Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.1 (alkaline phosphatase)
47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Splenic macrophages are highly efficient in trapping and concentrating foreign substances carried in the blood and also the major sites where antibodies are synthesised and from where they are released into the circulation. Lead and Arsenic as environmental agents are considered to be high priority toxic substances largely due to their carcinogenic potentials in humans. However, these heavy metals as carcinogens remain an enigma because while they are definitely active in humans, carcinogenesis in the rodent model has never been convincingly demonstrated. Although macrophages are predominantly recruited to the site of inflammation during inflammatory distress as well as in immune response, nothing is known about the interaction of lead and arsenic with macrophages and their possible role in immunotoxicologic effect. In the present study it is reported that in vivo lead acetate treatment (10 mg/kg body wt) inhibits the cell adhesion property and alters the cell morphology in the splenic macrophages. Results show that there is a significant decrease in alkaline phosphatase release in lead treated macrophages (6.7 +/- 0.88 IU/100 mL) with respect to control (14.17 +/- 0.18). In vivo exposure of sodium arsenite (0.5 mg/kg body wt) also decreases phagocytic activity for ingestion and digestion of exogenous antigens, such as whole microorganism, as evident from the phagocytic index, 11555.55 +/- 62.86 (in control) to 5555.5 +/- 1571.33 in arsenic treated cells. Arsenic exposed cells release 8.15 +/- 0.05 microM nitric oxide, whereas control cells release 10.95 +/- 0.15 microM of nitric oxide, which is also identical following LPS stimulation. Results show that the functional integrity of the target cell is also decreased after arsenic exposure as obtained from the percentage of DNA fragmentation. A greater percentage of DNA fragmentation upon arsenic treatment (43.1 +/- 0.05%) with respect to control (14.9 +/- 0.34%) indicates that arsenic induces apoptosis. In immune cells which are rapidly proliferating and differentiating, inhibition of these heavy metal induced functions may result in similar degree of toxicity and lead to diseased state.
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PMID:Effect of lead and arsenic on murine macrophage response. 1237 52

In a search for new inhibitors of the IFN-gamma mediated signal transduction in HeLa S3 cells using secreted alkaline phosphatase (SEAP) as reporter gene, a novel compound, designated as S14-95 was isolated from fermentations of the imperfect fungus Penicillium sp. 14-95. The compound inhibits the IFN-gamma mediated expression of the reporter gene with IC50 values of 2.5 to approximately 5 microg/ml (5.4 to approximately 10.8 microM). Furthermore the compound inhibited the expression of the proinflammatory enzymes COX-2 and NOS II at 5 microg/ml (10.8 microM) in LPS/IFN-gamma stimulated J774 mouse macrophages. Studies on the mode of action of the compound revealed that the inhibition of the IFN-gamma dependent signaling pathway is caused by an inhibition of the phosphorylation of the STAT1alpha transcription factor. In addition, S14-95 inhibited the activation of the p38 MAP kinase, which is involved in the inducible expression of many proinflammatory genes.
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PMID:S14-95, a novel inhibitor of the JAK/STAT pathway from a Penicillium species. 1281 6

The role of 5-lipoxygenase (5-LOX) in the pathophysiology of the organ injury/dysfunction caused by endotoxin is not known. Here, we investigate the effects of treatment with 5-LOX inhibitor zileuton in rats and targeted disruption of the 5-LOX gene in mice (5-LOX(-/-)) on multiple organ injury/dysfunction caused by severe endotoxemia. We also investigate the expression of beta2-integrins CD11a/CD18 and CD11b/CD18 on rat leukocytes by flow cytometry. Zileuton [3 mg/kg intravenously (i.v.)] or vehicle (10% dimethyl sulfoxide) was administered to rats 15 min prior to lipopolysaccharide (LPS; Escherichia coli, 6 mg/kg i.v.) or vehicle (saline). 5-LOX(-/-) mice and wild-type littermate controls were treated with LPS (E. coli, 20 mg/kg intraperitoneally) or vehicle (saline). Endotoxemia for 6 h in rats or 16 h in mice resulted in liver injury/dysfunction (increase in the serum levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, bilirubin), renal dysfunction (creatinine), and pancreatic injury (lipase, amylase). Absence of functional 5-LOX (zileuton treatment or targeted disruption of the 5-LOX gene) reduced the multiple organ injury/dysfunction caused by endotoxemia. Polymorphonuclear leukocyte infiltration (myeloperoxidase activity) in the lung and ileum as well as pulmonary injury (histology) were markedly reduced in 5-LOX(-/-) mice. Zileuton also reduced the LPS-induced expression of CD11b/CD18 on rat leukocytes. We propose that endogenous 5-LOX metabolites enhance the degree of multiple organ injury/dysfunction caused by severe endotoxemia by promoting the expression of the adhesion molecule CD11b/CD18 and that inhibitors of 5-LOX may be useful in the therapy of the organ injury/dysfunction associated with endotoxic shock.
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PMID:Reduction of the multiple organ injury and dysfunction caused by endotoxemia in 5-lipoxygenase knockout mice and by the 5-lipoxygenase inhibitor zileuton. 1532 37

Nuclear factor (NF)-cB is a transcription factor regulating the expression of inflammatory and immune genes. In the present study, an extract from stem bark of Cinnamomum cassia Blume(Lauraceae) was discovered to have an inhibitory effect on LPS-induced NF-KB transcriptional activity, which was determined using macrophages RAW 264.7 transfected stably with an alkaline phosphatase reporter construct containing four copies of the NF-KB binding KB sequence. Following activity-guided fractionation, trans-cinnamaldehyde and 2-methoxycinnamaldehyde were identified as the NF-KB inhibitors from C cassia with IC50 values of 43 MM and 31 pM, respectively. As a positive control, caffeic acid phenethyl ester (CAPE) showed an IC50 value of 2 uM on NF-KB transcriptional activity. Both trans-cinnamaldehyde and 2-methoxycinnamaldehyde inhibited LPS-induced DNA binding activity of NF-KB in addition to NF-KB transcription-al activity.
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PMID:Cinnamaldehyde and 2-methoxycinnamaldehyde as NF-kappaB inhibitors from Cinnamomum cassia. 1550 52

The hepatoprotective activity of aerial parts of Tridax procumbens was investigated against d-Galactosamine/Lipopolysaccharide (d-GalN/LPS) induced hepatitis in rats. d-GalN/LPS (300 mg/kg body weight/30 microg/kg body weight)-induced hepatic damage was manifested by a significant increase in the activities of marker enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase and gamma glutamyl transferase) and bilirubin level in serum and lipids both in serum and liver. Pretreatment of rats with a chloroform insoluble fraction from ethanolic extract of Tridax procumbens reversed these altered parameters to normal values. The biochemical observations were supplemented by histopathological examination of liver sections. Results of this study revealed that Tridax procumbens could afford a significant protection in the alleviation of d-GalN/LPS-induced hepatocellular injury.
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PMID:Hepatoprotective activity of Tridax procumbens against d-galactosamine/lipopolysaccharide-induced hepatitis in rats. 1592 95

A gas-liquid chromatographic-mass spectrometric (GLC-MS) method was applied to the detection of 3-deoxy-d-manno-2-octulosonic acid (Kdo), a constituent of bacterial lipopolysaccharide (LPS, endotoxin). Samples containing LPS were dried, methanolyzed with 2 M HCl in methanol at 60 degrees C for 1 h and acetylated with acetic anhydride and pyridine (1:1, v/v) solution at 100 degrees C for 30 min, then the products were analyzed by GLC-MS or GLC-MSMS. Four acetylated methylglycoside methyl ester derivatives of Kdo are formed in these conditions, namely one with pyranose ring (Kdo1), two derivatives in the furanose form (Kdo2 and 3) and one derivative of anhydro Kdo (Kdo4), as results from their mass fragmentation patterns. Synthetic Kdo produced mainly Kdo4 derivative, whereas Kdo1 of pyranose ring shape was the predominating derivative formed from LPS. The ion fragment of m/z 375 was selected for the specific detection of this Kdo1 derivative, which might be applied for the endotoxin determination. That approach was used for the analysis of preparations of bacteria, bacteriophages and samples of animal sera. In order to ensure the removal of phosphate substitutions from Kdo, methanolyzed samples can be treated with alkaline phosphatase (2.6 U, pH 9.2, 37 degrees C, 15 min), what was elaborated on Vibrio LPS preparation.
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PMID:Determination of endotoxin by the measurement of the acetylated methyl glycoside derivative of Kdo with gas-liquid chromatography-mass spectrometry. 1593 75

Because the development and activity of osteoclasts in bone remodeling is critically dependent on cell-cell and cell-matrix interactions, we used laser confocal microscopy to study the response of osteoclasts to lipopolysaccharide (LPS; 10 microg/ml), parathyroid hormone (PTH; 10(-8) M), and bisphosphonates (BPs; 1-25 microM clodronate or 0.1-2.5 microM risedronate) in cultured neonatal calvaria. Following treatment with LPS or PTH (<48 hr), osteopontin (OPN) and the alphavbeta3 integrin were found colocalized with the actin ring in the sealing zone of actively resorbing osteoclasts. In contrast, non-resorbing osteoclasts in BP-treated cultures showed morphological abnormalities, including retraction of pseudopods and vacuolization of cytoplasm. In the combined presence of LPS and BP, bone-resorbing osteoclasts were smaller and the sealing zone diffuse, reflecting reduced actin, OPN, and beta3 integrin staining. Depth analyses of calvaria showed that the area of resorbed bone was filled with proliferating osteoblastic cells that stained for alkaline phosphatase, collagen type I, and bone sialoprotein, regardless of the presence of BPs. These studies show that confocal microscopy of neonatal calvaria in culture can be used to assess the cytological relationships between osteoclasts and osteoblastic cells in response to agents that regulate bone remodeling in situ, avoiding systemic effects that can compromise in vivo studies and artifacts associated with studies of isolated osteoclasts.
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PMID:Osteoclast responses to lipopolysaccharide, parathyroid hormone and bisphosphonates in neonatal murine calvaria analyzed by laser scanning confocal microscopy. 1608 5

Changes in the functional and plasma membrane organizational states of human neutrophils were examined using two isolation procedures, which may simulate altered physiological states in vivo. A gelatin-based method of blood-neutrophil isolation was used to model in vivo priming, and neutrophils isolated by this method were compared with control populations prepared by a pyrogen-free, dextran-based method. Gelatin-prepared neutrophils were functionally primed for adherence and agonist-stimulated superoxide generation relative to unprimed, control neutrophils. The organizational state of the membrane cortex was examined by mapping the subcellular distribution of select cortical and transmembrane proteins by several methods, including subcellular fractionation, indirect immunofluorescence, and compositional analysis of Triton X-100-insoluble membrane skeleton preparations. Filamentous actin, fodrin, and the fodrin anchor, CD45, were largely cytoplasmic in unprimed neutrophils but translocated to plasma membranes upon priming, whereas CD43 and ezrin were exclusively surface-associated in both populations. Isopycnic sucrose density gradient analysis of N(2)-cavitated neutrophils revealed a major shift in the distribution of surface-associated transmembrane and membrane cortical components relative to the plasma membrane marker alkaline phosphatase in primed but not unprimed neutrophils. Similar results were obtained after neutrophil stimulation with known priming agents, LPS, TNF-alpha, or GM-CSF. Together, these results may suggest that priming of suspended, circulating neutrophils is associated with a large-scale reorganization of the plasma membrane and associated membrane cortex in a process that is independent of cellular adhesion and gross morphologic polarization.
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PMID:Reorganization of the human neutrophil plasma membrane is associated with functional priming: implications for neutrophil preparations. 2935 Aug 10

Pentoxifylline (POF) is a new candidate for the treatment of nonalcoholic steatohepatitis (NASH). Its effects on the cytokine production in patients with NASH are not completely understood. This study was designed to investigate the effect of POF on TNF-alpha production by peripheral blood mononuclear cells (PBMC) in patients with NASH. After preliminary experiments in healthy control subjects to determine the range of POF concentration to be used in NASH patients, PBMCs from patients with NASH (n = 13) were cultured in the presence of lipopolysaccharide (LPS, 100 ng/ml) and various concentrations of POF for 24 hr. Concentrations of TNF-alpha in culture supernatants were measured by ELISA and the transcriptional activity was determined by RT-PCR. As dictated by the results of our preliminary study in PBMC from healthy control subjects, we treated LPS stimulated PBMCs from NASH patients with 10, 100, and 500 microg/ml of POF. Stimulation of PBMCs from NASH patients with LPS resulted in a strong up-regulation of TNF-alpha production from median 355.9 (interquartile range, 206.7-463.5) pg/ml to 1,670 pg/ml (interquartile range, 1,121-2,414) pg/ml. In this LPS-stimulated culture system, POF caused a dose-dependent suppression of TNF-alpha levels (P < 0.001, ANOVA on ranks for repeated measures). TNF-alpha levels in culture supernatants decreased to 870.3 (range, 598.3-2,077) pg/ml with 10 microg/ml of POF treatment, and to levels similar to those obtained in baseline unstimulated cultures (133.4 (range, 95.8-1518.5) pg/ml) at 100 microg/ml. At 500 microg/ml, POF suppressed TNF-alpha production to levels significantly lower than that obtained in unstimulated (baseline) culture supernatants (76.3 (range, 33-94.5) pg/ml; P = 0.001). The mRNA expression was consistent with the effects on protein concentration. Demographic characteristics of the patients, laboratory results, such as AST, ALT, alkaline phosphatase, GGT, and triglyceride levels, and the liver histology did not seem to influence the in vitro TNF-alpha response of the PBMCs from NASH patients. POF can significantly decrease the LPS-stimulated TNF-alpha production by PBMCs in NASH patients. Our results support the notion that POF might be a good candidate for the treatment of NASH.
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PMID:Effects of pentoxifylline on TNF-alpha production by peripheral blood mononuclear cells in patients with nonalcoholic steatohepatitis. 1743 95

Chlamydia trachomatis is an obligate intracellular pathogen that primarily infects epithelial cells. Traditional methods for quantification of inclusion forming units (IFUs) rely upon infection of epithelial cell monolayers in vitro. Following incubation for approximately 2 days, inclusion bodies that result from infection of cells are detected by immunofluorescent staining with an antibody conjugated to a fluorescent dye. These inclusion bodies are then manually counted by microscopic examination of multiple, randomly selected fields of view. This requires substantial operator time and is subject to investigator bias. We have developed a novel method in which we utilize an automated microplate ImmunoSpot reader to count C. trachomatis IFUs. Following infection of epithelial cells in a 96-well plate and subsequent incubation, IFUs are fixed and detected with an anti-C. trachomatis LPS monoclonal antibody. Immobilized antibody is detected with a biotinylated secondary antibody and visualized enzymatically with streptavidin-alkaline phosphatase and the colorimetric substrate nitro-blue tetrazolium chloride/5-bromo-4-chloro-3-indolyl-phospate (NBT/BCIP). IFUs are then enumerated with the ImmunoSpot system. This method has been used to quantify IFUs from all cell lines traditionally used for chlamydial propagation, including L929, McCoy, HeLa and HaK cells. IFU numbers obtained are comparable to those determined by traditional microscopic counting. In addition, the method can be applied to rapid determination of serum-neutralizing titers for vaccine studies, and we have also applied this approach to quantify Chlamydia recovered from vaginal swabs collected from infected animals. This method provides for rapid enumeration of IFU counts while minimizing investigator bias and has potential applications for both research and diagnostic use.
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PMID:A novel automated method for enumeration of Chlamydia trachomatis inclusion forming units. 1755 19


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