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Sphingosine-1-phosphate

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https://www.readbyqxmd.com/read/28733584/therapeutic-effects-of-sphingosine-kinase-inhibitor-n-n-dimethylsphingosine-dms-in-experimental-chronic-chagas-disease-cardiomyopathy
#1
Juliana Fraga Vasconcelos, Cássio Santana Meira, Daniela Nascimento Silva, Carolina Kymie Vasques Nonaka, Pâmela Santana Daltro, Simone Garcia Macambira, Pablo Daniel Domizi, Valéria Matos Borges, Ricardo Ribeiro-Dos-Santos, Bruno Solano de Freitas Souza, Milena Botelho Pereira Soares
Chagas disease cardiomyopathy is a parasite-driven inflammatory disease to which there are no effective treatments. Here we evaluated the therapeutic potential of N,N-dimethylsphingosine(DMS), which blocks the production of sphingosine-1-phosphate(S1P), a mediator of cellular events during inflammatory responses, in a model of chronic Chagas disease cardiomyopathy. DMS-treated, Trypanosoma cruzi-infected mice had a marked reduction of cardiac inflammation, fibrosis and galectin-3 expression when compared to controls...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733250/sphingosine-kinase-1-protects-renal-tubular-epithelial-cells-from-renal-fibrosis-via-induction-of-autophagy
#2
Chunyang Du, Yunzhuo Ren, Fang Yao, Jialiang Duan, Hui'er Zhao, Yunxia Du, Xia Xiao, Huijun Duan, Yonghong Shi
Autophagy is an important homoeostatic mechanism for the lysosomal degradation of protein aggregates and damaged cytoplasmic components. Recent studies suggest that autophagy which is induced by TGF-β1 suppresses kidney fibrosis in renal tubular epithelial cells (RTECs) of obstructed kidneys. Sphingosine kinase 1(SK1), converting sphingosine into endogenous sphingosine-1-phosphate (S1P), was shown to modulate autophagy and involved in the processes of fibrotic diseases. Since SK1 activity is also up-regulated by TGF-β1, we explored its effect on the induction of autophagy and development of renal fibrosis in this study...
July 18, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28725183/bile-acid-mediated-sphingosine-1-phosphate-receptor-2-signaling-promotes-neuroinflammation-during-hepatic-encephalopathy-in-mice
#3
Matthew McMillin, Gabriel Frampton, Stephanie Grant, Shamyal Khan, Juan Diocares, Anca Petrescu, Amy Wyatt, Jessica Kain, Brandi Jefferson, Sharon DeMorrow
Hepatic encephalopathy (HE) is a neuropsychiatric complication that occurs due to deteriorating hepatic function and this syndrome influences patient quality of life, clinical management strategies and survival. During acute liver failure, circulating bile acids increase due to a disruption of the enterohepatic circulation. We previously identified that bile acid-mediated signaling occurs in the brain during HE and contributes to cognitive impairment. However, the influences of bile acids and their downstream signaling pathways on HE-induced neuroinflammation have not been assessed...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28724841/sphingosine-1-phosphate-and-atherosclerosis
#4
Makoto Kurano, Yutaka Yatomi
Sphingosine 1-phosphate (S1P) is a potent lipid mediator that works on five kinds of S1P receptors located on the cell membrane. In the circulation, S1P is distributed to HDL, followed by albumin. Since S1P and HDL share several bioactivities, S1P is believed to be responsible for the pleiotropic effects of HDL. Plasma S1P levels are reportedly lower in subjects with coronary artery disease, suggesting that S1P might be deeply involved in the pathogenesis of atherosclerosis. In basic experiments, however, S1P appears to possess both pro-atherosclerotic and anti-atherosclerotic properties; for example, S1P possesses anti-apoptosis, anti-inflammation, and vaso-relaxation properties and maintains the barrier function of endothelial cells, while S1P also promotes the egress and activation of lymphocytes and exhibits pro-thrombotic properties...
July 20, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28716816/sphingosine-1-phosphate-receptor-1-promotes-environment-induced-and-acquired-chemoresistance
#5
Veronica Lifshitz, Saul J Priceman, Wenzhao Li, Gregory Cherryholmes, Heehyoung Lee, Adar Makovski-Silverstein, Lucia Borriello, Yves A DeClerck, Hua Yu
Drug resistance is a major barrier for the development of effective and durable cancer therapies. Overcoming this challenge requires further defining the cellular and molecular mechanisms underlying drug resistance, both acquired and environment-mediated drug resistance (EMDR). Here, using neuroblastoma (NB), a childhood cancer with high incidence of recurrence due to resistance to chemotherapy, as a model we show that human bone marrow-mesenchymal stromal cells induce tumor expression of sphingosine-1-phosphate receptor-1 (S1PR1) leading to their resistance to chemotherapy...
July 17, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28711286/novel-therapeutic-targets-for-inflammatory-bowel-disease
#6
REVIEW
Marjorie Argollo, Gionata Fiorino, Pieter Hindryck, Laurent Peyrin-Biroulet, Silvio Danese
Inflammatory bowel disease (IBD), including Crohn's disease (CD) and Ulcerative Colitis (UC), are immune mediated conditions associated with progressive damage of the inflamed gut tissue, and have a considerable impact on the patient's quality of life. The pathogenesis remains uncertain, but it is clear that complex mechanisms associated with host and luminal factors are involved, generating an unbalance between pro- and anti-inflammatory signaling. It is well established that the purpose of an adequate and complete control of the intestinal inflammation measured not only by clinical symptoms, but also with more objective data such as fecal biomarkers (calprotectin) and endoscopy...
July 12, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28709801/lymphatic-endothelial-cells-control-initiation-of-lymph-node-organogenesis
#7
Lucas Onder, Urs Mörbe, Natalia Pikor, Mario Novkovic, Hung-Wei Cheng, Thomas Hehlgans, Klaus Pfeffer, Burkhard Becher, Ari Waisman, Thomas Rülicke, Jennifer Gommerman, Christopher G Mueller, Shinichiro Sawa, Elke Scandella, Burkhard Ludewig
Lymph nodes (LNs) are strategically situated throughout the body at junctures of the blood vascular and lymphatic systems to direct immune responses against antigens draining from peripheral tissues. The current paradigm describes LN development as a programmed process that is governed through the interaction between mesenchymal lymphoid tissue organizer (LTo) cells and hematopoietic lymphoid tissue inducer (LTi) cells. Using cell-type-specific ablation of key molecules involved in lymphoid organogenesis, we found that initiation of LN development is dependent on LTi-cell-mediated activation of lymphatic endothelial cells (LECs) and that engagement of mesenchymal stromal cells is a succeeding event...
July 18, 2017: Immunity
https://www.readbyqxmd.com/read/28709768/plasma-sphingosine-1-phosphate-concentrations-are-associated-with-systolic-heart-failure-in-patients-with-ischemic-heart-disease
#8
Amin Polzin, Kerstin Piayda, Petra Keul, Lisa Dannenberg, Annemarie Mohring, Markus Gräler, Tobias Zeus, Malte Kelm, Bodo Levkau
OBJECTIVE: Sphingosine-1-Phosphate (S1P) is a bioactive sphingolipid with important functions in immunity, inflammation and cardiovascular biology. S1P is associated with prevalence and severity of coronary artery disease and myocardial infarction. However, its relevance in ischemic cardiomyopathy is unknown. We aimed to investigate associations of plasma S1P and other sphingolipids with the extent of heart failure in patients with ischemic heart disease. METHODS AND RESULTS: 74 patients with ischemic heart disease were investigated in this observational study...
July 12, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28706199/defective-sphingosine-1-phosphate-metabolism-is-a-druggable-target-in-huntington-s-disease
#9
Alba Di Pardo, Enrico Amico, Abdul Basit, Andrea Armirotti, Piyush Joshi, Diana M Neely, Romina Vuono, Salvatore Castaldo, Anna F Digilio, Francesco Scalabrì, Giuseppe Pepe, Francesca Elifani, Michele Madonna, Se Kyoo Jeong, Bu-Mahn Park, Maurizio D'Esposito, Aaron B Bowman, Roger A Barker, Vittorio Maglione
Huntington's disease is characterized by a complex and heterogeneous pathogenic profile. Studies have shown that disturbance in lipid homeostasis may represent a critical determinant in the progression of several neurodegenerative disorders. The recognition of perturbed lipid metabolism is only recently becoming evident in HD. In order to provide more insight into the nature of such a perturbation and into the effect its modulation may have in HD pathology, we investigated the metabolism of Sphingosine-1-phosphate (S1P), one of the most important bioactive lipids, in both animal models and patient samples...
July 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698261/adipocyte-specific-deficiency-of-de-novo-sphingolipid-biosynthesis-leads-to-lipodystrophy-and-insulin-resistance
#10
Su-Yeon Lee, Hui-Young Lee, Jae-Hwi Song, Goon-Tae Kim, Suwon Jeon, Yoo-Jeong Song, Jae Sung Lee, Jang-Ho Hur, Hyun Hee Oh, Shi-Young Park, Soon-Mi Shim, Hyun Joo Yoo, Byung Cheon Lee, Xian-Cheng Jiang, Cheol Soo Choi, Tae-Sik Park
Sphingolipids have been implicated in the etiology of chronic metabolic diseases. Here, we investigated whether sphingolipid biosynthesis is associated with the development of adipose tissues and metabolic diseases. SPTLC2, a subunit of serine palmitoyltransferase, was transcriptionally upregulated in the adipose tissues of obese mice and in differentiating adipocytes. Adipocyte-specific SPTLC2-deficient (aSPTLC2 KO) mice had markedly reduced adipose tissue mass. Fatty acids that were destined for the adipose tissue were instead shunted to liver and caused hepatosteatosis...
July 11, 2017: Diabetes
https://www.readbyqxmd.com/read/28695300/new-fty720-docetaxel-nanoparticle-therapy-overcomes-fty720-induced-lymphopenia-and-inhibits-metastatic-breast-tumour-growth
#11
Heba Alshaker, Qi Wang, Shyam Srivats, Yimin Chao, Colin Cooper, Dmitri Pchejetski
PURPOSE: Combining molecular therapies with chemotherapy may offer an improved clinical outcome for chemoresistant tumours. Sphingosine-1-phosphate (S1P) receptor antagonist and sphingosine kinase 1 (SK1) inhibitor FTY720 (FTY) has promising anticancer properties, however, it causes systemic lymphopenia which impairs its use in cancer patients. In this study, we developed a nanoparticle (NP) combining docetaxel (DTX) and FTY for enhanced anticancer effect, targeted tumour delivery and reduced systemic toxicity...
July 10, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28690543/frontiers-in-drug-research-and-development-for-inflammatory-bowel-disease
#12
REVIEW
Diego Currò, Daniela Pugliese, Alessandro Armuzzi
Inflammatory bowel disease (IBD) is idiopathic, lifelong, immune-mediated diseases, for which curative therapies are not yet available. In the last 15 years, the introduction of monoclonal antibodies targeting tumor necrosis factor-α, a cytokine playing a key role in bowel inflammation, has revolutionized treatment paradigms for IBD. Despite their proven long-term efficacy, however, many patients do not respond or progressively lose response to these drugs. Major advances of knowledge in immunology and pathophysiology of intestinal inflammatory processes have made possible the identification of new molecular targets for drugs, thus opening several new potential therapeutic opportunities for IBD...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28687489/fas-s1p1-crosstalk-via-nf-%C3%AE%C2%BAb-activation-in-osteoclasts-controls-subchondral-bone-remodeling-in-murine-tmj-arthritis
#13
Islamy Rahma Hutami, Takashi Izawa, Akiko Mino-Oka, Takehiro Shinohara, Hiroki Mori, Akihiko Iwasa, Eiji Tanaka
Enhanced turnover of subchondral trabecular bone is a hallmark of rheumatoid arthritis (RA) and it results from an imbalance between bone resorption and bone formation activities. To investigate the formation and activation of osteoclasts which mediate bone resorption, a Fas-deficient MRL/lpr mouse model which spontaneously develops autoimmune arthritis and exhibits decreased bone mass was studied. Various assays were performed on subchondral trabecular bone of the temporomandibular joint (TMJ) from MRL/lpr mice and MRL+/+ mice...
July 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28684192/involvement-of-sphingosine-kinase-sphingosine-1-phosphate-metabolic-pathway-in-spondyloarthritis
#14
Carole Bougault, Alaeddine El Jamal, Anne Briolay, Saida Mebarek, Marie-Astrid Boutet, Thomas Garraud, Benoit Le Goff, Fréderic Blanchard, David Magne, Leyre Brizuela
Spondyloarthritis (SpA) is a relatively common chronic inflammatory joint disorder, with a prevalence of about 0.2-0.5% worldwide. The primary target of the pathological process is the enthesis, where tendons and ligaments attach to underlying bone. These insertion sites are hotspots of bone formation (enthesophytes), which can lead to ankylosis. Unfortunately, the mechanisms causing the onset and progression of entheseal ossification remain largely unknown. Sphingosine 1-phosphate (S1P), a lipid generated after sphingosine phosphorylation by sphingosine kinases 1 and 2 (SK1/2), plays important roles in cell proliferation, differentiation and survival...
July 3, 2017: Bone
https://www.readbyqxmd.com/read/28683966/%C3%AE-1-blockade-prevents-post-ischemic-myocardial-decompensation-via-%C3%AE-3ar-dependent-protective-sphingosine-1-phosphate-signaling
#15
Alessandro Cannavo, Giuseppe Rengo, Daniela Liccardo, Andres Pun, Ehre Gao, Alvin J George, Giuseppina Gambino, Antonio Rapacciuolo, Dario Leosco, Borja Ibanez, Nicola Ferrara, Nazareno Paolocci, Walter J Koch
BACKGROUND: Although β-blockers increase survival in patients with heart failure (HF), the mechanisms behind this protection are not fully understood, and not all patients with HF respond favorably to them. We recently showed that, in cardiomyocytes, a reciprocal down-regulation occurs between β1-adrenergic receptors (ARs) and the cardioprotective sphingosine-1-phosphate (S1P) receptor-1 (S1PR1). OBJECTIVES: The authors hypothesized that, in addition to salutary actions due to direct β1AR-blockade, agents such as metoprolol (Meto) may improve post-myocardial infarction (MI) structural and functional outcomes via restored S1PR1 signaling, and sought to determine mechanisms accounting for this effect...
July 11, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28680571/simvastatin-induced-sphingosine-1-phosphate-receptor-1-expression-is-klf2-dependent-in-human-lung-endothelial-cells
#16
Xiaoguang Sun, Biji Mathew, Saad Sammani, Jeffrey R Jacobson, Joe G N Garcia
We have demonstrated that simvastatin and sphingosine 1-phosphate (S1P) both attenuate increased vascular permeability in preclinical models of acute respiratory distress syndrome. However, the underlying mechanisms remain unclear. As Krüppel-like factor 2 (KLF2) serves as a critical regulator for cellular stress response in endothelial cells (EC), we hypothesized that simvastatin enhances endothelial barrier function via increasing expression of the barrier-promoting S1P receptor, S1PR1, via a KLF2-dependent mechanism...
March 2017: Pulmonary Circulation
https://www.readbyqxmd.com/read/28677769/valproic-acid-enforces-the-priming-effect-of-sphingosine-1-phosphate-on-human-mesenchymal-stem-cells
#17
Jisun Lim, Seungun Lee, Hyein Ju, Yonghwan Kim, Jinbeom Heo, Hye-Yeon Lee, Kyung-Chul Choi, Jaekyoung Son, Yeon-Mok Oh, In-Gyu Kim, Dong-Myung Shin
Engraftment and homing of mesenchymal stem cells (MSCs) are modulated by priming factors including the bioactive lipid sphingosine-1-phosphate (S1P), by stimulating CXCR4 receptor signaling cascades. However, limited in vivo efficacy and the remaining priming molecules prior to administration of MSCs can provoke concerns regarding the efficiency and safety of MSC priming. Here, we showed that valproic acid (VPA), a histone deacetylase inhibitor, enforced the priming effect of S1P at a low dosage for human umbilical cord-derived MSCs (UC-MSCs)...
July 3, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28672103/shingosine-1-phosphate-suppresses-chondrosarcoma-metastasis-by-up-regulation-of-tissue-inhibitor-of-metalloproteinase-3-through-suppressing-mir-101-expression
#18
Chun-Hao Tsai, Dong-Ying Yang, Chih-Yang Lin, Tsung-Ming Chen, Chih-Hsin Tang, Yuan-Li Huang
Chondrosarcoma is the second most common primary malignancy form of bone cancer, exhibiting resistance to chemotherapy and radiation therapy as well as developing high metastasis ability in late stage tumors. Thus, understanding the metastatic processes of chondrosarcoma is considered a strategy for treatment of this disease. Sphingosine 1-phosphate (S1P), a bioactive sphingolipid, is produced intracellularly by sphingosine kinase (SphK) and is regarded as a second signaling molecule that regulates inflammation, proliferation, angiogenesis, and metastasis...
July 3, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28668852/sphingosine-1-phosphate-receptor-1-as-a-marker-for-endothelial-cells-in-mouse-xenograft-models-of-human-cancer
#19
Nadine Lüders, Udo Schumacher
BACKGROUND/AIM: The sphingosine-1-phosphate (S1P) 1 receptor (S1P1R) is an important receptor for the modulation of endothelial cell function. We, therefore, wanted to investigate its expression as a blood vessel marker. MATERIALS AND METHODS: The expression of the S1P receptor 1 (S1P1R) in mouse blood vessel endothelium was investigated immunohistochemically in normal blood vessel endothelium and blood vessel endothelium of xenografted human tumors. RESULTS: The S1P1 receptor was expressed in the endothelium of most mouse organs...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28666250/the-novel-sphingosine-1-phosphate-receptors-antagonist-ad2900-affects-lymphocyte-activation-and-inhibits-t-cell-entry-into-the-lymph-nodes
#20
Jing Song, Arie Dagan, Zhanna Yakhtin, Shimon Gatt, Sean Riley, Hugh Rosen, Reuven Or, Osnat Almogi-Hazan
Sphingolipid derivatives play key roles in immune cell migration and function. Synthetic sphingolipid analogues are used as therapeutics to intervene various inflammatory and malignant conditions. We hypothesize that different analogs have different effects on immune cells and therefore can be used as treatment for specific diseases. This study examines the properties of the novel synthetic sphingolipid analog, AD2900, and its effects on immune cell activation and lymphocyte localization in homeostasis. AD2900 is an antagonist for all sphingosine-1-phosphate (S1P) receptors...
June 27, 2017: Oncotarget
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