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)

Peroxynitrite (PN), a nitric oxide (NO*)-derived anion, has been associated with NO* damage in various cell types. We examined the effects of adding PN to cultured human osteoblast-like (hOB) cells obtained after hip arthroplasty. Exposure to PN (0.1-0.4 mM) decreased both hOB proliferation and differentiation, measured by [3H]thymidine uptake and alkaline phosphatase production, respectively. Incubation with 3-morpholinosydnonimine (SIN-1; 0.25-1 mM), an NO* and O2- donor that leads to PN release, also reduced both hOB proliferation and differentiation. Coincubation with both superoxide dismutase (SOD; 100 U/ml) and catalase (CAT; 50 U/ml), rendering SIN-1 a pure NO* donor, reversed its effects on hOB proliferation and differentiation. However, SIN-1-induced NO* production, measured by nitrite release to the hOB medium, was not altered by cotreatment with SOD and CAT. Expression of nitrotyrosine by hOB, a marker of PN action, was significantly increased after SIN-1 addition, as compared with untreated cells, as revealed by Western blot analysis. Interleukin-1alpha (IL-1alpha) and interferon gamma (IFN-gamma) but not tumor necrosis factor alpha (TNF-alpha) also significantly increased nitrotyrosine expression in these cells. These data show that PN is at least partially responsible for osteoblast derangement by NO* and that cytokines released during inflammatory arthropathies can induce PN production in hOB cells.
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PMID:Evidence that peroxynitrite affects human osteoblast proliferation and differentiation. 1187 35

The consumption of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) is known to cause severe hyperthermia and liver damage in humans. The thermogenic response induced by MDMA is complex and partially determined by the prevailing ambient temperature (AT). This is of extreme importance since ecstasy is often consumed at "rave" parties, where dancing takes place in a warm environment, which may exacerbate the effect of MDMA on thermoregulation. In view of the fact that hyperthermia is a well-known pro-oxidant aggressive condition, its potential role in ecstasy-induced hepatocellular toxicity should be further studied. Thus, the present study was performed in order to evaluate the influence of AT on the effects of single administration of MDMA on body temperature and liver toxicity in Charles River mice. Animals were given an acute intraperitoneal dose of MDMA (5, 10 or 20 mg/kg) and placed in AT of 20+/-2 degrees C or 30+/-2 degrees C for 24 h. Body temperature was measured during the study using implanted transponders and a temperature probe reading device. Plasma and liver samples were used for biochemical analysis. Liver sections were also taken for histological examination. The parameters evaluated were (1) plasma levels of transaminases and alkaline phosphatase, (2) hepatic glutathione (GSH), (3) hepatic lipid peroxidation, (4) activity of hepatic antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, glutathione- S-transferase, copper/zinc superoxide dismutase and manganese superoxide dismutase), and (5) liver histology. The hyperthermic response elicited by MDMA was clearly dose-related and potentiated by high AT. Administration of MDMA produced some evidence of oxidative stress, expressed as GSH depletion at both ATs studied, as well as by lipid peroxidation and decreased catalase activity at high AT. High AT, by itself, decreased glutathione peroxidase activity. Histological examination of the liver revealed abnormalities of a dose- and AT-dependent nature. These changes included vacuolation of the hepatocytes, presence of blood clots and loss of typical hepatic cord organisation. The results obtained in the present study suggest that oxidative stress plays a part in the first stage of MDMA-induced liver damage and that liver antioxidant status is aggravated by increased AT. Thus, these findings are in accordance with the hypothesis that high AT may potentiate ecstasy-induced hepatotoxicity by increasing body hyperthermia.
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PMID:Effect of 3,4-methylenedioxymethamphetamine ("ecstasy") on body temperature and liver antioxidant status in mice: influence of ambient temperature. 1196 22

High-performance liquid chromatography (HPLC) separates three human bone alkaline phosphatase (BALP) isoforms in serum; two major BALP isoforms, B1 and B2, and a minor fraction, B/I, which is composed on average of 70% bone and 30% intestinal ALP. The current studies were intended to identify an in vitro source of the BALP isoforms for physical, biochemical, and immunological characterizations. The three BALP isoforms were identified in extracts of human osteosarcoma (SaOS-2) cells, by HPLC, after separation by anion-exchange chromatography. All three BALP isoforms were similar with respect to freeze-thaw stability, solubility, heat inactivation, and inhibition by L-phenylalanine, L-homoarginine, and levamisole. The isoforms were also kinetically similar (i.e., maximal velocity and KM at pH 8.8 and pH 10.0). The isoforms differed, however, with respect to sensitivity to precipitation with wheat germ agglutinin (WGA), P < 0.001, but not Concanavalin A. At 3.0 mg/ml, WGA precipitated approximately 25% of B/I but more than 80% of B1 and B2. Molecular weights were estimated by native gradient gel electrophoresis: B/I, 126 kDa; B1, 136 kDa; and B2, 141 kDa. Desialylation with neuraminidase reduced the apparent sizes of B1 and B2 to 127 kDa (i.e., approximately to that of B/I). The total carbohydrate content was calculated to be 18 kDa, 28 kDa, and 33 kDa (i.e., 14%, 21%, and 23%) for the BALP isofonns, B/I, B1, and B2, respectively. The number of sialic acid residues was estimated to be 29 and 45, for each B1 and B2 homodimer, respectively. Apparent discrepancies between these estimates of molecular weight and estimates based on gel filtration chromatography were attributed to nonspecific interactions between carbohydrate residues and the gel filtration beads. All three BALP isoforms showed similar dose-dependent linearity in the commercial Alkphase-B and Tandem-MP Ostase immunoassays, r = 0.944 and r = 0.985, respectively (P < 0.001). In summary, our data indicate that B1 and B2 have more (or more reactive) sialic acid residues compared with B/I, which mainly explains the apparent differences in molecular weight. Future investigations will focus on the clinical and functional significance of the revealed differences in sialic acid residues.
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PMID:Differences in sialic acid residues among bone alkaline phosphatase isoforms: a physical, biochemical, and immunological characterization. 1223 76

In vitro and in vivo studies were made with an alcohol extract of the seeds of Mucuna pruriens (Fabaceae) to investigate its antioxidant property. In vitro studies were carried out in rat liver homogenate to investigate the chemical interaction of various phytochemicals with different species of free radicals. The effect was also checked on iron-induced lipid peroxidation, oxidation of GSH content, and its interaction with hydroxyl and superoxide radicals. There was no change on the rate of aerial oxidation of GSH content but it significantly inhibited FeSO(4) induced lipid peroxidation. It also inhibited the specific chemical reactions induced by superoxides and hydroxyl radicals. The removal of these species was through direct chemical interaction. An in vivo study on albino rats for 30 days showed no toxic effect up to a dose of 600 mg/kg body weight, on oral administration. There was no change in the level of TBA-reactive substances, reduced glutathione content and SOD activity in the liver. The activity of serum GOT, GPT and alkaline phosphatase was also unchanged. Thus it could be concluded that the alcohol extract of the seeds of M. pruriens has an antilipid peroxidation property, which is mediated through the removal of superoxides and hydroxyl radicals.
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PMID:Effect of the alcohol extract of the seeds of Mucuna pruriens on free radicals and oxidative stress in albino rats. 1223 10

Nineteen monoclonal antibodies (MAbs) against tissue-nonspecific (liver/bone/kidney) alkaline phosphatase (TNALP) were investigated in the ISOBM TD-9 Workshop. These MAbs were generated with antigens obtained from human bone tissue (n = 9), human osteosarcoma cell lines (SaOS-2 and TPX; n = 7) and human liver tissue (n = 3). The evaluation included the following antigen forms: (a) commercially available preparations of human bone ALP (BALP) and liver ALP (LALP); (b) human BALP isoforms, B/I, B1 and B2; and (c) soluble secreted epitope-tagged recombinant human TNALP (setTNALP) expressed in COS-1, osteosarcoma (SaOS-2) and hepatoma (Huh2) cell lines. In addition, 16 TNALP mutant cDNAs corresponding to a wide spectrum of reported hypophosphatasia mutations were used in an attempt to map specific immunoreactive epitopes on the surface of the TNALP molecule. The TD-9 MAbs were evaluated by immunoradiometric (IRMA) assays, cross-inhibition and different enzyme immunoassay designs. No indications of explicit tissue discriminatory immunoreactivities of the investigated MAbs against TNALP were found. However, certain IRMA combinations of MAbs increased the specificity of BALP measurements. All MAbs bound to the three BALP isoforms B/I, B1 and B2, but none of the investigated MAbs were specific for any of the isoforms. Significant differences were, however, found in immunoreactivity between these isoforms, with cross-reactivities ranging from 21 to 109% between the two major BALP isoforms B1 and B2. Desialylation with neuraminidase significantly increased the MAb affinity for the BALP isoforms B/I, B1 and B2, and also decreased the observed differences in cross-reactivity between these isoforms. We suggest, therefore, that the MAb affinity is dependent on the amount/number of terminal sialic acid residues located at the five putative N-glycosylation sites. Based on the overall results, we present a putative three-dimensional model of the TNALP molecule with positioning of the four major antigenic domains (designated A-D) of the investigated MAbs. The TNALP molecule is depicted as a homodimer, hence most, but not necessarily all, epitopes are displayed twice. The antigenic domains were positioned with the following assumptions: domain A was positioned close to the active site since most of these MAbs interfered with the catalytic activity. Interestingly, both MAbs included in the commercial BALP kits were grouped with domain A. Moreover, 4 of the 5 putative N-glycosylation sites (with terminal sialic acid residues) are located within, or with close proximity to, domain A. Domain B was localized at the top flexible loop (crown domain) of the TNALP molecule. Domain C was clearly defined by the IRMA assay combinations and by site-directed mutants of TNALP to be close to residue E281, which is located near the fourth metal binding site, likely to be occupied by a calcium ion. Domain D was positioned close to residues A115, A162 and E174, but this domain was also close to the GPI anchor site. In conclusion, none of the 19 investigated TD-9 MAbs were entirely specific for BALP or LALP, thus indicating that all MAbs bind mainly to epitopes on the common protein core of BALP and LALP and/or common glycosylated epitopes. However, some MAbs (either single or in combination with other MAbs) work sufficiently well to measure BALP when the assayed samples do not contain elevated levels of LALP.
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PMID:Monoclonal antibodies against tissue-nonspecific alkaline phosphatase. Report of the ISOBM TD9 workshop. 1249 79

Modulatory effect of a formulated diet based on cereals, pulses and spices incorporated with crude palm oil (CPO), soybean oil (SBO) or cod liver oil (CLO) at 10% dietary level on oxidative stress and antioxidant enzymes was studied in liver and kidney tissues. Activity of alkaline phosphatase (ALP) and acid phosphatase (ACP) increased significantly in serum in various experimental groups. Significant increase in hepatic antioxidant enzymes, catalase, glutathione peroxidase (GPx) was also seen in the experimental groups. SOD activity showed a mixed response. Further, kidney antioxidant enzymes did not show much change compared to those in liver. The results indicated dietary lipid as the key players in determining cellular susceptibility to oxidative stress, which could be modulated by cereals, pulses and spices in the diet.
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PMID:Effect of oxidative stress on serum and antioxidant enzymes in liver and kidney of rats and their modulation through dietary factors. 1258 29

Male weaning rats were divided randomly into five groups. They were fed with diets containing zinc deficient(DZ), high zinc(HZ), normal zinc (NZ) and high zinc pair-fed with zinc deficient group(HZP) respectively. The rats in DZ and HZ groups were exchanged diets after 20 days. A part of rats in each group were killed at days 20, 50 and 70. The activities of alkaline phosphatase(ALP), 5'-nucleotidase(5'-NT) and copper-zinc-superoxidase dismutase(Cu-Zn-SOD), the zinc concentration in plasma and kidney were determined to assess the better indices for zinc nutrition. The results indicted that: The activities of ALP in DZ group at 20 d was significantly lower than that in the same group at the beginning, in the HZ group and in the HZP group, and increased significantly after the diet was changed to HZ diet after 30 days. The activities of 5'-NT in DZ group rats was decreasing with the extension of experimental period. These results indicated that the activities of ALP and 5'-NT were sensitive to zinc supplementation even though they were changed a little during zinc exhausted. The activity of ALP was decreasing with growing, and the activity of 5'-NT was increased with growing. Zinc concentration in plasma of DZ group was significantly lower than that of other groups which include DZ-HZ group at the 50th day, and it was also the lowest among groups at the end of experiment. Zinc concentration in the kidney of HZ-DZ group was significantly lower than that of HZ and DZ-HZ groups by the end of experiment. There were little changes of the activity of Cu-Zn SOD and the zinc content in kidney during the experiment period. These results indicated that the activities of both ALP and 5'-NT and plasma zinc were sensitive to zinc supplementacior and zinc deficiency.
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PMID:[Research on some enzyme activities in the assessment of zinc nutritional status of growing rats]. 1271 98

Glycosmis arborea is a plant possessing various medicinal properties. The aim of the present study was to investigate the hepatoprotective efficacy of the butanol extract obtained from the aerial parts of the plant. The test sample was prepared by extracting the material through different steps. The extract thus obtained was dissolved in normal saline. Albino rats were prophylactically treated with the extract (i.p.) for 3 weeks. At the end of 3rd week all the groups were injected with hepatotoxic agents. After 48 h of injection, blood was collected and livers were taken out. Different enzymes in the serum were assayed and histopathological study was performed with liver. Glycosmis arborea extract was able to overcome the toxic effects of hepatotoxic agents in terms of lowering the levels of serum GPT, alkaline phosphatase and increased level of SOD in serum. TBARS generation in liver was also altered. Moreover, necrosis of liver produced by carbon tetrachloride was reversed by the extract.
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PMID:Glycosmis arborea extract as a hepatoprotective agent. 1274 4

A family of proteins, the bone morphogenetic proteins (BMPs), which promote osteoblast differentiation and bone mineralization, have recently been identified. One, BMP-7, has shown the ability to induce cartilage and bone formation processes. In this report, the possibility that other cell lines, to CHO cells, may also be available as host cells for the expression of hBMP-7 was validated. Recombinant human BMP (rhBMP)-7 was produced in COS-7 cells, as a processed mature disulfide-linked homodimer, with an apparent molecular weight of 36,000. Examination of the expressions of the markers characteristic of osteoblast phenotypes showed that the rhBMP-7 specifically stimulated the inductions of alkaline phosphatase (ALP) (5-fold increase at 100 ng of rhBMP-7/ml), parathyroid hormone (PTH)-mediated intracellular cAMP production (4-fold increase at 100 ng of rhBMP-7/ml) and osteocalcin synthesis (5-fold increase at 100 ng of rhBMP- 7/ml). In summary, the in vitro mineralization assay results provide evidence that the rhBMP-7 peptide, produced by COS-7 expression system, possesses intact biological activity. A similar pattern of biological activity was observed for the BMP-7 in COS-7 cells compared to the corresponding CHO cell expression system. Thus, these findings can be experimentally utilized for the production of rhBMPs for in vitro or in vivo studies.
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PMID:The effects of recombinant human BMP-7, prepared from a COS-7 expression system, on the proliferation and differentiation of rat newborn calvarial osteoblasts. 1295 Jan 13

Stanniocalcin (STC) is a large polypeptide hormone that is widely distributed in tissues such as kidney, adrenal, and ovary. In most tissues, STC exists as a 50-kDa homodimer (STC50). The ovaries produce a higher molecular weight variant (big STC) in androgen-producing theca cell and interstitial cell compartments. Luteal cells, which do not express the STC gene, nonetheless contain high levels of STC protein, suggesting they are targeted by and sequester big STC through a receptor-mediated process. Recently, an STC.alkaline phosphatase fusion protein was used to characterize mitochondrial targeting and sequestration of STC50 and its receptor in liver and kidney. The main objective of the present study was to characterize big STC and its receptor in mammalian ovary and determine whether the ovarian STC variant was similarly targeted to luteal cell mitochondria. By in situ ligand binding, we identified large numbers of STC receptors on corpus luteal cells. However, a more detailed analysis of sub-cellular fractions revealed that both STC and its receptor were not preferentially targeted to mitochondria but instead to cholesterol/lipid storage droplets, which was more indicative of a role in steroidogenesis. Functional studies revealed that additions of big STC had concentration-dependent inhibitory effects on both basal and stimulated progesterone output by primary cultured luteal cells. Furthermore, STC receptor levels were up-regulated in luteal cells in response to protein kinase A activation. Taken together, these findings indicate that theca cell-derived big STC is targeted to the cholesterol/lipid storage droplets of luteal cells to regulate steroidogenesis. This constitutes the first reported description of polypeptide hormone and receptor targeting to cholesterol/lipid droplets and the first biological role for the big STC variant.
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PMID:Targeting of big stanniocalcin and its receptor to lipid storage droplets of ovarian steroidogenic cells. 1451 26


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