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China Medical Abstracts(Internal Medicine) 2024年第1期41卷 33-33页

作者：戚婷 Dept Nephrol Puren Hosp Affil to Wuhan Univ Sci&TechnolWuhan 430081

Objective To explore the effect of platycodin D(PD) on podocyte injury induced by high glucose and Cyclooxygenase-2 (COX-2)/nuclear factor kappa B(NF-κB) pathway in mice.Methods MPC5 cells were divided into normal co... 详细信息

关键词： Cyclooxygenase injury effect

Novel functional association of rat testicular membrane-associated cytosolic glutathione S transferases and Cyclooxygenase in vitro

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Asian Journal of Andrology 2005年第2期7卷 171-178,页

作者： S.Neeraja B.Ramakrishna A.S.Sreenath G.V.Reddy P.R.K.Reddy P.Reddanna Department of Animal Sciences School of Life SciencesUniversity of HyderabadHyderabad 500046India

Aim:To analyze the role of cytosolic glutathione S-transferases (cGSTs) and membrane-associated cytosolic GSTs (macGSTs) in prostaglandin biosynthesis and to evaluate the possible interaction between glutathione S-transferases (GSTs) and Cyclooxygenase (COX) in vitro.Methods:SDS-PAGE analysis was undertaken for characterization of GSTs,thin layer chromatography (TLC) to monitor the effect of GSTs on prostaglandin biosynthesis from arachi- donic acid (AA) and spectrophotometric assays were done for measuring activity levels of COX and GSTs.Results: SDS-PAGE analysis indicates that macGSTs have molecular weights in the range of 25-28 kDa.In a coupled assay involving GSTs,arachidonic acid and Cyclooxygenase-1,rat testicular macGSTs produced prostaglandin E2 and F2~, while the cGSTs caused the generation of prostaglandin D2,E2 and F_(2α).In vitro interaction studies on GSTs and COX at the protein level have shown dose-dependent inhibition of COX activity by macGSTs and vice versa.This effect, however,is not seen with cGSTs.The inhibitory effect of COX on macGST activity was relieved with increasing concentrations of reduced glutathione (GSH) but not with 1-chloro 2,4-dinitrobenzene (CDNB).The inhibition of COX by macGSTs,on the other hand,was potentiated by glutathione.Conclusion:We isolated and purified macGSTs and cGSTs from rat testis and analyzed their involvement in prostaglandin biosynthesis.These studies reveal a revers- ible functional interaction between macGSTs and COX in vitro,with possible interactions between them at the GSH binding site of macGSTs.

关键词： glutathione S-transferase Cyclooxygenase arachidonic acid glutathione prostaglandins

Novel selective inhibitors of hydroxyxanthone derivatives for human Cyclooxygenase-2

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Acta Pharmacologica Sinica 2007年第12期28卷 2027-2032页

作者： Yu-chian CHEN~2,Kun-tze CHENDepartment of Biological Science and Technology,China Medical University,Taichung,Taiwan China Department of Biological Science and Technology China Medical University Taichung China

Aim:To screen the selective inhibitors for human Cyclooxygenase-2 ((h)COX-2)utilizing molecular simulation.Methods:Eight xanthone derivatives,compoundsA-H,were employed by the structure-based research methodology.Resveratroland NS-398 were selected as the control compounds for COX-1 and COX-2,respectively.The docking results were scored and the interaction energies of thecomplexes were calculated by CHARMm forcefield.Results:NS-398 could notdock into the active site of COX-1.However,resveratrol,the specific selectivecompound for COX-1,gained lower interaction energy while docked in COX-1.The lower interaction energies were investigated,while compound B and F weredocked into the catalytic sites of COX-1 and COX-2,respectively.Compound A,1,3,6,7-tetrahydroxyxanthone,revealed high inhibitory potency to both COX-1and COX-2.Conclusion:The conformations of the docking would influence thevalues of interaction energies.The hydrogen bond could also increase the stabi-lity of the whole complex,which might suggest that compound B had a suitableconformation in the tunnel-like active site of COX-1.Compound F,a potent agentfor COX-2,revealed a strong hydrogen bond with Ser516 in human COX-2 to forma stable complex.

关键词： Cyclooxygenase non-steroidal anti-inflammatory drugs xanthone molecular simulation interaction energy inhibitors

Indoleamine-2,3-dioxygenase 1/Cyclooxygenase 2 expression prediction for adverse prognosis in colorectal cancer

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World Journal of Gastroenterology 2018年第20期24卷 2181-2190页

作者： Wen-Juan Ma Xing Wang Wen-Ting Yan Zhong-Guo Zhou Zhi-Zhong Pan Gong Chen Rong-Xin Zhang State Key Laboratory of Oncology in South China Sun Yat-sen UniversityGuangzhou 510060Guangdong ProvinceChina Collaborative Innovation Center of Cancer Medicine Guangzhou 510060Guangdong ProvinceChina Tongji Medical College Huazhong University of Science and TechnologyWuhan 430074Hubei ProvinceChina Department of Hepatobiliary Surgery Cancer CenterSun Yat-sen UniversityGuangzhou 510060Guangdong ProvinceChina Department of Colorectal Surgery Cancer CenterSun Yat-sen UniversityGuangzhou 510060Guangdong ProvinceChina

AIM To evaluate indoleamine-2,3-dioxygenase 1/Cyclooxygenase 2(IDO1/COX2) expression as an independent prognostic biomarker for colorectal cancer(CRC) patients.METHODS We retrospectively studied the medical records of 95 patients who received surgical resection from August 2008 to January 2010. All patients were randomly assigned to adjuvant treatment with or without celecoxib groups after surgery. We performed standard immunohistochemistry to assess the expression levels of IDO1/COX2 and evaluated the correlation of IDO1/COX2 with clinicopathological factors and overall survival(OS) outcomes.RESULTS The expression of nuclear IDO1 was significantly correlated with body mass index(P < 0.001), and IDO1 expression displayed no association with sex, age, tumor differentiation, T stage, N stage, carcinoembryonic antigen, cancer antigen 19-9, CD3+ and CD8+ tumor infiltrating lymphocytes, and COX2. In univariate analysis, we found that nuclear IDO1(P = 0.039), nuclear/cytoplasmic IDO1 [hazard ratio(HR) = 2.044, 95% confidence interval(CI): 0.871-4.798, P = 0.039], nuclear IDO1/COX2(HR = 3.048, 95%CI: 0.868-10.7, P = 0.0049) and cytoplasmic IDO1/COX2(HR = 2.109, 95%CI: 0.976-4.558, P = 0.022) all yielded significantly poor OS outcomes. Nuclear IDO1(P = 0.041), nuclear/cytoplasmic IDO1(HR = 3.023, 95%CI: 0.585-15.61, P = 0.041) and cytoplasmic IDO1/COX2(HR = 2.740, 95%CI: 0.764-9.831, P = 0.038) have significantly poor OS outcomes for the CRC celecoxib subgroup. In our multivariate Cox model, high coexpression of cytoplasmic IDO1/COX2 was found to be an independent predictor of poor outcome in CRC(HR = 2.218, 95%CI: 1.011-4.48, P = 0.047) and celecoxib subgroup patients(HR = 3.210, 95%CI: 1.074-9.590, P = 0.037).CONCLUSION Our results showed that cytoplasmic IDO1/COX2 coexpression could be used as an independent poor predictor for OS in CRC.

关键词： Prognosis Indoleamine-2,3-dioxygenase 1 Cyclooxygenase 2 Colorectal cancer

Interplay between post-translational Cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort

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World Journal of Gastroenterology 2019年第4期25卷 433-446页

作者： Patricia Prieto Rafael I Jaén Daniel Calle María Gómez-Serrano Estefanía Nú?ez María Fernández-Velasco Paloma Martín-Sanz Sergio Alonso Jesús Vázquez Sebastián Cerdán Miguel ángel Peinado Lisardo Boscá Department of Metabolism and Physiopathology of Inflammatory Diseases Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (Ciber-CV) Instituto de Salud Carlos III (ISCIII) Laboratorio de Imagen Médica Hospital Universitario Gregorio Mara?ón Laboratorio de Proteómica Cardiovascular Centro Nacional de Investigaciones Cardiovasculares (CNIC) Instituto de Investigación Sanitaria del Hospital Universitario la Paz(IdiPaz) Programa de Medicina Predictiva y Personalizada del Cáncer (PMPPC) Fundación Instituto de investigación en ciencias de la salud Germans Trias i PujolCtra Can Ruti

BACKGROUND Colorectal cancer(CRC) is the second most common cause of cancer death worldwide. It is broadly described that Cyclooxygenase-2(COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in humans.AIM To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic profile.METHODS Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge(Barcelona, Spain) and Germans Trias i Pujol University Hospital(Campus Can Ruti)(Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide N-glycosidase F(PNGase F). Prostaglandin E2(PGE2) levels were determined using a specific ELISA. 1 H high resolution magic angle spinning(HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-MS/MS) using a QExactive HF orbitrap MS.RESULTS Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after PNGase F incubation, showing higher PGE2 levels. M

关键词： Colon Carcinoma Cyclooxygenase Prostaglandin Proteomics High resolution magic angle spinning

Kinetic Analysis of the Interaction between Nonsteroidal Anti-inflammatory Drugs and Cyclooxygenase-2 Using Wavelength Modulation Surface Plasmon Resonance

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Chinese Journal of Chemistry 2011年第1期29卷 165-170页

作者： Liu, Xia Li, Ying Lin, Zhao College of Food Science and Technology Hunan Agricultural University Hunan Provincial Key Laboratory of Food Science and Biotechnology Changsha Hunan 410128 China

A surface plasmon resonance （SPR） biosensor based on wavelength modulation technology was developed and validated for the kinetic analysis of the interactions between two nonsteroidal anti-inflammatory drugs （NSAIDs） and Cyclooxygenase-2 （COX-2）. After the effect of different concentration COX-2 on the binding capacity of the SPR biosensor surface was studied, the COX-2 was immobilized covalently onto the biosensor surface using a standard amine coupling method. The affinity constants for indomethacin, ketoprofen binding to COX-2 are 7.5× 10^3 L/tool and 9.25 × 10^3 L/mol, respectively. The biosensor surface can be regenerated after being rinsed with 0.01 mol/L NaOH, and the biosensor can be used repeatedly. These indicated that the wavelength modulation SPR biosensor has the potential application in the fields of pharmacokinetics, pharmacodynamics and drug discovery.

关键词： surface plasmon resonance biosensor Cyclooxygenase drug affinity

Roles of Cyclooxygenase-2 in microvascular endothelial cell proliferation induced by basic fibroblast growth factor

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Chinese Medical Journal 2008年第24期121卷 2599-2603页

作者： QIAN Rui-zhe YUE Fei ZHANG Guo-ping HOU Li-kun WANG Xin-hong JIN Hui-ming Department of Physiology and Pathophysiology Shanghai Medical College Fudan University Shanghai 200032 China

Background The level of basic fibroblast growth factor （bFGF） increases rapidly after cerebral ischemia. However, the molecular mechanisms for the effects of bFGF on cerebral microvascular endothelial cells （cMVECs） have not yet been fully elucidated. In this study, a murine cMVEC line, bEnd.3, was employed to study the effects of bFGF on Cyclooxygenase （COX） expression and its downstream effects in cMVECs. Methods After treatment with bFGF, RT-PCR and Western blotting analyses were carried out to evaluate the changes in COX-2 mRNA and protein expression, respectively. MTT assays were performed to measure cell proliferation. The prostaglandin E2 （PGE2） and vascular endothelial growth factor （VEGF） concentrations in the culture medium were measured by enzyme-linked immunosorbent assay （ELISA）. Results COX-2 mRNA and protein expressions in bEnd.3 cells were induced by bFGF in time- and dose-dependent manners. The bFGF-induced COX-2 upregulation led to enhanced PGE2 production by bEnd.3 cells, and this effect was abolished by the selective COX-2 inhibitor NS-398. bFGF also increased VEGF production by bEnd.3 cells, and this effect was blocked by NS-398 and the EP1/2 （PGE2 receptors） antagonist AH6809. Furthermore, exogenous PGE2 increased VEGF production in bend.3 cells, and AH6809 blocked this effect. Conclusion bFGF increases VEGF production in an autocrine manner by increasing COX-2-generated PGE2 in cMVECs and subsequently stimulates MVEC proliferation and angiogenesis.

关键词： cerebral ischemia cerebral microvascular endothelial cell basic fibroblast growth factor Cyclooxygenase prostaglandin E2 vascular endothelial growth factor

Selective Cyclooxygenase-2 Inhibitors: Design and Synthesis

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Chinese Chemical Letters 1999年第6期10卷 469-472页

作者： Xin Sheng LEI Zong Ru GUO Ling Bo QU Qi Qing ZHU(Institute of Materia Medica. Chinese Academy of Medical SciencesAnd Peking Union Medical College. Beijing 100050) Institute of Materia Medica Chinese Academy of Medical Sciences Peking Union Medical College Beijing 100050 China

The discovery of COX-2 provides a novel target developing more effective NSAIDs with fewer side effects. On the basis of results from the structure-activity relationships (SAR) of selective COX-2 inhibitors, we have d... 详细信息

关键词： Cyclooxygenase Cyclooxygenase-2 inhibitor selective

Influence of nitric oxide synthase and Cyclooxygenase blockade on expression of Cyclooxygenase and hemodynamics in rats with portal hypertension

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Hepatobiliary & Pancreatic Diseases International 2006年第4期5卷 564-569页

作者： Hui Cao, Jia Xu, Hua Liu, Fang-Bin Meng, Jiang-Feng Qiu and Zhi-Yong Wu Department of Surgery, Renji Hospital, College of Medicine, Shanghai Jiaotong University, Shanghai 200127, China Department of Surgery Renji Hospital College of Medicine Shanghai Jiaotong University Shanghai 200127 China. xujia201800@***

BACKGROUND : The importance of nitric oxide (NO) in the pathogenesis of portal hypertension (PHT) has been extensively studied, but whether or not prostacyclin (PGI2) plays a role in formation and development of hyperdynamic circutatory state in PHT has not been verified. The present study was undertaken to investigate the possible interaction between prostacyclin (PGI2) and nitric oxide (NO) in the hyperdynamic circulatory state of rats with chronic portal hypertension (PHT), by measuring the hemodynamic changes and expression of Cyclooxygenase (COX) mRNA in vessels and small intestine after administration of Nω- nitro-L-arginine (L-NNA) or indomethacin (INDO) either in the short-term (7 days) or long-term (15 days). METHODS: Ninety-seven male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) induced by injection of CCl4, prehepatic portal hypertension (PHPH) induced by partial stenosis of the portal vein, and sham-operated controls (SO). Animals of each group received L-NNA or INDO either for 7 or 15 days, with saline as control. Splanchnic hemodynamics was measured by the radioactive microsphere technique. The concentration of NO in serum was determined as the nitrate; nitrite ratio (NO2-/NO3-, μmol/L) by a colorometric method, and that of PGI2 was measured by specific radioimmunoassay for its stable hydrolysis product 6-keto-PGF1α (pg/ml). The reverse transcription- polymerase chain reaction measured the levels of COX-1 mRNA in the superior mesenteric artery, thoracic aorta, and small intestine of these rats.RESULTS: Compared with SO rats, COX-1 mRNA expression and the concentrations of plasma 6-keto- PGF1α and serum NO2-/NO3- were enhanced in both IHPH and PHPH rats; splanchnic vascular resistance (SVR) decreased, but portal venous inflow (PVI) markedly increased (P<0.05). Seven or 15 days of L-NNA treatment reduced COX-1 mRNA expression in these vessels and the small intestine, concomitant with a significant decrease in the concentration of plasma PGI2 and serum NO

关键词： portal hypertension hyperhemodynamics prostacyclin Cyclooxygenase nitric oxide

Expression of Cyclooxygenase in hyperdynamic portal hypertensive rats

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Hepatobiliary & Pancreatic Diseases International 2006年第2期5卷 252-256页

作者： Hui Cao, Jia Xu, Rong Hua, Fang-Bin Meng, Jiang-Feng Qiu and Zhi-Yong Wu Department of Surgery, Renji Hospital, Shanghai Second Medical University, Shanghai 200127, China Department of Surgery Renji Hospital Shanghai Second Medical University Shanghai 200127 China.

BACKGROUND: By detecting hemodynamic changes, concentration of plasm prostacyclin ( PGI2) and expression of Cyclooxygenase( COX) in vasculature and splanchnic tissues, we evaluated the relative contributions of PGI2 and COX mRNA expression to the hyperdynamic circulatory state in chronic portal hypertensive rats. METHODS: Fifty male Sprague-Dawley rats were divided into 3 groups: intrahepatic portal hypertension (IHPH, n = 18) by injection of CCl4, prehepatic portal hypertension (PHPH, n = 18) by partial stenosis of the portal vein, and sham-operated controls (SO, n =14). Splanchnic hemodynamics was measured by radioactive microsphere techniques and the concentration of PGI2 was detected by specific radioimmunoassay for its stable hydrolysis product 6-keto-PGF1α. Semi-quantitive reverse transcriptase-polyme-rase chain reaction (RT-PCR) was performed to measure the levels of COX-1 mRNA and COX-2 mRNA in the thoracic aorta, superior mesenteric artery( SMA),and small intestine of IHPH, PHPH and SO rats, respectively. RESULTS: Hyperdynamic circulatory state was characterized by increased splanchnic blood flow and decreased splanchnic vascular resistance in IHPH and PHPH rats. The concentration of plasma 6-keto-PGF1α ( pg/ml) in IHPH (1093.75 ± 142.15) and PHPH (897. 42 ± 53. 29) rats was significantly higher than that in SO rats (730.13 ± 98. 67) (P <0.05). The expression of COX-1 mRNA in the thoracic aorta, SMA and small intestine was enhanced, whereas COX-2 mRNA expression was not detected in either of these vessels or the small intestine. The plasma 6-keto-PGF1α concentration and the expression of COX-1 mRNA in these vessels and the small intestine were closely correlated with such hemodynamic parameters as portal venous inflow (PVI), splanchnic vascular resistance (SVR) and free portal venous pressure (FPP) (P<0.05). CONCLUSION: The expression of COX-1 mRNA and the levels of PGI2 were closely related to the hyperdynamic circulatory state of portal hypertensive rats.

关键词： hypertension, portal hyperhemodynamics prostacyclin Cyclooxygenase