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:3.1.6.1 (sulfatase)
3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new method is described for the direct cytochemical demonstration of lysosomal arylsulfatases utilizing a synthetic substrate, 4-nitro-1,2-benzenediol mono(hydrogen sulfate), and a copper capture reaction. A small amount of Hatchett's brown (cupric ferrocyanide, Cu2Fe(CN)6-7 H2O) formed at the subcellular sites of copper capture is then utilized as a heterogeneous catalyst to effect the oxidative polymerization of 3,3'-diaminobenzidine which results in the formation of an insoluble, highly colored osmiophilic indamine polymer at the sites of enzymatic activity. The reaction product even at this stage prior to osmication is highly visible. It is readily seen with a light microscope in 50 mum sections of fixed tissues prepared with a mechanical chopper or in 10 micron cryostat sections treated for arylsulfatase activity. Upon osmication, an electron-opaque osmium black is formed which is much less soluble than the products of either the lead or barium capture reactions currently used for the demonstration of arylsulfatase with the electron microscope. The selection of areas of plastic-embedded tissues for ultrathin sectioning is facilitated by the ready visibility of these osmium black end products on 1-2 mum plastic sections which can be studied with the light microscope. This method gives permanent specimens demonstrating arylsulfatases A or B in lysosomes and autophagic vacuoles. In addition, enzyme activity is seen occasionally in the Golgi region or lamellae of certain cells believed to be elaborating sulfated products. In these instances, it may be demonstrating sulfotransferase activity.
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PMID:The demonstration of arylsulfatases with 4-nitro-1,2-benzenediol mono(hydrogen sulfate) by the formation of osmium blacks at the sites of copper capture. 4 59

Since human colorectal tumors are insensitive to most chemotherapeutic agents, there is a need for the discovery of new drugs that would show activity against this disease. In an attempt to better appreciate the relevance of a widely used mouse colon tumor (colon adenocarcinoma Co38) as a screening model for human colorectal tumors, we compared the main phase I and phase II drug-metabolizing enzyme systems in both tumoral and nontumoral colon tissues. The following enzymes were assayed by Western blot: cytochromes P-450 (1A1/A2, 2B1/B2, 2C, 2E1, and 3A), epoxide hydrolase, and glutathione-S-transferases (GST-alpha, -mu, and -pi). The activities of the following enzymes or cofactors were determined by spectrophotometric or fluorometric assays: total cytochrome P-450, 1-chloro-2,4-dinitrobenzene-GST, selenium-independent glutathione peroxidase, 3,4-dichloronitrobenzene-GST, ethacrynic acid-GST, total glutathione, epoxide hydrolase, UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase. Results obtained by Western blot showed that mouse colon adenocarcinoma Co38 did not express any of the probed cytochromes P-450, whereas human colorectal tumors expressed only low levels of cytochrome P-450 3A. GST-alpha and GST-pi were detected in all tumoral and nontumoral tissues of both species. The neutral GST-mu was expressed in all murine tissues investigated and was found to be polymorphic in human tissues. For human peritumoral and tumoral colorectal tissues there was no significant difference between GST isoenzyme levels, whereas mouse colon adenocarcinoma Co38 had a lower expression of GST-mu and GST-pi, compared to normal mouse colon. Enzymatic activities for glutathione peroxidase, 3,4-dichloronitrobenzene-GST, and ethacrynic acid-GST confirmed the Western blot results for GST-alpha, GST-mu, and GST-pi, respectively. Total GSH levels were similar between murine and human tumors but were 3-fold higher in human tumors than in peritumoral tissues, whereas they were 7-fold lower in mouse colon tumor Co38, compared to normal mouse colon. Epoxide hydrolase was not expressed in either mouse colon adenocarcinoma Co38 or normal mouse colon tissues, whereas it was expressed in human colon peritumoral and tumoral tissues at similar levels. No significant difference was observed between human tumors and peritumoral tissues for UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase. For murine colon tissues, the conjugation pathways (UDP-glucuronosyltransferase and sulfotransferase) were lower in colon adenocarcinoma Co38, whereas the converse was observed for the corresponding hydrolytic enzymes (beta-glucuronidase and sulfatase).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparison of mouse and human colon tumors with regard to phase I and phase II drug-metabolizing enzyme systems. 142 2

Sodium picosulfate, a laxative, was biotransformed to 4,4'-dihydroxydiphenyl-(2 pyridyl)-methane by intestinal flora that produced a novel sulfotransferase (not sulfatase). The biotransformation was activated by adding phenolic compounds such as phenol, acetaminophen and flavonoids. The enzyme activity related to this biotransformation was the highest in the contents of the caecum region of the intestine. The enzyme activity was 3.0 mumole/hr/g wet feces in humans and 0.75 in rats (pH 8.0). The optimal pH was 9.0.
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PMID:The role of intestinal bacteria in the transformation of sodium picosulfate. 150 49

Of the total number of breast cancers approx. 30-50% are hormone-dependent and estradiol is one of the main factors of cancerization. Consequently, the control of this hormone inside the cancer cell is of capital importance because it is well established that the inhibition of estradiol biosynthesis can have a positive effect on the evolution of the disease. The blockage of estradiol can be obtained by the action of anti-aromatases, anti-sulfatases, the control of the 17 beta-hydroxysteroid dehydrogenase activity or by the stimulation of the sulfotransferase which converted the estrogens in their sulfates. In breast cancer tissue estrone sulfate is quantitatively the most important source of estradiol. In the intact cell, estrone sulfatase activity is very intense in the hormone-dependent cell lines (e.g. MCF-7, T-47D) but very small activity is observed in the hormone-independent (e.g. MDA-MB-231, MDA-MB-436) cell lines. However, this activity became very strong after homogenization in the hormone-independent cells, suggesting the presence of repressive factor(s) for this enzyme or its sequestering in an inactive form, in the intact cells of these cell lines. In a series of previous studies it was found that in hormone-dependent cell lines different anti-estrogens: tamoxifen and derivatives, ICI 164,384, very significantly decrease the estradiol concentration originated from estrone sulfate, and recently it was observed that Decapeptyl (D-Trp6-gonadotropin-releasing hormone) in the presence of heparin can also decrease the conversion of estrone sulfate into estradiol. No significant effect was obtained in the presence of heparin or Decapeptyl alone. The estrone sulfatase activity can be inhibited by progesterone, the progestagen R-5020, and testosterone. In another series of recent studies the presence of very strong estrogen sulfotransferase activity has been shown in one breast cancer cell line, the MDA-MB-468. We can conclude that: (1) the control of estradiol concentration can be carried out in the breast cancer tissue itself; (2) estrone sulfate can play an important role in the bioavailability of estradiol in the breast cancer cell; and (3) as is the case for the aromatase, the control of: the estrogen sulfatase, estrogen sulfotransferase, and 17 beta-hydroxysteroid dehydrogenase can be new targets for therapeutic applications in breast cancer.
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PMID:Recent data on estrogen sulfatases and sulfotransferases activities in human breast cancer. 158 Sep 21

Glucuronidation and sulfation of 1-naphthol, 7-hydroxycoumarin, 4-nitrocatechol and phenolphthalein were studied in rabbit lung and liver. Pulmonary UDP-glucuronyltransferase and sulfotransferase activities in subcellular fractions were approximately 20-50% of those determined in the liver. Ethanol did not markedly induce these enzymes in either tissue. Glucuronidation and sulfation of 1-naphthol and 7-hydroxycoumarin were also studied in the isolated perfused rabbit lung as an intact cell model. Neither glucuronidation nor sulfation of 1-naphthol was observed. The absence of conjugate formation was due neither to the presence of beta-glucuronidase and/or sulfatase, nor to alternative biotransformation pathways. About 35% of the initial 7-hydroxycoumarin was conjugated, the majority being sulfate conjugate (14.4 nmol/h) with only minor amounts (0.12%) of the glucuronide. These results indicate the importance of studying both whole organ and in vitro metabolism.
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PMID:Glucuronidation and sulfation in subcellular fractions and in the isolated perfused rabbit lung: influence of ethanol. 190 11

We have shown previously that the administration of warfarin to 16-day-old mice results in a significant reduction in levels of sulfatides, and to a lesser degree a reduction of other sphingolipids in brain. Vitamin K stimulates biosynthesis of sulfatides in warfarin-treated mice. We now report that warfarin inhibits brain sulfotransferase activity. This inhibition is reversed by vitamin K. The treatment of normal mice with vitamin K stimulates the activities of sulfotransferase and arylsulfatase and the turnover rate of brain sulfatides. The ability of vitamin K to influence the activity of biosynthetic and catabolic enzymes and the turnover of sulfatides suggests a possible regulatory role for vitamin K in the maturing brain.
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PMID:Regulation of sulfotransferase activity by vitamin K in mouse brain. 196 27

Previous work from our laboratory (Biochem. J. 219:689-697 (1984] had shown that hydrocortisone stimulated the net accumulation of the myelin-specific sulfolipid in cultures of cells dissociated from embryonic mouse cerebra. This accumulation caused by hydrocortisone was shown to be due to a decrease of sulfolipid degradation by arylsulfatase A (ASA) and not due to a stimulation of its synthesis by a sulfotransferase. Both ASA activity and the turnover of sulfolipid were decreased by hydrocortisone to 60-62% of untreated cells. In current work the same decrease in enzyme activity was obtained and enzyme linked immunosorbent assays demonstrate that hydrocortisone decreased the number of ASA protein molecules to 61% of untreated cells [(-)hydrocortisone: 0.31 +/- 0.06 ng ASA/microgram protein; (+)hydrocortisone: 0.18 +/- 0.04 ng ASA/microgram protein]. This decrease in the number of ASA molecules correlates well with the decrease in both the enzyme activity and the sulfolipid turnover, which suggests that the major mode of inhibition of ASA activity by hydrocortisone involves a decrease in the concentration of ASA in the cells rather than some other mechanism of inhibition.
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PMID:Hydrocortisone regulates arylsulfatase A (cerebroside-3-sulfate-3-sulfohydrolase) by decreasing the quantity of the enzyme in cultures of cells dissociated from embryonic mouse cerebra. 198 Mar 45

The sulfate conjugate of the model compound 4-methylumbelliferone was taken up and hydrolyzed considerably more rapidly by isolated hepatocytes than was the glucuronide conjugate. Using intact hepatocytes or homogenates of hepatocytes, compounds were identified that either inhibited 4-methylumbelliferyl sulfate hydrolysis via arylsulfatase or impaired its uptake into cells. For example, sodium sulfate inhibited hydrolysis of 4-methylumbelliferyl sulfate by intact hepatocytes (half-maximal inhibition, 0.1 mM) but not by homogenates, suggesting a selective action on organic sulfate uptake at the plasma membrane. In contrast, cholesterol sulfate inhibited hydrolysis of 4-methylumbelliferyl sulfate by homogenates but not by hepatocytes, consistent with the hypothesis that cholesterol sulfate does not readily enter intact cells. Compounds that inhibited hydrolysis of 4-methylumbelliferyl sulfate by both isolated hepatocytes and microsomes include sodium sulfite (half-maximal inhibition, 0.1 mM), pregnenolone sulfate (half-maximal inhibition, 1 microM), and estrone sulfate (half-maximal inhibition, 10 microM). To test whether production of sulfate conjugates could be modified by agents affecting arylsulfatase in intact hepatocytes, we examined the effects of pregnenolone sulfate on the production of 4-methylumbelliferyl sulfate from 4-methylumbelliferone. Addition of pregnenolone sulfate (100 microM) to intact cells increased rates of 4-methylumbelliferone sulfate production and decreased the fraction of 4-methylumbelliferone converted into the glucuronide. Hydrolysis of 4-methylumbelliferyl sulfate by isolated microsomes was inhibited in a dose-dependent manner by adenosine 3'-phosphate 5'-phosphosulfate (PAPS) when cytosol, a source of sulfotransferase was present. Furthermore, addition of low concentrations of PAPS (0.5 microM) to a reconstituted system of microsomes and cytosol impaired the formation of fluorescent product from 4-methylumbelliferyl sulfate until PAPS was consumed, indicating that futile cycling via arylsulfatase and sulfotransferase occurred. Subsequent futile cycling of free 4-methylumbelliferone and 4-methylumbelliferyl sulfate occurred upon repeated additions of PAPS and was prevented by sodium sulfite, an inhibitor of arylsulfatase. These results argue strongly that sulfate conjugate production within hepatocytes is regulated by futile cycling via sulfotransferase and arylsulfatase. Thus, drugs and endogenous substances that affect arylsulfatase may have marked effects on sulfate conjugate production by the liver.
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PMID:Futile cycling of a sulfate conjugate by isolated hepatocytes. 200 78

Previous results have suggested that key intermediates in the activation of 2-nitrotoluene and 2,6-dinitrotoluene are 2-aminobenzyl alcohol and 2-amino-6-nitrobenzyl alcohol, respectively. In order to determine the metabolic pathway(s) involved in the activation steps, calf thymus DNA and [14C]-2-aminobenzyl alcohol or [14C]-2-amino-6-nitrobenzyl alcohol were incubated with male Fischer-344 rat hepatic cytosol and PAPS, microsomes and NADPH, or microsomes and cytosol with PAPS, NADPH, and acetyl coenzyme A. DNA was isolated and analyzed for radiolabel bound covalently. Analysis of the incubations containing [14C]-2-aminobenzyl alcohol revealed radiolabel bound covalently to DNA, as well as one major metabolite labile in both sulfatase and acid. The appearance of each required the presence of PAPS and cytosol and was inhibited by the sulfotransferase inhibitor 2,6-dichloro-4-nitrophenol. Neither NADPH nor acetyl coenzyme A played a role in the generation of detectable 14C bound to nucleic acids. 2-Amino-6-nitrobenzyl alcohol was converted to metabolites capable of binding to calf thymus DNA when incubated with cytosol and PAPS or with microsomes and NADPH. However, when cytosol and microsomes were incubated together, activation of 2-amino-6-nitrobenzyl alcohol appeared to require only PAPS, suggesting a minor role for NADPH-dependent enzymes in its activation. The results suggest that the metabolite of 2-nitrotoluene responsible for binding covalently to DNA is 2-aminobenzyl sulfate. There may be more than one pathway involved in the formation of metabolite(s) of 2,6-dinitrotoluene that bind covalently to DNA.
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PMID:In vitro activation of 2-aminobenzyl alcohol and 2-amino-6-nitrobenzyl alcohol, metabolites of 2-nitrotoluene and 2,6-dinitrotoluene. 251 19

Lactosylceramide sulfate and galactosylceramide sulfate were found to be increased markedly in human renal cell carcinoma (adenocarcinoma) as compared to uninvolved tissue, while neither of them were found in human nephroblastoma tissues. Activities of two sulfotransferases toward galactosyl ceramide and lactosylceramide as substrates were significantly elevated in the renal cell carcinoma compared to the uninvolved, endorsing enhanced synthesis of the two sulfatides in the renal cell carcinoma. The levels of elevated activities of two sulfotransferases were parallel in most renal cell carcinomas. In nephroblastoma tissues, the activity of sulfotransferase was not detected or only in trace, if any. No consistent change in the activity of arylsulfatase A which disulfate two sulfatides was observed in nephroblastoma and renal cell carcinoma as compared to that in the uninvolved tissue. In the nephroblastoma and the renal cell carcinoma, neolactosylceramide was detected but not in the uninvolved tissue. The present results show that the increased sulfatide (s) in the renal cell carcinoma and the disappearance of the sulfatides in the nephroblastoma are biochemical characteristics of histologically different carcinoma.
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PMID:[Glycolipid alterations in human kidney carcinoma]. 254 45


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