检索结果-南通市图书馆

The Sphingosine-1-phosphate/RhoA/Rho associated kinases/myosin light chain pathway in detrusor of female rats is down-regulated in response to ovariectomy

引用

Chinese Medical Journal 2020年第10期133卷 1203-1210页

作者： Wei Zhang Xiao-Dong Liu Jia-Wen Wang Ling-Feng Meng Yao-Guang Zhang Jian-Ye Wang Peking University Fifth School of Clinical Medicine Beijing 100730China Department of Urology Beijing HospitalNational Center of GerontologyBeijing 100730China.

Background:Dysuria is one of the main symptoms of genitourinary syndrome of menopause,which causes serious disruption to the normal life of peri-menopausal women.Studies have shown that it is related to decrease of detrusor contractile function,but the exact mechanism is still poorly understood.Previous results have suggested that the Sphingosine-1-phosphate(S1P)pathway can regulate detrusor contraction,and this pathway is affected by estrogen in various tissues.However,how estrogen affects this pathway in the detrusor has not been investigated.In this study,we detected changes of the S1P/RhoA/Rho associated kinases(ROCK)/myosin light chain(MLC)pathway in the detrusor of ovariectomized rats in order to explore the underlying mechanism of dysuria during peri-menopause.Methods::Thirty-six female Sprague-Dawley rats were randomly divided into SHAM(sham operation),OVX(ovariectomy),and E groups(ovariectomy+estrogen),with 12 rats in each group.We obtained bladder detrusor tissues from each group and examined the mRNA and protein levels of the major components of the S1P/RhoA/ROCK/MLC pathway using quantitative real-time polymerase chain reaction and Western blotting,respectively.We also quantified the content of S1P in the detrusor using an enzyme linked immunosorbent assay.Finally,we compared results between the groups with one-way analysis of variance.Results::The components of the S1P pathway and the RhoA/ROCK/MLC pathway of the OVX group were significantly decreased,as compared with SHAM group.The percent decreases of the components in the S1P pathway were as follows:sphingosine kinase 1(mRNA:39%,protein:45%)(both P0.05).The percent decreases of the components in the RhoA/ROCK/MLC pathway were as follows:ROCK2(protein:41%,mRNA:36%)(both P<0.0

关键词： Myosin light chains Ovariectomy Rats Rho-associated kinases Sphingosine-1-phosphate Urinary bladder

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Aryl hydrocarbon receptor signaling promotes ORMDL3- dependent generation of Sphingosine-1-phosphate by inhibiting Sphingosine-1-phosphate lyase

引用

Cellular & Molecular Immunology 2019年第10期16卷 783-790页

作者： 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 Department of Medical Research China Medical University HospitalChina Medical University40402 TaichungTaiwanChina Graduate Institute of Medicine College of MedicineKaohsiung Medical UniversityKaohsiungTaiwanChina Division of Allergy Asthma and RheumatologyDepartment of PediatricsChang Gung Memorial HospitalTaoyuanTaiwanChina National Institute of Environmental Health Sciences National Health Research InstitutesMiaoliTaiwanChina Research Center of Environmental Medicine Kaohsiung Medical UniversityKaohsiungTaiwanChina Center for Research Resources and Development Kaohsiung Medical UniversityKaohsiungTaiwanChina Community Medicine Research Center Chang Gung Memorial Hospital at KeelungKeelungTaiwanChina Department of Pediatrics Xiamen Chang Gung HospitalXiamenChina Johns Hopkins University School of Medicine BaltimoreMDUSA Key Laboratory of Neonatal Disease Children’s Hospital and Institute of Biomedical SciencesMinistry of HealthFudan University201102 ShanghaiChina Lou-Hu Hospital Shen-Zhen UniversityShen-ZhenChina

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.The reduction of S1PL activity was due to AhR-mediated oxidation of S1PL at residue 317,which was reversible by the addition of an antioxidant or in cells with knockdown of the ORMDL3 gene encoding an ER transmembrane protein,whereas C317A S1PL mutant-transfected cells were resistant to the AhR-mediated effect.Furthermore,analysis of AhR ligand-treated cells showed a time-dependent increase of the ORMDL3–S1PL complex,which was confirmed by FRET analysis.This change increased the S1P levels,which in turn,induced mast cell degranulation via S1PR2 signaling.In addition,elevated levels of plasma S1P were found in children with asthma compared to non-asthmatic subjects.These results suggest a new regulatory pathway whereby the AhR–ligand axis induces ORMDL3-dependent S1P generation by inhibiting S1PL,which may contribute to the expression of allergic diseases.

关键词： Aryl hydrocarbon receptor ORMDL sphingolipid biosynthesis regulator 3 Sphingosine-1-phosphate Sphingosine-1-phosphate lyase

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Regulatory role of sphingosine kinase and Sphingosine-1-phosphate receptor signaling in progenitor/stem cells

引用

World Journal of Stem Cells 2018年第9期10卷 119-133页

作者： Mei Li Ng Nagendra S Yarla Mario Menschikowski Olga A Sukocheva Centenary Institute of Cancer Medicine and Cell Biology Sydney NSW 2050Australia Department of Biochemistry and Bioinformatics Institute of ScienceGITAM UniversityRushikondaVisakhapatnam 530 045Andhra PradeshIndia Institute of Clinical Chemistry and Laboratory Medicine Carl Gustav Carus University HospitalTechnical University of DresdenDresden D-01307Germany College of Nursing and Health Sciences Flinders University of South AustraliaBedford Park SA 5042Australia

Balanced sphingolipid signaling is important for the maintenance of homeostasis. Sphingolipids were demonstrated to function as structural components, second messengers, and regulators of cell growth and survival in normal and disease-affected tissues. Particularly, sphingosine kinase 1 (SphK1) and its product Sphingosine-1-phosphate (S1P) operate as mediators and facilitators of proliferation-linked signaling. Unlimited proliferation (selfrenewal) within the regulated environment is a hallmark of progenitor/stem cells that was recently associated with the S1P signaling network in vasculature, nervous,muscular, and immune systems. S1P was shown to regulate progenitor-related characteristics in normal and cancerstemcells(CSCs) viaG-protein coupled receptorsS1Pn(n=1 to 5). The SphK/S1P axis is crucially involved in the regulation of embryonic development of vasculature and the nervous system, hematopoietic stem cell migration, regeneration of skeletal muscle, and development of multiple sclerosis. The ratio of the S1P receptor expression, localization, and specific S1P receptoractivated downstream effectors influenced the rate of selfrenewal and should be further explored as regeneration related targets. Considering malignant transformation,it is essential to control the level of self-renewal capacity.Proliferation of the progenitor cell should be synchronized with differentiation to provide healthy lifelong function of blood, immune systems, and replacement of damaged ordead cells. The differentiation-related role of SphK/S1P remains poorly assessed. A few pioneering investigations exploredpharmacologicaltoolsthattargetsphingolipid signaling and can potentially confine and direct self-renewal towards normal differentiation. Further investigation is required to test the role of the SphK/S1P axis in regulation of self-renewal and differentiation.

关键词： Sphingosine-1-phosphate Sphingolipids Embryonic stem cells Mesenchymal stem cells Bone marrow hematopoietic stem cells sphingosine kinase Progenitor

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

STAT3 and Sphingosine-1-phosphate in inflammation-associated colorectal cancer

引用

World Journal of Gastroenterology 2014年第30期20卷 10279-10287页

作者： Andrew V Nguyen Yuan-Yuan Wu Elaine Y Lin Department of Biological Sciences and Geology Queensborough-CUNYBaysideNY 10461United States Department of Pathology Montefiore Medical CenterAlbert Einstein College of MedicineBronxNY 10461United States Department of Medicine Einstein Cancer CenterAlbert Einstein College of MedicineBronxNY 10461United States

Accumulated evidences have demonstrated that signal transducer and activator of transcription 3(STAT3)is a critical link between inflammation and cancer.Multiple studies have indicated that persistent activation of STAT3 in epithelial/tumor cells in inflammation-associated colorectal cancer(CRC)is associated with Sphingosine-1-phosphate(S1P)receptor signaling.In inflammatory response whereby interleukin(IL)-6 production is abundant,STAT3-mediated pathways were found to promote the activation of sphingosine kinases(SphK1and SphK2)leading to the production of S1P.Reciprocally,S1P encourages the activation of STAT3 through a positive autocrine-loop signaling.The crosstalk between IL-6,STAT3 and sphingolipid regulated pathways may play an essential role in tumorigenesis and tumor progression in inflamed intestines.Therapeutics targeting both STAT3 and sphingolipid are therefore likely to contribute novel and more effective therapeutic strategies against inflammation-associated CRC.

关键词： Sphingosine-1-phosphate Signal transducer and acti

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Unveiling the biological role of Sphingosine-1-phosphate receptor modulators in inflammatory bowel diseases

引用

World Journal of Gastroenterology 2023年第1期29卷 110-125页

作者： Evanthia Tourkochristou Athanasia Mouzaki Christos Triantos Division of Gastroenterology Department of Internal MedicineMedical SchoolUniversity of PatrasPatras 26504Greece Division of Hematology Department of Internal MedicineMedical SchoolUniversity of PatrasPatras 26504Greece

Inflammatory bowel disease(IBD)is chronic inflammation of the gastrointestinal tract that has a high epidemiological prevalence worldwide.The increasing disease burden worldwide,lack of response to current biologic therapeutics,and treatment-related immunogenicity have led to major concerns regarding the clinical management of IBD patients and treatment efficacy.Understanding disease pathogenesis and disease-related molecular mechanisms is the most important goal in developing new and effective therapeutics.Sphingosine-1-phosphate(S1P)receptor(S1PR)modulators form a class of oral small molecule drugs currently in clinical development for IBD have shown promising effects on disease improvement.S1P is a sphingosine-derived phospholipid that acts by binding to its receptor S1PR and is involved in the regulation of several biological processes including cell survival,differentiation,migration,proliferation,immune response,and lymphocyte trafficking.T lymphocytes play an important role in regulating inflammatory responses.In inflamed IBD tissue,an imbalance between T helper(Th)and regulatory T lymphocytes and Th cytokine levels was found.The S1P/S1PR signaling axis and metabolism have been linked to inflammatory responses in IBD.S1P modulators targeting S1PRs and S1P metabolism have been developed and shown to regulate inflammatory responses by affecting lymphocyte trafficking,lymphocyte number,lymphocyte activity,cytokine production,and contributing to gut barrier function.

关键词： Inflammatory bowel disease Sphingosine-1-phosphate Intestinal inflammation T helper 1/T helper 17 sphingosine 1 phosphate Modulators Immune responses

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Roles of Sphingosine-1-phosphate signaling in angiogenesis

引用

World Journal of Biological Chemistry 2010年第10期1卷 298-306页

作者： Yoh Takuwa Yasuo Okamoto Noriko Takuwa Kazuaki Yoshioka Department of Health and Medical Sciences Ishikawa Prefectural Nursing University7-1 Nakanumatu KahokuIshikawa 929-1212Japan

Sphingosine-1-phosphate (S1P) is a blood-borne lipid mediator with pleiotropic biological activities. S1P acts via the specific cell surface G-protein-coupled receptors, S1P1-5. S1P1 and S1P2 were originally identified from vascular endothelial cells (ECs) and smooth muscle cells, respectively. Emerging evidence shows that S1P plays crucial roles in the regulation of vascular functions, including vascular formation, barrier protection and vascular tone via S1P1, S1P2 and S1P3. In particular, S1P regulates vascular formation through multiple mechanisms; S1P exerts both positive and negative effects on angiogenesis and vascular maturation. The positive and negative effects of S1P are mediated by S1P1 and S1P2, respectively. These effects of S1P1 and S1P2 are probably mediated by the S1P receptors expressed in multiple cell types including ECs and bone-marrow-derived cells. The receptor-subtype-specific, distinct effects ofS1P favor the development of novel therapeutic tactics for antitumor angiogenesis in cancer and therapeutic angiogenesis in ischemic diseases.

关键词： Sphingosine-1-phosphate Angiogenesis Angiogenic therapy Rac Akt Vascular maturation Endothelial cells Bone-marrow-derived cells

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Expressions of Sphingosine-1-phosphate (S1P) Receptors, sphingosine Kinases in Malignant Bone and Soft Tissue Tumors, and The role of sphingosine Kinase-1 in Growth of MFH Cell Lines

引用

Journal of Cancer Therapy 2011年第2期2卷 288-294页

作者： Shin-ichiro Kishimoto Toshihiro Akisue Kenta Kishimoto Hitomi Hara Masaya Imabori Yoshiyuki Okada Naomasa Fukase Teruya Kawamoto Ikuo Fujita Takuya Fujimoto Masahiro Kurosaka Department of Orthopaedic Surgery Kobe University Graduate School of Medicine Kusunoki-cho Chuo-ku Kobe JAPAN

Sphingolipids are ubiquitous components of cell membranes. Their metabolites ceramide, sphingosine, and Sphingosine-1-phosphate (S1P) have important physiological functions, including regulation of cell growth and survival. S1P is generated by phosphorylation of sphingosine catalyzed by sphingosine kinase-1 (SPHK1). The purpose of this study is to explore the roles of S1P, S1P receptors, and sphingosine kinases in malignant musculoskeletal tumors. Twenty-one tumor samples (7 liposarcomas, 3 chondrosarcomas, 6 osteosarcomas, 5 MFH) obtained at open biopsy, and four human MFH cell lines (Nara H, Nara F, TNMY1, GBS-1) were used. We examined the mRNA expression of S1P receptors by RT-PCR, and the expression levels of SPHK by Real-time PCR. We used 4 MFH cell lines to analyze SPHK1 proteins by Western blotting. SPHK1 siRNA was transfected into MFH cell lines by lipofection method. Cell proliferation (control and transfected with siRNA) was assayed using WST-8 (Cell Counting Kit-8) assay. All high grade malignant tumors expressed S1P1, S1P2, S1P3 receptors, whereas the expression of S1P1 receptor was detected in 50% of low-grade malignant tumors, S1P2 receptor in 30%, and S1P3 in 50%. No statistically significant difference was found in the expression level of SPHK1 between high-grade and low-grade malignant tumors by Real-time PCR. By results of Western blotting, proteins of SPHK1 were expressed in all MFH cell lines. In MFH cell lines, transfection with SPHK1 siRNA oligonucleotides resulted in approximately 50 to 80% suppression of SPHK1 mRNA expression as determined by real-time PCR. Down-regulation of SPHK1 with small interfering RNA significantly reduced SPHK1 protein levels by Western blotting. Knock down of SPHK1 expression significantly decreased cell proliferation of all MFH cells. These results suggest that the expression of S1P receptors may play an important role for cell proliferation and may correlate with histologic grade in malignant bone and soft tissue tumors, and that SPHK1 may be one of essential mo

关键词： Sarcoma Sphingosine-1-phosphate S1p Receptor sphingosine Kinase MIB-1 MFH

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Sphingosine-1-phosphate signaling in vasculogenesis and angiogenesis

引用

World Journal of Biological Chemistry 2010年第10期1卷 291-297页

作者： Kelley M Argraves Brent A Wilkerson W Scott Argraves Department of Regenerative Medicine and Cell Biology Medical University of South Carolina173 Ashley Avenue CharlestonSC 29425United States

Blood vessels either form de novo through the process of vasculogenesis or through angiogenesis that involves the sprouting and proliferation of endothelial cells in pre-existing blood vessels. A complex interactive network of signaling cascades downstream from at least three of the nine known G-protein-coupled Sphingosine-1-phosphate (S1P) receptors act as a prime effector of neovascularization that occurs in embryonic development and in association with various pathologies. This review focuses on the current knowledge of the roles of S1P signaling in vasculogenesis and angiogenesis, with particular emphasis on vascular cell adhesion and motility responses.

关键词： Sphingosine-1-phosphate Vasculogenesis Angiogenesis G-protein-coupled receptors Endothelium

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Role of sphingosine kinase and Sphingosine-1-phosphate in inflammatory arthritis

引用

World Journal of Biological Chemistry 2010年第11期1卷 321-326页

作者： Alirio J Melendez Bernard P Leung Division of Immunology Infection and InflammationGlasgow Biomedical Research CentreUniversity of Glasgow

The importance of sphingosine kinase(SphK)and Sphingosine-1-phosphate(S1P)in inflammation has been extensively demonstrated.As an intracellular second messenger,S1P plays an important role in calcium signaling and mobilization,and cell proliferation and survival.Activation of various plasma membrane receptors,such as the formyl methionyl leucyl phenylalanine receptor,C5a receptor,and tumor necrosis factor α receptor,leads to a rapid increase in intracellular S1P level via SphK stimulation.SphK and S1P are implicated in various chronic autoimmune conditions such as rheumatoid arthritis, primary Sjgren's syndrome,and inflammatory bowel disease.Recent studies have demonstrated the important role of SphK and S1P in the development of arthritis by regulating the pro-inflammatory responses.These novel pathways represent exciting potential therapeutic targets.

关键词： Cytokines Inflammation Rheumatoid arthritis sphingosine kinase Sphingosine-1-phosphate

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Siponimod exerts neuroprotective effects on the retina and higher visual pathway through neuronal S1PR1 in experimental glaucoma

引用

Neural Regeneration Research 2023年第4期18卷 840-848页

作者： Devaraj Basavarajappa Vivek Gupta Nitin Chitranshi Roshana Vander Wall Rashi Rajput Kanishka Pushpitha Samridhi Sharma Mehdi Mirzaei Alexander Klistorner Stuart L.Graham Department of Clinical Medicine Faculty of MedicineHealth and Human SciencesMacquarie UniversityNorth RydeSydneyNSWAustralia

Sphingosine-1-phosphate receptor(S1PR)signaling regulates diverse pathophysiological processes in the central nervous system.The role of S1PR signaling in neurodegenerative conditions is still largely unidentified.Siponimod is a specific modulator of S1P1 and S1P5 receptors,an immunosuppressant drug for managing secondary progressive multiple sclerosis.We investigated its neuroprotective properties in vivo on the retina and the brain in an optic nerve injury model induced by a chronic increase in intraocular pressure or acute N-methyl-D-aspartate excitotoxicity.Neuronal-specific deletion of Sphingosine-1-phosphate receptor(S1PR1)was carried out by expressing AAV-PHP.eB-Cre recombinase under Syn1 promoter in S1PR1mice to define the role of S1PR1 in neurons.Inner retinal electrophysiological responses,along with histological and immunofluorescence analysis of the retina and optic nerve tissues,indicated significant neuroprotective effects of siponimod when administered orally via diet in chronic and acute optic nerve injury models.Further,siponimod treatment showed significant protection against trans-neuronal degenerative changes in the higher visual center of the brain induced by optic nerve injury.Siponimod treatment also reduced microglial activation and reactive gliosis along the visual pathway.Our results showed that siponimod markedly upregulated neuroprotective Akt and Erk1/2 activation in the retina and the brain.Neuronal-specific deletion of S1PR1 enhanced retinal and dorsolateral geniculate nucleus degenerative changes in a chronic optic nerve injury condition and attenuated protective effects of siponimod.In summary,our data demonstrated that S1PR1signaling plays a vital role in the retinal ganglion cell and dorsolateral geniculate nucleus neuronal survival in experimental glaucoma,and siponimod exerts direct neuroprotective effects through S1PR1 in neurons in the central nervous system independent of its peripheral immuno-modulatory effects.Our findings suggest that neuronal S1PR1 is a neuroprotective

关键词： glaucoma intraocular pressure neurodegeneration neuroprotection optic nerve injury retinal ganglion cells siponimod Sphingosine-1-phosphate

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：