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 CadmiBel Study was a cross-sectional population study that investigated the health effects of environmental exposure to cadmium and lead. The 2327 participants constituted a random sample of the population of four Belgian districts, chosen in order to provide a wide range of environmental exposure to cadmium. After adjustment for confounding factors, such as smoking and occupational exposure, the urinary cadmium excretion, a measure of lifetime exposure, was nearly 30% higher in the polluted areas. The CadmiBel Study produced evidence inconsistent with the hypothesis that environmental exposure to cadmium and lead would lead to an increase in blood pressure and to a higher prevalence of hypertension and other cardiovascular diseases. On the other hand, the serum alkaline phosphatase activity and the urinary excretion of calcium were significantly and positively correlated with urinary cadmium in both sexes. These findings suggested that the homeostasis of calcium was gradually affected as cadmium accumulated in the body. Furthermore, several markers of renal tubular dysfunction (urinary excretion of retinol-binding-protein, N-acetyl-beta-glucosaminidase, beta 2-microglobulin and amino acids) were significantly and positively associated with urinary cadmium. Across 10 small areas of which six were polluted with cadmium, an inverse association existed between the creatinine clearance and several indexes of environmental exposure to cadmium (cadmium concentration in the soil, cadmium content of locally grown vegetables, the inhabitants' 24 h urinary cadmium excretion). In the CadmiBel Study, the creatinine clearance was also inversely correlated with the concentrations of lead and zinc protoporphyrin in the blood. Thus, environmental exposure to cadmium and lead was associated with alterations in renal function. The significance in terms of morbidity and mortality of the functional disturbances observed in the CadmiBel Study, and the possible strategies to prevent the transfer of cadmium from the environment to man are under investigation in the prospective PheeCad Study in which half of the Cadmibel participants have been enrolled (participation rate 80%).
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PMID:Public health implications of environmental exposure to cadmium and lead: an overview of epidemiological studies in Belgium. Working Groups. 878 28

The adult human Sertoli cells produced lactate, estradiol-17beta, transferrin and inhibin; germ cells modulate synthesis of these compounds. In order to study the functional features of human Sertoli cells in vitro, the aim of this study was to measure the lactic dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP) and creatine kinase activities (CK) in primary cultures of Sertoli cells prepared from young men (mean age: 29 years, n = 11). Five LDH isozymes have been found in Sertoli cells, the main fractions being the LDH3 and LDH4; each of them represented 30% of the total LDH activity. Furthermore, CK and ALP activities were measured in Sertoli cells. It is of note that the Sertoli cell ALP activity was 50% lower than that of germ cells. Whatever the Sertoli cell parameter measured herein, there is a great variability between patients and FSH (dbc AMP, as well as retinol, insulin, testosterone) is poorly effective in improving these enzymatic activities in vitro. We have confirmed that GGT was exclusively present in Sertoli cells and thus may be considered as a specific marker. LDH is involved in Sertoli cell glucose transformation and thus provided energetic substrates for germ cells. In contrast, the roles of CK and ALP remains to be clarified. In conclusion, we have demonstrated the existence of several enzymes namely LDH, GGT, ALP and CK in Sertoli cells prepared from adult human testis.
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PMID:Enzymatic properties of adult human Sertoli cells in vitro. 884 50

Understanding of the possible toxicity associated with hypervitaminosis A becomes increasingly important in view of the popularity of vitamin A supplementation. Hypervitaminosis A for many years may eventually lead to hepatocellular damage. In the present study, rats were treated for 7 days with high doses of retinol to study the early effects on the metabolism of different types of liver cells using (enzyme) histochemistry, immunohistochemistry and electron microscopy. Excessive intake of vitamin A activates Kupffer cells and induces accumulation of lipid droplets in fat-storing cells as well as proliferation of these cells. Moreover, it affects the metabolic heterogeneity in the liver lobules, but does not lead to apparent cell damage. Based on the changes in marker enzymes for different metabolic processes, it is concluded that the capacity for breakdown of purines, the antioxidant capacity, the potential for phagocytosis and the regulation of ammonia levels were largely decreased. Increased alkaline phosphatase activity in hepatocytes pointed to an activated process of transport of retinol esters over the bile canalicular membrane. The possible causes of these metabolic changes have been described in the discussion.
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PMID:Early effects of high doses of retinol (vitamin A) on the in situ cellular metabolism in rat liver. 886 71

When bovine beta-lactoglobulin (beta-LG) was refolded after extensive denaturation in 4.8 M guanidine hydrochloride (GuHCl), the functional activity of the protein, retinol binding, as measured by the enhancement of this ligand's fluorescence, was completely recovered. In contrast, the room-temperature tryptophan phosphorescence lifetime of the refolded protein, a local measure of the residue environment, was approximately 10 ms, significantly shorter than the phosphorescence lifetime of the untreated native protein (approximately 20 ms). The lability of the freshly refolded protein, as monitored by following the time course of its unfolding when incubated in 2.5 M GuHCl through the change in fluorescence intensity at 385 nm, was also determined and found to be increased significantly relative to untreated native protein. In contrast to the long term postactivation conformational changes detected previously in Escherichia coli alkaline phosphatase (Subramaniam V, Bergenhem NCH, Gafni A, Steel DG, 1995, Biochemistry 34:1133-1136), we found no changes in either the lability or phosphorescence decays of beta-LG during a period of 24 h. Our results are in agreement with the report by Hattori et al. (1993, J Biol Chem 268:22414-22419), using conformation-specific monoclonal antibodies to recognize native-like structure, that long-term changes occur in the protein conformation, compared with the native structure, on refolding.
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PMID:In vitro renaturation of bovine beta-lactoglobulin A leads to a biologically active but incompletely refolded state. 889 9

The action of retinol and carotenoids on bone cells was investigation in vitro by evaluating cell growth, alkaline phosphatase activity and the mRNA expression of a differentiation marker protein of osteoblastic cells. The clonal osteogenic cell line MC3T3-E1, established from newborn mouse calvaria, has a capacity of differentiation into osteoblast and mineralization in vitro. Retinol and beta-carotene inhibited the proliferation of MC3T3-E1 cells as well as DNA synthesis of the cells in a dose-dependent manner. Retinol induced differentiation of the MC3T3-E1 cells, by increasing alkaline phosphatase activity dose dependently, in a range from 1 to 100nm. Beta-carotene increased alkaline phosphatase activity is a dose-related manner in a range from 0.1 to 5 microM. Osteopontin is one of the matrix proteins which osteoblasts produce. Retinol increased the expression of osteopontin mRNA in a range from 1 to 100 nm. Beta-carotene also increased osteopontin mRNA expression, reaching a plateau at 1 microM. The induction of differentiation of MC3T3-E11 cells by beta-carotene was dose-dependent but was two orders of magnitude less active than that produced by retinoids. Within the MC3T3-E1 cells, part of the beta-carotene was effectively converted into retinol. Alpha-carotene, canthaxanthin and lycopene also inhibited cell proliferation at 1 microM and increased alkaline phosphatase activity and osteopontin mRNA expression, but less potently so than beta-carotene. Retinol and carotenoids were concluded to have a direct stimulatory effect on the differentiation of osteoblasts at the physiological concentration.
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PMID:Vitamin A and carotenoids stimulate differentiation of mouse osteoblastic cells. 926 18

Weanling male rats fed a vitamin A deficient (VAD) diet were compared with rats fed the same diet supplemented with vitamin A. Half of the VAD group was repleted with vitamin A at the age of 70 days. There was a decline in weight in the VAD group after 45 days. Serum and liver retinol concentrations were negligible in the VAD groups at 70 days of age. These levels returned to normal in the repleted group within 20 days of supplementation. Histological observations in the intestinal tissues of the experimental animals exhibited reduced villus height (p < 0.05) compared with the vitamin A supplemented group (VAS), reduced number of mucous secreting goblet cells and total enterocytes. In addition, a significantly higher number of proliferating cells was found along the crypt. Disaccharidases (sucrase and maltase), peptidases (gamma GT) and alkaline phosphatase activities were markedly lower along the brush border (p < 0.05) in the VAD group compared to the VAS group. We also determined the total DNA, RNA and protein in the jejunal tissues per 0.1 mg/tissue in both groups. The RNA production per cell in the VAD groups was notably lower than that of the controls (p < 0.05). Our observation indicates that brush border enzyme levels are altered in animals with vitamin A deficiency, and that phenomenon is augmented when calculated per single cell. This change may be attributed to direct effects of vitamin A on the rate of proliferation and differentiation of the epithelial tissue along the jejunum rather than to gross structural changes along the small intestine.
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PMID:Effect of vitamin A on small intestinal brush border enzymes in a rat. 978 59

Vitamin A is a potent inducer for liver/bone/kidney alkaline phosphatase (L/B/K ALP) in a variety of tissues. However, the evidence for induction of L/B/K ALP by vitamin A in small intestine is limited. In this study, we investigated the influence of vitamin A on L/B/K ALP expression in rat small intestinal crypt IEC-6 cells and fetal rat small intestine. Treatment of IEC-6 cells with all-trans retinoic acid (RA) increased the levels of activity, protein and mRNA of L/B/K ALP, whereas enterocyte-specific proteins, including intestinal ALP, sucrase-isomaltase and glucose transporter-2, were not induced. The reverse transcription-polymerase chain reaction technique revealed that this L/B/K ALP transcript had the bone-type but not the liver-type leader exon. IEC-6 cells constitutively expressed mRNAs of all subtypes of retinoic acid receptor (RAR) and retinoid X receptor (RXR) at varied concentrations. Among these receptor mRNAs, RARbeta mRNA quickly responded to RA treatment, and the level was doubled within 4 h. Gel mobility shift assay showed that RA induced an RXRE-binding activity in IEC-6 cells. The L/B/K ALP transcript, expressed in fetal rat small intestine, also contained the bone-type leader exon. Intragastric administration of 10 mg retinyl acetate to pregnant rats from gestational d 7 to 15 increased the levels of this transcript and enzyme in 15-d fetal rat small intestine. Our results suggest that vitamin A may be an important regulator for L/B/K ALP expression in fetal rat small intestine as well as in IEC-6 cells.
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PMID:Vitamin A up-regulates expression of bone-type alkaline phosphatase in rat small intestinal crypt cell line and fetal rat small intestine. 980 36

Asbestos fibers have been used in industry for decades. Deleterious effect of asbestos on the lungs has been documented. However, the mechanism of asbestos related diseases has not been fully explained yet. Numerous papers suggest there is a role of reactive oxygen intermediates (ROI) in asbestos-induced lung disease development. The excess ROI produced can be removed from the lungs by enzymatic and nonenzymatic antioxidants. The aim of our study was to compare the levels of antioxidants (ascorbic acid, retinol, alpha-tocopherol, glutathionperoxidase) as well as some markers of lung injury (lipid peroxides, total amount of protein, alkaline phosphatase) in asbestos treated Wistar-rats both 24 hr and 3 months after exposure to those in the controls, and to find out if the changes in antioxidant levels could affect impairment of the lungs. Decreased levels of antioxidants and increased values of lung tissue injury parameters in exposed groups suggest involvement of ROI in the mechanism of asbestos lung disease development, resulting in lung tissue injury, both 24 hr and 3 months after exposure.
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PMID:Impact of acute and subchronic asbestos exposure on some parameters of antioxidant defense system and lung tissue injury. 1044 8

Decidualization of stromal cells at the site of embryo implantation in the rat uterus is accompanied by expression of cellular retinol-binding protein and cellular retinoic acid-binding protein [CRABP(II)], whose presence has been shown to correlate with gain of ability to synthesize retinoic acid in other cells. Here we examined whether decidual cells also acquired the ability to synthesize retinoic acid, which would have important implications for understanding the implantation process. Decidual cells were isolated from the uterus on day 8 of pregnancy and cultured. When provided with retinol, they indeed synthesized and released retinoic acid to the medium. To follow acquisition of this ability more closely, artificial induction of decidualization was exploited. Ovariectomized rats were placed on a hormonal regimen that allows decidualization to occur in vivo, with oil stimulation, or in vitro, if cells are isolated on day 5 of the regimen and then cultured. Decidualization in vivo reproduced the expression of cellular retinol-binding protein and CRABP(II) seen during pregnancy. Stromal cells isolated on regimen day 2 synthesized little retinoic acid and expressed little alkaline phosphatase, a marker of decidualization. Stromal cells isolated on regimen day 5 had elevated levels of alkaline phosphatase, increasing during the 3 days of culture examined. The ability of the stromal cells to synthesize retinoic acid showed the same pattern: a substantially elevated production from that previously observed, on day 2, with production increasing significantly over the next 2 culture days. Thus, expression of CRABP(II) was correlated with gain of ability to synthesize retinoic acid. Retinoid signaling may be an important part of the process of embryo implantation.
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PMID:Retinoic acid synthesis and expression of cellular retinol-binding protein and cellular retinoic acid-binding protein type II are concurrent with decidualization of rat uterine stromal cells. 1065 Sep 63

Calcineurin was shown previously to be inhibited by members of the tyrphostin family of tyrosine kinase inhibitors, with the most effective inhibition suggested to be caused by the presence of a conjugated side chain (Martin BL, Biochem Pharmacol 56: 483-488, 1998). Retinoids are a family of naturally occurring biomolecules having non-aromatic ring structures and conjugated side chains as substituents on the ring. Three oxidation states of the all-trans configuration of retinoids (retinol, retinal, and retinoic acid) were tested as effectors of calcineurin. Only retinoic acid was found to inhibit calcineurin effectively, with an IC(50) value of approximately 50 microM. Retinol and retinal caused less than 30% inhibition at concentrations up to 100 microM. All three retinoids caused some precipitation of reaction components: retinoic acid and retinal above 50 microM, and retinol above 250 microM. Bacterial alkaline phosphatase was not inhibited by the retinoids, indicating that metal centers alone are insufficient for significant inhibition by retinoic acid. An aromatic ring was not required for inhibition and may not provide additional inhibition, inasmuch as an aromatic analog of retinoic acid (acitretin) showed less effective inhibition. These data are consistent with the presence of conjugated, unsaturated groups enhancing the inhibition of calcineurin.
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PMID:In vitro effect of retinoids on calcineurin activity. 1093 May 34


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