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)

The effect of recombinant interleukin 1 Beta (IL-1(beta)) was investigated on osteoblastic cell line MC3T3-E1 cloned from mouse calvaria. IL-1(beta) stimulated cell proliferation which increased cell number and caused dose-related stimulation of DNA synthesis, with a maximal effect at a concentration of 12.5 U/ml; suppressed alkaline phosphatase activity and collagen synthesis maximally at 0.5 and 62.5 U/ml, respectively; and increased the amount of free [3H] hydroxyproline in the cultures, but the amount was quite low. Prostaglandin E2 synthesis was also stimulated dose dependently by the presence of IL-1(beta), with a maximal increase at 2.5 U/ml, at which concentration the prostaglandin E2 level in the medium was 1.61 +/- 0.10 ng/ml. The increased prostaglandin E2 synthesis did not affect either the IL-1(beta)-mediated change in DNA or collagen synthesis or alkaline phosphatase activity. These results extend the possibility that IL-1(beta) is to act as a regulator of bone formation.
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PMID:Effect of interleukin 1 beta on osteoblastic clone MC3T3-E1 cells. 314 Oct 17

An ELISA for PGE2 has been developed which is sensitive to concentrations of 0.5 to 20.0 ng PGE2/ml. Mouse monoclonal anti-PGE2 ascites is utilized in a binding competition between the test sample and an adsorbed conjugate of PGE2-BSA. The antibody which remains bound to the solid phase is quantitated colorimetrically by incubation with alkaline phosphatase-conjugated goat anti-mouse IgG followed by incubation with p-nitro-phenylphosphate. PGE1, PGA1, PGA2, PGB2, 6-keto-PGF1 alpha, PGF2 alpha, 13,14-dihydro-15-keto-PGE2, thromboxane B2 and arachidonic acid showed minimal cross-reactivity with the anti-PGE2. The PGE2 ELISA permits the quantitative analysis of large numbers of samples at a fraction of the cost and time required to process a commercial RIA kit. When linked to the appropriate computer software, data collection and analysis can be performed in less than 10 minutes per 96-well plate. Furthermore, the use of an ELISA system eliminates the radioactive and toxic chemical waste generated by RIA methods.
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PMID:An ELISA for PGE2 utilizing monoclonal antibody. 316 99

Cloned MC3T3-E1 cells which have retained several osteoblast-like characteristics were derived from newborn mouse calvaria. In order to elucidate the function of osteoblasts, the effects of 1,25(OH)2D3, interleukin (IL)-1 beta, IL-3, interferon(INF)-gamma and epidermal growth factor(EGF) on the activity of alkaline phosphatase(Al-P'ase), DNA synthesis and the production of prostaglandin E2(PGE2) in MC3T3-E1 cells were studied. The influence of cyclosporin A(CSA), a potent immunosuppressive agent, was also studied. The following results were obtained: 1. 1,25(OH)2D3 increased the incorporation of [45Ca]Cl2 into matrix and accelerated the calcification of MC3T3-E1 cells. 2. Al-P'ase activity and the incorporation of [3H]-thymidine into MC3T3-E1 cells were increased by 1,25(OH)2D3 but decreased by IL-1 beta, INF-gamma, IL-3 and EGF. 3. IL-1 beta increased and INF-gamma decreased PG-E2 production by MC3T3-E1 cells. 4. CSA decreased either Al-P'ase activity or incorporation of [3H]-thymidine, and increased PG-E2 production in MC3T3-E1 cells. CSA which was simultaneously incubated with these various cell growth factors, showed a similar effect to that of CSA alone. These results suggest that cytokines produced from immune cells, could affect osteoblasts besides that of calcium regulating hormones like parathyroid hormone and 1,25(OH)2D3, implying a probability for the participation of immunocompetent cells in the regulation of bone metabolism.
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PMID:[The effects of various cell growth factors and cyclosporin A, an immunosuppressive agent, on cloned osteoblastic cell line, MC3T3-E1 cells]. 326 92

An early event of the decidual cell reaction in response to either natural or artificial deciduogenic stimuli is an increase in the activity of alkaline phosphatase in endometrial stromal cells. Since it is known that prostaglandins have a stimulatory role in other events of the decidual cell reaction, this study addressed whether prostaglandins have any role in the increase in alkaline phosphatase activity. Mature ovariectomized rats were sensitized for the decidual cell reaction with s.c. injections of estrogen and progesterone. To investigate the effect of inhibition of endogenous prostaglandin synthesis, rats received indomethacin (s.c. and via intrauterine infusion) or the vehicles sesame oil and phosphate-buffered saline with gelatin. Biochemical measurement of endometrial alkaline phosphatase activity and protein content revealed that, compared to the controls, indomethacin had no significant effect at 24 h after the initiation of infusion. At 48 h, unit activity (activity per unit protein) and total activity were substantially lower in indomethacin-treated than in vehicle-treated rats. At 72 h, there was a less dramatic difference between the unit activities of the two groups; however, there was a 10-fold difference between the total measureable activities of the two groups. Infusion of exogenous prostaglandins PGE2 or PGF2 alpha into rats treated with indomethacin overrode the inhibitory effect of indomethacin upon the increase in alkaline phosphatase activity. The dose-response relationship indicated that both PGE2 and PGF2 alpha have the same efficacy. In rats that had been treated similarly, localization of uterine alkaline phosphatase activity by histochemistry demonstrated a high correlation between the histochemical and biochemical data.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulatory effects of prostaglandins upon endometrial alkaline phosphatase activity during the decidual cell reaction in the rat. 340 81

Metabolic functions of the lung were examined in sixty patients undergoing coronary artery bypass surgery employing a method to separate right and left heart flow during surgery. Six study groups were employed to investigate the activity of normal serum electrolytes, minerals, enzymes and vasoactive prostanoids as they pass through the pulmonary vasculature. Various sample sites were employed to represent isolated segments of the vascular tree: pump (systemic) and right atrium (myocardium), aortic (bronchial flow). LDH, Ca++, phosphate and SGOT were documented to vary with passage through the pulmonary circulation while alkaline phosphatase, bilirubin, creatinine, urate, cholesterol, albumin and BUN remained essentially unchanged. Bronchial flow was calculated and directly related to temperature and pump flow with an average range of 15 ml/min +/- 6 ml/min. The stress of surgery produced elevated PGE2 in bronchial flow and urine that caused reproducible hypotension when rapidly reinfused into the patient. PGE2 production, though decreased with Indomethacin block, could be rapidly reversed with the stress of surgery.
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PMID:Metabolic activity of the lung during cardiopulmonary bypass. 347 60

Prostaglandins have been implicated in the process of uterine decidualization in vitro, but sites of action are uncertain. Since one of the earliest changes in endometrial stroma following induction of decidualization is an increase in alkaline phosphatase activity, we have investigated the effects of PGs on stromal cell alkaline phosphatase activity in vitro. Immature rats were pretreated with hormones to sensitize their uteri for the decidual cell reaction. Endometrial stromal cells were isolated and cultured for up to 4 days with PGE2 (0-10 micrograms/ml) or PGF2 (0-10 micrograms/ml). Analysis of variance revealed a highly significant interaction between day of culture and concentration of PGE2 in medium (P less than 0.01). Stromal cell alkaline phosphatase activity decreased significantly with increasing culture duration (P less than 0.01). In the presence of PGE2, alkaline phosphatase activity was significantly higher (P less than 0.01) regardless of day of culture. In contrast, PGF2 alpha had only a small and inconsistent effect. These data indicate that PGs, and in particular PGE2, can act directly upon stromal cells.
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PMID:Prostaglandin E2 enhances uterine stromal cell alkaline phosphatase activity in vitro. 347 73

The effects of Prostaglandin E-2 (PGE-2) on cortical bone turnover in ribs and femurs of 32 intact adult dogs were evaluated following 3 months treatment. Static and dynamic histomorphometric skeletal changes were characterized using terminal in vivo tetracycline double labeling. PGE-2 caused a dose dependent increase in the formation of subperiosteal fibrous-lamellar new bone in femurs, and an increase in bone remodeling within the (original) cortical compacta of both femurs and ribs. Increased cortical remodeling resulted in a new steady state, but only in ribs. Increased Haversian remodeling in ribs and femurs was characterized by increases in the activation frequency, the number of bone resorbing and forming foci, the percent of osteons with single labels, and the radial closure and bone formation rates, with no effect on appositional rate. While the mean ratios of the number of resorption to formation foci (R/F) were unremarkable in femurs of treated versus control males, the R/F ratios in treated females were approximately 50% lower than matched controls. In treated males, both femoral osteon resorption and formation times were 50% shorter than matched controls. In treated females, femoral osteon resorption time was 2-4-fold shorter than the decrease in osteon formation time. Calcium and phosphorus levels were normal in all treated dogs. Serum alkaline phosphatase levels were increased approximately two-fold in high dose (10.0 mg/kg) dogs and correlated well with the histologic findings of increased skeletal turnover and bone formation.
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PMID:Effects of orally administered prostaglandin E-2 on cortical bone turnover in adult dogs: a histomorphometric study. 348 54

Bone metastases of breast cancers produce not only osteolytic but also osteosclerotic lesions. The latter are often observed after androgenic treatment of the tumor. Potential production of osteoblast stimulating activity (ObSA) in breast cancer cell lines, and possible androgen control of this activity have been investigated. Conditioned media (CM) collected from 4 breast cancer cell lines (MCF-7, ZR75, MDA-MB 231, BT20) was tested in vitro on ROS 17/2,8 osteoblast-like cells and on osteoblasts derived from human bone biopsies. The parameters monitored in osteoblasts were [3H]thymidine incorporation, alkaline phosphatase activity, and osteocalcin secretion. Serum-free media conditioned during 24 h by MCF-7 cells presented the highest ObSA. CM decreased thymidine incorporation in DNA and increased alkaline phosphatase activity in a dose-dependent manner. Bone GLA protein (osteocalcin) secretion by human osteoblasts was not increased however in the presence of CM. MCF-7 cells were cultured in the presence of dihydrotestosterone (DHT) [1-100 nM] for 5 days. Serum-free, DHT-free CM collected after an additional 24 h, contained alkaline-phosphatase stimulating activity which was DHT dose-dependent. Estradiol and 1,25(OH)2D3 failed to elicit a comparable increase of the ObSA in the CM. In conclusion, MCF-7 cells product factor(s) that interfere with bone remodeling. The DHT modulation of ObSA parallels the estradiol control of MCF-7 cells osteolytic lesions in relation with Prostaglandin E secretion. Sex hormones at physiological and pharmacological levels might thus control both osteosclerotic and osteolytic lesions observed in bone deposits of hormone dependent cancers.
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PMID:Androgens increase osteoblast-stimulating activity of human breast cancer cells in vitro. 370 24

Prostaglandins have been reported to exert trophic effects on gastrointestinal tissues. To determine whether there is a direct interaction with enterocytes, prostaglandins PGE2, PGF2 alpha, PGA2, PGB2 and the stable PGE2 derivative suleprost as well as the prostacyclin derivative nileprost were tested in rabbit ileal mucosa under organ culture conditions. At concentrations between 10(-9) and 10(-5) M, none of the prostaglandins significantly affected biopsy DNA or protein content, or the activity of the brush border enzymes alkaline phosphatase, lactase, sucrase or maltase. The inhibition of endogenous prostaglandin synthesis with indomethacin also failed to alter these parameters. Moreover, the growth rate of a rat duodenal crypt cell line was unaffected when cultured in the presence of PGE2, PGF2 alpha or indomethacin. Thus, there was no evidence for a direct effect of exogenous or endogenous prostaglandins or their deficiency on the differentiation or growth in cultured small intestinal cells.
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PMID:Prostaglandins are not involved in the differentiation or growth of cultured small intestinal cells. 381 31

An intramuscular dose schedule of 15(S)-15-methyl-prostaglandin E2-methyl ester (15-(S)-ME PGE2) was evaluated for its application as a midtrimester abortifacient route. 20 healthy gravidas aged 18-42 years and 8-22 menstrual weeks of gestation were aborted in the Clinical Research Unit of the University of North Carolina Memorial Hospital. The subjects were given 5 mcg of the PGE2 methyl ester every 4 hours. 85% (17/20) aborted within 48 hours, 65% (13/20) of these within 24 hours. Mean induction-abortion interval was 21 hours. Trials were defined as complete in 55%, incomplete in 30%, and failure in 15%. Shivering, fever, pain, vomiting, and diarrhea were the most common side effects. The transient shivering occurred in 13 (65%) of the subjects within 20 minutes of the first dose. Fever usually started after shivering, and both resolved spontaneously. 2 patients had estimated blood loss exceeding 500 ml, but they were not given transfusions. No clinically significant changes occurred in mean hemotocrit, platelet count, serum creatinine, bilirubin, alkaline phosphatase, electrolytes, serum glutamic oxalacetic transaminase, and serum glutamic pyruvic transaminase. Mean blood cell and neutrophil counts increased, but neither increase was statistically significant.
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PMID:Intramuscular administration of 15(S)-15-methylprostaglandin E2-methyl ester for induction of abortion. 442 93


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