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Fu-Ju Lei, Bi-Hua Cheng, Pei-Yin Liao, Hsiao-Ching Wang, Wei-Chun Chang, Hsueh-Chou Lai, Juan-Cheng Yang, Yang-Chang Wu, Li-Ching Chu, Wen-Lung Ma
Sphingosine-1-phosphate (S1P) is a bioactive lipid that exerts various pathophysiological functions through binding to its receptor family (S1PRs). Since first report of the breast cancer (BCA) promoting function by S1P production (through the function of sphingosine kinases) and S1P/S1PR signaling, their antagonists have never been successfully progress to clinics after three decades. Taking advantage of bioinformatics linking to gene expression to disease prognosis, we examined the impact of associated genes in BCA patients...
June 20, 2018: Cancer Medicine
Elena Guzzolino, Elena Chiavacci, Neha Ahuja, Laura Mariani, Monica Evangelista, Chiara Ippolito, Milena Rizzo, Deborah Garrity, Federico Cremisi, Letizia Pitto
Sphingosine-1-phosphate is a bioactive lipid and a signaling molecule integrated into many physiological systems such as differentiation, proliferation and migration. In mammals S1P acts through binding to a family of five trans-membrane, G-protein coupled receptors (S1PRs) whose complex role has not been completely elucidated. In this study we use zebrafish, in which seven s1prs have been identified, to investigate the role of s1pr1 . In mammals S1PR1 is the most highly expressed S1P receptor in the developing heart and regulates vascular development, but in zebrafish the data concerning its role are contradictory...
2018: Frontiers in Cell and Developmental Biology
Dong Kyu Lee, Young Sil Min, Seong Su Yoo, Hyun Sub Shim, Sun Young Park, Uy Dong Sohn
A comprehensive collection of proteins senses local changes in intracellular Ca2+ concentrations ([Ca2+ ]i ) and transduces these signals into responses to agonists. In the present study, we examined the effect of sphingosine-1-phosphate (S1P) on modulation of intracellular Ca2+ concentrations in cat esophageal smooth muscle cells. To measure [Ca2+ ]i levels in cat esophageal smooth muscle cells, we used a fluorescence microscopy with the Fura-2 loading method. S1P produced a concentration-dependent increase in [Ca2+ ]i in the cells...
June 19, 2018: Biomolecules & Therapeutics
Marta Budkowska, Ewa Ostrycharz, Adrianna Wojtowicz, Zuzanna Marcinowska, Jarosław Woźniak, Mariusz Z Ratajczak, Barbara Dołęgowska
The number of hematopoietic stem/progenitor cells (HSPCs) circulating in peripheral blood (PB) is regulated by a circadian rhythm, and more HSPCs circulate in PB in the morning hours than at night. Different mechanisms have been proposed that might regulate this process, including changes in tonus of β-adrenergic innervation of bone marrow (BM) tissue. Our group reported that in mice circadian changes in the number of HSPCs circulating in PB correlates with diurnal activation of the complement cascade (ComC) and that the mice deficient in C5 component of ComC (C5-KO mice) do not show circadian changes in the number of circulating HSPCs in PB...
June 17, 2018: Stem Cell Reviews
Shuzo Urata, Yukiko Uno, Yohei Kurosaki, Jiro Yasuda
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a high mortality rate. Currently, no licensed vaccines or therapeutic agents have been approved for use against SFTSV infection. Here, we report that the cholesterol, fatty acid, and triglyceride synthesis pathways regulated by S1P is involved in SFTSV replication, using CHO-K1 cell line (SRD-12B) that is deficient in site 1 protease (S1P) enzymatic activity, PF-429242, a small compound targeting S1P enzymatic activity, and Fenofibrate and Lovastatin, which inhibit triglyceride and cholesterol synthesis, respectively...
June 12, 2018: Biochemical and Biophysical Research Communications
Jung-Chien Cheng, Evan Y Wang, Yuyin Yi, Avinash Thakur, Shu-Huei Tsai, Pamela A Hoodless
Dysregulation of the Hippo pathway in the liver results in overgrowth and eventually tumorigenesis. To date, several upstream mechanisms have been identified that affect the Hippo pathway; that ultimately regulate YAP, the major downstream effector of the pathway. However, upstream regulators of the Hippo pathway in the liver remain poorly defined. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that has been shown to stimulate hepatocellular carcinoma (HCC) cell proliferation, but whether the Hippo pathway is involved in S1P-stimulated HCC cell proliferation remains to be determined...
June 14, 2018: Molecular Cancer Research: MCR
Mohammed-Salleh M Ardawi, Abdulrahim A Rouzi, Nawal S Al-Senani, Mohammed H Qari, Ayman Z Elsamanoudy, Shaker A Mousa
Background: Higher sphingosine 1-phosphate (S1P) plasma levels are associated with decreased bone mineral density (BMD), and increased risk of prevalent vertebral fracture. So, we hypothesized that postmenopausal women with increased baseline plasma S1P levels have a greater risk for future incident fracture (osteoporosis-related fractures [ORFs]). Methods: This study was conducted in a prospective longitudinal cohort of 707 women recruited in 2004 and followed up annually for a mean period of 5...
May 2018: Journal of Bone Metabolism
Sascha Marx, Maximilian Splittstöhser, Frederik Kinnen, Eileen Moritz, Christy Joseph, Sebastian Paul, Heiko Paland, Carolin Seifert, Madlen Marx, Andreas Böhm, Edzard Schwedhelm, Kerstin Holzer, Stephan Singer, Christoph A Ritter, Sandra Bien-Möller, Henry W S Schroeder, Bernhard H Rauch
Patients with glioblastoma multiforme (GBM) suffer from an increased incidence of vascular thrombotic events. However, key influencing factors of the primary hemostasis have not been characterized in GBM patients to date. Thus, the present study determines the activation level of circulating platelets in GBM patients, in-vitro reactivity to agonist-induced platelet stimulation and the formation of circulating platelet-leucocyte conjugates as well as the plasma levels of the proinflammatory lipid mediator sphingosine-1-phosphate (S1P)...
May 25, 2018: Oncotarget
Mianhuan Li, Yi Lv, Feng Chen, Xiaoyan Wang, Jiang Zhu, Hao Li, Jia Xiao
BACKGROUND: One of the major obstacles facing stem cell therapy is the limited number of functional stem cells available after transplantation due to the harsh microenvironment surrounding the damaged tissue. The aim of this study was to delineate the mechanistic involvement of lysophosphatidic acid receptors (LPARs) and sphingosine-1-phosphate receptors (S1PRs) in the regulation of anti-stress and transplantation efficacy of stem cells. METHODS: Human adipose-derived mesenchymal stem cells (hADMSCs) were treated with chemical toxin or ethanol to induce cell stress...
June 14, 2018: Stem Cell Research & Therapy
Tingfang Yang, Xianfeng Zhang, Cuimei Ma, Yan Chen
Ischemia-reperfusion (IR) injury is usually associated with a high risk of cardiomyocyte death in patients with acute myocardial infarction. Sphingosine 1-phosphate (S1P) and transforming growth factor (TGF)-β are thought to be involved in the protection of cardiomyocyte and heart function following IR-induced injury. However, the possible association of S1P and S1P receptor 1 (S1PR1) with the TGF-β/Smad3 pathway as the potential protective mechanism has remained to be investigated. In the present study, an in vitro ischemia/reperfusion injury model was established and evaluated by analysis of apoptosis, lactate dehydrogenase (LDH) release and caspase3 activity...
July 2018: Experimental and Therapeutic Medicine
Olivia M Yu, Jorge A Benitez, Steven W Plouffe, Daniel Ryback, Andrea Klein, Jeff Smith, Jason Greenbaum, Benjamin Delatte, Anjana Rao, Kun-Liang Guan, Frank B Furnari, Olga Meiri Chaim, Shigeki Miyamoto, Joan Heller Brown
The role of YAP (Yes-associated protein 1) and MRTF-A (myocardin-related transcription factor A), two transcriptional co-activators regulated downstream of GPCRs (G protein-coupled receptors) and RhoA, in the growth of glioblastoma cells and in vivo glioblastoma multiforme (GBM) tumor development was explored using human glioblastoma cell lines and tumor-initiating cells derived from patient-derived xenografts (PDX). Knockdown of these co-activators in GSC-23 PDX cells using short hairpin RNA significantly attenuated in vitro self-renewal capability assessed by limiting dilution, oncogene expression, and neurosphere formation...
June 11, 2018: Oncogene
Rita Romani, Giorgia Manni, Chiara Donati, Irene Pirisinu, Caterina Bernacchioni, Marco Gargaro, Matteo Pirro, Mario Calvitti, Giorgia Manni, Francesco Bagaglia, Amirhossein Sahebkar, Graziano Clerici, Davide Matino, Giovanni Pomili, Gian Carlo Di Renzo, Vincenzo Nicola Talesa, Paolo Puccetti, Francesca Fallarino
Stem cells have high potential for cell therapy in regenerative medicine. We previously isolated stem cell types from human amniotic fluid, derived from prenatal amniocentesis. One type, characterized by a fast doubling time, was designated as fast human amniotic stem cells (fHASCs). These cells exhibited high differentiation potential and immunoregulatory properties. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite that influences stem-cell pluripotency, differentiation, mobility, and regulates immune functions...
June 7, 2018: European Journal of Pharmacology
Junfei Jin, Zhongyang Lu, Yanchun Li, Ji Hyun Ru, Maria F Lopes-Virella, Yan Huang
It has been well established that patients with diabetes or metabolic syndrome (MetS) have increased prevalence and severity of periodontitis, an oral infection initiated by bacteria and characterized by tissue inflammation and destruction. To understand the underlying mechanisms, we have shown that saturated fatty acid (SFA), which is increased in patients with type 2 diabetes or MetS, and LPS, an important pathogenic factor for periodontitis, synergistically stimulate expression of proinflammatory cytokines in macrophages by increasing ceramide production...
June 8, 2018: Journal of Leukocyte Biology
Shujun Xiao, Jian Yang
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite, which regulates a broad range of physiological and pathophysiological processes. The signaling of S1P via its cell surface receptor S1PR1 has been identified to play an important role in carcinogenesis, cancer growth and survival, and tumor metastasis. In this study, we evaluated whether a monoclonal antibody against S1PR1 (S1PR1 -antibody) could impose any effect on cell growth of human breast cancer SK-BR-3 and MDA-MB-231 cells. The S1PR1 -antibody exhibited cytostatic effect against both cell lines at the concentration of 4000 ng/mL...
June 2, 2018: Investigational New Drugs
Yujiao Han, Xiuling You, Wenhui Xing, Zhong Zhang, Weiguo Zou
The skeleton is a dynamic organ that is constantly remodeled. Proteins secreted from bone cells, namely osteoblasts, osteocytes, and osteoclasts exert regulation on osteoblastogenesis, osteclastogenesis, and angiogenesis in a paracrine manner. Osteoblasts secrete a range of different molecules including RANKL/OPG, M-CSF, SEMA3A, WNT5A, and WNT16 that regulate osteoclastogenesis. Osteoblasts also produce VEGFA that stimulates osteoblastogenesis and angiogenesis. Osteocytes produce sclerostin (SOST) that inhibits osteoblast differentiation and promotes osteoclast differentiation...
2018: Bone Research
Zhijing Zhao, Junfeng Ma, Baoquan Hu, Yi Zhang, Shushu Wang
Thyroid carcinoma is characterized by an aggressive behavior, lack of effective targeted therapies and a high rate of relapse. Sphingosine kinase 1 (SPHK1) has been reported to be a critical regulatory factor in the progression of thyroid carcinoma, but the correlation between SPHK1 and clinical prognosis of patients with thyroid carcinoma has remained to be fully elucidated. The present study aimed to systematically assess the roles of SPHK1 in thyroid carcinoma metastasis and further investigate the possible underlying mechanisms...
June 2018: Experimental and Therapeutic Medicine
Hang Wang, Hao Huang, Shi-Fang Ding
Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that involves in numerous pathophysiological processes. Endothelial progenitor cells (EPCs) play a crucial role in endothelial repair and tumor angiogenesis. The aim of study was to determine the effects of S1P on proliferation and anti-apoptosis of EPCs and their signaling pathways. In this study, we showed that S1P, SEW2871 (a selective S1P receptor 1 (S1PR1) agonist ), or CYM5541 (a selective S1P receptor 3 (S1PR3) allosteric agonist promotes the proliferation and attenuates apoptosis of bone marrow (BM)-derived EPCs...
May 23, 2018: Cell Biology International
Jung H Suh, Émilie Degagné, Elizabeth E Gleghorn, Mala Setty, Alexis Rodriguez, K T Park, Sofia G Verstraete, Melvin B Heyman, Ashish S Patel, Melissa Irek, Ginny L Gildengorin, Neil E Hubbard, Alexander D Borowsky, Julie D Saba
Goal: The aim of this study was to investigate gene expression levels of proteins involved in sphingosine-1-phosphate (S1P) metabolism and signaling in a pediatric inflammatory bowel disease (IBD) patient population. Background: IBD is a debilitating disease affecting 0.4% of the US population. The incidence of IBD in childhood is rising. Identifying effective targeted therapies that can be used safely in young patients and developing tools for selecting specific candidates for targeted therapies are important goals...
May 18, 2018: Inflammatory Bowel Diseases
Kirsi Riento, Qifeng Zhang, Jonathan Clark, Farida Begum, Elaine Stephens, Michael J Wakelam, Benjamin J Nichols
Sphingosine-1-phosphate (S1P) is an important lipid signalling molecule. S1P is produced via intracellular phosphorylation of sphingosine (Sph). As a lipid with a single fatty alkyl chain, Sph may diffuse rapidly between cellular membranes and through the aqueous phase. Here, we show that the absence of microdomains generated by multimeric assemblies of flotillin proteins results in reduced S1P levels. Cellular phenotypes of flotillin knockout mice, including changes in histone acetylation and expression of Isg15, are recapitulated when S1P synthesis is perturbed...
2018: PloS One
Teruaki Takasaki, Kanako Hagihara, Ryosuke Satoh, Reiko Sugiura
Fingolimod hydrochloride (FTY720) is a first-in-class of sphingosine-1-phosphate (S1P) receptor modulator approved to treat multiple sclerosis by its phosphorylated form (FTY720-P). Recently, a novel role of FTY720 as a potential anticancer drug has emerged. One of the anticancer mechanisms of FTY720 involves the induction of reactive oxygen species (ROS) and subsequent apoptosis, which is largely independent of its property as an S1P modulator. ROS have been considered as a double-edged sword in tumor initiation/progression...
2018: Oxidative Medicine and Cellular Longevity
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