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)

The activities of arylsulfatases A and B were determined in human primary and secondary tumor tissues (total, 53 cases) of various histological types. Significantly higher activities of these sulfatases were found in almost all the primary lung carcinomas as compared to their corresponding uninvolved tissues. No significant correlation was demonstrated between the enzyme activities and histological figures (stroma amounts, etc.). Lung adenocarcinoma and squamous cell carcinoma showed the presence of an additional arylsulfatase component (B1) which was not detected in normal human lung. The tumor arylsulfatase B1 had an isoelectric point (pI) of 6.7 and was clearly distinguished from arylsulfatase A (pI 4.9) and arylsulfatase B (pI 9.1 to 9.2) in normal lung and lung tumor. The tumor B1 enzyme was demonstrated to be most probably an isoenzyme of arylsulfatase B, since this unusual enzyme was indistinguishable from arylsulfatase B in terms of Ag+ inhibition; its kinetic parameters of Km for p-nitrocatechol sulfate, which was 2.9 mM with B1; optimum pH of 6.3 for B1; heat stability; and substrate specificity for three synthetic and two physiological substrates.
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PMID:Elevated activities and properties of arylsulfatases A and B and B-variant in human lung tumors. 743 63

Trypan blue is known to act as a lysosome membrane destabilizer. We investigated the effect of this dye on the activity of cathepsin D, acid phosphatase and arylsulfatase in tissue homogenates of B16 melanotic melanoma, transplanted subcutaneously in C57BL/6J black male mice. We also examined the tumor growth and the ultrastructure of its cells. The mice were given subcutaneous injections of the suspension of B16 cells (10(6)), and then received the trypan blue solution intraperitoneally in four divided doses, reaching the total does of 0.1 mg/g b.w. (group I) or 0.4 mg/g b.w. (group II). The dye was administered each other day after the tumor transplantation. The control mice were injected with melanoma cells only. The animals were killed 2 weeks after the beginning of the experiment. We found that the activity of lysosome hydrolases was increased by 30% to 50% in groups I and II, respectively, as compared to the control animals. The tumor growth in groups I and II was accelerated, and some ultrastructural changes in the melanoma cells were observed. These included irregular shape of the nucleus, uneven dispersion of the chromatin, increased number of premelanosomes and Golgi structures. The number of lysosomes, however, remained unaltered. We postulate that the trypan blue promotes tumor growth through the enhancement of the activity of lysosomal hydrolases; this may be due to the increased permeability of lysosome membranes caused by the trypan blue.
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PMID:Effect of trypan blue on the activity of lysosomal enzymes, tumor growth and cell ultrastructure in B16 melanotic melanoma in mice. 765 82

Inhibition of estrogen production provides effective therapy for patients with hormone-dependent breast cancer. The source of estrogens in premenopausal women is predominantly the ovary, but after the menopause, estradiol is synthesized in peripheral tissues through the aromatization of androgens to estrogens. Uptake from plasma is the primary mechanism for maintenance of estradiol concentrations in breast cancer tissue in premenopausal women, whereas several steps may be operant in postmenopausal women. These include enzymatic synthesis of estradiol via sulfatase, aromatase, and 17 beta-hydroxysteroid dehydrogenase in the tumor itself. Aromatization of androgens secreted by the adrenal to estrogens in peripheral tissues and transport to the tumor via circulation in the plasma provides another means of maintaining breast tumor estradiol levels in postmenopausal women. These various sources contribute to the high tissue estrogen levels measured in breast tumor tissue. To effectively suppress tissue concentrations of estrogens and circulating estradiol in postmenopausal patients, various aromatase inhibitors have been developed recently. These include steroidal inhibitors such as 4-hydroxy-androstenedione as well as non-steroidal compounds with imidazole and triazole structures. The most potent of these, CGS 20267, is reported to suppress levels of active estrogens (i.e., estrone, estrone sulfatase, and estradiol) by more than 95%. This compound can suppress both serum and 24-hr urine estrogens to a greater extent than produced by the second generation inhibitor, CGS 16949A. CGS 20267 is highly specific since it does not affect cortisol and aldosterone serum levels during ACTH stimulation tests nor sodium and potassium balance in 24-hr urine samples.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aromatase inhibitor development for treatment of breast cancer. 774 29

Dehydroepiandrosterone (DHEA) has been shown to affect the growth of mammary carcinomas both in vitro and in vivo. In humans, very high levels of DHEA and/or dehydroepiandrosterone sulfate (DHEAS) have been found in breast tissues and secretions, and epidemiological studies suggest a role of these steroids in the modulation of breast cancer growth. An uptake from plasma and a transformation from precursors can be both postulated, but the main source of the adrenal C19 steroids found within the breast is debated. Attempting to clarify this point, in ten patients undergoing surgery for breast cancer we studied: a) DHEAS and DHEA concentrations in tumor tissue; b) the differences between DHEAS (or DHEA) concentration in peripheral venous plasma and that draining the affected breast, that we assume to reflect the arteriovenous gradient of these steroids; c) DHEA sulfatase activity in tumor tissue. Results show that DHEA sulfatase activity is not related to DHEAS or DHEA concentrations in breast cancer tissue. A negative DHEA plasma gradient across the breast is unveiled, whereas DHEAS levels are not different in blood supplying and draining the breast with cancer. The DHEA plasma gradient across the breast is positively related to DHEA concentration in tumor tissue. Data are consistent with the hypothesis that the plasma source contributes remarkably to DHEA found within breast cancer tissue.
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PMID:Dehydroepiandrosterone concentration in breast cancer tissue is related to its plasma gradient across the mammary gland. 774 43

A scheme is described for the purification of a lipid-mobilizing factor from a cachexia-inducing murine tumor (MAC16) using a combination of ion exchange (Mono Q), exclusion (Superose), and hydrophobic (C8) chromatography. This process yields an active material with an apparent molecular weight of 24,000 with an overall purification of 3,500 from the tumor homogenate and representing 0.005% of the total protein present. The material tends to aggregate to high molecular mass, is acidic (pI < 4), and displays heterogeneity of charge as evidenced by a broad elution profile on ion exchange and exclusion chromatography and multiple peaks on hydrophobic columns. The purified material was heat and alkali (pH 10.4) labile and activity could be completely inhibited by sulfatase, suggesting that the negative charge could arise from sulfate residues. There was no evidence that the material possessed triglyceride lipase activity. Animals transplanted with the MAC16 tumor and with a delayed weight loss contained in their serum antibodies that recognized a M(r) 24,000 band on Western blots. This material copurified with the lipid-mobilizing factor. Such antibodies were not present in the serum of mice transplanted with the MAC13 tumor, which does not induce cachexia, suggesting that the antibodies were directed to the induction of cachexia rather than the tumor itself. Urine from patients with cancer cachexia also contained a lipid-mobilizing factor which adhered to DEAE-cellulose and gave an apparent M(r) of 24,000 by exclusion chromatography. Western blotting using serum from MAC16 tumor-bearing animals showed the presence of a band of M(r) 24,000 in such fractions, which was not detected using serum from mice bearing the MAC13 tumor. This band was not present in Western blots of urine from normal subjects. The fact that serum from mice bearing the MAC16 tumor can detect the human lipid-mobilizing activity suggests a high degree of structural similarity between the two and raises the possibility that cachexia in humans may be caused by the same species as in the mouse.
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PMID:Purification and characterization of a lipid-mobilizing factor associated with cachexia-inducing tumors in mice and humans. 788 53

Despite numerous studies on arylsulfatase A, the structure of the glycans present in each of its two subunits has not been determined. This is important because the carbohydrate component of human arylsulfatase A synthesized in tumor tissues and transformed cells has been shown to undergo apparent changes. This study elucidates some of their major features. Glycan chain analysis of native and deglycosylated arylsulfatase A as well as its subunits was performed with the use of a Glycan Differentiation Kit and lectin affinity chromatography. Each of the two subunits of arylsulfatase A from placenta, separated electrophoretically on polyacrylamide gel in reducing conditions, reacted with digoxigenin-labelled Galantus nivalis agglutinin and Aleuria aurantia agglutinin, while those from liver enzyme reacted with the former only. The subunits of both enzymes did not react with Sambucus nigra, Maakia amuriensis, Datura stramonium or Peanut agglutinin. Deglycosylation of arylsulfatase A with peptide N-glycosidase F and endo-beta-N-acetylglucosaminidase F resulted in complete cleavage of its carbohydrate component from each subunit. Their molecular weights decreased by 3 kDa. Neuraminidase treatment of the enzyme from liver and placenta followed by isoelectrofocusing separation showed the presence of sialylated forms which constituted a small percentage of total enzyme activity. Placental arylsulfatase A became bound to Lens culinaris agglutinin agarose, while no interaction with Ricinus communis or Griffonia simplicifolia agglutinin agarose was observed. The study shows that both subunits of arylsulfatase A from human placenta possess two high mannose/hybrid type glycans as major structures, with at least one 6-O-L-fucose bound to the innermost N-acetylglucosamine on each.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of human arylsulfatase A glycans. 789 Jan 20

Mouse colon adenocarcinoma Co38 is widely used as a screening model for human colon tumors. To understand better the influence of tumor size on the main drug-metabolizing enzyme systems, we tested 15 mouse Co38 tumors at different sizes. The average weight was 917 +/- 444 mg (range, 300-1,400 mg). Cytochromes P-450 (1A1/1A2, 2B1/B2, 2C8-10, 2E1, 3A4), epoxide hydrolase (EH), and glutathione-S-transferases (GST-alpha, -mu, and -pi) were assayed by immunoblotting. The activities of the following enzymes or cofactors were determined by spectrophotometric or fluorometric assays: 1-chloro-2,4-dinitrobenzene-GST (CDNB-GST), selenium-independent glutathione peroxidase (GPX), 3,4-dichloronitrobenzene-GST (DCNB-GST), ethacrynic acid-GST (EA-GST), total glutathione (GSH), uridine diphosphate-glucuronosyltransferase (UDP-GT), beta-glucuronidase (beta G), sulfotransferase (ST), and sulfatase (S). Our results showed the absence of all probed P-450s and EH in Co38 tumors. No relationship was found between the Co38 tumor weights and GPX, GST-alpha, and EA-GST (regression analysis). However, a significant correlation was found between the tumor weights and all other enzymes investigated. For certain enzymes or cofactors, a linear decrease (P < 0.05) was observed as a function of tumor weight (CDNB-GST, DCNB-GST, GST-mu, GST-pi, GSH, and beta G). Other enzymatic activities (UDP-GT, S, and ST) were found to decrease in medium-size tumors and to increase in large tumors (P < 0.05; quadratic correlation). These data demonstrate that the expression of many drug-metabolizing enzyme systems is altered during tumor growth and suggest that tumoral response to chemotherapy could be altered as a function of tumor size.
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PMID:Influence of tumor size on the main drug-metabolizing enzyme systems in mouse colon adenocarcinoma Co38. 792 60

Since drug-metabolizing enzymes may influence the toxic response of tissues or organs to drugs, we studied their expression in human and colon tumor tissues, in an attempt to find new targets for chemotherapy and also to explain the intrinsic drug-insensitivity of most colon tumors to anticancer drugs. In the present work, we compared human colorectal tumors and peritumoral tissues to a mouse colorectal tumor (Co38) and normal murine colon with regard to their main drug-metabolizing enzyme systems. We investigated cytochromes P-450 (1A1/1A2, 2B1/B2, 2C, 2E1, 3A) and epoxide hydrolase (EH) by immunoblotting. Total glutathione (GSH) and the activities of the following enzymes: total GST, selenium-independent glutathione peroxidase (GPX), 1,2-dichloro-4-nitrobenzene-GST (DCNB-GST), ethacrynic acid-GST (EA-GST), UDP-glucuronosyltransferase 1 (UDPGT), beta-glucuronidase (beta G), sulfotransferase (ST) and sulfatase (S) were investigated by fluorometric and spectrophotometric assays. Results obtained by immunoblotting showed that mouse colon tumor Co38 did not express any of the probed cytochromes P-450, whereas human tumors showed the presence of cytochrome P-450 3A. EH was not expressed in either mouse colon tumor Co38 or normal mouse colon, whereas it was expressed in human peritumoral and tumoral colon tissues at similar levels. GPX and EA-GST were detected in all tumoral and non tumoral tissues of both species. DCNB-GST was expressed in all murine tissues investigated, but was not found in human tissues. For human peritumoral and tumoral colorectal tissues there was no significant difference between GST isoenzymes levels, whereas mouse colon tumor Co38 had a lower expression of DCNB-GST and EA-GST compared to normal mouse colon. No significant difference was observed between human tumors and peritumoral tissues for total GST, UDPGT1, beta G, ST and S activities. For murine colon tissues, the conjugation pathways (total GST, UDPGT1 and ST) were lower in Co38, whereas the opposite was observed for the hydrolytic enzymes (beta G and S). In conclusion, despite similarities between human and murine colon tumors, mouse colon tumor Co38 appears different from human colon tumors for many drug-metabolizing enzyme systems. These interspecies differences may have implications with regard to drug screening methodologies and preclinical evaluation of candidate anticancer drugs useful in the chemotherapy of human colorectal tumors.
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PMID:[Screening of principal enzymes involved in the metabolism of anticancer drugs in human and murine colonic tumors]. 817 93

Quercetin is highly mutagenic in vitro, yet is not carcinogenic when administered chronically at large doses to rodents for 12 months. We hypothesized that catechol-O-methyltransferase-catalyzed O-methylation of quercetin and other mutagenic catechol-containing flavonoids may provide an efficient inactivation in vivo and may therefore prevent tumor induction by these flavonoids. After one intraperitoneal administration of 50 mg/kg quercetin to hamsters, a urinary ether extract contained 2% quercetin and 97% 3'-O-methylquercetin. When the urine was treated first with beta-glucuronidase and sulfatase, 13% quercetin and 87% 3'-O-methylquercetin were recovered. Quercetin was rapidly O-methylated by either porcine liver or hamster kidney catechol-O-methyltransferase, with Km values of 6.1 and 6.9 microM and Vmax values of 14,870 and 200 pmol/mg of protein/min, respectively. S-Adenosyl-L-homocysteine exhibited a potent feedback inhibition of the catechol-O-methyltransferase-catalyzed O-methylation of quercetin by a competitive mechanism with respect to S-adenosyl-L-methionine and by a competitive plus noncompetitive mechanism with respect to the substrate. A comparison of the O-methylation rates and kinetic characteristics (Km, Vmax, and Vmax/Km) demonstrated that rates of O-methylation of quercetin and fisetin were up to three orders of magnitude higher than those of catechol estrogens and catecholamines. In conclusion, the rapid metabolic inactivation of mutagenic flavonoids catalyzed by catechol-O-methyltransferase may be a major reason for the lack of their carcinogenic activities in vivo.
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PMID:Catechol-O-methyltransferase-catalyzed rapid O-methylation of mutagenic flavonoids. Metabolic inactivation as a possible reason for their lack of carcinogenicity in vivo. 827 10

Since protein binding to the 3' end of mRNA is believed to be involved in the control of mRNA stability, the time course of alterations in glucagon-induced phosphoenolpyruvate-carboxykinase-mRNA (PCK) levels, in the absence and presence of insulin, was correlated with the time course of changes in the binding of cytosolic protein from 24-h cultured rat hepatocytes to the 3' end of PCK mRNA. PCK-mRNA levels were monitored by Northern blot analysis and protein binding was analyzed by an electrophoretic mobility-shift assay. In 24-h cultured rat hepatocytes, binding of cytosolic protein to the PCK-mRNA 3' end and PCK-mRNA levels were increased to a transient maximum at 2 h and 2-4 h, respectively, by a 1-nM glucagon treatment, added with a change of medium. 100 nM insulin, added simultaneously with glucagon, reduced the glucagon-induced maximum of protein binding by 80% and the increase of PCK mRNA by about 30%. In controls without hormonal treatment protein binding at 1 h was also increased; this increase was prevented by insulin. 100 nM insulin, added 1 h after glucagon, reversed protein binding to the 3' end of PCK mRNA to nearly initial levels within 1 h and impaired the glucagon-induced increase in PCK-mRNA levels by 30%. The transcriptional inhibitor cordycepin, added 1 h after glucagon, did not prevent the further increase in glucagon-enhanced protein binding nor its reversal by insulin. It did, however, prevent a further significant increase in PCK mRNA. Hormonally regulated protein binding could be localized to the 256 distal bases of the PCK-mRNA 3' end. The proximal 466 bases of the PCK-mRNA 3' end as well as the 1050 bases of the histone-H1(0)-mRNA 3' end and the 1200 bases of the arylsulfatase-A-mRNA 3' end also bound cytosolic protein(s), but this protein binding was not altered by treatment with glucagon or insulin. The 3' end of PCK, arylsulfatase A and H1(0) mRNA exhibited strong binding of cytosolic protein(s) from diverse rat tissues such as heart, liver and lung as well as Fao rat hepatoma cells. Cytosolic protein(s) from spleen showed weak binding and proteins from HeLa and U937 tumor cells did not bind. Protein binding was most prominent with the 3' end of PCK mRNA and cytosolic extracts from liver.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The glucagon-insulin antagonism in the regulation of cytosolic protein binding to the 3' end of phosphoenolpyruvate carboxykinase mRNA in cultured rat hepatocytes. Possible involvement in the stabilization of the mRNA. 835 60


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