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 actions of butyrate and related short-chain fatty acids were analyzed on the 9-1C retinoid-responsive rat prostatic adenocarcinoma cell. The 9-1C cells, which are inducible for alkaline phosphatase (AP) by retinoic acid, were also inducible for the enzyme by three- to six-carbon fatty acids. The most effective inducer was the four-carbon acid, butyrate, which caused an essentially linear increase in AP activity in the concentration range of 2 to 10 mM. A comparison of AP induction by butyrate and retinoic acid showed the retinoid to be a more potent inducer of the enzyme by several orders of magnitude. Butyrate and related short-chain fatty acids also suppressed 9-1C cell growth, an effect which is not mediated by retinoic acid in these cells. Total growth suppression was achieved at butyrate concentrations of 5 mM and above; 1.5 mM caused 50% inhibition. As in the case of AP induction, all three- to six-carbon fatty acids suppressed growth to some extent, although butyrate was the most effective. The order of carbon chain length effectiveness for both AP induction and growth suppression by the fatty acids was 4 greater than 5 greater than 3 greater than 6. Butyrate appeared to be unique among the various fatty acids in causing an increase in cell protein. The protein content of 9-1C cells cultured in the presence of 4 mM butyrate for 72 h was more than 4-fold greater than that of control cells. This observation paralleled observations on cell volumes analyzed by forward-angle light-scatter flow cytometry, which showed a concentration-related increase in the cross-sectional areas of 9-1C cells following butyrate treatment. This effect has also been shown, in a recent study, to be mediated by retinoids. One of the most striking effects of butyrate treatment was on cellular morphology. The fatty acid caused 9-1C cells, which normally grow in a disorganized array with no apparent affinity for each other, to spread out and become organized into parallel tracts through the monolayer.
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PMID:Control of growth, morphology, and alkaline phosphatase activity by butyrate and related short-chain fatty acids in the retinoid-responsive 9-1C rat prostatic adenocarcinoma cell. 398 74

Parallel changes in the enzyme activities of CA2+ATPase and alkaline phosphatase were observed in HeLa cells. Both enzymes were inhibited to a similar degree by L-phenylalanine, L-tryptophan, and L-leucine, while being relatively resistant to L-homoarginine. Exposure to heat (56 degrees C, 60 degrees C, and 65 degrees C) resulted in a loss of both enzyme activities. Both alkaline phosphatase and Ca2+ ATPase, when treated with EGTA, required Ca2+ for the restoration of activity. Cells grown in the presence of agents that affect alkaline phosphatase (dexamethasone, butyric acid, and hyperosmolar NaCl) showed similar changes in the activities of both enzymes.
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PMID:Similarities between alkaline phosphatase and Ca2+ ATPase activities in HeLa cells. 645 Jul 71

Placental alkaline phosphatase activity was induced in choriocarcinoma cells by sodium butyrate. Butyrate stimulated de novo synthesis of the enzyme and the increase in phosphatase activity could be completely accounted for by the increase in phosphatase protein: the increases in placental alkaline phosphatase immunoactivity and placental alkaline phosphatase biosynthesis as measured by incorporation of the radioactive precursors, L-[35S]methionine, [3H]mannose, and [3H] glucosamine were similar to the increase in phosphatase activity. Sodium butyrate increased the rates of placental alkaline phosphatase biosynthesis but had no effect on the rate of placental alkaline phosphatase degradation or processing. Both control and butyrate-induced cells contained polypeptides of 61,500 and 64,500 apparent molecular weights that were identified as the precursor and fully processed forms of the placental alkaline phosphatase monomer, respectively. Further, processing of the 61,500-dalton polypeptide to the 64,500-dalton polypeptide involved the incorporation of additional glucosamine and N-acetylneuraminic acid moieties. Gel electrophoresis of anti-placental alkaline phosphatase-precipitable polypeptides from an in vitro protein-synthesizing system directed by RNA isolated from control or butyrate-induced cells demonstrated that sodium butyrate induced the synthesis of placental alkaline phosphatase mRNA. Our data indicate that sodium butyrate induces the specific transcription of the placental alkaline phosphatase gene.
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PMID:Induction of placental alkaline phosphatase biosynthesis by sodium butyrate. 669 79

Studied were 12 cows with protracted, recurrent acidosis of the rumen, 4 cows with alkalosis, and 2 calves with experimental acidosis, following up the changes in the rumen content and their impact on the liver. The diseased animals were investigated both clinically and by laboratory tests with regard to alkaline phosphatase, plasma cholinesterase, SGOT, SGPT, alkali reserves, bilirubin, blood sugar, protein function of the liver (flocculation tests), biopsy of the liver, urine pH, urobilinogen, sedimentation test and ketone bodies, rumen pH, rumen infusoria, glucose-fermenting and cellulose-digesting activity, breakdown of nitrates, butyric acid, and ammonia gas. It was found that recurrent physiologic deviations of the rumen content play an essential pathogenetic role in liver injury. The more substantial and continuous the deviations the more severe the liver diseases. Studies revealed that along with other factors the recurrent acidosis and alkalosis of the rumen content could be claimed to be an immediate cause of the liver diseases in high producing cows. Histologically, the liver of cows with slightly expressed acidosis of the rumen showed granular degeneration, and of cows with protracted acidosis--fatty degeneration, activation of the reticulo-endothelial system, and leukocytes in the capillar sinusoids. Liver biopsy in the case of experimental acidosis demonstrated also decrease in the glycogen content of the hepatocytes.
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PMID:[Liver diseases and their relationship to forestomach function in highly productive cows]. 734 34

The hypothesis that the colonic epithelium is diffusely abnormal in ulcerative colitis was examined by comparing disease related responses in expression of markers of differentiation by colonic crypt cells to culture with and without butyrate. Cells were isolated from patients with normal colon (15), cancer (24), ulcerative colitis (19), or Crohn's disease (16). Alkaline phosphatase activities were measured in cell homogenates and the rate of glycoprotein synthesis assessed at the end of 24 hours of culture and expressed relative to the rate of protein synthesis as the G:P ratio. Alkaline phosphatase activities, but not G:P ratios, differed across the groups before and after 24 hour culture (p < 0.05), activities being lowest in the cancer group and highest in inflammatory bowel disease groups. Butyrate (1 mM) suppressed alkaline phosphatase activities in the cancer group by mean (SEM) of 17 (4) (p = 0.006) compared with no change in the other groups. Butyrate suppressed G:P ratios only in the cancer (6 (3)%, p = 0.03) and ulcerative colitis groups (5 (3)%, p = 0.04) and the changes in both were different (p < 0.05) from those in normal cells (increase of 10 (7)%). Changes in ulcerative colitis were different from those in Crohn's disease (p = 0.029). Responses were independent of the presence or absence of mucosal inflammation. These data confirm the diffuse nature of epithelial abnormalities in colorectal cancer. In ulcerative colitis, a different pattern of abnormality occurs, supporting the notion that the epithelium is also diffusely abnormal independent of mucosal inflammation.
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PMID:Colonic epithelium is diffusely abnormal in ulcerative colitis and colorectal cancer. 761 74

Differentiated villus intestinal epithelial cells express globotriaosylceramide, the Shiga-like toxin 1 (SLT-1) receptor, and are sensitive to toxin-mediated cytotoxicity, whereas undifferentiated crypt cells neither express Gb3 nor respond to toxin. To investigate if SLT-1 receptors are maturationally regulated in human intestinal cells, we examined the effect of butyrate, a known transcriptional regulator of differentiation genes in many cell types, using cultured colonic cancer-derived epithelial cell lines. Exposure to butyrate increased villus cell marker enzymes such as alkaline phosphatase, sucrase, and lactase, expression of toxin receptors, and sensitivity to SLT-1 in villus-like CaCo-2A and HT-29 cells. These effects were reversibly inhibited by preincubation of CaCo-2A cells with actinomycin D or cycloheximide. Butyrate-treated CaCo-2A cells unable to bind fluoresceinated SLT-1 B subunit were undifferentiated as assessed by alkaline phosphatase activity. HT-29 cells induced to differentiate by another signal, glucose deprivation, upregulated receptor content and response to toxin. Crypt-like T-84 cells responded to butyrate with a modest increase in alkaline phosphatase and toxin binding, but no induction of sucrase or lactase, and no change in sensitivity to toxin. The results demonstrate that expression of SLT-1 toxin receptors and toxin sensitivity are coregulated with cellular differentiation in cultured intestinal cells.
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PMID:Maturational regulation of globotriaosylceramide, the Shiga-like toxin 1 receptor, in cultured human gut epithelial cells. 765 8

Iodothyronine 5'-deiodinase isoenzymes generate the thyroid hormone 3,3',5-triiodothyronine from the prohormone L-T4. Basal and retinoic acid (RA)-induced type I 5'-deiodinase (5'DI) activities were studied in human thyroid carcinoma cell lines. In the follicular thyroid carcinoma line FTC-133, nanomolar concentrations of 9-cis, 13-cis-, and all-trans-RA induced 5'DI activity. Kinetics with all-trans-RA revealed 5'DI stimulation after 1 day and a maximal effect after 3 days. Increased abundance of the p27 5'DI subunit was demonstrated after RA treatment by N-bromoacetyl-[125I]T4 affinity labeling. Actinomycin-D and cycloheximide blocked RA-mediated induction. RA stimulated 5'DI activity to a lesser extent in FTC-238 cells, whereas neither basal 5'DI activity nor stimulation by RA was found in anaplastic thyroid carcinoma, human lung, or leukemia cell lines. Steady state messenger ribonucleic acid levels of RA receptor-alpha and -beta were increased after incubation of FTC-133 cells with all-trans-RA. The high 5'DI activity of differentiated rat thyroid FRTL-5 cells was not further induced by RA. Butyrate did not alter 5'DI, but increased the activity of the differentiation marker alkaline phosphatase in FTC-133 and FTC-238 cells. T4 and T3 had no effect on basal or RA-stimulated 5'DI activity. These data suggest that expression and retinoid induction of 5'DI may serve as a sensitive and functional differentiation parameter of follicular thyroid carcinoma cells.
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PMID:Retinoids stimulate type I iodothyronine 5'-deiodinase activity in human follicular thyroid carcinoma cell lines. 807 63

The human colon cancer cell line SW-620 produces two alkaline phosphatases (ALPs) which are not expressed by normal colon. They are the heat-stable, term-placental and the heat-labile, L-homoarginine-sensitive, liver/bone/kidney ALPs. Butyrate, an ALP inducer, has strikingly dissimilar effects on the activity of these enzymes: whereas high (2.0 mM) butyrate concentrations exclusively induce increased activity levels of liver/bone/kidney ALP, low (0.5 mM) concentrations increase the activity of both, albeit induction of term-placental ALP is less pronounced. These observations indicate that the effect of butyrate on the two ALPs is non-coordinate and suggest that their expression by SW-620 cells is independently modulated.
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PMID:Divergent effects of butyrate on the alkaline phosphatases of SW-620 cells. 842 35

Glutathione S-transferases (GSTs) are a multigene family of detoxification and metabolizing enzymes that have been linked with the susceptibility of tissues to environmental carcinogens. In addition to their role as the main energy source in the colonic mucosa, short-chain fatty acids (SCFAs) have been found to act as potent antiproliferative and differentiating agents in various cancer cell lines. The objective of this study was to evaluate the effects of SCFAs on the induction of GSTpi in the intestine as a possible new anticarcinogenic mechanism of SCFAs. Studies were performed in Caco-2 cells, a cell line resembling functionally normal enterocytes. Cells, cultured in DMEM supplemented with 10% fetal calf serum, were studied from day 0 dpc (days post confluence) until 21 dpc and culture. SCFAs (acetate, propionate, butyrate) were added to give a final concentration of 5 mmol L(-1). At 0, 3, 6, 9, 15, and 21 dpc, protein, lactate dehydrogenase (LDH), alkaline phosphatase (AP) and GSTpi were measured. Butyrate supplementation significantly (P < or = 0.01) increased GSTpi levels compared with controls in a concentration-dependent manner. The effect was detectable within 3 dpc with a maximum at 15 dpc. In contrast to butyrate, the other SCFAs tested had no (acetate) or little effect (propionate). In conclusion, the data suggest that the anticancer effect of butyrate in part may be based on the induction of GSTpi activity, resulting in an enhanced detoxification capacity of the gut.
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PMID:Induction of glutathione-S-transferase-pi by short-chain fatty acids in the intestinal cell line Caco-2. 868 62

Control of paracellular permeability in the colonic epithelium is fundamental to its functional competence. This study examines the relationship between physiologically relevant short-chain fatty acids (SCFAs) and paracellular permeability using the Caco-2 cell line model. Butyrate induced a concentration-dependent, reversible increase in transepithelial resistance (TER) that was maximal after 72 h. Butyrate (2 mM) increased TER by 299 +/- 69% (mean +/- SE; n = 5; P < 0.05; t-test) and reduced mannitol flux to 52 +/- 11% (P < 0.05) of control. The effect of butyrate was dependent on protein synthesis and gene transcription but not dependent on its oxidation or activation of adenosine 3',5'-cyclic monophosphate. The other SCFAs, propionate and acetate, also induced a concentration-dependent increase in TER. The effect of butyrate paralleled changes in cellular differentiation, because alkaline phosphatase activity, carcinoembryonic antigen expression, and dome formation were increased. Furthermore, other differentiating agents (dimethyl sulfoxide and retinoic acid) also increased TER. Thus SCFAs reduce paracellular permeability in the Caco-2 cell line, possibly by promotion of a more differentiated phenotype. If such an effect occurs in vivo, it may have ramifications for the biology and pathobiology of colonic mucosa.
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PMID:Effect of short-chain fatty acids on paracellular permeability in Caco-2 intestinal epithelium model. 914 99


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