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https://www.readbyqxmd.com/read/29776397/the-conserved-p-arg108-residue-in-s1pr2-dfnb68-is-fundamental-for-proper-hearing-evidence-from-a-consanguineous-iranian-family
#1
Michaela A H Hofrichter, Majid Mojarad, Julia Doll, Clemens Grimm, Atiye Eslahi, Neda Sadat Hosseini, Mohsen Rajati, Tobias Müller, Marcus Dittrich, Reza Maroofian, Thomas Haaf, Barbara Vona
BACKGROUND: Genetic heterogeneity and consanguineous marriages make recessive inherited hearing loss in Iran the second most common genetic disorder. Only two reported pathogenic variants (c.323G>C, p.Arg108Pro and c.419A>G, p.Tyr140Cys) in the S1PR2 gene have previously been linked to autosomal recessive hearing loss (DFNB68) in two Pakistani families. We describe a segregating novel homozygous c.323G>A, p.Arg108Gln pathogenic variant in S1PR2 that was identified in four affected individuals from a consanguineous five generation Iranian family...
May 18, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29766830/impact-of-sphingolipid-mediators-on-determination-of-cochlear-survival-in-ototoxicity
#2
Keiji Tabuchi, Akira Hara
BACKGROUND AND OBJECTIVE: Sphingolipid metabolites, including ceramide, sphingosine, and their phosphorylates (ceramide-1-phosphonate [C1P] and sphingosine-1-phosphate [S1P]), regulate diverse cellular processes including apoptosis, the cell cycle, and cellular differentiation. Recent studies have shown that these sphingolipid metabolites are generated in response to ototoxic agents and play important roles in determining the fate of cochlear hair cells in ototoxic injury. METHODS: This review summarizes the current knowledge on the roles of sphingolipid mediators in cochlear ototoxicity...
May 15, 2018: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29733947/sphingolipid-signaling-modulates-trans-endothelial-cell-permeability-in-dengue-virus-infected-hmec-1-cells
#3
M G Anupriya, Sneha Singh, Neha Vijay Hulyalkar, Easwaran Sreekumar
Dengue has emerged as a major mosquito-borne disease in the tropics and subtropics. In severe dengue, enhanced microvascular endothelial permeability leads to plasma leakage. Direct dengue virus (DENV) infection in human microvascular endothelial cells (HMEC-1) can enhance trans-endothelial leakage. Using a microarray-based analysis, we identified modulation of key endothelial cell signaling pathways in DENV-infected HMEC-1 cells. One among them was the sphingolipid pathway that regulates vascular barrier function...
May 4, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29700602/influence-of-sphingosine-1-phosphate-signaling-on-hcmv-replication-in-human-embryonal-lung-fibroblasts
#4
Anika Zilch, Christian Rien, Cynthia Weigel, Stefanie Huskobla, Brigitte Glück, Katrin Spengler, Andreas Sauerbrei, Regine Heller, Markus Gräler, Andreas Henke
The human cytomegalovirus (HCMV) is a common pathogen, which causes severe or even deadly diseases in immunocompromised patients. In addition, congenital HCMV infection represents a major health concern affecting especially the lung tissue of the susceptible individuals. Antivirals are a useful strategy to treat HCMV-caused diseases. However, all approved drugs target viral proteins but significant toxicity and an increasing resistance against these compounds have been observed. In infected cells, numerous host molecules have been identified to play important roles during HCMV replication...
April 26, 2018: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/29620575/sphingosine-1-phosphate-receptor-2-signaling-promotes-caspase-11-dependent-macrophage-pyroptosis-and-worsens-escherichia-coli-sepsis-outcome
#5
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/29615404/the-tumor-suppressive-tgf-%C3%AE-smad1-s1pr2-signaling-axis-is-recurrently-inactivated-in-diffuse-large-b-cell-lymphoma
#6
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
https://www.readbyqxmd.com/read/29604582/syntheses-and-in-vitro-evaluation-of-new-s1pr1-compounds-and-initial-evaluation-of-a-lead-f-18-radiotracer-in-rodents
#7
Zonghua Luo, Adam J Rosenberg, Hui Liu, Junbin Han, Zhude Tu
Thirteen new sphingosine-1-phosphate receptor 1 (S1PR1) ligands were designed and synthesized by replacing azetidine-3-carboxylic acid moiety of compound 4 with new polar groups. The in vitro binding potency of these new analogs toward S1PR1 was determined. Out of 13 new compounds, four compounds 9a, 10c, 12b, and 16b displayed high S1PR1 binding potency with IC50 values of 13.2 ± 3.2, 14.7 ± 1.7, 9.7 ± 1.6, and 6.3 ± 1.3 nM, respectively; further binding studies of these four ligands toward S1PR2-5 suggested they are highly selective for S1PR1 over other S1PRs...
March 14, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29572542/aryl-hydrocarbon-receptor-signaling-promotes-ormdl3-dependent-generation-of-sphingosine-1-phosphate-by-inhibiting-sphingosine-1-phosphate-lyase
#8
Hsueh-Chun Wang, Tzu-Hsuan Wong, Li-Ting Wang, Hsiang-Han Su, Hsiu-Yueh Yu, Ai-Hsuan Wu, Yu-Chun Lin, Hua-Ling Chen, Jau-Ling Suen, Shih-Hsien Hsu, Li-Chen Chen, Yufeng Zhou, Shau-Ku Huang
Aryl hydrocarbon receptor (AhR), a cellular chemical sensor, controls cellular homeostasis, and sphingosine-1-phosphate (S1P), a bioactive intermediate of sphingolipid metabolism, is believed to have a role in immunity and inflammation, but their potential crosstalk is currently unknown. We aimed to determine whether there is a functional linkage between AhR signaling and sphingolipid metabolism. We showed that AhR ligands, including an environmental polycyclic aromatic hydrocarbon (PAH), induced S1P generation, and inhibited S1P lyase (S1PL) activity in resting cells, antigen/IgE-activated mast cells, and mouse lungs exposed to the AhR ligand alone or in combination with antigen challenge...
March 23, 2018: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/29534379/-effect-of-s1pr2-inhibition-on-epithelial-ovarian-cancer-skov3-cell-proliferation-in-vitro-and-in-vivo
#9
L Dai, Y X Liu, L Xie, W Di
Objective: To study the effect and mechanism of S1PR2 inhibition on epithelial ovarian cancer SKOV3 cell proliferation in vitro and in vivo. Methods: (1) A pair of S1PR2 gene small interference RNA (siRNA) , namely si-S1PR2, and a pair of negative control siRNA were designed. Western blot methods were used to detect the silence efficiency of the S1PR2 in the si-S1PR2 group, blank control group and negative control group. (2) Study in vitro: the experiment included three groups, namely si-S1PR2 group, blank control group and negative control group...
February 25, 2018: Zhonghua Fu Chan Ke za Zhi
https://www.readbyqxmd.com/read/29511860/dj-1-is-involved-in-epigenetic-control-of-sphingosine-1-phosphate-receptor-expression-in-vascular-neointima-formation
#10
Kang Pa Lee, Suji Baek, Seung Hyo Jung, Long Cui, Donghyen Lee, Dong-Youb Lee, Wahn Soo Choi, Hyun Woo Chung, Byeong Han Lee, Bokyung Kim, Kyung Jong Won
DJ-1 and sphingosine-1-phosphate (S1P) receptors (S1PRs) are implicated in the control of physiology and pathophysiology of cardiovascular systems such as blood pressure, atherosclerosis, and restenosis. Here, we investigated whether DJ-1 with antioxidant function participates in the regulation of S1PR1 and S1PR2 expression in vascular smooth muscle cells (VSMCs) and whether this response is related to vascular neointima formation. In vitro studies used cellular migration assay, western blot, reverse transcriptase and real-time PCR analysis, and immunocytochemistry...
March 6, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29475983/s1p-s1pr2-axis-mediates-homing-of-muse-cells-into-damaged-heart-for-long-lasting-tissue-repair-and-functional-recovery-after-acute-myocardial-infarction
#11
Yoshihisa Yamada, Shohei Wakao, Yoshihiro Kushida, Shingo Minatoguchi, Atsushi Mikami, Kenshi Higashi, Shinya Baba, Taeko Shigemoto, Yasumasa Kuroda, Hiromitsu Kanamori, Mohamad Amin, Masanori Kawasaki, Kazuhiko Nishigaki, Masato Taoka, Toshiaki Isobe, Chisako Muramatsu, Mari Dezawa, Shinya Minatoguchi
RATIONALE: Multilineage-differentiating stress enduring (Muse) cells, pluripotent marker stage-specific embryonic antigen-3+ cells, are nontumorigenic endogenous pluripotent-like stem cells obtainable from various tissues including the bone marrow. Their therapeutic efficiency has not been validated in acute myocardial infarction. OBJECTIVE: The main objective of this study is to clarify the efficiency of intravenously infused rabbit autograft, allograft, and xenograft (human) bone marrow-Muse cells in a rabbit acute myocardial infarction model and their mechanisms of tissue repair...
April 13, 2018: Circulation Research
https://www.readbyqxmd.com/read/29458005/14-3-3%C3%AE-promotes-esophageal-squamous-cell-carcinoma-invasion-by-repressing-s1pr2-protein-expression-through-nf-%C3%AE%C2%BAb-signaling
#12
Song Tong, Sheng-Cai Chen, Kai-Ying Xu, Bin Fang, Si-Hua Wang, Jian-Jun Wang
14-3-3ζ is overexpressed in several cancers, including esophageal squamous cell carcinoma (ESCC), and plays an important role in tumorigenesis. However, the mechanisms underlying its tumorigenesis remain unclear. Here we report that 14-3-3ζ was upregulated in ESCC tumors, compared with adjacent normal tissues; 14-3-3ζ levels were positively correlated with ESCC lymph node metastasis and recurrence. Overexpression of 14-3-3ζ promoted the tumor growth and invasion of ESCC in vitro and in vivo, whereas depletion of 14-3-3ζ suppressed these effects...
April 2, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29453251/a-novel-adipokine-fam19a5-inhibits-postinjury-neointima-formation-through-sphingosine-1-phosphate-receptor-2
#13
Yingbao Wang, Dixin Chen, Yan Zhang, Pingzhang Wang, Can Zheng, Songyang Zhang, Bing Yu, Lu Zhang, Guizhen Zhao, Baihui Ma, Zeyu Cai, Nan Xie, Shiyang Huang, Ziyi Liu, Xiaoning Mo, Youfei Guan, Xian Wang, Yi Fu, Dalong Ma, Ying Wang, Wei Kong
Background -Obesity plays crucial roles in the development of cardiovascular diseases (CVDs). However, the mechanisms that link obesity and CVDs remain elusive. Compelling evidence indicates that adipokines play an important role in obesity-related CVDs. Here, we found a new adipokine named family with sequence similarity 19, member A5 (FAM19A5), a protein with unknown function that was predicted to be distantly related to the CC-chemokine family. We aimed to test whether adipose-derived FAM19A5 regulates vascular pathology upon injury...
February 16, 2018: Circulation
https://www.readbyqxmd.com/read/29428555/the-inflammatory-molecule-sphingosine-1-phosphate-is-not-effective-to-evoke-or-sensitize-cough-in-na%C3%A3-ve-guinea-pigs
#14
Simona Svajdova, Lenka Mazurova, Mariana Brozmanova
Sphingosine-1-phosphate (S1P) is an inflammatory mediator increased in the tissue in the number of inflammatory conditions. Preliminary data indicate that the vagal afferent neurons express several S1P receptors including S1PR2-3 . We therefore evaluated the hypothesis that S1P induces cough and/or enhances the cough evoked by other tussive stimuli (TRPA1 and TRPV1 activators) in naïve guinea pigs. Inhalation of S1P in the concentrations of 0.1 mM and 1 mM did not evoke cough. Preinhalation and continuing inhalation of S1P (1 mM) during citric acid (0...
February 8, 2018: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/29401609/microrna-149-5p-regulates-blood-brain-barrier-permeability-after-transient-middle-cerebral-artery-occlusion-in-rats-by-targeting-s1pr2-of-pericytes
#15
Yan Wan, Hui-Juan Jin, Yi-Yi Zhu, Zhi Fang, Ling Mao, Quanwei He, Yuan-Peng Xia, Man Li, Yanan Li, Xiaoqian Chen, Bo Hu
Blood-brain barrier (BBB) disruption caused by reperfusion injury after ischemic stroke is an intractable event conducive to further injury. Brain pericytes play a vital role in maintaining BBB integrity by interacting with other components of the BBB. In this study, we found that sphingosine-1-phosphate receptor (S1PR)2 expressed in pericytes was significantly up-regulated after ischemia in vivo and in vitro. By using a S1PR2 antagonist (JTE-013), we showed that S1PR2 plays a critical role in the induction of BBB permeability of transient middle cerebral artery occlusion (tMCAO) rats and the in vitro BBB model...
January 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29286094/sphingosine-1-phosphate-ameliorates-the-cardiac-hypertrophic-response-through-inhibiting-the-activity-of-histone-deacetylase-2
#16
Hui Yan, Shaowei Yi, Hang Zhuang, Lujin Wu, Dao Wen Wang, Jiangang Jiang
Inhibition of histone deacetylase-2 (HDAC2), which is a prohypertrophic factor in the heart, can functionally attenuate cardiac hypertrophy. The present study aimed to investigate whether sphingosine‑1‑phosphate (S1P), which has recently been reported to suppress HDAC2 activity, could ameliorate the cardiac hypertrophic response and improve cardiac function in mice with transverse aortic constriction (TAC), as well as to determine the underlying mechanisms. Briefly, 8‑week‑old male C57BL/6 mice were randomly divided into sham, TAC and TAC + S1P groups; the results indicated that S1P treatment attenuated TAC‑induced cardiac dysfunction...
March 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29249563/design-and-synthesis-of-pyrazolopyridine-derivatives-as-sphingosine-1-phosphate-receptor-2-ligands
#17
Zonghua Luo, Xuyi Yue, Hao Yang, Hui Liu, Robyn S Klein, Zhude Tu
Eleven new sphingosine 1-phosphate receptor 2 (S1PR2) ligands were synthesized by modifying lead compound N-(2,6-dichloropyridin-4-yl)-2-(4-isopropyl-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridin-6-yl)hydrazine-1-carboxamide (JTE-013) and their binding affinities toward S1PRs were determined in vitro using [32 P]S1P and cell membranes expressing recombinant human S1PRs. Among these ligands, 35a (IC50  = 29.1 ± 2.6 nM) and 35b (IC50  = 56.5 ± 4.0 nM) exhibit binding potency toward S1PR2 comparable to JTE-013 (IC50  = 58...
December 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29237776/human-naive-and-memory-t-cells-display-opposite-migratory-responses-to-sphingosine-1-phosphate
#18
Annabelle Drouillard, Antoinette Neyra, Anne-Laure Mathieu, Antoine Marçais, Mélanie Wencker, Jacqueline Marvel, Alexandre Belot, Thierry Walzer
The role of sphingosine-1 phosphate (S1P) in leukocyte trafficking has been well deciphered in mice but remains largely unaddressed in humans. In this study, we assessed the ex vivo response to S1P of primary human T cell subsets. We found that tonsil but not blood leukocytes were responsive to S1P gradients, suggesting that T cell responsiveness is regulated during their recirculation in vivo. Tonsil naive T cells were readily chemoattracted by S1P in an FTY720-sensitive, S1PR1-dependent manner. Surprisingly, S1P had the opposite effect on effector memory T cells, resident memory T cells, and recently activated T cells, inhibiting their spontaneous or chemokine-induced migration...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29208234/vitamin-d-attenuates-sphingosine-1-phosphate-s1p-mediated-inhibition-of-extravillous-trophoblast-migration
#19
Melissa Westwood, Khiria Al-Saghir, Sarah Finn-Sell, Cherlyn Tan, Elizabeth Cowley, Stéphane Berneau, Daman Adlam, Edward D Johnstone
INTRODUCTION: Failure of trophoblast invasion and remodelling of maternal blood vessels leads to the pregnancy complication pre-eclampsia (PE). In other systems, the sphingolipid, sphingosine-1-phosphate (S1P), controls cell migration therefore this study determined its effect on extravillous trophoblast (EVT) function. METHODS: A transwell migration system was used to assess the behaviour of three trophoblast cell lines, Swan-71, SGHPL-4, and JEG3, and primary human trophoblasts in the presence or absence of S1P, S1P pathway inhibitors and 1,25(OH)2 D3 ...
December 2017: Placenta
https://www.readbyqxmd.com/read/29168342/sphingosine-1-phosphate-s1p-enhances-glomerular-endothelial-cells-activation-mediated-by-anti-myeloperoxidase-antibody-positive-igg
#20
Xiao-Jing Sun, Min Chen, Ming-Hui Zhao
Cumulating evidences suggested an important role of sphingosine-1-phosphate (S1P) and its receptors in regulating endothelial barrier integrity. Our previous study revealed that the circulating S1P levels and renal expression of S1PRs correlated with disease activity and renal damage in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study investigated the role of S1P and its receptors in myeloperoxidase (MPO)-ANCA-positive IgG-mediated glomerular endothelial cell (GEnC) activation...
March 2018: Journal of Cellular and Molecular Medicine
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