Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.1 (sulfatase)
 3,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arylsulfatase B deficiency was demonstrated in peripheral leukocytes, cultured skin fibroblasts, and a lymphoid line derived from a patient with MLS. The patient's parents demonstrated levels of arylsulfatase B that were intermediate between those found in patient and those in control subjects. The activity (mean plus or minus SD) in leukocytes from normal subjects, the patient's parents, and the patient was 113.7 plus or minus 36.2, 31.0, and 5.2 nmol 4-nitrocatechol/mg protein/hr, respectively. In skin fibroblasts of the same subjects the activity was 145.2 plus or minus 41.6, 58.5, and 7.0, respectively. Nine other lysosomal enzymes were normal in skin fibroblasts of the patient. No arylsulfatase B activity was detected in a lymphoid line established from the patient with MLS. The arylsulfatase B activity in cultured amniotic fluid cells from 10 normal pregnancies was 203.2 plus or minus 49.9.
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PMID:Arylsulfatase B deficiency in Maroteaux-Lamy syndrome: Cellular studies and carrier identification. 80 52

The enzyme activity of arylsulfatase A and arylsulfatase B was studied in Epstein-Barr virus-transformed lymphoid cell lines established from control individuals and patients affected with metachromatic leukodystrophy, mucopolysaccharidosis type VI (or Maroteaux-Lamy syndrome) and multiple sulfatase deficiency. Lymphoid cells derived from patients with metachromatic leukodystrophy showed a severe deficiency in cerebroside sulfatase activity, as measured using radiolabelled sulfatide, but some residual activity of arylsulfatase A when measured with the chromogenic substrate, para-nitrocatechol sulfate. Lymphoid cells from mucopolysaccharidosis type VI had virtually no arylsulfatase B activity. In cells from patients with multiple sulfatase deficiency, the activities of lysosomal sulfatases as well as steroid sulfatase were deficient. Study of the molecular forms of arylsulfatases confirmed the complete deficiency of arylsulfatase A and arylsulfatase B activities in metachromatic leukodystrophy and mucopolysaccharidosis type VI lymphoid cells, respectively. The arylsulfatase A defect in metachromatic leukodys-lymphoid cells, respectively. The arylsulfatase A defect in metachromatic leukodystrophy cells could be demonstrated on focused fractions even using the artificial substrates, para-nitrocatechol sulfate and 4-methylumbelliferyl sulfate. To investigate the discrepancy of the arylsulfatase A activity data observed between whole cell homogenates and focused fractions when using the synthetic substrates, assays were tentatively performed for optimizing the determination of arylsulfatase A on crude homogenates of lymphoid cells. Although this work has indicated methodological limitations of the enzymatic assay of arylsulfatase A in lymphoid cells using methylumbelliferyl sulfate, it emphasizes the validity of lymphoid cell lines as an experimental model for the study of inborn deficiencies of arylsulfatases A and B.
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PMID:Arylsulfatases A and B in EBV-transformed lymphoid cell lines: studies on their molecular forms in cells from patients with inborn sulfatase deficiencies. Comparative diagnostic value of enzymatic assays. 168 73

We investigated the capacity of murine T lymphocytes, isolated from various lymphoid organs of normal or antigen-primed donors, to produce IL-2 or IL-4 after activation with anti-CD3 or specific antigen. Our results established that T cells resident within lymphoid organs being drained by nonmucosal tissue sites (e.g., axillary, inguinal, brachial lymph nodes, or spleen) produced IL-2 as the predominant T cell growth factor (TCGF) after activation. Conversely, activated T cells from lymphoid organs being drained by mucosal tissues (Peyer's patches, and cervical, periaortic, and parathymic lymph nodes) produced IL-4 as the major species of TCGF. Analysis of the lymphoid tissues obtained from adoptive recipients of antigen-primed lymphocytes provided by syngeneic donors provided evidence that direct influences were being exerted on T cells during their residence within defined lymphoid compartments. These lymphoid tissue influences appeared to be responsible for altering the potential of resident T cells to produce distinct species of TCGF. Steroid hormones, known transcriptional enhancers and repressors of specific cellular genes, were implicated in the controlling mechanisms over TCGF production. Glucocorticoids (GCs) were found to exert a systemic effect on all recirculating T cells, evidenced by a marked dominance in IL-4 production by T cells obtained from all lymphoid organs of GC-treated mice, or after a direct exposure of normal lymphoid cells to GCs in vitro before cellular activation with T cell mitogens. Further, the androgen steroid DHEA appeared to be responsible for providing an epigenetic influence to T cells trafficking through peripheral lymphoid organs. This steroid influence resulted in an enhanced potential for IL-2 secretion after activation. Anatomic compartmentalization of the DHEA-facilitated influence appears to be mediated by differential levels of DHEA-sulfatase in lymphoid tissues. DHEA-sulfatase is an enzyme capable of converting DHEA-sulfate (inactive) to the active hormone DHEA. We find very high activities of this enzyme isolated in murine macrophages. The implications of our findings to immunobiology are very great, and indicate that T cells, while clonally restricted for antigen peptide recognition, also appear to exhibit an extreme flexibility with regards to the species of lymphokines they produce after activation. Regulation of this highly conservative mechanism appears to be partially, if not exclusively, controlled by cellular influences being exerted by distinct species of steroid hormones, supplied in an endocrine or a paracrine manner where they mediate either systemic or tissue-localized influences, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of murine lymphokine production in vivo. III. The lymphoid tissue microenvironment exerts regulatory influences over T helper cell function. 213 6

Bone marrow-derived leukocytes of murine epidermis can express two phenotypes: typical Langerhans cells, which are Ia+ and Thy-1-, and a recently discovered second population that is Thy-1+ and Ia-. To verify that these phenotypes are expressed by two different cell types, and to help understand their lineage and function, we have studied morphology and reactivity with a large panel of antibodies. Dual antibody immunofluorescence combined with electron microscopy showed that Thy-1+ and Ia+ cells were each distributed in a regular fashion and formed adjacent dendritic systems in or close to the basal layer. Double-labeling studies with anti-Ia and a second monoclonal antibody revealed that all Langerhans cells expressed F4/80 (macrophage), Mac-1 (C3bi receptor), and 2.4G2 (Fc receptor), as well as the thymus leukemia (TL) and heat-stable (M1.69/16) antigens. A large fraction expressed S100 and all exhibited membrane ATPase and nonspecific esterase. In contrast, Thy-1+ cells lacked all these features of Langerhans cells, except that a minority were strongly reactive with 2.4G2. Thy-1+ cells also lacked differentiation antigens of most other types of leukocytes, except they were rich in asialo GM1. By electron microscopy, Thy-1+ cells had cytoplasmic granules that were similar in structure and in their aryl sulfatase content to those previously described in natural killer cells. The granules were enlarged in beige mice, suggesting a lysosomal origin, and were present in mast cell-deficient W/Wv mice, indicating no relation to mast cells. We conclude that Thy-1+ epidermal cells are thoroughly distinct from Langerhans cells. On the basis of morphology and phenotype, they may represent a type of tissue natural killer cell. Thy-1+ natural killer cells are now being identified in several nonlymphoid sites, such as gut epithelium and the livers of mice given adjuvants. If Thy-1+ epidermal cells prove to be natural killer cells, it is noteworthy that they represent a resident population regularly distributed in the basal layer of all mouse strains. The notion that Thy-1+ epidermal cells are immature natural killer cells is intriguing in light of recent evidence that Ia+ Langerhans cells are also immature with respect to accessory cell function. The epidermis may not have the functional capacities of a lymphoid organ, but it could contribute immature cells important for both natural and acquired resistance.
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PMID:The Thy-1-bearing cell of murine epidermis. A distinctive leukocyte perhaps related to natural killer cells. 286 Dec 45

The metabolism of cholesterol sulfate (CS) was investigated in immortalized, Epstein-Barr virus-transformed lymphoid cell lines derived from normal individuals and patients affected with recessive X-linked ichthyosis (XLI). Normal lymphoid cells expressed arylsulfatase C and steroid sulfatase (including cholesterol sulfatase) activities, and these two sulfohydrolases showed the same enzyme properties as in other human cells, e.g., leukocytes or skin fibroblasts. XLI-derived lymphoid cell lines exhibited extremely deficient activity of both arylsulfatase C and steroid sulfatase. While normal and XLI intact, living lymphoid cells could take up exogenous radiolabelled CS through a non-receptor-mediated process. XLI cells were completely unable to degrade CS to cholesterol. However, despite their defect in CS degradation, steroid sulfatase-deficient cells did not accumulate CS because of outflux of this sterol. The potential implications of these findings to the pathogenesis of increased CS content in plasma and epidermis of XLI patients are discussed. This study also demonstrates that immortalized lymphoid cell lines may represent a useful experimental model system for the study of XLI.
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PMID:Cholesterol sulfate is not degraded but does not accumulate in Epstein-Barr virus-transformed lymphoid cells from patients with X-linked ichthyosis. 754 38

We show here that human immunodeficiency virus (HIV) envelope glycoproteins (gp160/gp120) bind to sulfatide and galactosyl ceramide. By immunofluorescence labeling with monoclonal antibody (mAb) A2B5, specific for ganglioside/sulfatide, we detect negatively charged glycolipids on CD4+ cells of the macrophage lineage and lymphocytes. Labeling of monocyte-derived macrophages (MDM) with mAb A2B5 was reproducibly found in 29 healthy donors, independently of the culture method and duration up to 11 days. The binding of the mAb to neuraminidase-treated MDM was unchanged relative to control cells, but mAb binding decreased after arylsulfatase treatment, which indicates that MDM membrane sulfatide is its major ligand. Preincubating MDM with the mAb partially (40-60%) but significantly inhibited the binding of HIV-1LAI radiolabeled recombinant gp160 to the cells. Similarly, the mAb entailed limited (32%) but significant inhibition of gp160 binding to cells of the monocytic U937 line but not to lymphoid CEM cells. However, mAb A2B5 did not inhibit the infection of CEM nor of U937 cells by HIV-1LAI strain, nor of MDM by monocytotropic HIV-1BaL. Thus, although sulfatide may be involved in the binding of HIV env glycoprotein to MDM or monocytic U937 cells, this does not play a significant role in HIV infection of these CD4+ cells.
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PMID:A monoclonal antibody directed to sulfatide inhibits the binding of human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein to macrophages but not their infection by the virus. 831 76

Non-Hodgkin's lymphomas (NHL) are one of the most chemosensitive human malignancies. Complete response (CR) is often achieved, but many patients relapse and a second CR is difficult to obtain because of the development of chemoresistance. In an attempt to better understand the biology and the chemosensitivity of these lymphoid tumors, we assessed the main drug-metabolizing enzyme systems in normal lymphocytes, chemosensitive NHL and chemoresistant NHL. Cytochromes P-450 (1A1/A2, 2B1/B2, 2C8-10, 2E1, 3A4), epoxide hydrolase and glutathione S-transferases (GST-alpha, -mu, -pi) were assayed by immunoblotting. UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, sulfatase, GST activity, and glutathione (GSH) content, were determined by spectral assays. Results showed the absence of all probed cytochromes P-450 in normal lymphocytes and NHL cells tested. GST activity was significantly lower in chemoresistant NHL compared to normal lymphocytes. GST-alpha was not detected in either normal lymphocytes or NHL cells. GST-pi was the predominant isoenzyme, and GST-mu was not detected in chemosensitive NHL. GSH content was significantly lower in chemoresistant NHL compared to other lymphoid tissues tested. The conjugating enzymes UDP-glucuronosyltransferase and sulfatase were similar in either chemoresistant NHL compared to chemosensitive NHL. The activity of the hydrolytic enzyme beta-glucuronidase was lower in chemoresistant compared to chemosensitive NHL, whereas sulfatase was higher in sensitive NHL compared to normal lymphocytes. Epoxide hydrolase was not detected in either normal or NHL cells tested. In conclusion, these studies did not show any cytochrome P-450 in human lymphoid cells tested, but pointed out noteworthy differences for other enzyme systems tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Main drug-metabolizing enzyme systems in human non-Hodgkin's lymphomas sensitive or resistant to chemotherapy. 853 97

Cystic fibrosis (CF) is associated with mutation and abnormal function of the cystic fibrosis transmembrane conductance regulator (CFTR) that affects cellular chloride transport. Clinically, CF of the lung is associated with excessive accumulation of secretions, including the sulfated glycosaminoglycans, chondroitin sulfate and dermatan sulfate (DS), both of which contain sulfated N-acetylgalactosamine residues. The sulfatase enzymes, which are a highly conserved group of enzymes with high specificity for designated sulfate groups, include arylsulfatase B, a lysosomal enzyme. Arylsulfatase B, also known as N-acetyl galactosamine 4-sulfatase, can degrade DS and chondroitin-4 sulfate. Previously reported data demonstrated diminished activity of arylsulfatase B in lymphoid cell lines of patients with CF compared to normal control subjects. Frequent infections with Pseudomonas, a sulfatase-producing organism, occur in patients with CF, whereas infections with Mycobacterium tuberculosis, which lacks sulfatase activity, are infrequent. Additional investigation to determine if diminished function of arylsulfatase B is a consistent finding in cells of patients with CF may be informative, and may help to correlate the molecular, biochemical, and clinical characteristics of CF.
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PMID:Does deficiency of arylsulfatase B have a role in cystic fibrosis? 1279 51

Psoriasis is a clinical conundrum that affects an estimated 1-3% of the world's population. The psoriatic disease process, characterized by a type 1 cytokine pattern, is supposed to be maintained by a continuing immune response in a "peripheral lymphoid tissue" that forms in lesional skin and is composed of T cells, dendritic cells, and vessels arranged like a T-dependent zone in lymph nodes. Dehydroepiandrosterone (DHEA), produced from dehydroepiandrosterone sulfate (DHEAS) through the enzymatic activity of DHEA-sulfatase, plays a pivotal role in the development of the type 1 immune response generated in peripheral lymphoid organs. Taken together, it could be reasoned that DHEA-sulfatase inhibitors may have utility in the treatment of psoriasis. Furthermore, the addition of DHEA-sulfatase inhibitors to calcipotriol, which encourages type 2 immune response, may provide an additive or synergistic inhibition of the type 1 immune response underlying psoriasis. It has been shown that topical application of cholesterol sulfate in the hairless mouse causes epidermal hyperkeratosis, which can be prevented by co-application of topical cholesterol. Therefore, as the inhibition of conversion of cholesterol sulfate to cholesterol can induce epidermal hyperkeratosis and may thus abbreviate the benefit obtained by inhibition of DHEAS to DHEA conversion, topical sulfatase inhibitors should preferably be co-applied with topical cholesterol, though it is also possible that the beneficial immunological effects of steroid sulfatase inhibitors outweigh their possible hyperkeratosis stimulation. Alternatively, the production of specific DHEA-sulfatase inhibitors can resolve the above concern. DHEA-sulfatase inhibitors may prove invaluable in the treatment of psoriasis.
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PMID:Steroid sulfatase inhibitors as novel additions to the antipsoriatic armamentarium. 1573 72