic dysfunction results in some of the most debilitating and fatal diseases, including pancreatic cancer and diabetes. Several transcription factors regulating pancreas lineage specification have been identified, and Notch signalling has been implicated in lineage allocation, but it remains unclear how these processes are coordinated...
March 2017: PLoS Biology
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