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At least 415 records · Page 23Linked to original sources
PubMed1984

A comparative study on steroid sulfatase and arylsulfatase C in fibroblast clones from 45,X/47,XXX and 69,XXY.

Steroid sulfatase (STS) and arylsulfatase C ( ARSC ) were studied in fibroblast clones from a 45,X/47,XXX mosaic and from a 69,XXY triploidy with one or two active X chromosomes. The comparison of the 47,XXX with 45,X clones showed an incomplete gene dosage effect (1.8 for STS and 2.0 for ARSC ). This was not the case for the triploid clones with different X-inactivation patterns. These results confirm previous reports on the non-inactivation of the STS gene, and establish X linkage and non-inactivation for the ARSC gene as well.

Adult↗
PubMed1988

Inactivation and reactivation of sex-linked steroid sulfatase gene in murine cell culture.

The murine X-linked steroid sulfatase gene (Sts) normally escapes X inactivation. However, we have observed that most long-term murine cell cultures are deficient in STS activity even though only the L cells are known to be derived from an STS- mouse strain. To investigate this phenomenon, we developed a selective system whereby STS+ cells could be selected from STS- populations. The system is based on making cells dependent on cholesterol-sulfate as the sole source of cholesterol, allowing only STS+ cells to grow. Two STS- cell lines, after treatment with either 5-azacytidine (5AC) or ethyl methane sulfonate (EMS), yielded STS+ revertants, suggesting that their STS- phenotype was due to hypermethylation. To study the evolution of STS- cell lines, we established XO and XX primary lines from STS+ strains; the XX cell line remained STS+ after more than 200 cell doublings whereas the XO became STS- after about 100 doublings. Treatment of this STS- XO cell line with 5AC produced clones with restored STS activity. All the revertants showed a growth disadvantage compared to their STS- counterparts. It would appear that aberrant methylation is the basis for much of the STS deficiency observed in established murine lines and that its propagation is due to the growth advantage of STS- over STS+ cells.

Animals↗
PubMed1988

Recurrent bilateral corneal erosions due to an association of epidermolysis bullosa simplex Köbner and X-linked ichthyosis with steroid sulfatase deficiency.

Since early infancy a male patient now 24 years of age had suffered from painful, recurrent, bilateral corneal erosions and blister formation after minimal skin trauma. Corneal erosions are quite unusual in non-scarring types of epidermolysis bullosa. The dermatological examination disclosed that the patient had clinical hallmarks of two rare genetic skin disorders, epidermolysis bullosa simplex (Köbner) and X-linked ichthyosis. Both disorders could be traced back in the patient's maternal family to the mother's father and his brother, who were both said to have had similar eye complaints. Using biochemical means and electron microscopy of skin biopsy specimens, both diagnoses could be proven in the patient and his mother. We discuss the importance of lid hyperkeratoses in hemizygous males as a causative factor for the recurrence of bilateral corneal erosions due to the unique combination of epidermolysis bullosa simplex (Köbner) and X-linked ichthyosis with steroid sulfatase deficiency.

Adult↗
PubMed1985

Prevalence of partial cerebroside sulfate sulfatase (arylsulfatase A) defect in adult psychiatric patients.

Metachromatic leukodystrophy (MLD) is a disease caused by a deficiency of the enzyme sulfatide sulfatase, also known as arylsulfatase A (ASA). We compared the activity of this enzyme in adult psychiatric patients and normal volunteers using nitrocatechol sulfate (ASA-NCS) and cerebroside sulfate (ASA-CS) as substrates. Our results showed that ASA-NCS activity in urine and leukocytes was significantly lower in psychiatric than in normal individuals, but that there were no differences between these two groups in the sulfatide excretion in urine or the ASA-CS activity in leukocytes. There was no correlation between enzyme activity in urine and in leukocytes, indicating that activity in urine does not truly reflect the levels of the enzyme in tissues. The correlation between ASA-NCS and ASA-CS activity in leukocytes was poor (0.51 for psychiatric patients and 0.59 for normals), suggesting that for a valid measure of the enzyme activity the assays should be carried out with CS as substrate. Results of our study also indicate that in 39 of the 145 psychiatric patients studied, the ASA-CS activity in leukocyte was less than 4 nmoles/mg protein/hr, which is below 50% of the normal means, whereas only one of the 30 normal subjects had a value this low. The presence of low levels of ASA-CS activity in a significantly large number of adult patients with varying psychiatric manifestations suggests that such patients may be asymptomatic carriers of the sulfatidase defect (heterozygotes for MLD), and that behavioral and functional disturbances in these patients may at least in part be related to sulfatidase deficiency. The significance of the ASA-NCS abnormality (reduction) in psychiatric patients is unclear.

Cerebroside-Sulfatase↗
PubMed1987

Regional distribution of arylsulfatase C and estrone-sulfate sulfatase activities in rat brain and hypophysis.

Regional distributions of arylsulfatase C and estrone-sulfate sulfatase activities were studied in rat brain and hypophysis by both histochemical and biochemical methods. Both methods showed that high activities of both enzymes were localized in pineal gland, choroid plexus, and adenohypophysis. Ultracytochemical techniques visualized the arylsulfatase C activity in the endoplasmic reticulum and the nuclear envelope of pineal cells, ependymal cells, and some types of cells of the adenohypophysis.

Animals↗
PubMed1986

Regulation of serum testosterone in men with steroid sulfatase deficiency: response to human chorionic gonadotropin.

Human chorionic gonadotropin (hCG; 5000 IU) was administered to 6 control men and 6 patients with recessive x-linked ichthyosis (RXLI) with verified 3 beta-hydroxysteroid sulfate sulfatase (3 beta-HSS) deficiency in their skin biopsy samples. Concentrations of steroids and their sulfate conjugates were determined in peripheral serum specimens collected a day before and 4 days after hCG administration. Testosterone concentrations were identical in patients and controls. Baseline serum LH concentrations were also identical in the 2 groups showing that there were no major differences in the regulation of the hypothalamic-pituitary-gonadal axis. The significantly increased (31-82%) serum concentrations of sulfated pregnenolone, 17-hydroxypregnenolone, dehydroepiandrosterone and 5-androstene-3 beta,17 beta-diol in patients compared with controls indicated that their circulating concentrations were regulated by 3 beta-HSS. This is in line with the fact that the baseline concentrations of the same unconjugated steroids were significantly lower (32-90%) in patients with RXLI, suggesting that a proportion of these circulating steroids were derived from the corresponding sulfated precursors. The response patterns and actual concentrations of testosterone, 17-hydroxyprogesterone and estradiol were similar in the patients and the controls after hCG. The decreased concentrations of testosterone sulfated at carbon 17 under baseline conditions and after hCG in patients with RXLI remains enigmatic. In conclusion, testosterone production and the response to hCG seem to be identical in patients with RXLI and controls despite the fact that significant differences were observed in the circulating concentrations of several unconjugated and sulfated testosterone precursors.

Adult↗
PubMed1988

Ontogenesis and regulation of steroid sulfatase activity in Leydig cells and seminiferous tubules in the Long-Evans rat.

Steroid sulfatase (STS) activity was studied in Long-Evans rat testis. The affinity of the enzyme was shown to increase during postnatal development and to be always higher in purified Leydig cells than in seminiferous tubules. STS activity appeared to be higher in the seminiferous tubules at the earlier stages. In vivo injection of 100 IU hCG resulted in a decrease in the affinity and an increase in the activity of the enzyme expressed in Leydig cells with no such modification in seminiferous tubules. This suggests that STS could play a regulatory role in testosterone production by Leydig cells.

Aging↗
PubMed1989

Testicular steroid sulfatase in a cryptorchid rat strain.

Steroid sulfatase (STS) activity was studied in scrotal and abdominal testes from genetically unilateral cryptorchid rats. Specific STS activity was significantly increased in microsomes from abdominal and scrotal testes of the cryptorchid animals as compared to that of control ones. When expressed per gonad, STS activity was only enhanced in the scrotal testis. No difference in the enzyme affinity was observed between descended and undescended testes. Testosterone content was markedly reduced in the abdominal testes. Normal plasma testosterone levels together with elevated LH levels were measured in the cryptorchid rats. The existence of differences in STS expression between descended and undescended testes gives additional support for this enzymatic activity being implicated in testicular function.

Animals↗
PubMed1988

The human X-linked steroid sulfatase gene and a Y-encoded pseudogene: evidence for an inversion of the Y chromosome during primate evolution.

The mammalian X and Y chromosomes are thought to have evolved from a common, nearly homologous chromosome pair. Although there is little sequence similarity between the mouse or the human X and Y, there are several regions in which moderate to extensive sequence homologies have been found, including, but not limited to, the so-called pseudoautosomal segment, in which X-Y pairing and recombination take place. The steroid sulfatase gene is in the pseudoautosomal region of the mouse, but not in man. We have cloned and characterized the human STS X-encoded locus and a pseudogene that is present on the long arm of the Y chromosome. Our data in humans and other primates suggest that there has been a pericentric inversion of the Y chromosome during primate evolution that has disrupted the former pseudoautosomal arrangement of these genes. These results provide additional insight into the evolution of the sex chromosomes and into the nature of this interesting portion of the human genome.

Animals↗
PubMed1983

The target sizes of the in situ and solubilized forms of human placental steroid sulfatase as measured by radiation inactivation.

Whole microsomal membrane preparations and Triton X-100-solubilized human placental steroid sulfatase were subjected to radiation inactivation analysis using gamma rays from a 60Co irradiator in order to assess the size of the physiological form of the enzyme. The data indicate that the enzyme exists as a monomer of molecular weight 78600 in Triton-containing buffers and as a polymer of molecular weight 533000 within the microsomal membrane.

Female↗
PubMed1985

Iduronate sulfatase from human placenta.

The major enzyme component of iduronate sulfatase from human placenta was purified 30 000-fold by a five-step procedure. Sucrose gradient centrifugation of the native enzyme gave a molecular weight estimate of 80 000 +/- 10 000. Electrophoresis in sodium dodecyl sulfate of the enzyme reduced with mercaptoethanol showed a protein band of Mr 82 000. We suggest that the enzyme is composed of a single polypeptide chain of Mr 80 000-90 000.

Female↗
PubMed1989

Molecular heterogeneity of steroid sulfatase deficiency: a multicenter study on 57 unrelated patients, at DNA and protein levels.

Steroid sulfatase (STS) deficiency is the biochemical defect of X-linked ichthyosis (XLI), one of the most common X-linked disorders. We studied 57 European unrelated patients affected by STS deficiency. Twenty-eight patients were from Italy, 24 from the United Kingdom, 4 from The Netherlands, and 1 from Denmark. In two families XLI was associated with Kallmann syndrome (hypogonadotropic hypogonadism and anosmia). STS enzymatic activity was profoundly deficient in all cases. Direct DNA analysis, using cDNA and genomic probes from the STS gene and linked regions, demonstrated heterogeneity of the molecular defect. Forty-eight patients (84%) showed a deletion of the STS gene. In 44 cases the deletion also involved the STS flanking locus DXS237. In 1 patient a partial deletion of the STS gene was detected and in 9 patients no evidence of deletion was found. Locus DXS31 (probe M1A), previously mapped to Xp22.3-pter, was not deleted either in 24 patients with X-linked ichthyosis or in two families with X-linked ichthyosis associated with Kallmann syndrome. Consequently, the following loci order could be suggested: telomere--DXS31--(DXS237, STS)--Kallmann--centromere. Immunoblotting experiments, performed using anti-STS polyclonal antibodies, revealed the absence of cross-reacting material to STS in all cases tested, including 4 patients without evidence of deletions.

Arylsulfatases↗
PubMed1978

A substrate for direct measurement of L-iduronic acid 2-sulfate sulfatase.

Commercially available sodium heparinate has been sequentially treated with methanolic 0.06M hydrogen chloride and nitrous acid. The nondegraded material was separated by gel filtration from the nonsulfated and monosulfated disaccharides produced. The latter ones, obtained in 10% yield, have been used as a substrate for the direct measurement of the enzyme L-iduronic acid 2-sulfate sulfatase present in human plasma and fibroblast homogenates. Studies of the kinetics and pH optimum of the enzyme, by use of plasma of a patient with mucolipidosis II, indicated an apparent Km of 2.5mM and a pH optimum of 4.6--4.8. The levels of activity in normal plasma and plasma of a patient with Hunter's disease were found to be 20.4 +/- 1.22 units (mumol sulfate/24 h/g protein) and 3.25 +/- 0.35 units, respectively. In homogenates of cultured skin fibroblasts, the levels were 137.6 +/- 10.7 units for normal controls and 6.4 +/- 5.1 for patients with Hunter's disease. The plasma two obligated heterozygotes gave intermediate levels of activity, whereas the plasma of two possible heterozygotes gave either intermediate levels or entirely normal levels of activity.

Disaccharides↗
PubMed1998

Conversion of cysteine to formylglycine in eukaryotic sulfatases occurs by a common mechanism in the endoplasmic reticulum.

Sulfatases undergo an unusual protein modification leading to conversion of a specific cysteine residue into alpha-formylglycine. This conversion is essential for catalytic activity. In arylsulfatase A the alpha-formylglycine is generated inside the endoplasmic reticulum at a late stage of protein translocation. Using in vitro translation in the presence of transport-competent microsomes we found that arylsulfatase B is also modified in a similar way by the formylglycine-generating machinery. Modification depended on protein transport and on the correct position of the relevant cysteine. Arylsulfatase A and B did not compete for modification, as became apparent in co-expression experiments. This could argue for an association of the modification machinery with the protein translocation apparatus.

Alanine↗
PubMed1980

Expression of an X-linked gene from an inactive human X chromosome in mouse-human hybrid cells: further evidence for the noninactivation of the steroid sulfatase locus in man.

Somatic cell hybrid clones were derived from the fusion of hypoxanthine phosphoribosyltransferase (HPRT; EC 2.4.2.8)-deficient mouse cells and two different human fibroblast strains, each carrying an X chromosome-autosome translocation. One of these had an X/11 translocation [46,X,t(X;11)(p21;q13)] and the other had an X/19 translocation [46,X,t(X;19)(q22;q13)]. The structurally normal human X chromosome is the late-replicating (genetically inactive) chromosome in these two cell strains; the rearranged X chromosome is early replicating (genetically active). One primary hybrid clone carrying both the translocated X chromosome and the structurally normal X chromosome was isolated in hypoxanthine/aminopterin/thymidine medium from each of these two cell fusion experiments. These clones were then selected in medium containing 8-azaguanine to achieve the loss of the active human HPRT locus. Five subclones from the cell hybrid with the X/11 translocation failed to express two known human X-chromosome markers [glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) and phosphoglycerate kinase (PGK; EC 2.7.2.3)] but did express human microsomal steroid sulfatase (STS; sterol-sulfate sulfohydrolase, EC 3.1.6.2). Three of these were cytogenetically analyzed and found to contain a structurally normal human X chromosome but not the X/11 translocation. Two subclones were isolated in 8-azaguanine from the hybrid with the X/19 translocation. Cytogenetic analysis of these two clones showed the presence of a structurally normal human X chromosome; the X/19 translocation was not present. They did not express human G6PD, PGK, or HPRT but did express human STS. These results indicate that human STS is expressed from a locus on the inactive human X chromosome and support our earlier finding that the STS locus escapes X-inactivation in man.

Animals↗
PubMed1983

Immunological evidence for deficiency in an activator protein for sulfatide sulfatase in a variant form of metachromatic leukodystrophy.

Cultured skin fibroblasts from the patient described by Shapiro and co-workers as having a variant form of metachromatic leukodystrophy (MLD) [Shapiro, L.J., Aleck, K. A., Kaback, M.M., Itabashi, H., Desnick, R.J., Brand, N., Stephens, R.L., Fluharty, A.L. & Kihara, H. (1979) Pediatr. Res. 13, 1179-1181] were confirmed to have a partial deficiency (25-40% of controls) of arylsulfatase A activity in vitro and a severe inability to metabolize [14C]stearic acid-labeled sulfatide presented in the medium. When 150 micrograms of purified activator protein for GM1 ganglioside beta-galactosidase and sulfatide sulfatase was added in 4 ml of medium with the 14C-labeled sulfatide, correction of the sulfatide metabolism to the normal range was found. Monospecific antibodies to this activator protein were prepared in rabbits, and they were used to examine cultured cells for the presence of crossreacting material by Ouchterlony double immunodiffusion and rocket immunoelectrophoresis. Cell extracts from controls and from patients with GM1 gangliosidosis and MLD were found to have a single line of identity. By comparison to known concentrations of purified activator protein, cell extracts from controls were found to have 0.76 +/- 0.32 micrograms of activator protein (mean +/- 1 SD, n = 10) per mg of solubilized protein, whereas those from patients with type 1 GM1 gangliosidosis and late infantile MLD had 1.53 and 1.41 micrograms/mg, respectively. Cell extracts from the patient with a variant form of MLD had no visible precipitin line by Ouchterlony double immunodiffusion and only a diffuse nonspecific region of staining by rocket immunoelectrophoresis. These immunologic studies provide evidence for a deficiency in the activator protein required for normal catabolism of sulfatide in the cells from this patient and possibly provide a method for diagnosis of similar patients.

Cells, Cultured↗
PubMed1996

Feline mucopolysaccharidosis type VI. Characterization of recombinant N-acetylgalactosamine 4-sulfatase and identification of a mutation causing the disease.

Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive disease caused by a deficiency of N-acetylgalactosamine 4-sulfatase (4S) leading to the lysosomal accumulation and urinary excretion of dermatan sulfate. MPS VI has also been described in the Siamese cat. As an initial step toward enzyme replacement therapy with recombinant feline 4S (rf4S) in MPS VI cats, the feline 4S cDNA was isolated and expressed in CHO-KI cells and rf4S was immunopurified from the culture medium. SDS-polyacrylamide gel electrophoresis analysis showed that the precursor form of immunopurified rf4S was a 66-kDa polypeptide that underwent maturation to a 43-44-kDa polypeptide. Endocytosis of rf4S by cultured feline MPS VI myoblasts was predominantly mediated by a mannose 6-phosphate receptor and resulted in the correction of dermatan sulfate storage. The mutation causing feline MPS VI was identified as a base substitution at codon 476, altering a leucine codon to a proline (L476P). The L476P allele displayed no detectable 4S activity when expressed in CHO-KI cells and was observed only as a "precursor" polypeptide that was not secreted into the medium. Identification of the mutation has allowed the development of a rapid PCR-based screening method to genotype individuals within the cat colony.

Animals↗
PubMed1997

Feline mucopolysaccharidosis type VI: correction of glycosaminoglycan storage in myoblasts by retrovirus-mediated transfer of the feline N-acetylgalactosamine 4-sulfatase gene.

Mucopolysaccharidosis type VI (MPS VI) is an autosomal recessive lysosomal storage disorder characterised by the deficiency of N-acetylgalactosamine 4-sulfatase (4S). MPS VI has also been described in the cat. As an initial step toward muscle-mediated gene therapy in the MPS VI cat, we have made two retroviral constructs (pLf4S and pLf4SSN) that transduce the feline 4S gene. Both constructs were designed to express the feline 4S sequence from the viral long terminal repeat promoter. In addition pLf4SSN expressed the neomycin resistance gene from the SV40 early promoter. Amphotrophic virus was produced for each construct and used to transduce feline MPS VI myoblasts. Lf4S- and Lf4SSN-transduced MPS VI feline myoblasts demonstrated correction of glycosaminoglycan storage and contained 55-fold and 3.5-fold elevated levels of 4S activity when compared with normal feline myoblasts respectively. Recombinant feline 4S (rf4S) secreted by Lf4S-transduced MPS VI myoblasts was shown to be endocytosed by MPS VI feline cells via the mannose-6-phosphate receptor system, leading to metabolic correction. The results from this study demonstrate that muscle-mediated gene replacement therapy may be a viable method for achieving circulating levels of recombinant f4S (rf4S) in the MPS VI cat.

Animals↗