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At least 1,279 records · Page 71Linked to original sources
PubMed1991

Improved synthesis of [1-14C]acyl-sphingosine-galactose-3-sulfate (sulfatide) for diagnosis of metachromatic leukodystrophy: usefulness of radioscanning.

We report an improved method for the radiolabelling of [1-14C 00acyl-sphingosine-galactose-3-sulfate (sulfatide), requiring preparation of lysosulfatide (sulfogalactosyl-sphingosine) by alkaline hydrolysis of sulfatide and reacylation of the sphingosine amino group with a [1-14C]stearoyl chloride. We found that the yield of labeled sulfatide could be considerably increased using stringent chromatographic conditions for the preparation of lysosulfatide and strict anhydrous conditions for the formation of the acylchloride and its coupling to lysosulfatide. Radioscanning was used at different steps to check the purity of the labeled compounds. Radioscanning was also used to determine the formation of cerebroside when measuring cerebroside sulfate sulfatase activity and sulfatide metabolism in intact fibroblasts in controls and patients with metachromatic leukodystrophy. It could demonstrate and measure with accuracy the cerebroside sulfate storage characteristic of the disease.

Carbon Radioisotopes↗
PubMed1989

Structure and tissue-specific developmental expression of a sea urchin arylsulfatase gene.

Arylsulfatases are a group of enzymes that remove sulfate moieties from a diverse set of substrates including glycoproteins, steroids, and cerebrosides. We have isolated recombinant cDNA clones corresponding to an arylsulfatase (SpARS) message that encodes an abundant protein of pluteus larvae of the sea urchin Strongylocentrotus purpuratus. Although vertebrate arylsulfatases have broad tissue distributions, in situ hybridization with a probe for SpARS shows that the sea urchin message accumulates in the embryo only in the single cell type of aboral ectoderm and its precursors. The message is first detectable by RNase protection assays around hatching blastula stage and accumulates through pluteus larva stage. The open reading frame of cDNA clones is 1701 nt long and encodes a deduced protein with a predicted molecular mass of 61 kDa. Analysis of corresponding genomic DNA clones reveals that the pre-mRNA contains six exons. Consistent with the fact that arylsulfatase enzyme activity is extracellular, this polypeptide has a hydrophobic leader sequence and three potential glycosylation sites. Furthermore, hybridization in situ shows that in blastulae arylsulfatase message is preferentially concentrated around nuclei at the basal sides of cells. The S. purpuratus sequence is very similar to that recently reported for the same enzyme from Hemicentrotus pulcherrimus and 30% of the amino acid residues are also identical to those of both human arylsulfatase C (steroid sulfatase) and arylsulfatase A. Sequence relationships among these four mRNAs suggest that, assuming equal rates of evolution, the duplication separating the human genes occurred at about the time of separation of the echinoderm and vertebrate lineages.

Age Factors↗
PubMed1996

Hyperactivity of cathepsin B and other lysosomal enzymes in fibroblasts exposed to azithromycin, a dicationic macrolide antibiotic with exceptional tissue accumulation.

Azithromycin accumulates in lysosomes where it causes phospholipidosis. In homogenates prepared by sonication of fibroblasts incubated for 3 days with azithromycin (66 microM), the activities of sulfatase A, phospholipase A1, N-acetyl-beta-hexosaminidase and cathepsin B increased from 180 to 330%, but not those of 3 non-lysosomal enzymes. The level of cathepsin B mRNA was unaffected. The hyperactivity induced by azithromycin is non-reversible upon drug withdrawal, prevented by coincubation with cycloheximide, affects the Vmax but not the Km, and is not reproduced with gentamicin, another drug also causing lysosomal phospholipidosis. The data therefore suggest that azithromycin increases the level of lysosomal enzymes by a mechanism distinct from the stimulation of gene expression but requiring protein synthesis, and is not in direct relation to the lysosomal phospholipidosis.

Animals↗
PubMed1992

Proteolytic processing of human lysosomal arylsulfatase A.

Arylsulfatase A purified from human placenta contained an unreported component with an apparent molecular mass of 7 kDa in addition to the two known components with apparent molecular masses of 58 and 50 kDa. The detailed relationship between the 58 kDa component and the 50 kDa component is as yet unknown. The present study was undertaken to define the structure of the subunits of the sulfatase. The N-terminal sequence of the 50 kDa component was identical to that of the 58 kDa component. Furthermore, the peptide maps of the 50 kDa component, which was separately digested with trypsin and Achromobacter proteinase I, were quite similar to those of the 58 kDa one. Through sequence analysis of the incompatible peaks in the peptide maps, the 50 kDa component was found to lack a sequence from Val-445 to the C-terminus. On the other hand, the N-terminal sequence of the 7 kDa component began with Ala-448, though there was a minor sequence commencing with Thr-449. These observations suggest that the 50 and 7 kDa components were produced by limited proteolysis near the C-terminus of the 58 kDa component. Through analysis using unreducing SDS-PAGE, the 58 and the 7 kDa components were found to be linked by disulphide bonds. Arylsulfatase A purified from human liver was also composed of the same subunits as the placental one. This finding suggests that human arylsulfatase A undergoes similar proteolytic processing regardless of the tissue involved.

Amidohydrolases↗
PubMed1992

Cloning and sequencing of Pseudomonas genes determining sodium dodecyl sulfate biodegradation.

The nucleotide sequences of two genes involved in sodium dodecyl sulfate (SDS) degradation, by Pseudomonas, have been determined. One of these, sdsA, codes for an alkyl sulfatase (58,957 Da) and has similarity (31.8% identity over a 201-amino acid stretch) to the N terminus of a predicted protein of unknown function from Mycobacterium tuberculosis. The other gene, sdsB, codes for a positive activator protein (33,600 Da) that has extensive similarity with the lysR family of helix-turn-helix DNA-binding activator proteins.

Amino Acid Sequence↗
PubMed1991

Linkage analysis in X-linked ocular albinism.

We studied the linkage of X-linked Nettleship-Falls ocular albinism (OA1) to Xp22.1-Xp22.3 RFLPs at 12 loci in five families, including one in which OA1 cosegregates with a deletion of steroid sulfatase (STS). We found evidence for tight linkage of OA1 to the Xp22.3 loci DXS143, STS, and DXS452. DXS452, a newly described polymorphism detected by the probe E25B1.8, is part of the sequence family "DXS278" (pCRI-S232), but represents a single genetic locus. Every female in this study was heterozygous for the DXS452 RFLP. Thus, this marker will be extremely useful for family studies and genetic counseling. Analysis of individual recombinations suggests that OA1 maps between DXS143 and DXS85. Multipoint linkage analysis was consistent with this localization but was not statistically significant. These data suggest that OA1 lies proximal to the deletion in a previously described family with OA1 and STS deletion, but maps within the Xp22.3-Xp22.2 region.

Albinism, Ocular↗
PubMed1992

Detection of point mutations and a gross deletion in six Hunter syndrome patients.

We have used screening with the polymerase chain reaction and chemical mismatch detection of amplified cDNA to detect and characterize deletions and point mutations in six Hunter Syndrome patients. A high degree of mutational heterogeneity was observed. The first patient is completely deleted for the gene coding for alpha-L-iduronate sulfate sulfatase, while the second has a point mutation that creates a stop codon. The third patient shows a point mutation that creates a novel splice site that is preferentially utilized and results in partial loss of one exon in the RNA. Patients 4, 5, and 6 have point mutations resulting in single amino acid substitutions. Four of the six single-base changes observed in this study were examples of transitions of the highly mutable dinucleotide CpG to TpG. This study has demonstrated a procedure capable of detecting all types of mutation that affect the function of the IDS protein and should enable direct carrier and prenatal diagnosis for Hunter syndrome families.

Amino Acid Sequence↗
PubMed1992

Cell-to-cell contact between normal fibroblasts and lymphoblasts deficient in lysosomal enzymes.

Human lymphoblasts deficient in iduronate sulfatase or in alpha-N-acetylglucosaminidase acquire discrete levels of enzyme activity after co-culture with human normal skin fibroblasts. This occurs by direct cell-to-cell contact and not by uptake of secreted fibroblast enzyme. The process is dependent on time and on the number of fibroblasts used. Electron-microscopic examination of the co-culture of the two cell types reveals extensive region of intimate contact. Fibroblastic projections appear frequently in close apposition with lymphoblast invaginations; a diffuse micropinocytotic activity is evident only in fibroblastic cells.

Acetylglucosaminidase↗
PubMed1993

Generation of estradiol within the pregnant guinea pig uterine compartment with special reference to the myometrium.

Between about 50 and 58 days of gestation, the guinea pig chorion becomes attached in its entirety to the uterine wall, suggesting a facilitation of transfer of agents such as steroids between these tissues. At a time between 59 and 64 days, relaxation of the pubic symphysis starts, and anywhere from 5 to 8 days after that event delivery takes place. The present in vitro study was undertaken to evaluate estrone sulfate as a substrate for local production of estradiol, via the action of estrogen sulfatase and 17-hydroxysteroid dehydrogenase, in chorion, endometrium and myometrium taken at four distinct stages of gestation, as follows: 50 days, representing pre-chorion attachment to the uterus (stage 50); 1 or 2 days before pubic symphysis relaxation (minus 1 day, or -1 day); 1 day following relaxation (+1 day); and 1-2 days before delivery (late, or L). At these same stages, the metabolite patterns formed from estradiol were evaluated for endometrium and myometrium. Each of the tissues behaved somewhat differently. Overall hydrolysis of estrone sulfate by endometrium and myometrium exceeded that by chorion. Generation of free steroid from estrone sulfate increased 3-fold in chorion between stages 50 and -1 and during this period estradiol production from estrone sulfate increased 9-fold and continued to rise until delivery. Cytosolic estrogen sulfotransferase activity of chorion decreased 7-fold between stages 50 and -1. This suggested a tissue environment geared to producing potentially active estradiol. However, myometrium converted very little estrone into estradiol until just before delivery despite the facile formation of estrone from estradiol at stages -1, +1 and L. The control of estrogen metabolism by interaction of tissues in the uterus and by some form of enzyme regulation in these tissues suggests a possible role for locally produced estrogen in the stages leading up to parturition.

17-Hydroxysteroid Dehydrogenases↗
PubMed1994

Inhibition of human placental sterylsulfatase by synthetic analogs of estrone sulfate.

Synthetic analogs of estrone sulfate which carry differently substituted sulfonyl groups at position 3 of an invariable 3-desoxyestrone (dE1) moiety were tested in vitro as inhibitors of the human placental sterylsulfatase. Using both placental microsomes and a highly purified placental sterylsulfatase preparation as the enzyme source and dehydroepiandrosterone [35S]sulfate or estrone [35S]sulfate as the substrate, the following order of inhibitory potencies was observed: dE1-3-sulfonylchloride > dE1-3-sulfonylfluoride approximately dE1-3-sulfonate > dE1-3-sulfonamide approximately 3-methylsulfonyl-dE1. According to the results, the association of enzyme and inhibitor appears to be favored by an electronegative substituent at the sulfur atom (-C1, -F, -O-). Since, however, even the most potent synthetic inhibitor was bound by the enzyme with significantly lower affinity than was the natural substrate estrone sulfate, an oxygen function between the aromatic ring and the sulfur atom may be necessary for high affinity binding towards the sterylsulfatase. In addition to its fast reversible association with the enzyme, dE1-3-sulfonylchloride further affected the sulfatase activity in a time-dependent manner. This latter inhibitory activity which may be due to a covalent modification (alkylation) of sterylsulfatase by the analog was partially prevented in the presence of substrate.

Arylsulfatases↗
PubMed2003

Gender differences in the levels of bisphenol A metabolites in urine.

The metabolism of bisphenol A (BPA), a suspected endocrine disruptor, should be considered for monitoring human exposure to BPA, because the conjugation with beta-D-glucuronide and sulfate reduces the estrogenic activity. In this study, BPA levels in 30 healthy Koreans (men, N=15, 42.6+/-2.4 years; women, N=15, 43.0+/-2.7 years) were analyzed from urine treated with/without beta-glucuronidase and/or sulfatase by an RP-HPLC with fluorescence detection. The total BPA concentrations including free BPA and the urinary conjugates were similar in men and women (2.82+/-0.73 and 2.76+/-0.54 ng ml(-1), respectively), but gender differences were found in the levels of urinary BPA conjugates. Men had significantly higher levels of BPA-glucuronide (2.34+/-0.85 ng ml(-1)) than women (1.00+/-0.34 ng ml(-1)), whereas women had higher levels of BPA-sulfate (1.20+/-0.32 ng ml(-1)) than men (0.49+/-0.27 ng ml(-1)).

Adult↗
PubMed2004

Calcium binding to biliary mucins is dependent on sodium ion concentration: relevance to cystic fibrosis.

Because hypersecretion of gallbladder (GB) mucus occurs in gallstone formation and because binding of Ca(2+) to biliary lipids only accounts for 50% of the total Ca(2+) in GB bile, we investigated the binding of Ca(2+) to human biliary mucin. Biliary mucin was purified from GB bile and binding to Ca(2+) studied. Scatchard plot analysis suggested two binding sites. Removal of sialic acid by neuraminidase resulted in 10% reduction of Ca(2+) binding, whereas, sulfatase treatment reduced Ca(2+) binding by 30%. Using a hypotonic NaCl solution, Ca(2+) binding to mucin increased curvilinearly with mucin concentration. However, binding decreased with increasing ionic strength of the NaCl solution. We conclude that binding of Ca(2+) to mucin is effected mainly through sulfate. Binding to Ca(2+) can be displaced by Na(+). Ca(2+) binding to mucins is enhanced in the setting of low Na(+) concentrations. This phenomenon has pathophysiologic implications for the formation of thick mucus in cystic fibrosis epithelia.

Bile↗
PubMed2003

Intracrine mechanism of estrogen synthesis in breast cancer.

It has been demonstrated that biologically active estrogens are locally produced from circulating inactive steroids in an intracrine mechanism in the breast carcinoma. The in situ production of estrogens is considered to play an important role in the proliferation of breast cancer cells, especially in the postmenopausal women. Therefore, the total blockade of this pathway may lead to an improvement in the prognosis in breast cancer patients due to the inhibition of estrogenic actions. In this review, we describe the recent studies of enzymes related to intracrine mechanism of estrogen synthesis, including aromatase, steroid sulfatase (STS), and 17beta-hydroxysteroid dehydrogenase, in human breast carcinoma tissues, and discuss the biological significance of local production of estrogens in human breast cancer.

17-Hydroxysteroid Dehydrogenases↗
PubMed2005

Metabolism of sulfolipids in isolated renal tubules from rat.

Proximal-rich tubules were prepared from rat kidneys by using collagenase treatment. The isolated rat renal tubules were compared with the intact kidney on the following characteristics. (1) Composition of the sulfoglycolipid. (2) Sulfoglycolipid metabolism based on incorporation of [35S]sulfate or some properties of sulfoglycolipid metabolism, including the activities of anabolic and catabolic enzymes. The results indicated following characteristics of the isolated renal tubules in comparison to the kidney in vivo. (1) The sulfoglycolipid compositions are qualitatively similar, except that the content of glucosyl sulfatide, Gg3Cer II3-sulfate, and GM4 was slightly higher in the isolated tubules. (2) The apparent half-lives (15-55 min) of sulfoglycolipids in the isolated tubules could indicate the existence of a rapid turnover pool of these lipids. (3) The sulfotransferase and sulfatase activities related to sulfoamphiphiles in the renal tubule were similar to those reported for the whole kidney. Based on the above criteria, we conclude that the isolated rat renal tubule should be a useful metabolic system for clarification of the short-term physiological events, up to 90 min, of proximal tubular sulfoglycolipids. By using the present system, we showed that biosynthesis of the renal total sulfoglycolipid was significantly elevated in rats deprived of water for 24 h.

Animals↗
PubMed2006

Deletion of distal promoter of VCXA in a patient with X-linked ichthyosis associated with borderline mental retardation.

BACKGROUND: X-linked ichthyosis (XLI) is caused by deficiency of steroid sulfatase (STS) activity. About 90% XLI patients have large deletions involving the entire STS gene and flanking regions. Recently, VCXA, which is located approximately 0.7Mb telomeric to the STS gene, was reported as a candidate gene for mental retardation (MR) in patients with XLI. OBJECTIVE: To delineate the X-chromosomal deletion of a XLI patient with borderline mental retardation. METHODS: We carried out FISH analysis to show that the whole STS gene is deleted, and PCR analysis for fine-scale deletion mapping. RESULTS: The deleted segment is approximately 1.6Mb in size, and includes the entire STS and VCXB1 genes. VCXA itself is intact, but its promoter is deleted. CONCLUSION: A deletion that includes the VCXA promoter is associated with borderline mental retardation in a patient with XLI.

Adult↗
PubMed2004

Enzyme replacement therapy in mucopolysaccharidosis VI (Maroteaux-Lamy syndrome).

OBJECTIVES: To evaluate the safety and efficacy of weekly treatment with human recombinant N-acetylgalactosamine 4-sulfatase (rhASB) in humans with mucopolysaccharidosis type VI (MPS VI). STUDY DESIGN: An ongoing Phase I/II, randomized, two-dose, double-blind study. Patients were randomized to weekly infusions of either high (1.0 mg/kg) or low (0.2 mg/kg) doses of rhASB. Six patients (3 male, 3 female; age 7-16 years) completed at least 24 weeks of treatment, five of this group have completed at least 48 weeks. RESULTS: No drug-related serious adverse events, significant laboratory abnormalities, or allergic reactions were observed in the study. The high-dose group experienced a more rapid and larger relative reduction in urinary glycosaminoglycan that was sustained through week 48. Improvements in the 6-minute walk test were observed in all patients with dramatic gains in those walking <100 meters at baseline. Shoulder range of motion improved in all patients at week 48 and joint pain improved in patients with significant pain at baseline. CONCLUSIONS: rhASB treatment was well-tolerated and reduced lysosomal storage as evidenced by a dose-dependent reduction in urinary glycosaminoglycan. Clinical responses were present in all patients, but the largest gains occurred in patients with advanced disease receiving high-dose rhASB.

Adolescent↗
PubMed2005

Estrogen actions and in situ synthesis in human vascular smooth muscle cells and their correlation with atherosclerosis.

Various epidemiological studies have demonstrated a relatively low incidence of cardiovascular events in premenopausal women and its marked increment after menopause. In addition, estrogens have been postulated to exert direct anti-atherogenic effects via binding to estrogen receptors (ERs) in vascular smooth muscle cells (VSMCs). However, not all postmenopausal women develop atherosclerosis despite decreased levels of serum estrogen. Therefore, it is considered important to examine the status of estrogen metabolism in situ and of ER expression in the human cardiovascular system. Estrone sulfate (E1S) is a major circulating plasma estrogen that is converted into the biologically active estrogen, estrone (E1) by steroid sulfatase (STS). E1 is also sulfated and reverted into E1S by estrogen sulfotransferase (EST). These two enzymes have recently been shown to play important roles in the in situ estrogen actions of estrogen-dependent human tissues. STS and EST, however, have not been studied in detail in the human vascular system associated with atherosclerotic changes. Therefore, the relative abundance of STS- and EST-immunoreactive protein and mRNA expression in human aorta were evaluated using immunohistochemistry and reverse transcription followed by quantitative polymerase chain reaction in addition to enzyme activity. Furthermore, we evaluated the relative abundance of messenger RNA (mRNA) of both ER subtypes (ERalpha and ERbeta) in the human aorta using reverse transcription followed by quantitative polymerase chain reaction (RT-qPCR), as well as the immunoreactivity of both ERs in VSMCs of human atherosclerotic lesions. STS expression levels were found to be significantly higher in the VSMCs obtained from female aortas with mild atherosclerotic changes than in those with severe atherosclerotic changes and in male aortas regardless of atherosclerotic changes. EST expression levels in the VSMCs of these aortas, however, were significantly higher in female aortas with severe atherosclerotic changes and in male aortas than in female aortas with mild atherosclerotic changes. In addition, the number of ERalpha and/or ERbeta double positive cells in the neointima was higher in female aortas with a mild degree of atherosclerosis than in female aortas with severe atherosclerosis. They indicate that both abundance of these estrogen-metabolizing enzymes in female aorta and relative levels of ER in VSMCs of female neointima may be associated with the status of atherosclerotic changes.

Aorta↗
PubMed2006

Down-regulation of messenger ribonucleic acid encoding an importer of sulfoconjugated steroids during human chorionic gonadotropin-induced follicular luteinization in vivo.

Members of the organic anion transporting polypeptide (SLCO/OATP) superfamily are capable of importing anionic compounds across the lipid bilayer in a sodium-independent manner. Member 2B1 has been shown to transport few substrates, two of which are dihydroepiandrosterone-3-sulfate (DHEA-S) and estrone-3-sulfate. Steroid sulfatase (STS) catalyses the hydrolysis of these steroids into their unconjugated counterparts. The objective of this study was to investigate the regulation of SLCO2B1 and STS mRNAs during human chorionic gonadotropin (hCG)-induced ovulation/luteinization. The equine SLCO2B1 cDNA was cloned and shown to encode a 709-amino acid protein (OATP2B1) that is highly conserved when compared to mammalian orthologs. RT-PCR/Southern blot analyses were performed to study the regulation of SLCO2B1 and STS transcripts in equine preovulatory follicles isolated between 0 and 39h after hCG treatment. Results showed high levels of SLCO2B1 mRNA expression before hCG, with a marked decrease observed in follicles obtained 24-39h post-hCG (P<0.05). Analyses of isolated granulosa and theca interna cells identified high mRNA expression in both cell types prior to hCG treatment, with granulosa cells showing a more rapid SLCO2B1 mRNA down-regulation. No significant change in STS mRNA was observed in intact follicle walls. However, when both cell types were isolated, a significant decrease in STS mRNA was observed in granulosa cells 24-39h post-hCG. Collectively, these results demonstrate that the hCG-dependent induction of follicular luteinization is accompanied by the down-regulation of SLCO2B1 and STS transcripts. Considering that OATP2B1 can import sulfoconjugated DHEA and estrogens, and that STS can remove the sulfonate moiety from these steroids, their down-regulation in luteinizing preovulatory follicles may provide an additional biochemical basis for the decrease in ovarian 17beta-estradiol biosynthesis after the LH surge.

Amino Acid Sequence↗