Search results for "isoenzymes"
showing 10 items of 244 documents
Effects of some isoxazolpyrimidine derivatives on nitric oxide and eicosanoid biosynthesis
2000
Abstract The inhibitory effect of some isoxazolpyrimidine derivatives on iNOS and COX-2 endotoxin induction in mouse peritoneal macrophages has been studied. Three of these compounds inhibited nitrite and PGE2 accumulation in a concentration dependent-manner at μM range. None of these active compounds affected iNOS, COX-2, COX-1 or PLA2 activities, although some reduced iNOS or COX-2 expression. Besides, no effect was observed on human neutrophil inflammatory responses (LTB4 biosynthesis and Superoxide or elastase release). Active compounds were assayed by oral administration in the mouse air pouch model, where they inhibited nitrite accumulation without affecting PGE 2 levels or leukocyte …
eNOS S-nitrosylates β-actin on Cys374 and regulates PKC-θ at the immune synapse by impairing actin binding to profilin-1.
2017
The actin cytoskeleton coordinates the organization of signaling microclusters at the immune synapse (IS); however, the mechanisms involved remain poorly understood. We show here that nitric oxide (NO) generated by endothelial nitric oxide synthase (eNOS) controls the coalescence of protein kinase C-¿ (PKC-¿) at the central supramolecular activation cluster (c-SMAC) of the IS. eNOS translocated with the Golgi to the IS and partially colocalized with F-actin around the c-SMAC. This resulted in reduced actin polymerization and centripetal retrograde flow of ß-actin and PKC-¿ from the lamellipodium-like distal (d)-SMAC, promoting PKC-¿ activation. Furthermore, eNOS-derived NO S-nitrosylated ß-…
An anti-inflammatory ditriazine inhibiting leukocyte functions and expression of inducible nitric oxide synthase and cyclo-oxygenase-2.
2000
A ditriazine derivative (4,10-dichloropyrido[5,6:4,5]thieno[3,2-d':3, 2-d]-1,2,3-ditriazine (DTD)) inhibited neutrophil functions, including degranulation, superoxide generation, and leukotriene B(4) production, without any effect on 5-lipoxygenase activity. This compound reduced nitric oxide (NO) and prostaglandin E(2) production in mouse peritoneal macrophages stimulated with lipopolysaccharide, whereas no influence on the activity of inducible NO synthase, cyclo-oxygenase-2 or cyclo-oxygenase-1 was observed. DTD significantly reduced mouse paw oedema induced by carrageenan and also markedly reduced NO and prostaglandin E(2) levels in exudates from 24-h zymosan-stimulated mouse air pouch.…
Novel anti-inflammatory chalcone derivatives inhibit the induction of nitric oxide synthase and cyclooxygenase-2 in mouse peritoneal macrophages
1999
AbstractIn a previous work, we tested a series of chalcone derivatives as possible anti-inflammatory compounds. We now investigate the effects of three of those compounds, CH1, CH8 and CH12, on nitric oxide and prostanoid generation in mouse peritoneal macrophages stimulated with lipopolysaccharide and in the mouse air pouch injected with zymosan, where they showed a dose-dependent inhibition with inhibitory concentration 50% values in the μM range. This effect was not the consequence of a direct inhibitory action on enzyme activities. Our results demonstrated that chalcone derivatives inhibited de novo inducible nitric oxide synthase and cyclooxygenase-2 synthesis, being a novel therapeuti…
Expressional control of the ‘constitutive’ isoforms of nitric oxide synthase (NOS I and NOS III)
1998
Nitric oxide synthase (NOS) exists in three established isoforms. NOS I (NOS1, ncNOS) was originally discovered in neurons. This enzyme and splice variants thereof have since been found in many other cells and tissues. NOS II (NOS2, iNOS) was first identified in murine macrophages, but can also be induced in many other cell types. NOS III (NOS3, ecNOS) is expressed mainly in endothelial cells. Whereas NOS II is a transcriptionally regulated enzyme, NOS I and NOS III are considered constitutively expressed proteins. However, evidence generated in recent years indicates that these two isoforms are also subject to expressional regulation. In view of the important biological functions of these …
Solid-phase synthesis and inhibitory effects of some pyrido[1,2-c]pyrimidine derivatives on leukocyte formations and experimental inflammation.
2001
A number of pyrido[1,2-c]pyrimidines bearing a nitrogen, oxygen, or sulfur functionality at C-1 were synthesized on solid-phase using the iminophosphorane methodology and tested for their effects on leukocyte functions in vitro and antiinflammatory activity. Compound 5c was found to be a strong scavenger of superoxide anion and an inhibitor of chemiluminescence induced by 12-O-tetradecanoylphorbol 13-acetate in human neutrophils. These pyrido[1,2-c]pyrimidines inhibited the generation of PGE(2) by COX-2 in RAW 264.7 macrophages stimulated with lipopolysaccharide. Compounds 7, 5f, 6, and 8 inhibited enzyme activity, whereas the remaining compounds also acted on the induction phase. In additi…
6-Dimethylamino 1H-pyrazolo[3,4-d]pyrimidine derivatives as new inhibitors of inflammatory mediators in intact cells.
2003
The synthesis of 6-dimethylamino 1H-pyrazolo[3,4-d]pyrimidines substituted at positions 1 and 4, and their effects on murine macrophage and human neutrophil functions are described. Several compounds and especially 4b-6b are potent inhibitors of PGE2 generation in murine macrophages. This action is related to a direct effect on COX-2 activity without affecting the enzyme expression. Some of these compounds also inhibited COX-1 and COX-2 in human monocytes and 4b showed selectivity for COX-2 inhibition. © 2003 Elsevier Science Ltd. All rights reserved.
ttCH, a selective inhibitor of inducible nitric oxide synthase expression with antiarthritic properties
2003
In a previous work, we investigated the effects of a series of dimethoxy- and trimethoxychalcone derivatives, with various patterns of fluorination, on nitric oxide production in lipopolysaccharide-stimulated murine RAW 264.7 cells. The present study was designed to determine if 2,4,6-trimethoxy-2'-trifluoromethylchalcone (ttCH) could modulate the production of nitric oxide (NO) and/or prostaglandins in vitro and in vivo. On the mouse macrophage cell line RAW 264.7, ttCH inhibited dose-dependently NO and prostaglandin E(2) production, with IC(50) in the micromolar range. This compound had no direct inhibitory effect on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 activities. …
Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinoma
2000
Abstract Background/Aims: It has been known for at least 50 years that alterations in methionine metabolism occur in human liver cirrhosis. However, the molecular basis of this alteration is not completely understood. In order to gain more insight into the mechanisms behind this condition, mRNA levels of methionine adenosyltransferase ( MAT1A ), glycine methyltransferase ( GNMT ), methionine synthase ( MS ), betaine homocysteine methyltransferase ( BHMT ) and cystathionine β-synthase ( CBS ) were examined in 26 cirrhotic livers, five hepatocellular carcinoma (HCC) tissues and ten control livers. Methods: The expression of the above-mentioned genes was determined by quantitative RT-PCR analy…
Acid Dnase Activities In Peripheral, Mononuclear Blood Cells: A Possible Parameter To Detect Proliferating Cell Populations
1992
After electrophoresis in DNA -containing polyacrylamide gels, two acid DNase activities can be detected in peripheral, mononuclear cells of the human blood. One of these acid DNase activities correlates with cell proliferation; its isoelectrical point is at pI 7.4. By means of this DNase activity, a quantity of less than 1% leukemic cells can be detected. The increased acid DNase activity can indicate the proliferation of malignant cell populations and possibly the proliferation of cell populations during immunological reactions