Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Sulfates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8Linked to original sources
PubMedDate not supplied

Sulfation of acetaminophen and acetaminophen-induced alterations in sulfate and 3'-phosphoadenosine 5'-phosphosulfate homeostasis in rats with deficient dietary intake of sulfur.

Sulfation of drugs depends on the availability of 3'-phosphoadenosine 5'-phosphosulfate (PAPS), which requires inorganic sulfate for its synthesis. Therefore, decreased alimentary intake of inorganic sulfate or its precursor, cysteine, may compromise sulfation of xenobiotics. To test this hypothesis, separate groups of rats were maintained for 5 days on synthetic diets, which lacked sulfate, or cysteine, or both sulfate and cysteine. These dietary restrictions did not cause growth retardation or depletion of glutathione in liver. Under anesthesia, the animals were injected with acetaminophen (0.5 mmol/kg, i.v.) and elimination of acetaminophen from blood and excretion of acetaminophen metabolites in urine and bile was simultaneously quantified. Deficient intake of inorganic sulfate or cysteine alone did not significantly change elimination and biotransformation of acetaminophen. Combined nutritional deficiency of sulfate and cysteine, however, resulted in a 40% reduction in the excretion of acetaminophen-sulfate, quantitatively the most significant metabolite. Concomitantly, these animals eliminated acetaminophen from blood at a slower rate and converted more acetaminophen to its toxic intermediate, as indicated by increased excretion of acetaminophen-thioether conjugates. Serum and tissue sulfate concentrations were decreased to significantly lower levels in rats on sulfate and cysteine deficient diets, than in rats with a sufficient sulfur supply. Thus, reduced sulfation is apparently caused by diminished availability of inorganic sulfate for PAPS synthesis, even though hepatic and renal PAPS levels were not depleted more by acetaminophen in rats with deficient dietary supply of sulfate and cysteine than in rats with adequate sulfur intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetaminophen↗
PubMed1992

Chondroitin sulfate proteoglycan and heparan sulfate proteoglycan production by cultured pigeon peritoneal macrophages.

Proteoglycan production was examined in cultures of thioglycollate-elicited peritoneal macrophages obtained from White Carneau and Show Racer pigeons. Following a 24-h incubation in the presence of [35S]sulfate and [3H]serine, total production and distribution of 35S-labeled proteoglycan into media (60-65%), pericellular (21-27%), and intracellular (13-14%) compartments was similar in White Carneau and Show Racer macrophage cultures. Media proteoglycans consisted of high-molecular-weight chondroitin sulfate proteoglycan, low-molecular-weight chondroitin sulfate proteoglycan, and heparan sulfate proteoglycan. High-molecular-weight chondroitin sulfate proteoglycan was predominantly 6-sulfated (80%) and contained a core protein larger than 200 kd, whereas low-molecular-weight chondroitin sulfate proteoglycan was 4-sulfated and contained a 28-kd core protein. Pericellular proteoglycan was similar in size to low-molecular-weight proteoglycan and consisted of a predominantly 6-sulfated (75%) chondroitin sulfate proteoglycan and heparan sulfate proteoglycan. Intracellular 35S-labeled chondroitin sulfate and heparan sulfate were smaller than media and pericellular proteoglycans, suggestive of intracellular degradative processing.

Animals↗
PubMed1987

Ca2+-mediated association of human serum amyloid P component with heparan sulfate and dermatan sulfate.

The serum amyloid P component (SAP) is a precursor glycoprotein of amyloid P component found in all types of amyloid deposits. The binding of human SAP to heparan sulfate and dermatan sulfate was studied using Sepharose-immobilized SAP. The apparent dissociation constants of heparan sulfate and dermatan sulfate for immobilized-SAP were estimated to be approximately 2 X 10(-7) M in the presence of 2 mM CaCl2 at neutral pH and physiological ionic strength. Both the binding affinity of SAP for these glycosaminoglycans and the numbers of binding sites of SAP depended on calcium concentration. Cadmium partially substituted for calcium as an activator of glycosaminoglycan binding to SAP. No binding occurs in the absence of added metal, or in the presence of barium, copper, magnesium, manganese, and strontium. The calcium-dependent binding of [3H]heparan sulfate and [3H]dermatan sulfate to SAP was strongly inhibited by heparan sulfate, heparin, and dermatan sulfate. Chondroitin 6-sulfate was a moderate inhibitor, whereas hyaluronic acid, chondroitin 4-sulfate, and keratan sulfate were not potent inhibitors. The calcium-dependent binding of amyloid P component to heparan sulfate and/or dermatan sulfate may be a cause of the coexistence of the particular glycoprotein and these glycosaminoglycans in amyloid tissues.

Animals↗
PubMed1996

Enzymatic sulfation of galactose residue of keratan sulfate by chondroitin 6-sulfotransferase.

We have previously found that the purified chondroitin 6-sulfotransferase (C6ST), which transfers sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to position 6 of N-acetylgalactosamine in chondroitin, catalyzed the sulfation of keratan sulfate, and that both the C6ST activity and the keratan sulfate sulfotransferase (KSST) activity were expressed in COS-7 cells when C6ST cDNA was transfected. In this report we describe some properties of the KSST activity contained in the purified C6ST, and characterize the sulfated products formed from keratan sulfate and partially desulfated keratan sulfate. Optimal pH, requirement for cationic activators, and Km value for PAPS of the KSST activity were very similar to those of the C6ST activity. 35S-Labeled glycosaminoglycans formed from keratan sulfate and partially desulfated keratan sulfate were N-deacetylated by treatment with hydrazine/hydrazine sulfate and then cleaved with HNO2 at pH 4, and the resulting products were reduced with NaB3H4. Analysis of the degradation products with paper chromatography and high performance liquid chromatography provided evidence that C6ST transferred sulfate to position 6 of galactose residue which was glycosidically linked to N-acetylglucosamine 6-sulfate residue or to N-acetylglucosamine residue. Northern blot analysis using poly (A)+ RNA from 12-d-old chick embryos indicated that the message of C6ST was expressed not only in the cartilage but also in the cornea in which keratan sulfate is actively synthesized.

Animals↗
PubMed2004

Structural analysis of CYP2C9 and CYP2C5 and an evaluation of commonly used molecular modeling techniques.

This work had two separate aims: to evaluate different modeling techniques and to make a detailed structural characterization of CYP2C9. To achieve these goals, the consensus principal component analysis (CPCA) technique and distance measurements were used to explore available crystal structures, newly built homology models, and repeated molecular dynamics simulations. The CPCA was based on molecular interaction fields focused on the active site regions of the proteins and include detailed amino acid analysis. The comparison of the CYP2C9 and CYP2C5 crystal structures revealed differences in the flexible regions such as the B-C and F-G loop and the N and C termini. Cross homology models of CYP2C9 and CYP2C5, using their respective crystal structures as templates, indicated that such models were more similar to their templates than to their target proteins. Inclusion of multiple templates slightly improved the similarity to the crystal target in some cases and could be recommended even though it requires a careful manual alignment process. The application of molecular dynamics simulations to highly flexible proteins such as cytochromes P450 is also explored and the information is extracted by the CPCA. Advantages and drawbacks are presented for the different modeling techniques. Despite the varying modeling success, the models give insight and understanding by the mutual forming and discarding of hypotheses. This is a dynamic process since the crystal structures are improving with time and, therefore, the answers to the models are also changing accordingly.

Aryl Hydrocarbon Hydroxylases↗
PubMed1989

Undersulfated heparan sulfate in a Chinese hamster ovary cell mutant defective in heparan sulfate N-sulfotransferase.

Heparan sulfate N-sulfotransferase catalyzes the transfer of sulfate groups from adenosine 3'-phosphate, 5'-phosphosulfate to the free amino groups of glucosamine residues in heparan sulfate. We have identified a Chinese hamster ovary cell mutant, designated pgsE-606, which is 3-5-fold defective in N-sulfotransferase activity. The residual enzyme activity is indistinguishable from the wild-type enzyme with respect to Km values for adenosine 3'-phosphate,5'-phosphosulfate and N-desulfoheparin, pH dependence, Arrhenius activation energy, and thermal lability. The mutation is recessive, and mixing experiments indicate that the mutant does not produce soluble antagonists of N-sulfotransferase. Inspection of the heparan sulfate chains from the mutant showed that the extent of N-sulfation is reduced about 2-3-fold. The addition of sulfate to hydroxyl groups on the chain is reduced to a similar extent, suggesting that N-sulfation and O-sulfation are normally coupled. Nitrous acid fragmentation of the chains showed that N-sulfated glucosamine residues are spaced much less frequently than in heparan sulfate from wild-type cells. The close correlation of enzyme activity to the number and position of N-sulfate groups indicates that N-sulfotransferase plays a pivotal role in determining the extent of sulfation of heparan sulfate.

Animals↗
PubMed1994

Core protein structure and sequence determine the site and presence of heparan sulfate and chondroitin sulfate on syndecan-1.

Most proteoglycans bear either chondroitin sulfate or heparan sulfate chains linked to serine residues at Ser-Gly attachment sites on the core protein. However, only a fraction of proteins with Ser-Gly sites exhibit glycosaminoglycan chains. A variable proportion of these sites may be glycanated, and an unknown mechanism distinguishes whether these sites are for chondroitin sulfate or heparan sulfate. To evaluate the core protein features that determine whether and where chondroitin sulfate or heparan sulfate will be linked, we have studied mouse syndecan-1, a transmembrane proteoglycan that is invariably glycanated and can contain both chondroitin sulfate and heparan sulfate chains. The extracellular domain of the syndecan-1 core protein contains five Ser-Gly sites, three clustered near its N terminus and two adjacent to the transmembrane domain near its C terminus. We have established the distribution of glycosaminoglycans on these attachment clusters. In contrast to the C-terminal cluster, the N-terminal cluster was always glycanated, suggesting that this domain of the core protein contains sequences responsible for the invariable attachment of glycosaminoglycan chains. Solely chondroitin sulfate was found on the C-terminal cluster. This cluster contains the sequences EGSGE and ETSGE, both estimated to be on the protein surface in a hydrophilic environment. Heparan sulfate was found solely on the N-terminal cluster, which also bears some chondroitin sulfate. This cluster contains the sequences FSGSGTG and DGSGD, the former estimated to be in a hydrophobic pocket and the latter, similar to the sequence on the C-terminal cluster, in an exposed hydrophilic region. This glycosaminoglycan distribution was identical on mouse syndecan-1 produced by either mouse epithelial (NMuMG) or hamster mesenchymal (CHO) cells, suggesting that site-specific attachment of glycosaminoglycans is independent of cell type. These results implicate a cellular mechanism that distinguishes among the potential sites and attaches the correct glycosaminoglycan type unambiguously. Thus, structural elements of the core protein other than the Ser-Gly attachment sites determine if a site will be glycanated and, if so, whether with chondroitin sulfate or heparan sulfate.

Amino Acid Sequence↗
PubMed1983

Serum concentration and renal excretion by normal adults of inorganic sulfate after acetaminophen, ascorbic acid, or sodium sulfate.

Depletion of endogenous inorganic sulfate can have pronounced effects on the elimination kinetics and metabolic fate of phenolic drugs. Our purpose was to determine the effects of acetaminophen (which is partly metabolized to acetaminophen sulfate), ascorbic acid (subject to more limited sulfation than acetaminophen), and sodium sulfate (useful for sulfate repletion by the oral route) on the serum concentration and renal excretion of inorganic sulfate in healthy adults. Six men and two women, 26 to 35 yr old, were studied on four occasions that were at least 4 days apart. They received no medication, 1.5 gm acetaminophen, 6 gm ascorbic acid, or 9 gm sodium sulfate decahydrate orally, in aqueous solution. A blood sample was obtained 2 hr later and urine was collected from 1 to 3 hr. Serum inorganic sulfate concentrations (mean +/- SD), 0.410 +/- 0.043 mM in the control period, were decreased after acetaminophen (0.311 +/- 0.043 mM, P less than 0.001), increased after sodium sulfate (0.513 +/- 0.055 mM, P less than 0.001), and apparently unchanged after ascorbic acid (0.417 +/- 0.059 mM). The urinary excretion of inorganic sulfate was decreased after acetaminophen and increased after sodium sulfate. The renal clearance of endogenous creatinine was not affected by any of the treatments. The renal tubular reabsorption of inorganic sulfate is capacity limited, as evidenced by the decrease of the reabsorbed fraction with increasing glomerular filtration rate of the anion (r = -0.54, P less than 0.005). This saturable reabsorption facilitates sulfate homeostasis.

Acetaminophen↗
PubMed1996

An animal cell mutant defective in heparan sulfate hexuronic acid 2-O-sulfation.

The interaction of heparan sulfate with protein ligands depends on unique oligosaccharide sequences containing iduronic acid (IdUA), N-sulfated glucosamine residues, and O-sulfated sugars. To study the role of O-sulfation in greater detail, we isolated a Chinese hamster ovary cell mutant defective in 2-O-sulfation of iduronic acid. The mutant, pgsF-17, was identified by a colony blotting assay in which colonies of mutagen-treated cells were replica plated to two disks of polyester cloth. One disk was blotted with 125I-labeled basic fibroblast growth factor (bFGF) to measure binding to cell surface proteoglycans. The other disk was incubated with 35SO4 to measure proteoglycan biosynthesis. Autoradiography revealed a colony that did not bind 125I-bFGF, but incorporated 35SO4 normally (mutant pgsF-17). Complete deaminative cleavage of heparan sulfate revealed that material from pgsF-17 lacked IdUA(2OSO3)-GlcNSO3 and IdUA(2OSO3)-GlcNSO3(6OSO3), but contained a higher proportion of glucuronic acid GlcUA-GlcNSO3(6OSO3) and IdUA-GlcNSO3(6OSO3). Assay of the 2-O-sulfotransferase that acts on IdUA residues showed that mutant 17 lacked enzyme activity. Interestingly, the alteration resulted in accumulation of GlcNSO3 groups, suggesting that under normal conditions 2-O-sulfation decreases GlcNAc N-deacetylation/N-sulfation, and that the reactions occur simultaneously. The formation of IdUA and 6-O-sulfated glucosaminyl residues appears to be independent of 2-O-sulfation. pgsF-17 also lacks 2-O-sulfated GlcUA residues, suggesting that the same enzyme is responsible for 2-O-sulfation of IdUA and GlcUA residues. Mutant 17 provides a useful tool for studying the regulation of heparan sulfate biosynthesis and the relationship of heparan sulfate fine structure to its biological function.

Animals↗
PubMed2000

Oxygen-dependent growth of the sulfate-reducing bacterium Desulfovibrio oxyclinae in coculture with Marinobacter sp. Strain MB in an aerated sulfate-depleted chemostat.

A chemostat coculture of the sulfate-reducing bacterium Desulfovibrio oxyclinae and the facultatively aerobic heterotroph Marinobacter sp. strain MB was grown for 1 week under anaerobic conditions at a dilution rate of 0.05 h(-1). It was then exposed to an oxygen flux of 223 micromol min(-1) by gassing the growth vessel with 5% O(2). Sulfate reduction persisted under these conditions, though the amount of sulfate reduced decreased by 45% compared to the amount reduced during the initial anaerobic mode. After 1 week of growth under these conditions, sulfate was excluded from the incoming medium. The sulfate concentration in the growth vessel decreased exponentially from 4.1 mM to 2.5 microM. The coculture consumed oxygen effectively, and no residual oxygen was detected during either growth mode in which oxygen was supplied. The proportion of D. oxyclinae cells in the coculture as determined by in situ hybridization decreased from 86% under anaerobic conditions to 70% in the microaerobic sulfate-reducing mode and 34% in the microaerobic sulfate-depleted mode. As determined by the most-probable-number (MPN) method, the numbers of viable D. oxyclinae cells during the two microaerobic growth modes decreased compared to the numbers during the anaerobic growth mode. However, there was no significant difference between the MPN values for the two modes when oxygen was supplied. The patterns of consumption of electron donors and acceptors suggested that when oxygen was supplied in the absence of sulfate and thiosulfate, D. oxyclinae performed incomplete aerobic oxidation of lactate to acetate. This is the first observation of oxygen-dependent growth of a sulfate-reducing bacterium in the absence of either sulfate or thiosulfate. Cells harvested during the microaerobic sulfate-depleted stage and exposed to sulfate and thiosulfate in a respiration chamber were capable of anaerobic sulfate and thiosulfate reduction.

Colony Count, Microbial↗
PubMed1988

Metabolic labeling of human thyroglobulin with [35S]sulfate: incorporation into chondroitin 6-sulfate and endoglycosidase-F-susceptible carbohydrate units.

To study the incorporation of sulfate into thyroglobulin, human thyroid tissue was incubated with [35S]sulfate. Labeled thyroglobulin was purified by ammonium sulfate precipitation, gel exclusion chromatography, and equilibrium density gradient centrifugation, the last of these specifically to remove proteoglycans. [35S]Sulfate was found in thyroglobulin with low density, indicating that sulfate was incorporated into newly synthesized molecules before their iodination. Chondroitin ABC lyase and chondroitin AC lyase released equal amounts of [35S]sulfate, demonstrating the presence of chondroitin units, and TLC showed this to be predominantly chondroitin 6-sulfate. Additional [35S]sulfate was released by endoglycosidase-F (Endo-F), but not by Endo-H. The Endo-F-sensitive sulfate-labeled complex carbohydrate units were heterogeneous, one fraction passing through a Concanavalin-A-Sepharose column without delay and another fraction showing weak affinity for the lectin. More than 90% of the incorporated [35S]sulfate was accounted for by the chondroitin ABC lyase and Endo-F-sensitive fractions. Thus, human thyroglobulin contains sulfate in at least three types of carbohydrate units, 1) chondroitin 6-sulfate units, 2) complex units with no affinity for Concanavalin-A (tri- or tetraantennary forms), and 3) complex units with weak affinity for Concanavalin-A (biantennary forms).

Ammonium Sulfate↗
PubMed2006

Monoalkyl sulfates as alkylating agents in water, alkylsulfatase rate enhancements, and the "energy-rich" nature of sulfate half-esters.

Alkyl sulfate monoesters are involved in cell signaling and structure. Alkyl sulfates are also present in many commercial detergents. Here, we show that monomethyl sulfate acts as an efficient alkylating agent in water, reacting spontaneously with oxygen nucleophiles >100-fold more rapidly than do alkylsulfonium ions, the usual methyl donors in living organisms. These reactions of methyl sulfate, which are much more rapid than its hydrolysis, are insensitive to the nature of the attacking nucleophile, with a Brønsted beta(nuc) value of -0.01. Experiments at elevated temperatures indicate a rate constant of 2 x 10(-11) s(-1) for the uncatalyzed hydrolysis of methyl sulfate at 25 degrees C (t(1/2) = 1,100 y), corresponding to a rate enhancement of approximately 10(11)-fold by a human alkylsulfatase. Equilibria of formation of methyl sulfate from methanol and sodium hydrogen sulfate indicate a group transfer potential (DeltaG'(pH7)) of -8.9 kcal/mol for sulfate ester hydrolysis. The magnitude of that value, involving release of the strong acid HSO(4)(-), helps to explain the need for harnessing the free energy of hydrolysis of two ATP molecules in activating sulfate for the biosynthesis of sulfate monoesters. The "energy-rich" nature of monoalkyl sulfate esters, coupled with their marked resistance to hydrolysis, renders them capable of acting as sulfating or alkylating agents under relatively mild conditions. These findings raise the possibility that, under appropriate circumstances, alkyl groups may undergo transfer from alkyl sulfate monoesters to biological target molecules.

Alkylating Agents↗
PubMed2004

Antithrombin-mediated anticoagulant activity of sulfated polysaccharides: different mechanisms for heparin and sulfated galactans.

We investigated the mechanisms of anticoagulant activity mediated by sulfated galactans. The anticoagulant activity of sulfated polysaccharides is achieved mainly through potentiation of plasma cofactors, which are the natural inhibitors of coagulation proteases. Our results indicated the following. 1) Structural requirements for the interaction of sulfated galactans with coagulation inhibitors and their target proteases are not merely a consequence of their charge density. 2) The structural basis of this interaction is complex because it involves naturally heterogeneous polysaccharides but depends on the distribution of sulfate groups and on monosaccharide composition. 3) Sulfated galactans require significantly longer chains than heparin to achieve anticoagulant activity. 4) Possibly, it is the bulk structure of the sulfated galactan, and not a specific minor component as in heparin, that determines its interaction with antithrombin. 5) Sulfated galactans of approximately 15 to approximately 45 kDa bind to antithrombin but are unable to link the plasma inhibitor and thrombin. This last effect requires a molecular size above 45 kDa. 6) Sulfated galactan and heparin bind to different sites on antithrombin. 7) Sulfated galactans are less effective than heparin at promoting antithrombin conformational activation. Overall, these observations indicate that a different mechanism predominates over the conformational activation of antithrombin in ensuring the antithrombin-mediated anticoagulant activity of the sulfated galactans. Possibly, sulfated galactan connects antithrombin and thrombin, holding the protease in an inactive form. The conformational activation of antithrombin and the consequent formation of a covalent complex with thrombin appear to be less important for the anticoagulant activity of sulfated galactan than for heparin. Our results demonstrate that the paradigm of heparin-antithrombin interaction cannot be extended to other sulfated polysaccharides. Each type of polysaccharide may form a particular complex with the plasma inhibitor and the target protease.

Animals↗
PubMed1983

Sulfate reducers can outcompete methanogens at freshwater sulfate concentrations.

Acetate and hydrogen metabolism by sulfate reducers and methanogens in the profundal sediments of an oligotrophic lake were examined. Inhibition of sulfate reduction with molybdate stimulated methane production from both hydrogen and acetate. Molybdate did not stimulate methane production in sediments that were preincubated to deplete the sulfate pool. Sulfate reduction accounted for 30 to 81% of the total of terminal metabolism proceeding through sulfate reduction and methane production in Eckman grab samples of surface sediments. The ability of sulfate reducers to effectively compete with methanogens for acetate was related to the sulfate reducers' lower half-saturation constant for acetate metabolism at in situ sulfate concentrations. Processes other than sulfate reduction and methanogenesis consumed hydrogen at elevated hydrogen partial pressures and prevented a kinetic analysis of hydrogen uptake by sulfate reducers and methanogens. The demonstration that sulfate reducers can successfully compete with methanogens for hydrogen and acetate in sediments at in situ sulfate concentrations of 60 to 105 muM extends the known range of sediment habitats in which sulfate reduction can be a dominant terminal process.

Journal Article↗
PubMed1984

A sulfotransferase-sulfatase system in avian oviduct which catalyzes a conversion of UDP-N-acetylgalactosamine 4-sulfate to the 6-sulfate isomer.

Magnum from quail oviduct was subfractionated to yield epithelium and tubular glands. The in vitro enzymatic activities involved in sulfated sugar nucleotide biosynthesis were assayed in these isolated tissues. The results demonstrated that the activities necessary for a series of reactions, UDP-N-acetylgalactosamine----UDP-N-acetylgalactosamine 4-sulfate----UDP-N-acetylgalactosamine 4,6- bisulfate ----UDP-N-acetylgalactosamine 6-sulfate, are located predominantly in the tubular gland. Both time course and pulse-chase studies with [35S]sulfate gave results that were consistent with this reaction scheme. A microsomal preparation from the magnum was shown to be capable of labeling all three sulfate sugar nucleotides with [35S]sulfate upon incubation with UDP-N-acetylgalactosamine and 3'- phosphoadenylyl [35S]sulfate. Again, their relative labeling rates were in the order necessary to allow for a synthesis of sulfated sugar nucleotides in the sequence described above. Furthermore, incubation of the microsomal preparation with UDP-N-[14C]acetylgalactosamine 4-sulfate and 3'- phosphoadenylyl sulfate resulted in the formation of UDP-N-[14C]acetylgalactosamine 6-sulfate. Also shown was the existence in the microsomal preparation of a sulfatase specific for the sulfate at position 4 of UDP-N-acetylgalactosamine 4,6- bisulfate . The results, together with those obtained in previous investigations, suggest that the tubular gland of quail oviduct contains a microsomal multienzyme system which catalyzes a series of sulfation and desulfation of N-acetylgalactosamine residues at the nonreducing terminal position of either sugar nucleotides or polysaccharide chains.

Animals↗
PubMed1999

Thymic epithelial cells synthesize a heparan sulfate with a highly sulfated region.

Epithelial cells are important components of the thymus microenvironment and are involved in thymocyte differentiation. The production and secretion of sulfated glycosaminoglycans by these cells grown in culture were investigated using labeling with radioactive 35S-Na2SO4 and 3H-glucosamine. The major glycosaminoglycans synthesized by these cells are heparan sulfate and hyaluronic acid. The structure of the heparan sulfate was investigated by the pattern of degradation products formed by deaminative cleavage with nitrous acid. The ratio 35S-sulfate/ H-glucosamine is high in the segments of the heparan sulfate released during the deaminative cleavage with nitrous acid but low in the resistant portion of the molecule. Thus, the heparan sulfate synthesized by the thymic epithelial cells contains a highly sulfated region. Digestion with heparitinase reveals that this highly sulfated region is a heparin-like segment of the molecule. The heparan sulfate is rapidly incorporated into the cell surface but its secretion to the extracellular medium requires a longer incubation period. Finally, heparin was used to mimic the possible effect of this heparan sulfate with a highly sulfated region, as ascertained by its ability to modulate thymocyte adhesion to thymic epithelial cells. Since heparin actually enhanced thymocyte adhesion, it is suggested that the heparan sulfate described herein, secreted by the thymic epithelium, may play a role upon intrathymic heterotypic cellular interactions.

Animals↗
PubMed1992

Sulfated polymers inhibit the interaction of human cytomegalovirus with cell surface heparan sulfate.

Several sulfated polysaccharides (dextran sulfate, pentosan polysulfate, heparin) and copolymers of acrylic acid with vinylalcohol sulfate have proved to be potent inhibitors of human cytomegalovirus (CMV) infectivity in vitro. Sulfated alpha-cyclodextrins are only weak inhibitors of CMV. A close correlation was found between the 50% inhibitory concentrations of the sulfated polymers for CMV cytopathogenicity, virus-cell binding, and expression of immediate early antigens (IEA) in human embryonic lung (HEL) cells. CMV particles bound specifically to heparin-Sepharose. Sulfated polymers specifically eluted the virus particles from this matrix. Enzymatic digestion of cell surface heparan sulfate, but not of chondroitin sulfate, prevented the cells from being infected with CMV. Moreover, radiolabeled CMV bound efficiently to, and were infective for wild-type Chinese hamster ovary (CHO) cells, whereas virus binding to, and infection of, mutant CHO cell lines that were deficient in either all glycosaminoglycans or heparan sulfate only was significantly impaired. The mechanism of action of the sulfated polymers can be attributed to an inhibitory effect on the binding of CMV particles to the host cells. Presumably, the sulfated polymers interact with the viral envelope site(s) involved in the attachment of the CMV virions to cell surface heparan sulfate.

Acrylic Resins↗
PubMed1997

Regulation of sulfur assimilation in higher plants: a sulfate transporter induced in sulfate-starved roots plays a central role in Arabidopsis thaliana.

Proton/sulfate cotransporters in the plasma membranes are responsible for uptake of the environmental sulfate used in the sulfate assimilation pathway in plants. Here we report the cloning and characterization of an Arabidopsis thaliana gene, AST68, a new member of the sulfate transporter gene family in higher plants. Sequence analysis of cDNA and genomic clones of AST68 revealed that the AST68 gene is composed of 10 exons encoding a 677-aa polypeptide (74.1 kDa) that is able to functionally complement a Saccharomyces cerevisiae mutant lacking a sulfate transporter gene. Southern hybridization and restriction fragment length polymorphism mapping confirmed that AST68 is a single-copy gene that maps to the top arm of chromosome 5. Northern hybridization analysis of sulfate-starved plants indicated that the steady-state mRNA abundance of AST68 increased specifically in roots up to 9-fold by sulfate starvation. In situ hybridization experiments revealed that AST68 transcripts were accumulated in the central cylinder of sulfate-starved roots, but not in the xylem, endodermis, cortex, and epidermis. Among all the structural genes for sulfate assimilation, sulfate transporter (AST68), APS reductase (APR1), and serine acetyltransferase (SAT1) were inducible by sulfate starvation in A. thaliana. The sulfate transporter (AST68) exhibited the most intensive and specific response in roots, indicating that AST68 plays a central role in the regulation of sulfate assimilation in plants.

Amino Acid Sequence↗