检索结果-南通市图书馆

sphingosine kinase 1 knockout alleviates hepatic ischemia/reperfusion injury by attenuating inflammation and oxidative stress in mice

引用

Hepatobiliary & Pancreatic Diseases International 2019年第3期18卷 255-265页

作者： Guang-Hui Qiang Zhong-Xia Wang An-Lai Ji Jun-Yi Wu Yin Cao Guang Zhang Yi-Yang Zhang Chun-Ping Jiang Department of Hepatobiliary Surgery Nanjing Drum Tower Hospital Drum Tower Clinical College of Nanjing Medical University Nanjing 210008 China Department of Hepatobiliary Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 China Department of Gastroenterology Nanjing Drum Tower Hospital Drum Tower Clinical College of Nanjing Medical University Nanjing 210008 China

Background: Hepatic ischemia/reperfusion(I/R) injury remains a significant problem in clinical practice. sphingosine kinase 1(Sph K1) phosphorylates sphingosine to sphingosine-1-phosphate(S1 P) which participates in multiple bioactive processes. However, little is known about the role of Sph K1 in hepatic I/R injury. This study aimed to investigate the effect of Sph K1 knockout on liver I/R injury and to explore underlying mechanisms. Methods: Sph K1 knockout and wild type mice were subjected to 70% partial hepatic I/R. Serum alanine aminotransferase was determined to indicate the degree of liver damage. Hematoxylin-eosin staining and TUNEL assay were used to assess histological changes and hepatocellular apoptosis, respectively. Immunohistochemistry was performed to detect the expression and translocation of phosphorylated p65 and signal transducer and activator of transcription 3(STAT3). Western blotting was used to determine the expression of S1 P receptor 1(S1 PR1), phosphorylated p65 and STAT3. Real-time PCR was used to demonstrate the changes of proinflammatory cytokines. Oxidative stress markers were also determined through biochemical assays. Results: Sph K1 knockout significantly ameliorated I/R-induced liver damage, mitigated liver tissue necrosis and apoptosis compared with wild type control. I/R associated inflammation was alleviated in Sph K1 knockout mice as demonstrated by attenuated expression of S1 PR1 and reduced phosphorylation of nuclear factor kappa B p65 and STAT3. The proinflammatory cytokines interleukin-1 β, interleukin-6 and tumor necrosis factor-α were also inhibited by Sph K1 genetic deletion. The oxidative stress markers were lower in Sph K1 knockout mice after I/R injury than wild type mice. Conclusions: Knockout of Sph K1 significantly alleviated damage after hepatic I/R injury, possibly through inhibiting inflammation and oxidative stress. Sph K1 may be a novel and potent target in clinical practice in I/R-related liver injury.

关键词： Ischemia/reperfusion injury sphingosine kinase 1 Inflammation Oxidative stress

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

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 *** 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

Inhibition of sphingosine kinase 1 ameliorates acute liver failure by reducing high-mobility group box 1 cytoplasmic translocation in liver cells

引用

World Journal of Gastroenterology 2015年第46期21卷 13055-13063页

作者： Yan-Chang Lei Ling-Ling Yang Wen Li Pan Luo Pei-Fen Zheng Department of Infectious Diseases Zhejiang Hospital Infectious Disease Hospital of Nanchang University Department of Gastroenterology Zhejiang Hospital

AIM: To determine the therapeutic potential of sphingosine kinase 1(Sphk1) inhibition and its underlying mechanism in a well-characterized mouse model of D-galactosamine(D-Gal N)/lipopolysaccharide(LPS)-induced acute liver failure(ALF).METHODS: Balb/c mice were randomly assigned to different groups,with ALF induced by intraperitoneal injection of D-Ga IN(600 mg/kg) and LPS(10 μg/kg). The Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels at different time points within one week were determined using a multi-parametric analyzer. Serum high-mobility group box 1(HMGB1),tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6,IL-10,and sphingosine-1-phosphate were detected by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after acute liver injury induction were assessed by hematoxylin and eosin staining. HMGB1 expression in hepatocytes and cytoplasmic translocation were detected by immunohistochemistry. Expression of Sphk1 in liver tissue and peripheral blood mononuclear cells(PBMCs) was analyzed by Western ***: The expression of Sphk1 in liver tissue and PBMCs was upregulated in Gal N/LPS-induced ALF. Upregulated Sphk1 expression in liver tissue was mainly caused by Kupffer cells,the resident macrophages of the liver. The survival rates of mice in the N,Ndimethylsphingosine(DMS,a specific inhibitor of Sph K1) treatment group were significantly higher than that of the control group(P < 0.001). DMS treatment significantly decreased the levels of serum ALT and AST at 6,12,and 24 h compared with that of the control group(P < 0.01 for all). Serum HMGB1 levels at 6,12,and 24 h,as well as serum TNF-α,IL-6,and IL-1β levels at 12 h,were significantly lower in the DMS treatment group than in the control group(P < 0.01 for all). Furthermore,hepatic inflammation,necrosis,and HMGB1 cytoplasm translocation in liver cells were significantly decreased in the DMS treatment g

关键词： Acute liver failure sphingosine kinase 1 High-mobi

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 signal transducer and activator of transcription 3 signaling pathway contributes to baicalein-mediated inhibition of dextran sulfate sodium-induced experimental colitis in mice

引用

Chinese Medical Journal 2020年第3期133卷 292-300页

作者： Jing Yao Tao Liu Rui-Jiao Chen Jing Liang Jun Li Chuan-Gong Wang Department of Pharmacology School of Basic MedicineJining Medical UniversityJiningShandong 272000China Department of Otorhinolaryngology Affiliated Hospital of Jining Medical UniversityJiningShandong 272000China Department of Chemistry School of Basic MedicineJining Medical UniversityJiningShandong 272000China School of Life Sciences Qufu Normal UniversityQufuShandong 273100China.

Background:Baicalein has been shown to have anti-inflammatory and anti-tumor ***,the mechanisms underlying its anti-inflammatory effect on colitis remain ***:A dextran sodium sulfate(DSS)-induced model of acute colitis was established in BALB/c mice(6-8 weeks old,weighing 18-22 g).Six groups of mice received:(1)water for 10 days(control),n=6;(2)DSS 4%solution in the drinking water for 7 days,followed by normal water for 3 days,n=7;(3),(4),and(5)as for group 2 plus baicalein(10,20,40 mg/kg)administered once daily starting on day 1,n=6;and(6)as for(2)plus 5-aminosalicylic acid(50 mg/kg)administered once daily starting on day 1,n=*** weights,stool consistency,and hematochezia were recorded,and the severity of colitis was evaluated using a disease activity *** day 11,the mice were euthanized,and organs and blood were collected for *** inflammatory factors were detected by enzyme-linked immunosorbent assay;CD11b-positive cells were analyzed by immunofluorescence microscopy;expression of retinoic-acid-receptor-related orphan nuclear receptor gamma,sphingosine kinase 1(SPHK1),and phosphorylated signal transducer and activator of transcription 3(p-STAT3)was detected by immunohistochemistry;and expression of nucleotide-binding oligomerization domain 2(NOD2),SPHK1,sphingosine 1-phosphate receptor 1(S1PR1),total STAT3,and p-STAT3 were detected by western blotting ***-group differences were compared using Student’s t ***:Baicalein treatment dose-dependently reduced DSS-induced weight loss(P<0.01 or P<0.05),splenomegaly(P<0.01),and colonic damage,as reflected by amelioration of diarrhea,rectal bleeding,and colonic ulceration,congestion,edema(shown as colon length,P<0.05 or P<0.01),and inflammatory cell *** also significantly decreased the levels of inflammatory mediators in the serum(P<0.01)and colon,and significantly inhibited expression of NOD2 SPHK1,S1PR1,and p-STAT3 in the colon(P<0.05).Conc

关键词： Baicalein Colitis STAT3 sphingosine kinase 1

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

sphingosine kinase 1 dependent protein kinase C-δ activation plays an important role in acute liver failure in mice

引用

World Journal of Gastroenterology 2015年第48期21卷 13438-13446页

作者： Yan-Chang Lei Ling-Ling Yang Wen Li Pan Luo Department of Infectious Diseases Zhejiang Hospital Infectious Disease Hospital of Nanchang University

AIM: To investigate the role of protein kinase C(PKC)-δ activation in the pathogenesis of acute liver failure(ALF) in a well-characterized mouse model of D-galactosamine(D-Gal N)/lipopolysaccharide(LPS)-induced ***: BALB/c mice were randomly assigned to five groups, and ALF was induced in mice by intraperitoneal injection of D-Ga IN(600 mg/kg) and LPS(10 μg/kg). Kaplan-Meier method was used for survival analysis. Serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels at different time points within one week were determined using a multiparameteric analyzer. Serum levels of high-mobility group box 1(HMGB1), tumor necrosis factor(TNF)-α, interleukin(IL)-1β, IL-6, and IL-10 as well as nuclear factor(NF)-κB activity were determined by enzyme-linked immunosorbent assay. Hepatic morphological changes at 36 h after ALF induction were assessed by hematoxylin and eosin staining. Expression of PKC-δ in liver tissue and peripheral blood mononuclear cells(PBMCs) was analyzed by Western ***: The expression and activation of PKC-δ were up-regulated in liver tissue and PBMCs of mice with D-Gal N/LPS-induced ALF. Inhibition of PKC-δ activation with rottlerin significantly increased the survival rates and decreased serum ALT/AST levels at 6, 12 and 24 h compared with the control group(P sphingosine kinase 1(Sph K1) dependent PKC-δ activation played an important role in promoting NF-κB activation and inflammatory cytokine production in ***: Sph K1 dependent PKC-δ activation plays an important role in promoting NF-κB activation and inflammatory response in ALF, and inhibition of PKC-δ activation might be a potential therapeutic strat

关键词： Acute liver failure Protein kinase C-δ sphingosine kinase 1 Nuclear factor-κB

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 t

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

Role of sphingosine kinase localization in sphingolipid signaling

引用

World Journal of Biological Chemistry 2010年第12期1卷 362-368页

作者： Binks W Wattenberg Clinical and Translational Research Building Room 419 505 South Hancock St. Louisville KY 40202 United States

The sphingosine kinases, SK1 and SK2, produce the potent signaling lipid sphingosine-1-phosphate (S1P). These enzymes have garnered increasing interest for their roles in tumorigenesis, inflammation, vascular diseases, and immunity, as well as other functions. The sphingosine kinases are considered signaling enzymes by producing S1P, and their activity is acutely regulated by a variety of agonists. However, these enzymes are also key players in the control of sphingolipid metabolism. A variety of sphingolipids, such as sphingosine and the ceramides, are potent signaling molecules in their own right. The role of sphingosine kinases in regulating sphingolipid metabolism is potentially a critical aspect of their signaling function. A central aspect of signaling lipids is that their hydrophobic nature constrains them to membranes. Most enzymes of sphingolipid metabolism, including the enzymes that degrade S1P, are membrane enzymes. Therefore the localization of the sphingosine kinases and S1P is likely to be important in S1P signaling. sphingosine kinase localization affects sphingolipid signaling in several ways. Translocation of SK1 to theplasma membrane promotes extracellular secretion of S1P. SK1 and SK2 localization to specific sites appears to direct S1P to intracellular protein effectors. SK localization also determines the access of these enzymes to their substrates. This may be an important mechanism for the regulation of ceramide biosynthesis by diverting dihydrosphingosine, a precursor in the ceramide biosynthetic pathway, from the de novo production of ceramide.

关键词： Sphingolipid Lipid signaling Ceramide sphingosine-1-phosphate sphingosine

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 *** an intracellular second messenger,S1P plays an important role in calcium signaling and mobilization,and cell proliferation and *** 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 *** and S1P are implicated in various chronic autoimmune conditions such as rheumatoid arthritis, primary Sjgren's syndrome,and inflammatory bowel *** studies have demonstrated the important role of SphK and S1P in the development of arthritis by regulating the pro-inflammatory *** 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

Roles of sphingosine 1-phosphate on tumorigenesis

引用

World Journal of Biological Chemistry 2011年第2期2卷 25-34页

作者： Hsinyu Lee Department of Life Science College of Life ScienceNational Taiwan UniversityTaipei 10617TaiwanChina Institute of Zoology National Taiwan University

sphingosine 1-phosphate (S1P) is a bioactive sphingolipid with a variety of biological *** is generated from the conversion of ceramide to sphingosine by ceramidase and the subsequent conversion of sphingosine to S1P,which is catalyzed by sphingosine *** increasing its intracellular levels by sphingolipid metabolism and binding to its cell surface receptors,S1P regulates several physiological and pathological processes,including cell proliferation,migration,angiogenesis and *** processes are responsible for tumor growth,metastasis and invasion and promote tumor *** ceramide and S1P have distinct functions in regulating in cell fate decision,the balance between the ceramide/sphingosine/S1P rheostat becomes a potent therapeutic target for cancer ***,we summarize our current understanding of S1P signaling on tumorigenesis and its potential as a target for cancer therapy.

关键词： sphingosine 1-phosphate sphingosine kinase Ceramide Angiogenesis Autophagy Tumorigenesis

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 kinase-2 induced autophagy activation mediates ischemic tolenrance in primary cortical neurons

引用

中国药理学通报 2015年第B11期31卷 90-90页

Aim This study is aimed to determine whether SPK2 （sphingosine kinase-2） is involved in isoflurane preconditioning induced autophagy activation in primary cultured neurons. We also examined whether SPK2 pro- tects neurons from ischemic injury by activating autophagy, and explored the molecular mechanism of SPK2 contrib- uting to the autophagy activation in neurons. Methods Isoflurane preconditioning （ISO） and oxygen glucose dep- rivation （OGD） model was established in primary cultured murine cortical neurons. Neurons were transfected by siRNA to interfere SPK2 and Beclin 1, or lentivirus to overexpress SPK2. Protein expression of SPK2, LC3, and Beclinl were detected with immunofluorescence and Western blot analysis. The neurons were treated with lysosomal inhibitor ammonium chloride （NH4 C1） to test the autophagy flux. The protection of SPK2 on OGD/R induced neu- ronal death was detected with CCK-8 （cell counting kit-8） and LDH cytotoxicity assay kit. Autophagy inhibitor 3- MA （3-Methyladenine） was used to detect the protection of autophagy on SPK2 induced isehemie tolerance. Co-im- munoprecipitation was used to detect the interaction between Beclin 1 and Bel-2. Results In primary cultured neu- ISO enhanced SPK2 and LC3 immunofluorescenee. SPK2 siRNA inhibits LC3II upregulation induced by rons, ISO. Beclin 1 siRNA also inhibits LC3II upregulation induced by ISO. Lentivirus-indueed SPK2 overexpression in- creased LC3II/LC3I ratio and enhanced the autophagy flux in neurons. SPK2 overexpression also exerted neuropro- teetion against OGD model in cortical neurons, as evidenced by improvement of neuronal morphology, increased cellular viability and reduced LDH leakage, while 3-MA partly abolished the SPK2-induced neuroprotection. After SPK2 overexpression, Beclin 1 siRNA inhibited SPK2 induced LC3II upregulation, and the coimmunoprecipitation of Beclin 1 and Bcl-2 was reduced.. Conclusion ISO increases SPK2 and activates autophagy in neurons. SPK2 or Beclin 1 interferen

关键词： sphingosine kinase 2 isoflurane preconditioning neuroprotection autophagy cortical neurons

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

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：