Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two estrogen sulfatases, arylsulfatase C-estrone sulfatase (ASC-ES) and d-equilenin sulfatase (EqS) were demonstrated histochemically in the normal human female breast, in benign breast diseases and in infiltrating mammary ductal carcinomas to study their significance in the pathogenesis of epithelial proliferations. By hydrolyzing estrone sulfate, the amount of which in female blood is about ten times greater than that of estradiol or estrone, estrogen sulfatases can produce a high local concentration of estrogens. A simultaneous azo-coupling method for histochemical demonstration of ASC-ES is described in the present study; EqS was demonstrated by a previously described method. Estrogen sulfatases were not found in the normal female breast. Both estrogen sulfatases were found in epithelial cells in some examples of mastopathic disease and in fibroadenomas, while ASC-ES was found in periductal fibroblasts. In some cases of infiltrating ductal carcinomas, estrogen sulfatases were present in carcinoma cells. In most of these tumors ASC-ES activity was observed in fibroblasts around infiltrative cell cords. There was no correlation between the presence of estrogen sulfatases and of hormone receptors in carcinomas. It is concluded that estrogen sulfatases play no role in the early stages of benign or malignant epithelial proliferations. However, the induction of estrogen sulfatases may promote epithelial proliferation in some cases if estrogen receptors are present in epithelial cells.
Virchows Arch B Cell Pathol Incl Mol Pathol 1985
PMID:Histochemistry of estrogen sulfatases in human breast diseases. 286 35

Suramin-induced lysosomal storage disease reproduced in the rat was extended to the mouse with the attempt to characterize enzymatically and morphologically heterogeneous responses of various organs to the drug. Suramin administration strikingly decreased (3-6 days afterward) the activity of beta-glucuronidase in all tissues studied (kidney, liver, heart, and skeletal muscle). The enzymatic responses were small in the activities of beta-N-acetyl-glucosaminidase. The activity of arylsulfatase A decreased to a varying degree in mouse tissues, but in rats the activity increased in liver and skeletal muscle. The activity of cathepsin D increased in rat tissues. Suramin induced morphological changes characteristic to lysosomal storage diseases in kidney and liver but not in heart and skeletal muscle of both mice and rats. Kidney was appreciably more susceptible to suramin than liver. The occurrence of lysosomal accumulations, membranous lamellar inclusions, and granular material were most prominent in tubular cells of kidney and in Kupffer cells of liver. These cells also presented intensive Alcian blue staining. Interestingly, the enzymatic and morphological responses did not correlate with each other, which may reflect differences in the regulation of lysosomal functions in various cell types.
Exp Mol Pathol 1986 Aug
PMID:Morphological and enzymatic heterogeneity of suramin-induced lysosomal storage disease in some tissues of mice and rats. 287 99

The regulatory gene cys-3+ controls the synthesis of a number of enzymes involved in sulfur metabolism. cys-3 mutants show a multiple loss of enzymes in different pathways of sulfur metabolism. The cys-3+ gene was isolated by transformation of an aro-9 qa-2 cys-3 inl strain with a clone bank followed by screening with the "sib selection" method. The library used (pRAL1) contained inserts of Sau3a partial digest fragments of about 9 kilobases as well as the Neurospora qa-2+ gene. Double selection for qa-2+ and cys-3+ function was carried out. The transformants obtained with the isolated cys-3+ clone show recovery of the enzyme activities associated with the cys-3 mutation (e.g., arylsulfatase and sulfate permease). Restriction fragment length polymorphism experiments confirmed the identity of the clone, mRNA studies with Northern blots show that the expression of the cys-3+ gene is inducible. In contrast to cys-3+, the cys-3 (P22) mutant gene was not expressed at a higher level under sulfur-derepressed conditions.
Mol Cell Biol 1987 Jul
PMID:Molecular cloning and characterization of the cys-3 regulatory gene of Neurospora crassa. 288 8

The metabolism of 17 beta-estradiol in both estrogen receptor positive and negative human breast cancer cell lines has been compared. Initial experiments in which confluent cells were exposed to 1 nM [3H]17 beta-estradiol for 24 h, revealed that the main metabolites formed by estrogen receptor positive MCF-7 and ZR-75-1 cells were 17 beta-estradiol-3-sulfate (together with lesser amounts of estrone sulfate) and estrone. In estrogen receptor negative cell lines, production of estrogen sulfates was either significantly lower (MDA-MB-231 cells) than receptor positive cells, or failed to be produced at all (MDA-MB-330 cells). In both these receptor negative cell lines, production of estrone was significantly higher than in receptor positive cells. Accumulation of estrogen sulfates resulted from attainment of a steady state between synthesis catalysed by estrogen sulfotransferase and degradation catalysed by estrogen sulfatase. The former was present in the cytosol and showed a very high affinity for 17 beta-estradiol and estrone (low nM range). Complex initial velocity versus estrogen substrate curves were obtained with enzyme purified 106-fold by affinity chromatography. Such curves were consistent with a rate equation of degree 3 or 4 and suggest the presence of cooperatively linked dependent binding sites.
Mol Cell Endocrinol 1988 Aug
PMID:Metabolic fate of estradiol in human mammary cancer cells in culture: estrogen sulfate formation and cooperativity exhibited by estrogen sulfotransferase. 320 95

The hydrolysis of 4-methylumbelliferyl sulfate by liver sulfatases to free fluorescent 4-methylumbelliferone and the subsequent formation of the glucuronide conjugate were studied in the isolated perfused rat liver. In livers from fed, phenobarbital-treated rats, 4-methylumbelliferyl sulfate (0.25-1.5 mM) was hydrolyzed rapidly to free 4-methylumbelliferone at maximal rates of about 5 mumol/g/hr. A major fraction of the free 4-methylumbelliferone formed was converted to the glucuronide at maximal rates around 20 mumol/g/hr. Similar rates of hydrolysis were observed in livers from fasted, phenobarbital-treated or normal rats, although the ratio of glucuronide to free product was decreased markedly by fasting. In liver homogenates, however, rates of organic sulfate hydrolysis exceeded those observed in the perfused liver by at least 2-fold, suggesting that 4-methylumbelliferyl sulfate content is an important determinant of rates of hydrolysis in the perfused liver. There was a good correlation (r = 0.91) between rates of product formation and fluorescence of 4-methylumbelliferone detected from the liver surface with fiber optic light guides. Fluorescence of 4-methylumbelliferone produced from hydrolysis of 4-methylumbelliferyl sulfate was also monitored with micro-light guides placed on periportal and pericentral areas of the liver lobule for the estimation of local rates of product formation. When perfusions were in the anterograde direction, desulfation of 4-methylumbelliferyl sulfate was about 50% higher in pericentral (28.8 +/- 9.3 mumol/g/hr) than in periportal (18.2 +/- 2.7 mumol/g/hr) areas. Furthermore, 4-methylumbelliferyl sulfate content determined in microdissected samples was 1.5- to 2-fold higher in pericentral than in periportal regions of the liver lobule but the activity of 4-methylumbelliferyl sulfate sulfatase was identical in both zones of the liver lobule. We conclude, therefore, that the local substrate content is an important determinant of rates of 4-methylumbelliferyl sulfate hydrolysis in sublobular zones of the liver.
Mol Pharmacol 1986 Jun
PMID:Hydrolysis of organic sulfates in periportal and pericentral regions of the liver lobule: studies with 4-methylumbelliferyl sulfate in the perfused rat liver. 371 3

Latencies and phosphomannosyl-enzyme receptors of lysosomal enzymes were studied in the skeletal muscles of NMRI mice during the appearance (0-1 days) and the repair (3-9 days) of muscle fiber injuries after a single bout of prolonged running (9 hr, 13.5 m/min). The unsedimentable, releasable, and bound activities of arylsulfatase, beta-N-acetylglucosaminidase, beta-D-glucuronidase, cathepsin C, and ribonuclease as well as the content and occupancy of phosphomannosyl-enzyme receptors of lysosomal enzymes were assayed. The distribution of enzyme activities in different fractions as well as the changes after exertion greatly varied between different lysosomal enzymes. In general, the total activities and also the distribution of enzyme activities in different fractions were unaffected 1 hr after exertion, but on the day after exertion small increases were observed in the free and releasable activities. The highest enzyme activities both in the homogenate and in different fractions were recorded 3 days after exertion, after which the activities slowly decreased. The increases of enzyme activities were higher in the free and releasable fractions than in the homogenate but the changes in the proportional distributions of lysosomal enzyme activities between different fractions were minor. The present study also showed the presence of phosphomannosyl-enzyme receptors of lysosomal enzymes in the membranes of skeletal muscles. The total content of phosphomannosyl-enzyme receptors was unchanged 0-3 days after exertion but a small increase occurred 5-8 days after exertion. Instead, the occupancy of these lysosomal receptors with endogenous enzymes was significantly increased 1-5 days after exertion and decreased later to the control level.
Exp Mol Pathol 1984 Dec
PMID:Latencies and phosphomannosyl-enzyme receptors of lysosomal enzymes during the appearance and repair of exercise injuries in mouse skeletal muscles. 609 63

Using electron microscopy and cytochemical techniques we investigated structures which are associated with long-term hypertension and ageing in the myocardial cell of the rat. Lysosomes, demonstrated by acid phosphatase and aryl sulfatase activities, were found mainly in the perinuclear region in young rats. With age these organelles appeared with increasing frequency in other regions of the cell. Spontaneously hypertensive rats (SHR) showed an earlier apparent migration of lysosomes than did normotensive rats (WKY). Our observations indicate that lysosomes were closely associated with autophagic vacuoles, membrane swirls , translucent mitochondria, myelin figures and other structures linked with degenerative events. In the oldest SHR lysosomes, autolysosomes (autophagic vacuoles with lysosomal activity), and degenerative structures were observed in various regions of the myocardial cell. Peroxisomes, as demonstrated by catalase activity, did not seem to be affected by hypertension or age. A number of dense osmophilic structures did not react for any of the enzymes studied; these included myelin figures, mitochondrial inclusions and diffuse dense bodies. Our observations implicate both ageing and hypertension in the enhancement of lysosomes and their end products.
J Mol Cell Cardiol 1984 Mar
PMID:Cytochemistry of myocardial structures related to degenerative processes in spontaneously hypertensive and normotensive rats. 623 95

Arylsulfatases A and B were measured in the liver of mice infected with Schistosoma mansoni. The increase of total arylsulfatases paralleled enlargement of the granulomas. It began at 7 weeks after infection and reached a maximum at 10 to 14 weeks when the enzyme activity became about 2.5 times that of normal liver. The elevated enzyme activity was due to granulomatous tissue, because when granulomas were separated from hepatic cells, the former contained the increased activity but the latter did not. Arylsulfatase A, arylsulfatase B, and arylsulfatase Bv, in both normal liver and granulomas, were separated by anion-exchange column chromatography and differences in net charges of these enzymes were demonstrated by polyacrylamide gel electrophoresis. Biochemical properties were indistinguishable between arylsulfatase B and arylsulfatase Bv while they differed from arylsulfatase A. Granulomas at 8 weeks after infection showed 3.0-, 3.5-, and 5.0-fold increases in activity for arylsulfatase A, B, and Bv, respectively. As the granulomas enlarged, by 12 weeks, arylsulfatases B and Bv activities further increased but the arylsulfatase A value remained the same as that of 8 weeks. The finding suggests that arylsulfatases are involved in granuloma development and arylsulfatases B and Bv activities may reflect functions of macrophages and other cells including fibroblasts.
Exp Mol Pathol 1984 Feb
PMID:Biochemical characterization of arylsulfatases detected in granulomatous inflammation. 669 6

The evaluation of estrogens (estrone, estradiol, and their sulfates) in the breast tissue of post-menopausal patients with breast cancer indicates high levels, particularly of estrone sulfate (E1S) which is 15-25 times higher than in the plasma. Breast cancer tissue contains the enzymes necessary for local synthesis of estradiol and it was demonstrated that, despite the presence of the sulfatase and its messenger in hormone-dependent and hormone-independent breast cancer cells, this enzyme operates particularly in hormone-dependent cells. Different progestins: Nomegestrol acetate, Promegestone, progesterone, as well as Danazol, can block the conversion of E1S to E2 very strongly in hormone-dependent breast cancer cells. The last step in the formation of estradiol is the conversion of E1 to this estrogen by the action of 17 beta-hydroxysteroid dehydrogenase. This activity is preferentially in the reductive direction (formation of E2) in hormone-dependent cells, but oxidative (E2-->E1) in hormone-independent cells. Using intact hormone-dependent cells it was observed that Nomegestrol acetate can block the conversion of E1 to E2. It is concluded, firstly, that in addition to ER mutants other factors are involved in the transformation of hormone-dependent breast cancer to hormone-independent, this concerns the enzymatic activity in the formation of E2; it is suggested that stimulatory or repressive factor(s) involved in the enzyme activity are implicated as the cancer evolves to hormone-independence; secondly, different drugs can block the conversion of E1S to E2. Clinical trials of these "anti-enzyme" substances in breast cancer patients could be the next step to investigate new therapeutic possibilities for this disease.
J Steroid Biochem Mol Biol 1995 Jun
PMID:Estrone sulfate-sulfatase and 17 beta-hydroxysteroid dehydrogenase activities: a hypothesis for their role in the evolution of human breast cancer from hormone-dependence to hormone-independence. 762 88

In view of the possible participation of estrogen 3-sulfoconjugates in reproductive events, such as reproductive cycles, gestation and parturition, an experiment was carried out where the conversion of labeled estrone sulfate ([3H]E1S) to estrone ([3H]E1) was measured during in vitro incubation with minced uterine tissues representing implantation sites (IS) and non-implanted areas (NIS), from pregnant rats at the time of blastocyst implantation. Significant hydrolysis of the 3-sulfate, by the action of the estrogen sulfatase, was found in both tissues being less in IS than in NIS, when expressed either as pmol of E1 formed/mg wet tissue/h (238 +/- 37 vs 337 +/- 15, respectively) or as pmol of E1 formed/mg protein/h (1278 +/- 198 vs 1773 +/- 81). Both differences are statistically significant at the 0.001 level. The results obtained here suggest that E1S present in uterine fluids may be taken up and hydrolyzed by the sulfatase present in both intrauterine tissues of the 6-days pregnant rat. However, the decreased formation of E1 found in IS suggests that rat blastocyst is able to regulate the local concentration of unconjugated estrogens required at IS by modulating the activity of the estrogen sulfatase.
J Steroid Biochem Mol Biol 1995 Mar
PMID:Hydrolysis of estrone sulfate in uterine minces of the 6-days pregnant rat. 769 49


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