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)

Break-Free CLP((R)) is a commercial cleaning, lubricating and preserving compound used in both the military and civilian sectors for maintenance of small- and large-caliber weapons. Like many commercial mixtures, there is very little information available on the toxicity of Break-Free CLP. Studies were conducted to characterize the biological effects of single or repeat dermal application of Break-Free CLP to the clipped backs of CD-1 mice. Break-Free CLP was applied neat, 50 microl three times of week for up to 2 weeks. Foci of epithelial ulceration were observed in skin sections from 22% of Break-Free CLP-treated animals in conjunction with markedly thickened epithelium suggesting that robust epithelial regeneration was occurring in these animals. Skin histopathology of Break-Free CLP-treated animals closely matched the histopathology from mice treated repeatedly with 2% croton oil in acetone (dermal irritation positive control). Serum alkaline phosphatase activity was significantly (P < 0.05) lower for mice treated with Break-Free CLP, 2% croton oil or 7,12-dimethylbenz[a]anthracene (DMBA) compared with negative and vehicle control mice. Skin nitric oxide (NO) levels were not significantly elevated for mice treated with Break-Free CLP but were significantly elevated for mice treated with dermal irritation positive control compound DMBA. The cumulative skin changes in Break-Free CLP-treated animals support conducting a subchronic dermal application study. The observed decreases in serum alkaline phosphatase activity suggest that future studies should include the liver and bone as possible target organs. Additionally, dermal penetration studies could provide key health risk assessment information for characterizing the potential health risks associated with chronic dermal exposure to Break-Free CLP.
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PMID:Acute and subacute dermal toxicity of Break-Free CLP: a weapons cleaning and maintenance compound. 1602 32

The role of regucalcin in the regulation of osteoblastic cell function was investigated. Osteoblastic MC3T3-E1 cells with subconfluent monolayers were cultured in a medium containing regucalcin (10(-10)-10(-8) M) without fetal bovine serum (FBS). The proliferation of osteoblastic cells was not significantly altered in the presence of regucalcin. The results of reverse transcription-polymerase chain reaction (RT-PCR) analysis with specific primers showed that the expression of Runx2 (Cbfa1) and insulin-like growth factor-I (IGF-I) mRNAs in osteoblastic cells was significantly suppressed in the presence of regucalcin (10(-10) or 10(-9) M). Transforming growth factor-beta1 mRNA levels were significantly enhanced in the 24 h-culture with regucalcin (10(-10) or 10(-9) M). Alpha1(I) collagen and glyceroaldehyde-3-phosphate dehydrogenase (G3PDH) mRNA levels were not significantly changed by culture with regucalcin (10(-10) or 10(-9) M). Alkaline phosphatase activity was significantly decreased in the lysate of cells cultured for 24 or 48 h with regucalcin (10(-10)-10(-8) M). Moreover, the expression of regucalcin in osteoblastic cells was demonstrated by RT-PCR and Western blot analysis. When regucalcin (10(-7) M) was added into the enzyme reaction mixture containing the lysate of osteoblastic cells cultured in the absence of regucalcin, alkaline phosphatase activity was significantly decreased. Also, Ca2+/calmodulin-dependent nitric oxide (NO) synthase activity in the cell lysate was significantly decreased by addition of regucalcin (10(-10)-10(-8) M) into the reaction mixture. The presence of anti-regucalcin monoclonal antibody (5 or 10 ng/ml) in the enzyme reaction mixture caused a significant increase in NO synthase activity in the cell lysate in the presence or absence of Ca2+/calmodulin, suggesting a role of endogenous regucalcin. When osteoblastic cells with subconfluency were cultured in the presence of regucalcin (10(-10) or 10(-9) M) for 3, 9, or 18 days, the results with Alizarin red staining showed that the mineralization was markedly suppressed by culture with regucalcin for 3, 9, or 18 days. This study demonstrates that regucalcin regulates the function of osteoblastic cells, and that the protein suppresses cell differentiation and mineralization.
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PMID:Suppressive effect of regucalcin on cell differentiation and mineralization in osteoblastic MC3T3-E1 cells. 1605 80

Gut-derived lipopolysaccharide (LPS) plays a role in the pathogenesis of liver diseases like fibrosis. The enzyme alkaline phosphatase (AP) is present in, among others, the intestinal wall and liver and has been previously shown to dephosphorylate LPS. Therefore, we investigated the effect of LPS on hepatic AP expression and the effect of AP on LPS-induced hepatocyte responses. LPS-dephosphorylating activity was expressed at the hepatocyte canalicular membrane in normal and fibrotic animals. In addition to this, fibrotic animals also displayed high LPS-dephosphorylating activity around bile ducts. The enzyme was shown to dephosphorylate LPS from several bacterial species. LPS itself rapidly enhanced the intrahepatic mRNA levels for this enzyme within 2 h by a factor of seven. Furthermore, in vitro and in vivo studies showed that exogenous intestinal AP quickly bound to the asialoglycoprotein receptor on hepatocytes. This intestinal isoform significantly attenuated LPS-induced hepatic tumor necrosis factor-alpha and nitric oxide (nitrite and nitrate) responses in vitro. The enzyme also reduced LPS-induced hepatic glycogenolysis in vivo. This study shows that LPS enhances AP expression in hepatocytes and that intestinal AP is rapidly taken up by these same cells, leading to an attenuation of LPS-induced responses in vivo. Gut-derived LPS-dephosphorylating activity or enzyme upregulation within hepatocytes by LPS may therefore be a protective mechanism within the liver.
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PMID:On the role and fate of LPS-dephosphorylating activity in the rat liver. 1622 48

Most pomegranate (Punica granatum Linn., Punicaceae) fruit parts are known to possess enormous antioxidant activity. The present study evaluated antioxidant and hepatoprotective activity of pomegranate flowers. Alcoholic (ethanolic) extract of flowers was prepared and used in the present study. The extract was found to contain a large amount of polyphenols and exhibit enormous reducing ability, both indicative of potent antioxidant ability. The extract showed 81.6% antioxidant activity in DPPH model system. The ability of extract to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) was tested and it was found to significantly scavenge superoxide (O(2)(.-)) (by up to 53.3%), hydrogen peroxide (H(2)O(2)) (by up to 30%), hydroxyl radicals (()OH) (by up to 37%) and nitric oxide (NO) (by up to 74.5%). The extract also inhibited (.)OH induced oxidation of lipids and proteins in vitro. These results indicated pomegranate flower extract to exert a significant antioxidant activity in vitro. The efficacy of extract was tested in vivo and it was found to exhibit a potent protective activity in acute oxidative tissue injury animal model: ferric nitrilotriacetate (Fe-NTA) induced hepatotoxicity in mice. Intraperitoneal administration of 9 mg/kg body wt. Fe-NTA to mice induced oxidative stress and liver injury. Pretreatment with pomegranate flower extract at a dose regimen of 50-150 mg/kg body wt. for a week significantly and dose dependently protected against Fe-NTA induced oxidative stress as well as hepatic injury. The extract afforded up to 60% protection against hepatic lipid peroxidation and preserved glutathione (GSH) levels and activities of antioxidant enzymes viz., catalase (CAT), glutathione peroxidase (GPX) glutathione reductase (GR) and glutathione-S-transferase (GST) by up to 36%, 28.5%, 28.7%, 40.2% and 42.5% respectively. A protection against Fe-NTA induced liver injury was apparent as inhibition in the modulation of liver markers viz., aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin and albumin in serum. The histopathological changes produced by Fe-NTA, such as ballooning degeneration, fatty changes, necrosis were also alleviated by the extract. These results indicate pomegranate flowers to possess potent antioxidant and hepatoprotective property, the former being probably responsible for the latter.
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PMID:Punica granatum (pomegranate) flower extract possesses potent antioxidant activity and abrogates Fe-NTA induced hepatotoxicity in mice. 1642 22

Wear particles generated following total joint arthroplasty interact with cells at the periprosthetic margin and induce an inflammatory response that contributes to osteolysis, aseptic loosening, and implant failure. This study examined the long-term effects of particles from two commonly implanted materials, titanium (Ti) and polymethylmethacrylate (PMMA), on cell viability and metabolism over a 21-day time course, using the human osteoblast-like cell line MG-63. Addition of particles was not associated with increased cell death or nitric oxide production at the particle concentration chosen. Collagen production was increased with exposure to titanium particles, whereas alkaline phosphatase and osteocalcin expression remained unchanged following exposure to both types of particles. The data show that titanium but not PMMA particles shifts bone cell metabolism to preferentially produce fibrous tissue rather than bone.
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PMID:The effects of titanium and polymethylmethacrylate particles on osteoblast phenotypic stability. 1648 50

An association has been previously established between uncompensated diabetes mellitus and the loss of bone mineral density and/or quality. In this study, we evaluated the effects of metformin on the growth and differentiation of osteoblasts in culture. Treatment of two osteoblast-like cells (UMR106 and MC3T3E1) with metformin (25-500 microM) for 24 h led to a dose-dependent increase of cell proliferation. Metformin also promoted osteoblastic differentiation: it increased type-I collagen production in both cell lines and stimulated alkaline phosphatase activity in MC3T3E1 osteoblasts. In addition, metformin markedly increased the formation of nodules of mineralization in 3-week MC3T3E1 cultures. Metformin induced activation and redistribution of phosphorylated extracellular signal-regulated kinase (P-ERK) in a transient manner, and dose-dependently stimulated the expression of endothelial and inducible nitric oxide synthases (e/iNOS). These results show for the first time a direct osteogenic effect of metformin on osteoblasts in culture, which could be mediated by activation/redistribution of ERK-1/2 and induction of e/iNOS.
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PMID:Osteogenic actions of the anti-diabetic drug metformin on osteoblasts in culture. 1656 24

It is known that metallic elements of joint endoprostheses undergo elastic strain due to their mechanical function. This is one of the factors which may be responsible for the loosening of endoprostheses. Since mechanisms involved in it remain unclear, it seems valuable to verify if cells responsible for bone regeneration are affected by a strain of the implant. Our experiment examines the influence of elastic strain applied to Ti6Al4V samples on osteoblasts cultured on their surface in vitro. Human bone-derived cells are observed in contact with metallic plates. Titanium alloy was chosen as a support since it is one of the most commonly used materials for stems in joint endoprostheses. Cyclic elastic deformation of 0.1% was applied to the support once daily for 7 days. Two thousand cycles were applied each time. Samples which were not subject to strain served as control. After the observation period XTT assay was performed, alkaline phosphatase activity as well as osteocalcin concentration and nitric oxide secretion were determined and compared with the results obtained in the control group. It was found that the number of viable cells in the mechanically stimulated population was significantly higher than in control, while both alkaline phosphatase activity and osteocalcin concentration were significantly lower in the experimental group. Nitric oxide secretion was found in the culture which was subject to elastic strain, but not in the control. The possible clinical implication is that elastic strain of the metallic endoprostheses may influence osteoblasts which are in contact with the implant in vivo.
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PMID:Osteoblast response to the elastic strain of metallic support. 1661 73

Estrogen stimulates endothelial nitric oxide (NO) production and attenuates endothelial dysfunction in ischemia/repurfusion and menopause. Recent studies have shown that phytoestrogens from dietary sources improve endothelial function and reduce cardiovascular risks. The Thai medicinal plant Pueraria mirifica (PM) contains many potent phytoestrogens including miroestrol and deoxymiroestrol but no study on vascular function has been established. Ground powder of PM was orally given to ovariectomized White New Zealand rabbits (OVX + PM group) (n = 4) weighing 3.2-4.0 kg at the dose of 100 mg/kg for 90 days. Saline-treated ovariectomized rabbits were assigned as a control group (OVX group) (n = 5). At the end of treatment thoracic aorta was isolated for functional evaluation. Maximal relaxant response to acetylcholine (ACh) was significantly increased (24%) with 3.5-fold decrease in EC50 while no change in relaxant response to sodium nitroprusside was observed Minimal and maximal responses to 17beta-estradiol (E2) were increased in the OVX + PM group and L-NAME (100 mM) attenuated Emax of E2. PM significantly decreased maximal contractile responses to norepinephrine (NE), but no change in EC50 was observed. In addition to vascular study, the authors found no significant alteration in serum cholesterol, LDL, triglyceride, HDL, ALT AST alkaline phosphatase, and lipid peroxidation in OVX + PM rabbits. These data demonstrate that PM (100 mg/kg/d) improved endothelial function through NO-dependent pathway and increased response to E2 while sensitivity to NE was reduced. In addition, it had no impact on lipid profile, liver enzymes, and ALP activities. PM is a potential source of phytoestrogens for postmenopausal women to improve cardiovascular function or reduce cardiovascular risks.
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PMID:Effects of Pueraria mirifica on vascular function of ovariectomized rabbits. 1686 67

To prevent bone loss that occurs with increasing age, certain nutritional and pharmacological factors are needed. In the present study, the ethanol extract from the fruit of Rubus coreanus Miq. (RCE) was investigated for its effect on the function of osteoblastic MC3T3-E1 cells. RCE (10approximately50 microg/ml) caused a significant elevation in cell viability, alkaline phosphatase (ALP) activity, collagen content, and osteocalcin secretion in the cells. The effect of RCE (50 microg/ml) in increasing cell viability, ALP activity, and collagen content was prevented by the presence of 10(-6) M cycloheximide and 10(-6) M tamoxifen, suggesting that RCE's effect results from a newly synthesized protein component and might be partly involved in estrogen action. We then examined the effect of RCE on the H(2)O(2)-induced apoptosis and production of local factors in osteoblasts. Treatment with RCE (10approximately50 microg/ml) decreased the 0.2 mM H(2)O(2)-induced apoptosis and production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and nitric oxide (NO) in osteoblasts. Our data indicate that the enhancement of osteoblast function by Rubus coreanus Miq. may result in the prevention of osteoporosis and inflammatory bone diseases.
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PMID:Rubus coreanus Miq. extract promotes osteoblast differentiation and inhibits bone-resorbing mediators in MC3T3-E1 cells. 1688 35

Osteocytes are thought to orchestrate bone remodeling, but it is unclear exactly how osteocytes influence neighboring bone cells. Here, we tested whether osteocytes, osteoblasts, and periosteal fibroblasts subjected to pulsating fluid flow (PFF) produce soluble factors that modulate the proliferation and differentiation of cultured osteoblasts and periosteal fibroblasts. We found that osteocyte PFF conditioned medium (CM) inhibited bone cell proliferation, and osteocytes produced the strongest inhibition of proliferation compared to osteoblasts and periosteal fibroblasts. The nitric oxide (NO) synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) attenuated the inhibitory effects of osteocyte PFF CM, suggesting that a change in NO release is at least partially responsible for the inhibitory effects of osteocyte PFF CM. Furthermore, osteocyte PFF CM stimulated osteoblast differentiation measured as increased alkaline phosphatase activity, and l-NAME decreased the stimulatory effects of osteocyte PFF CM on osteoblast differentiation. We conclude that osteocytes subjected to PFF inhibit proliferation but stimulate differentiation of osteoblasts in vitro via soluble factors and that the release of these soluble factors was at least partially dependent on the activation of a NO pathway in osteocytes in response to PFF. Thus, the osteocyte appears to be more responsive to PFF than the osteoblast or periosteal fibroblast with respect to the production of soluble signaling molecules affecting osteoblast proliferation and differentiation.
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PMID:Osteocytes subjected to pulsating fluid flow regulate osteoblast proliferation and differentiation. 1690 67


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