Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To clarify the effects of cadmium (Cd) on bone formation, a clonal osteogenetic cell, MC3T3-E1, was used in the present study. After 24 h of culture, Cd at 1 ppm and above decreased DNA synthesis and alkaline phosphatase activity, but Cd at 1.5 ppm caused no significant decrease in collagen content. The cells treated with Cd (0.03-1.0 ppm) for 24 h showed the dose-dependent effects on metallothionein-like protein synthesis. The marked increase of Cd content unbound to metallothionein (MT)-like protein with cadmium at 1 ppm may be responsible for the toxic effects of cadmium. After 10 days of culture, the accumulation of 45Ca to the cell layer decreased with increasing level of cadmium at 0.03 and 0.1 ppm. The cadmium-treated cell layer showed a weaker reaction to histochemical staining for mineral compared with control culture. This result suggests that Cd inhibits an initial process of calcification.
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PMID:The effects of cadmium on a clonal osteogenetic cell, MC3T3-E1: inhibition of calcification and induction of metallothionein-like protein by cadmium. 373 28

In Reuber rat hepatoma cells (R-Y121B), alkaline phosphatase activity increased without de novo enzyme synthesis (Sorimachi, K., and Yasumura, Y. (1986) Biochim. Biophys. Acta 885, 272-281). The enzyme was partially purified by butanol extraction from the particulate fractions. The incubation of the extracted alkaline phosphatase with the cytosol fraction induced a large increase in enzyme activity (5-10-fold of control). The dialyzed cytosol was more effective than the undialyzed cytosol during an early period of incubation at 37 degrees C. This difference between the dialyzed and the undialyzed cytosol fractions was due to endogenous Na+. For maximal activation of the enzyme, both Mg2+ above 1 mM and Zn2+ at low concentrations (below 0.01 mM) were needed, although Zn2+ at high concentrations (above 0.1 mM) showed an inhibitory effect. Zn2+ and Mg2+ alone slightly increased alkaline phosphatase activity. This activation of the enzyme was temperature dependent and was not observed at 0 or 4 degrees C. Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate showed that the increase in alkaline phosphatase activity did not involve the fragmentation of the enzyme and that 65Zn2+ bound to it during enzyme activation with 65Zn2+ and Mg2+. The cytosol fraction not only supplied Zn2+ to the nascent enzyme but also increased the maximal enzyme activity more than did direct addition of metal ions. Ferritin and metallothionein contributed to the activation of alkaline phosphatase with the metal ions. Since the binding of Zn2+ and Mg2+ to the nascent alkaline phosphatase is disturbed in Reuber rat hepatoma cells (R-Y121B), the apoenzyme is accumulated inside the cells. The binding of Zn2+ and Mg2+ to the apoenzyme readily takes place in the cell homogenates accompanied by an increase in catalytic activity without new enzyme synthesis.
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PMID:Activation of alkaline phosphatase with Mg2+ and Zn2+ in rat hepatoma cells. Accumulation of apoenzyme. 380 40

A lipolytic zinc-copper protein has been isolated from the cytosol of chick liver. This material had a molecular weight of 6000 daltons, contained four atoms of zinc and one atom of copper per molecule. The 6000 dalton fraction aggregated at high ionic strength or in the presence of sodium dodecyl sulphate. Lipolytic activity was observed towards triolein, tripalmitin , phosphatidyl choline and retinyl palmitate, and was stimulated by cholate, Ca and high NaCl concentrations, and was inhibited by sulphydryl reagents, inhibitors of serine esterases, alkaline phosphatase and chelating agents. It appears that this copper-zinc protein is distinct from metallothionein which has no lipolytic activity.
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PMID:A low molecular weight zinc-copper lipolytic protein from chick liver. 672 48

The effect of acute and subacute administration of cadmium chloride on calcium homeostasis and the trace metal content of the bone was investigated in the male rat. A single subcutaneous injection of cadmium chloride (1.5 mg Cd++/kg) produced a decreased plasma concentration of calcium and a decrease in the femur concentration of both calcium and zinc. repeated administration of cadmium chloride (1.5 mg Cd++/kg) daily, for 28 days) caused a marked hypocalciuria that persisted throughout the period of cadmium treatment. There was an accompanying increased excretion of alkaline phosphatase into the urine, and plasma inorganic phosphate was also elevated in these animals. Both of these effects are considered to be evidence of kidney damage. A possible mechanism for this cadmium-induced effect may involve a disturbance of the renal biotransformation of vitamin D, and decreased bioavailability of the essential trace metals due to metallothionein synthesis and excessive loss into the urine.
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PMID:The acute and subacute effects of cadmium an calcium homeostasis and bone trace metals in the rat. 725 89

In this study, we compared results obtained in protein calorie malnourished (PCM) monkeys and controls given Cd2+ (5 mg Cd2+/kg body wt./day) orally for 24 weeks. After 16 weeks of Cd2+ exposure, an indolent renal failure develops in PCM monkeys which resulted in significant increase in urinary excretion of total protein, Cd2+, Zn2+ and Ca2+ as compared to corresponding to Cd(2+)-treated control group. In isolated proximal tubule brush border membrane vesicles (BBMV), Cd2+, Zn2+ and Ca2+ transport were significantly impaired in Cd(2+)-exposed PCM monkeys as compared to Cd(2+)-treated controls. The mechanism of higher urinary excretion of Cd2+, Zn2+ and Ca2+ was examined by analyzing the kinetic parameters of transport systems. The kinetic studies of Cd2+, Zn2+ and Ca2+ transport systems in the BBMV preparations of Cd(2+)-exposed PCM monkeys exhibited a significant decrease in Vmax and an appreciable increase in Km as compared to Cd(2+)-treated controls. These findings suggested that Cd2+ treatment of PCM monkeys caused either a decrease in the number of transporters in the brush border membrane or an increase in the number of less active transporters for Cd2+, Zn2+ and Ca2+. Furthermore, brush border membrane-bound enzymes, viz. alkaline phosphatase and leucine aminopeptidase, activities were significantly impaired in Cd(2+)-exposed PCM monkeys. Cadmium content in kidney cortex of Cd(2+)-exposed PCM monkeys was 3.34-fold higher than Cd(2+)-exposed controls. These findings also established that Cd2+ not bound to metallothionein (MT) was significantly higher in Cd-exposed PCM monkeys, which may be an important determinant in renal toxicity by interacting with sensitive sites in the renal cells and causing renal damage in Cd-exposed PCM monkeys.
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PMID:Cadmium-induced nephrotoxicity in rhesus monkeys (Macaca mulatta) in relation to protein calorie malnutrition. 762 86

Changes in zinc status in response to folic acid supplementation and the effect of zinc intake on folate utilization were evaluated in 12 men (20-34 y old) consuming a diet containing 3.5 or 14.5 mg zinc/d for two 25-d intervals. Deuterium-labeled folic acid (800 micrograms/d) or a placebo was administered orally during each phase. No differences in plasma zinc, erythrocyte zinc, urinary zinc, erythrocyte metallothionein or serum alkaline phosphatase, due to supplemental folic acid, were detected at either level of zinc intake. Differences in the response to folic acid supplementation, due to the level of zinc intake, were not detected for serum, erythrocyte or urinary (labeled and unlabeled) folate. Within the constraints of this short-term folic acid supplementation study, adverse effects on zinc status were not observed and our data suggest that folic acid utilization was not influenced by level of zinc intake.
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PMID:Zinc status is not adversely affected by folic acid supplementation and zinc intake does not impair folate utilization in human subjects. 781 78

There is a clear lack of information on the toxicological risk of dietary intake of cadmium-metallothionein (CdMt). The present study aimed at establishing dose-dependent cadmium (Cd) disposition and to investigate differences in renal toxicity after long-term dietary exposure to CdMt or cadmium chloride (CdCl2) in rats. Male Wistar rats were fed diets containing 0.3, 3, 30, or 90 mg Cd/kg either as CdMt or as CdCl2 for 10 months. In rats fed 30 and 90 mg/kg Cd as CdCl2 the Cd concentrations in intestine, liver, and kidneys were all higher than in rats fed the same doses in the form of CdMt. The kidney/liver Cd concentration ratio was higher with CdMt than with CdCl2. At the lower Cd concentrations (0.3 and 3 mg/kg), no differences in Cd accumulation between CdMt and CdCl2 groups were observed and the kidney/liver Cd ratio was also similar. When based on the amount of CdMt per milligram Cd in the tissue, rats fed CdMt and those fed CdCl2 had a similar relative CdMt concentration in liver and kidney. First signs of renal injury, indicated by an increase of urinary lactate dehydrogenase (LDH) activity, were seen 4 months after exposure to 90 mg/kg Cd as CdCl2. After 8 and 10 months the renal effect of 90 mg/kg Cd as CdCl2 became more pronounced and urinary enzyme activities of LDH, N-acetyl-beta-D-glucosaminidase and alkaline phosphatase were all elevated. The only clinical effect of CdMt at the dose level of 90 mg/kg was a slight increase in urinary gamma-glutamyl transpeptidase activity at 8 and 10 months.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of renal toxicity after long-term oral administration of cadmium chloride and cadmium-metallothionein in rats. 786 6

Zn deficiency is hypothesized to produce poor resistance to injury involving oxidative stress. This could occur by impairing Zn antioxidant function(s) or by indirectly limiting adaptive protective mechanisms such as a rise in acute-phase proteins. The present study examined rats fed diets adequate or moderately low in Zn (4 or 25 micrograms/g diet) for 9 d. The lower intake produced a mild Zn deficiency based on body weight, plasma Zn and plasma alkaline phosphatase (EC 3.1.3.1) activity. Galactosamine injection, an oxidative stress, produced much more liver injury in the mildly Zn-deficient rats. However, injury was strongly inhibited in rats from each dietary group by an acute-phase response due to turpentine-induced leg inflammation. Mild Zn deficiency did not prevent a rise in levels of the acute-phase protein caeruloplasmin (EC 1.16.3.1), but did limit the usual inflammation-induced rise in hepatic levels of metallothionein, a Zn protein with possible antioxidant function. In conclusion, high degrees of galactosamine-induced hepatitis were associated with mild Zn deficiency, but the liver injury was blocked by prior stimulation of an acute-phase response, regardless of Zn status.
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PMID:Effects of mild zinc deficiency, plus or minus an acute-phase response, on galactosamine-induced hepatitis in rats. 798 91

The effects of short-term starvation on serum and tissue levels of zinc, metallothionein (MT), and the activity of alkaline phosphatase (EC 3.1.3.1, ALP) were investigated with 6-month-old rats. The rats were fed a diet with adequate zinc (92mg/kg of Zn, 1.12% phytic acid) before they were starved for 0h (control), 12h, 24h, and 36h and then killed by decapitation. Fasting was accompanied by typical changes in serum parameters such as reduced glucose and protein concentrations, elevated ketogenesis, and a rapid breakdown of liver glycogen. Fasting did not alter serum zinc levels, but it did lead to a significant elevation in the percent of unsaturated serum-zinc binding capacity. Liver concentrations of zinc and MT, based both on fresh and dry weight, were increased throughout starvation. However, total liver zinc was reduced by up to 23% in response to fasting and total liver MT was slightly elevated. The increased concentrations of liver zinc and MT are, therefore, mainly a consequence of reduced liver weight. A part of the liver zinc, however, was bound to newly synthesized MT to prevent greater zinc loss. Starvation evoked no altered mucosa MT levels. Changes in kidney zinc and kidney medulla MT caused by starvation were small and not significant. In contrast to this observation some variation of kidney cortex MT was apparent. Starvation produced a permanent reduction of the serum and intestinal activity of ALP. In the liver and the medulla of the kidneys no significant differences of ALP activity could be observed. However, kidney cortex ALP was induced after 36h of fasting.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Zinc metabolism in fasted rats. 815 85

Adult rat primary hepatocytes maintained in DMEM/F12 (Ham) media were used as a model system for studying the role of fetal calf serum (FCS) and agonists of the phosphoinositide cascade in the metabolism of metallothionein (MT) and alkaline phosphatase (ALP). Experiments were performed both after a 24 h preincubation with FCS and with bovine serum albumin (BSA). Hepatocytes were treated with dexamethasone (DEX), zinc (Zn) and with the agonists of the phosphoinositide cascade A23187, 1,2-dioctanoyl-sn-glycerol (DiC8), 12-O-tetradecanoylphorbol-13-acetate (TPA), angiotensin II (AT), platelet activating factor (PAF), Arg8-vasopressin (VP) and were analyzed for MT and ALP activity in cell homogenates. Cell viability was evaluated by lactate dehydrogenase (LDH) liberation into culture medium, induction of tyrosine aminotransferase (TAT) through DEX and by trypan blue exclusion. Overall, cell viability was improved by the FCS pretreatment and by DEX. Exposure of hepatocytes to the established direct inducers Zn and DEX of MT resulted in a manifold increase in MT, independent of whether the cultures were FCS pretreated or not. The FCS preincubation produced a moderate elevation of ALP activity by stimulating cell viability. However, ALP was unaltered in response to Zn and DEX. None of the experiments conducted with agonists of the phosphoinositide cascade led to an elevation of MT and ALP. Only the incubation of hepatocytes with A23187 resulted in a concentration dependent significant decrease of MT and ALP. This observation was due to a cytotoxic effect of A 23187, displayed by LDH leakage and an increase in the number of cells stained with trypan blue. In conclusion, in primary hepatocyte cultures agonists of the phosphoinositide did not have an effect on the metabolism of MT and ALP. Previous in vivo results indicating alterations of Zn metabolism in liver, therefore seem to be caused by indirect systemic responses.
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PMID:Studies on the metabolism of metallothionein and alkaline phosphatase of adult rat primary hepatocyte cultures: role of fetal calf serum and agonists of the phosphoinositide cascade. 823 77


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