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https://www.readbyqxmd.com/read/29045386/mfsd2b-is-essential-for-the-sphingosine-1-phosphate-export-in-erythrocytes-and-platelets
#1
Thiet M Vu, Ayako-Nakamura Ishizu, Juat Chin Foo, Xiu Ru Toh, Fangyu Zhang, Ding Ming Whee, Federico Torta, Amaury Cazenave-Gassiot, Takayoshi Matsumura, Sangho Kim, Sue-Anne E S Toh, Toshio Suda, David L Silver, Markus R Wenk, Long N Nguyen
Sphingosine-1-phosphate (S1P), a potent signalling lipid secreted by red blood cells and platelets, plays numerous biologically significant roles. However, the identity of its long-sought exporter is enigmatic. Here we show that the major facilitator superfamily transporter 2b (Mfsd2b), an orphan transporter, is essential for S1P export from red blood cells and platelets. Comprehensive lipidomic analysis indicates a dramatic and specific accumulation of S1P species in Mfsd2b knockout red blood cells and platelets compared with that of wild-type controls...
October 18, 2017: Nature
https://www.readbyqxmd.com/read/29044290/protease-activated-receptor-par-4-an-inducible-switch-between-thrombosis-and-vascular-inflammation
#2
Anke C Fender, Bernhard H Rauch, Tobias Geisler, Karsten Schrör
Thrombin triggers activation of platelets through protease-activated receptor 1 (PAR-1) and PAR-4. Both receptors are widely expressed and exert multiple platelet-independent functions. PAR signalling contributes to healing responses after injury, by promoting cytokine activity and cellular growth and mobility. Uncontrolled PAR activation, however, can prevent timely resolution of inflammation, enhance thrombogenic endothelial function and drive adverse remodelling. The specific role of PAR-4 in thromboinflammatory vascular disease has been largely underestimated, given the relatively limited expression of PAR-4 in non-platelet cells under healthy conditions...
October 10, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29036438/a-selective-sphingosine-1-phosphate-receptor-1-agonist-sew-2871-aggravates-gastric-cancer-by-recruiting-myeloid-derived-suppressor-cells
#3
Yujing Zhou, Feng Guo
The immune status of tumor microenvironment in gastric cancer is poorly understood, which limits the development of novel strategies in this field. Sphingosine-1-phosphate (S1P) acts as an immune modulator, but the role of S1P in gastric cancer is elusive. Here, we aim to investigate S1P receptor 1 (S1P1)-mediated effect of S1P in gastric cancer. We generated a xenograft mouse model and used SEW-2871, a S1P1 specific agonist to activate S1P1 signaling. Tumor-infiltrating lymphocytes (TILs) were isolated and analyzed using flow cytometry...
October 3, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/29033951/sphingosine-1-phosphate-receptor-5-modulates-early-stage-processes-during-fibrogenesis-in-a-mouse-model-of-systemic-sclerosis-a-pilot-study
#4
Katrin G Schmidt, Martina Herrero San Juan, Sandra Trautmann, Lucija Berninger, Anja Schwiebs, Florian M Ottenlinger, Dominique Thomas, Frank Zaucke, Josef M Pfeilschifter, Heinfried H Radeke
Systemic sclerosis (SSc) is a rare multi-organ autoimmune disease characterized by progressive skin fibrosis. Inflammation, type 2 immunity, and fibrogenic processes are involved in disease development and may be affected by sphingolipids. However, details about early-stage pathophysiological mechanisms and implicated mediators remain elusive. The sphingolipid sphingosine-1-phosphate (S1P) is elevated in the sera of SSc patients, and its receptor S1P5 is expressed in skin tissue. Nevertheless, almost nothing is known about the dermatological contribution of S1P5 to inflammatory and pro-fibrotic processes leading to the pathological changes seen in SSc...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29029455/mobilization-studies-in-mice-deficient-in-sphingosine-kinase-2-support-a-crucial-role-of-the-plasma-level-of-sphingosine-1-phosphate-in-the-egress-of-hematopoietic-stem-progenitor-cells
#5
Mateusz Adamiak, Lakshman Chelvarajan, Kevin R Lynch, Webster L Santos, Ahmed Abdel-Latif, Mariusz Z Ratajczak
Sphingosine-1-phosphate (S1P) is a bioactive lipid involved in cell signaling and, if released from cells, also plays a crucial role in regulating the trafficking of lympho-hematopoietic cells, including primitive hematopoietic stem/progenitor cells (HSPCs). It has been demonstrated that S1P chemoattracts HSPCs, and its level in peripheral blood creates a gradient directing egress of these cells during mobilization. In this paper we analyzed hematopoiesis in mice deficient in sphingosine kinase 2 (Sphk2-KO mice) and studied the effect of this mutation on plasma S1P levels...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29028945/sphingosine-kinase-1-expression-in-peritoneal-macrophages-is-required-for-colon-carcinogenesis
#6
Hideki Furuya, Paulette M Tamashiro, Yoshiko Shimizu, Kayoko Iino, Rafael Peres, Runpu Chen, Yijun Sun, Yusuf A Hannun, Lina M Obeid, Toshihiko Kawamori
Accumulating evidence suggests that the sphingosine kinase 1 (SphK1)/sphingosine 1-phosphate (S1P) pathway plays a pivotal role in colon carcinogenesis. Our previous studies indicate that the SphK1/S1P pathway mediates colon carcinogenesis at least by regulating COX-2 expression and prostaglandin E2 (PGE2) production. However, the mechanisms by which this pathway regulates colon carcinogenesis are still unclear. First, we show that SphK1 deficient mice significantly attenuated azoxymethane (AOM)-induced colon carcinogenesis as measured by colon tumor incidence, multiplicity, and volume...
September 23, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29027248/ursodeoxycholic-acid-protects-cardiomyocytes-against-cobalt-chloride-induced-hypoxia-by-regulating-transcriptional-mediator-of-cells-stress-hypoxia-inducible-factor-1%C3%AE-and-p53-protein
#7
Anis Syamimi Mohamed, Noorul Izzati Hanafi, Siti Hamimah Sheikh Abdul Kadir, Julina Md Noor, Narimah Abdul Hamid Hasani, Sharaniza Ab Rahim, Rosfaiizah Siran
In hepatocytes, ursodeoxycholic acid (UDCA) activates cell signalling pathways such as p53, intracellular calcium ([Ca(2+) ]i ), and sphingosine-1-phosphate (S1P)-receptor via Gαi -coupled-receptor. Recently, UDCA has been shown to protect the heart against hypoxia-reoxygenation injury. However, it is not clear whether UDCA cardioprotection against hypoxia acts through a transcriptional mediator of cells stress, HIF-1α and p53. Therefore, in here, we aimed to investigate whether UDCA could protect cardiomyocytes (CMs) against hypoxia by regulating expression of HIF-1α, p53, [Ca(2+) ]i , and S1P-Gαi -coupled-receptor...
October 12, 2017: Cell Biochemistry and Function
https://www.readbyqxmd.com/read/29023711/alteration-of-sphingolipid-metabolism-as-a-putative-mechanism-underlying-lps-induced-bbb-disruption
#8
Rajkumar Vutukuri, Robert Brunkhorst, Roxane-Isabelle Kestner, Lena Hansen, Nerea Ferreiros Bouzas, Josef Pfeilschifter, Kavi Devraj, Waltraud Pfeilschifter
Septic encephalopathy with confusion and agitation occurs early during sepsis and contributes to the severity of the disease. A decrease of the sphingosine-1-phosphate (S1P) blood levels has been shown in patients and in animal models of sepsis. The lipid mediator S1P is known to be involved in endothelial barrier function in a context-dependent manner. We utilized LPS injected mice as a model for septic encephalopathy and first performed tracer permeability assays to assess the BBB breakdown in vivo. At time points corresponding to the BBB breakdown post LPS injection, we aimed to characterize the regulation of the sphingolipid signaling pathway at the blood-brain barrier (BBB) during sepsis...
October 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29023478/regeneration-of-glycocalyx-by-heparan-sulfate-and-sphingosine-1-phosphate-restores-inter-endothelial-communication
#9
Solomon A Mensah, Ming J Cheng, Homa Homayoni, Brian D Plouffe, Arthur J Coury, Eno E Ebong
Vasculoprotective endothelium glycocalyx (GCX) shedding plays a critical role in vascular disease. Previous work demonstrated that GCX degradation disrupts endothelial cell (EC) gap junction connexin (Cx) proteins, likely blocking interendothelial molecular transport that maintains EC and vascular tissue homeostasis to resist disease. Here, we focused on GCX regeneration and tested the hypothesis that vasculoprotective EC function can be stimulated via replacement of GCX when it is shed. We used EC with [i] intact heparan sulfate (HS), the most abundant GCX component; [ii] degraded HS; or [iii] HS that was restored after enzyme degradation, by cellular self-recovery or artificially...
2017: PloS One
https://www.readbyqxmd.com/read/28991193/sphingosine-kinase-1-and-sphingosine-1-phosphate-signaling-in-colorectal-cancer
#10
REVIEW
Yonghua Bao, Yongchen Guo, Chenglan Zhang, Fenghua Fan, Wancai Yang
Sphingosine kinase 1 (Sphk1) is a highly conserved lipid kinase that phosphorylates sphingosine to form sphingosine-1-phosphate (S1P). Growing studies have demonstrated that Sphk1 is overexpressed in various types of solid cancers and can be induced by growth factors, cytokines, and carcinogens, leading to the increase of S1P production. Subsequently, the increased Sphk1/S1P facilitates cancer cell proliferation, mobility, angiogenesis, invasion, and metastasis. Therefore, Sphk1/S1P signaling plays oncogenic roles...
October 8, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28986832/assays-to-assess-arenaviral-glycoprotein-function
#11
Junjie Shao, Xiaoying Liu, Yuying Liang, Hinh Ly
Arenaviruses, such as Lassa virus (LASV) and Pichindé virus (PICV), are enveloped viruses with a bi-segmented ambisense RNA genome. The large (L) genomic segment encodes the Z matrix protein and the L RNA-dependent RNA polymerase, whereas the small (S) genomic segment encodes the nucleoprotein (NP) and the glycoprotein precursor complex (GPC). GPC is processed by signal peptidase in the endoplasmic reticulum into the stable signal peptide (SSP) and GP1/GP2, which is further cleaved by the Golgi-resident subtilisin kexin isozyme-1 (SKI-1)/site-1 protease (S1P) into the cellular receptor-recognition subunit GP1 and the transmembrane subunit GP2, which helps promote the membrane fusion reaction to allow virus entry into the cell...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28986246/sphingosine-1-phosphate-alleviates-coxsackievirus-b3-induced-myocarditis-by-increasing-invariant-natural-killer-t-cells
#12
Xinggang Wang, Yong Yu, Minghui Li, Ying Yu, Guijian Liu, Yeqing Xie, Yuxi Liu, Xiangdong Yang, Yunzeng Zou, Junbo Ge, Ruizhen Chen
Sphingosine 1-phosphate (S1P), via binding to its specific receptors of S1PR1, participates in the regulation of both innate and adaptive immunity. Recent reports have identified S1P as a messenger mediating inflammation. However, roles of S1P in Coxsackievirus B3 (CVB3)-induced myocarditis were largely unknown. Here, we investigated the effect of S1P treatment on CVB3-induced myocarditis in vivo. We found that CVB3 infection downregulated S1PR1 expression in spleen and decreased the proportion of invariant natural killer T cells (iNKT) in CD3 positive T cells both in spleen and in blood from left ventricle, which accompanied by severe inflammation lesions and more virus capsid protein (VP1) expression in heart tissue...
October 3, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28983319/loss-of-sphingosine-kinase-alters-life-history-traits-and-locomotor-function-in-caenorhabditis-elegans
#13
Jason P Chan, Jaylene Brown, Brandon Hark, Abby Nolan, Dustin Servello, Hannah Hrobuchak, Trisha A Staab
Sphingolipid metabolism is important to balance the abundance of bioactive lipid molecules involved in cell signaling, neuronal function, and survival. Specifically, the sphingolipid sphingosine mediates cell death signaling, whereas its phosphorylated form, sphingosine-1-phosphate (S1P), mediates cell survival signaling. The enzyme sphingosine kinase produces S1P, and the activity of sphingosine kinase impacts the ability of cells to survive under stress and challenges. To examine the influence of sphingolipid metabolism, particularly enzymes regulating sphingosine and S1P, in mediating aging, neuronal function and stress response, we examined life history traits, locomotor capacities and heat stress responses of young and old animals using the model organism Caenorhabditis elegans...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28977376/plasma-sphingolipids-are-associated-with-gait-parameters-in-the-mayo-clinic-study-of-aging
#14
Alexandra M V Wennberg, Marissa J Schafer, Nathan K LeBrasseur, Rodolfo Savica, Hai H Bui, Clinton E Hagen, John H Hollman, Ronald C Petersen, Michelle M Mielke
Background: Disrupted gait has been associated with an increased risk of frailty, disability, and death, but the causal molecular pathways are not well understood. Sphingolipids, including ceramides, are associated with multiple age-related diseases. Ceramides promote atrophy, necrosis, and proteolysis in cellular and animal models, and ceramide C16:0 levels are negatively correlated with muscle mass in men. However, there is a paucity of evidence examining sphingolipids and physical function...
July 25, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28970286/obesity-stimulated-aldosterone-release-is-not-related-to-a-s1p-dependent-mechanism
#15
Stephan Werth, Helge Müller-Fielitz, Walter Raasch
Aldosterone has been identified as an important factor in obesity-associated hypertension. Here, we investigated whether sphingosine-1-phophate (S1P), which has previously been linked to obesity, increases aldosterone release. S1P-induced aldosterone release was determined in NCI H295R cells in the presence of S1P receptor (S1PR) antagonists. In vivo release of S1P (100-300 µg/kg bw) was investigated in pithed, lean Sprague Dawley (SD) rats, diet-obese spontaneous hypertensive rats (SHR), as well as in lean or obese Zucker rats...
October 2, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28968647/genetic-deletion-of-sphingosine-kinase-1-suppresses-mouse-breast-tumor-development-in-a-her2-transgenic-model
#16
Yoshiko Shimizu, Hideki Furuya, Paulette M Tamashiro, Kayoko Iino, Owen T M Chan, Steve Goodison, Ian Pagano, Kanani Hokutan, Rafael Peres, Lenora W M Loo, Brenda Hernandez, Aung Naing, Clayton D K Chong, Charles J Rosser, Toshihiko Kawamori
Aberrant sphingolipid metabolism has been reported to promote breast cancer progression. Sphingosine kinase 1 (SphK1) is a key metabolic enzyme for the formation of pro-survival S1P from pro-apoptotic ceramide. The role of SphK1 in breast cancer has been well studied in estrogen receptor (ER)-positive breast cancer, however, its role in human epidermal growth factor 2 (HER2)-positive breast cancer remains unclear. Here we show that genetic deletion of SphK1 significantly reduced mammary tumor development with reduced tumor incidence and multiplicity in the MMTV-neu transgenic mouse model...
September 11, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28966593/sphingosine-1-phosphate-receptor-modulator-fingolimod-fty720-attenuates-myocardial-fibrosis-in-post-heterotopic-heart-transplantation
#17
Naseer Ahmed, Daniele Linardi, Nazeer Muhammad, Cristiano Chiamulera, Guido Fumagalli, Livio San Biagio, Mebratu A Gebrie, Muhammad Aslam, Giovanni Battista Luciani, Giuseppe Faggian, Alessio Rungatscher
Background and Objective: Sphingosine 1-phosphate (S1P), and S1P receptor modulator fingolimod have been suggested to play important cardioprotective role in animal models of myocardial ischemia/reperfusion injuries. To understand the cardioprotective function of S1P and its mechanism in vivo, we analyzed apoptotic, inflammatory biomarkers, and myocardial fibrosis in an in vivo heterotopic rat heart transplantation model. Methods: Heterotopic heart transplantation is performed in 60 Sprague-Dawley (SD) rats (350-400 g)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28961752/targeting-s1p-in-inflammatory-bowel-disease-new-avenues-for-modulating-intestinal-leukocyte-migration
#18
Silvio Danese, Federica Furfaro, Stefania Vetrano
Sphingosine 1 phosphate (S1P) is a bioactive lipid mediator involved in the regulation of several cellular processes though the activation of a G protein-coupled receptor family known as the S1P receptors (S1PRs). Advances in the understanding of the biological activities mediated by S1PRs have sparked great interest in the S1P/S1PRs axes as new therapeutic targets for the modulation of several cellular processes. In particular, S1P/ S1PR1 axis has been identified as key regulator for the lymphocyte migration from lymph nodes...
July 28, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28956531/the-ceramide-synthase-2b-gene-mediates-genomic-sensing-and-regulation-of-sphingosine-levels-during-zebrafish-embryogenesis
#19
Karen Mendelson, Suveg Pandey, Yu Hisano, Frank Carellini, Bhaskar Das, Timothy Hla, Todd Evans
Sphingosine-1-phosphate (S1P) is generated through phosphorylation of sphingosine by sphingosine kinases (Sphk1 and Sphk2). We show that sphk2 maternal-zygotic mutant zebrafish embryos (sphk2(MZ)) display early developmental phenotypes, including a delay in epiboly, depleted S1P levels, elevated levels of sphingosine, and resistance to sphingosine toxicity. The sphk2(MZ) embryos also have strikingly increased levels of maternal transcripts encoding ceramide synthase 2b (Cers2b), and loss of Cers2b in sphk2(MZ) embryos phenocopies sphingosine toxicity...
September 28, 2017: ELife
https://www.readbyqxmd.com/read/28954861/the-balance-between-g%C3%AE-i-cdc42-rac-and-g%C3%AE-12-13-rhoa-pathways-determines-endothelial-barrier-regulation-by-sphingosine-1-phosphate
#20
Nathalie R Reinhard, Marieke Mastop, Taofei Yin, Yi Wu, Esmeralda K Bosma, Theodorus W J Gadella, Joachim Goedhart, Peter L Hordijk
The bioactive sphingolipid S1P is present in plasma, bound to carrier proteins, and is involved in many physiological processes, including angiogenesis, inflammatory responses and vascular stabilization. S1P can bind to several G-protein-coupled receptors (GPCRs) activating a number of different signalling networks. At present, the dynamics and relative importance of signalling events activated immediately downstream of GPCR activation are unclear. To examine this, we used a set of FRET-based biosensors for different RhoGTPases (Rac1, RhoA/B/C, Cdc42) as well as for heterotrimeric G-proteins in a series of live-cell imaging experiments in primary human endothelial cells...
September 27, 2017: Molecular Biology of the Cell
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