Sugar sulfates are not hydrolyzed by the acid-inducible sulfatase AslA from Salmonella enterica Enteritidis NalR and Kentucky 3795 at pH 5.5.

PubMed

Ganguly, Arpeeta; Joerger, Rolf D

2017-08-01

The open reading frames SEN0085 and SeKA_A4361, from Salmonella enterica serovar Enteritidis Nal R and serovar Kentucky 3795, respectively, corresponding to the acid-inducible sulfatase gene aslA from Salmonella enterica serovar Typhimurium, were previously suggested by microarray analysis to be differentially expressed under acid conditions. However, growth and enzyme activity tests in the present study demonstrated that both wild-type strains exhibited sulfatase activity with 4-nitrophenyl sulfate and 5-bromo-4-chloro-3 indolyl sulfate at pH 5.5. The acid sulfatase does not appear to be involved in sugar sulfate, tyrosine sulfate, 4-hydroxy-3-methoxyphenylglycol sulfate, heparin sulfate, or chondroitin sulfate hydrolysis at pH 5.5. Adhesion and invasion assays did not reveal differences between the serotypes and their corresponding aslA deletion mutants. Thus, the role and substrate(s) of AslA, a protein unique to salmonella and encoded in all sequenced Salmonella strains, remain elusive.

Glycosulfatase-Encoding Gene Cluster in Bifidobacterium breve UCC2003.

PubMed

Egan, Muireann; Jiang, Hao; O'Connell Motherway, Mary; Oscarson, Stefan; van Sinderen, Douwe

2016-11-15

Bifidobacteria constitute a specific group of commensal bacteria typically found in the gastrointestinal tract (GIT) of humans and other mammals. Bifidobacterium breve strains are numerically prevalent among the gut microbiota of many healthy breastfed infants. In the present study, we investigated glycosulfatase activity in a bacterial isolate from a nursling stool sample, B. breve UCC2003. Two putative sulfatases were identified on the genome of B. breve UCC2003. The sulfated monosaccharide N-acetylglucosamine-6-sulfate (GlcNAc-6-S) was shown to support the growth of B. breve UCC2003, while N-acetylglucosamine-3-sulfate, N-acetylgalactosamine-3-sulfate, and N-acetylgalactosamine-6-sulfate did not support appreciable growth. By using a combination of transcriptomic and functional genomic approaches, a gene cluster designated ats2 was shown to be specifically required for GlcNAc-6-S metabolism. Transcription of the ats2 cluster is regulated by a repressor open reading frame kinase (ROK) family transcriptional repressor. This study represents the first description of glycosulfatase activity within the Bifidobacterium genus. Bifidobacteria are saccharolytic organisms naturally found in the digestive tract of mammals and insects. Bifidobacterium breve strains utilize a variety of plant- and host-derived carbohydrates that allow them to be present as prominent members of the infant gut microbiota as well as being present in the gastrointestinal tract of adults. In this study, we introduce a previously unexplored area of carbohydrate metabolism in bifidobacteria, namely, the metabolism of sulfated carbohydrates. B. breve UCC2003 was shown to metabolize N-acetylglucosamine-6-sulfate (GlcNAc-6-S) through one of two sulfatase-encoding gene clusters identified on its genome. GlcNAc-6-S can be found in terminal or branched positions of mucin oligosaccharides, the glycoprotein component of the mucous layer that covers the digestive tract. The results of this study provide

Glycosulfatase-Encoding Gene Cluster in Bifidobacterium breve UCC2003

PubMed Central

Egan, Muireann; Jiang, Hao; O'Connell Motherway, Mary; Oscarson, Stefan

2016-01-01

ABSTRACT Bifidobacteria constitute a specific group of commensal bacteria typically found in the gastrointestinal tract (GIT) of humans and other mammals. Bifidobacterium breve strains are numerically prevalent among the gut microbiota of many healthy breastfed infants. In the present study, we investigated glycosulfatase activity in a bacterial isolate from a nursling stool sample, B. breve UCC2003. Two putative sulfatases were identified on the genome of B. breve UCC2003. The sulfated monosaccharide N-acetylglucosamine-6-sulfate (GlcNAc-6-S) was shown to support the growth of B. breve UCC2003, while N-acetylglucosamine-3-sulfate, N-acetylgalactosamine-3-sulfate, and N-acetylgalactosamine-6-sulfate did not support appreciable growth. By using a combination of transcriptomic and functional genomic approaches, a gene cluster designated ats2 was shown to be specifically required for GlcNAc-6-S metabolism. Transcription of the ats2 cluster is regulated by a repressor open reading frame kinase (ROK) family transcriptional repressor. This study represents the first description of glycosulfatase activity within the Bifidobacterium genus. IMPORTANCE Bifidobacteria are saccharolytic organisms naturally found in the digestive tract of mammals and insects. Bifidobacterium breve strains utilize a variety of plant- and host-derived carbohydrates that allow them to be present as prominent members of the infant gut microbiota as well as being present in the gastrointestinal tract of adults. In this study, we introduce a previously unexplored area of carbohydrate metabolism in bifidobacteria, namely, the metabolism of sulfated carbohydrates. B. breve UCC2003 was shown to metabolize N-acetylglucosamine-6-sulfate (GlcNAc-6-S) through one of two sulfatase-encoding gene clusters identified on its genome. GlcNAc-6-S can be found in terminal or branched positions of mucin oligosaccharides, the glycoprotein component of the mucous layer that covers the digestive tract. The results of

Molecular analysis of mucopolysaccharidosis IVA: Common mutations and racial difference

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomatsu, S.; Hori, T.; Nakashima, Y.

1994-09-01

Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive disorder caused by a deficiency in N-acetylgalactosamine -6-sulfate sulfatase (GALNS). Studies on the molecular basis of MPS IVA have been facilitated following cloning of the full-length cDNA and genomic DNA. In this study we detected mutations from 20 Caucasian and 19 Japanese MPS IVA patients using SSCP system and compared mutations of Caucasian origin with those of Japanese origin. The results showed the presence of 16 various mutations (3 small, deletions, 2 nonsense and 11 missense mutations) for Caucasian patients and 15 (1 deletion, 1 large alteration and 13 missense mutations) formore » Japanese. Moreover, two common mutations existed; one is double gene deletion characteristic for Japanese (6 alleles; 15%) and the other is a point mutation (1113F A{yields}T transition) characteristic for Caucasian (9 alleles; 22.5%). And the clear genotype/phenotype relationship among 1342delCA, IVS1(-2), P151S, Q148X, R386C, I113F, Q473X, W220G, P151L, A291T, R90W, and P77R, for a severe type, G96B N204K and V138A for a milder type, was observed. Only R386 mutation was seen in both of the populations. Further, the precise DNA analysis for double gene deletion of a common double gene deletion has been performed by defining the breakpoints and the results showed that one deletion was caused by homologous recombination due to Alu repetitive sequences and the other was due to nonhomologous recombination of short direct repeat. Haplotype analysis for six alleles with double deletion were different, indicating the different origin of this mutation or the frequent recombination events before a mutational event. Thus the mutations in GALNS gene are very heterogeneous and the racial difference is characteristic.« less

Human O-sulfated metabolites of (-)-epicatechin and methyl-(-)-epicatechin are poor substrates for commercial aryl-sulfatases: implications for studies concerned with quantifying epicatechin bioavailability.

PubMed

Saha, S; Hollands, W; Needs, P W; Ostertag, L M; de Roos, B; Duthie, G G; Kroon, P A

2012-06-01

Epicatechin is a widely consumed dietary flavonoid and there is substantial evidence that it contributes to the health benefits reported for flavanol-rich cocoa products including dark chocolate. Numerous reports have described the appearance of epicatechin and epicatechin phase-2 conjugates (sulfates and glucuronides of epicatechin and methylepicatechin) in blood and urine samples of subjects following ingestion of epicatechin. The most widely reported method of quantifying total epicatechin in plasma and urine samples involves hydrolysis with a mixture of β-glucuronidase and sulfatase to convert the conjugates to epicatechin aglycone which is subsequently quantified. We observed a lack of hydrolysis of epicatechin sulfates and methylepicatechin sulfates using commercial sulfatases and investigated this further. Samples of urine or plasma from subjects who had consumed epicatechin were subjected to enzyme hydrolysis and then analysed using LC-MS/MS, or analysed without enzyme hydrolysis. Attempts to increase the extent of hydrolysis of epicatechin conjugates were made by increasing the amount of enzyme, hydrolysis pH and length of incubations, and using alternative sources of enzyme. The standard hydrolysis conditions failed to hydrolyse the majority of epicatechin sulfates and methylepicatechin sulfates. Even when the quantity of enzyme and incubation period was increased, the pH optimised, or alternative sources of sulfatases were used, epicatechin monosulfates and methylepicatechin monosulfates remained as major peaks in the chromatograms of the samples. An assessment of literature data strongly suggested that the majority of reports where enzyme hydrolysis was used had significantly underestimated epicatechin bioavailability in humans. Methods for quantifying epicatechin concentrations in blood and urine need to take account of the lack of hydrolysis of (methyl)epicatechin-sulfates, for example by quantifying these directly using LC-MS/MS. Copyright © 2012

Sulfatase-mediated manipulation of the astrocyte-Schwann cell interface.

PubMed

O'Neill, Paul; Lindsay, Susan L; Pantiru, Andreea; Guimond, Scott E; Fagoe, Nitish; Verhaagen, Joost; Turnbull, Jeremy E; Riddell, John S; Barnett, Susan C

2017-01-01

Schwann cell (SC) transplantation following spinal cord injury (SCI) may have therapeutic potential. Functional recovery is limited however, due to poor SC interactions with host astrocytes and the induction of astrogliosis. Olfactory ensheathing cells (OECs) are closely related to SCs, but intermix more readily with astrocytes in culture and induce less astrogliosis. We previously demonstrated that OECs express higher levels of sulfatases, enzymes that remove 6-O-sulfate groups from heparan sulphate proteoglycans, than SCs and that RNAi knockdown of sulfatase prevented OEC-astrocyte mixing in vitro. As human OECs are difficult to culture in large numbers we have genetically engineered SCs using lentiviral vectors to express sulfatase 1 and 2 (SC-S1S2) and assessed their ability to interact with astrocytes. We demonstrate that SC-S1S2s have increased integrin-dependent motility in the presence of astrocytes via modulation of NRG and FGF receptor-linked PI3K/AKT intracellular signaling and do not form boundaries with astrocytes in culture. SC-astrocyte mixing is dependent on local NRG concentration and we propose that sulfatase enzymes influence the bioavailability of NRG ligand and thus influence SC behavior. We further demonstrate that injection of sulfatase expressing SCs into spinal cord white matter results in less glial reactivity than control SC injections comparable to that of OEC injections. Our data indicate that sulfatase-mediated modification of the extracellular matrix can influence glial interactions with astrocytes, and that SCs engineered to express sulfatase may be more OEC-like in character. This approach may be beneficial for cell transplant-mediated spinal cord repair. GLIA 2016 GLIA 2017;65:19-33. © 2016 The Authors. Glia Published by Wiley Periodicals, Inc.

The Role of Heparanase and Sulfatases in the Modification of Heparan Sulfate Proteoglycans within the Tumor Microenvironment and Opportunities for Novel Cancer Therapeutics

PubMed Central

Hammond, Edward; Khurana, Ashwani; Shridhar, Viji; Dredge, Keith

2014-01-01

Heparan sulfate proteoglycans (HSPGs) are an integral and dynamic part of normal tissue architecture at the cell surface and within the extracellular matrix. The modification of HSPGs in the tumor microenvironment is known to result not just in structural but also functional consequences, which significantly impact cancer progression. As substrates for the key enzymes sulfatases and heparanase, the modification of HSPGs is typically characterized by the degradation of heparan sulfate (HS) chains/sulfation patterns via the endo-6-O-sulfatases (Sulf1 and Sulf2) or by heparanase, an endo-glycosidase that cleaves the HS polymers releasing smaller fragments from HSPG complexes. Numerous studies have demonstrated how these enzymes actively influence cancer cell proliferation, signaling, invasion, and metastasis. The activity or expression of these enzymes has been reported to be modified in a variety of cancers. Such observations are consistent with the degradation of normal architecture and basement membranes, which are typically compromised in metastatic disease. Moreover, recent studies elucidating the requirements for these proteins in tumor initiation and progression exemplify their importance in the development and progression of cancer. Thus, as the influence of the tumor microenvironment in cancer progression becomes more apparent, the focus on targeting enzymes that degrade HSPGs highlights one approach to maintain normal tissue architecture, inhibit tumor progression, and block metastasis. This review discusses the role of these enzymes in the context of the tumor microenvironment and their promise as therapeutic targets for the treatment of cancer. PMID:25105093

Aryl sulfate formation in sea urchins (Strongylocentrotus droebachiensis) ingesting marine algae (Fucus distichus) containing 2,6-dimethylnapthalene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Malins, D.C.; Roubal, W.T.

1982-04-01

The metabolism of tritiated 2,6-dimethylnapthalene (2,6-DMN) was studied in sea urchins (Strongylocentrotus droebachiensis) feeding on marine algae (Fucus distichus). The Fucus accumulated this hydrocarbon from sea water without converting it to metabolites. Most of the tritium accumulated by the sea urchins (e.g., 70.8% after 3 days) from feeding on 2,6-DMN-exposed Fucus was present in the exoskeleton (shell and spines). Moreover, after 3 days feeding, about 90% of the tritium in the total metabolite fraction of the gonads and digestive tract of the sea urchin was present as sulfate derivatives. These metabolites were identified through hydrolysis with aryl sulfatase, followed bymore » thin-layer chromatography of the products. After 14 days of feeding, the tritium associated with the sulfate derivatives decreased in the gonads and digestive tract to 61 and 65%, respectively, of the total metabolite fraction. Hydroxy compounds from sulfatase hydrolysis were chromatographed using multiple elutions with toluene. The hydroxy isomers were separated and the R/sub f/ values were compared to those of pure reference compounds. The data indicated that 80% of the 2,6-dimethylnaphtyl sulfate contained the sulfate on the 1 and/or 3 position of the aromatic ring. Moreover, 6-methyl-2-naphthalenemethanol was not detected, which implies that sea urchins, unlike fish, metabolize alkyl-substituted aromatic hydrocarbons primarily through aromatic ring oxidations.« less

Bioinformatic Analysis of the Human Recombinant Iduronate 2-Sulfate Sulfatase

PubMed Central

Morales-Álvarez, Edwin D.; Rivera-Hoyos, Claudia M.; Landázuri, Patricia; Poutou-Piñales, Raúl A.; Pedroza-Rodríguez, Aura M.

2016-01-01

Mucopolysaccharidosis type II is a human recessive disease linked to the X chromosome caused by deficiency of lysosomal enzyme Iduronate 2-Sulfate Sulfatase (IDS), which leads to accumulation of glycosaminoglycans in tissues and organs. The human enzyme has been expressed in Escherichia coli and Pichia pastoris in attempt to develop more successful expression systems that allow the production of recombinant IDS for Enzyme Replacement Therapy (ERT). However, the preservation of native signal peptide in the sequence has caused conflicts in processing and recognition in the past, which led to problems in expression and enzyme activity. With the main object being the improvement of the expression system, we eliminate the native signal peptide of human recombinant IDS. The resulting sequence showed two modified codons, thus, our study aimed to analyze computationally the nucleotide sequence of the IDSnh without signal peptide in order to determine the 3D structure and other biochemical properties to compare them with the native human IDS (IDSnh). Results showed that there are no significant differences between both molecules in spite of the two-codon modifications detected in the recombinant DNA sequence. PMID:27335624

alpha-L-iduronidase, beta-D-glucuronidase, and 2-sulfo-L-iduronate 2-sulfatase: preparation and characterization of radioactive substrates from heparin.

PubMed

Hopwood, J J

1979-03-01

Radioactive disaccharide substrates for alpha-L-iduronidase, beta-D-glucuronidase, and 2-sulfo-L-iduronate 2-sulfatase have been prepared from heparin by deaminative cleavage followed by reduction with NaBT4. Six disaccharides were isolated from this reaction mixture and identified. Acid hydrolysis of the major disaccharide, O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1 linked to 4)-(2,5-anhydro-D-mannitol-l-t 6-sulfate (IdAs--Ms), produced 48% of O-(alpha-L-idopyranosyluronic acid)-(1 linked to 4)-(2,5-anhydro-D-mannitol-l-t 6-sulfate) (IdA--Ms) and 25% of O-(alpha-L-idopyranosyluronic acid)-(1 linked to 4)-2,5-anhydro-D-mannitol-l-t. The most-sensitive substrate for determining alpha-L-iduronidase activity was IdA--Ms which, when incubated with leucocyte and skin-fibroblast homogenates prepared from patients having a deficiency of alpha-L-iduronidase (Mucopolysaccharidosis Type I; MPS-I), was hydrolysed to yield 2,5-anhydro-D-mannitol-l-t 6-sulfate at a rate 50-times less than that found for normal control-preparations. Similarly, O-(beta-D-glucopyranosyluronic acid)-(1 linked to 4)-(2,5-anhydro-D-mannitol-l-t 6-sulfate) was degraded by whole-cell homogenates prepared from beta-D-glucuronidase-deficient (Mucopolysaccharidosis, Type VII) fibroblasts, to yield 2,5-anhydro-D-mannitol-l-t 5-sulfate at a rate 60-times less that that found for MPS-I and normal control-preparations. IdAs--Ms was degraded by 2-sulfo-L-iduronate 2-sulfatase at a rate more than 45-times greater than that found for O-(alpha-L-idopyranosyluronic acid 2-sulfate)-(1 linked to 4)-2,5-anhydro-D-mannitol-l-t. C-6 Sulfation of the anhydro-D-mannitol-l-t residue is an important structural determinant in the mechanism of action of both alpha-L-iduronidase and 2-sulfo-L-iduronate 2-sulfatase on disaccharide substrates.

Purification and characterization of a 3'-phosphoadenylylsulfate:chondroitin 6-sulfotransferase from arterial tissue.

PubMed

Hollmann, J; Niemann, R; Buddecke, E

1986-01-01

A 3'-phosphoadenylylsulfate:chondroitin sulfotransferase (EC 2.8.2.5) was purified to homogeneity (about 760-fold) from the cytosolic fraction of calf arterial tissue by Con A-Sepharose, ion exchange and affinity chromatography. The enzyme has a molecular mass of 38000 Da, optimal activity at pH 6.0 (100%) and 7.25 (75%), requires divalent cations for maximal activity (Mn2+ greater than Mg2+, Ca2+) and exhibits specificity towards desulfated chondroitin sulfate and oligosaccharides derived therefrom. The enzyme transfers sulfate groups from [35S]phosphoadenylylsulfate exclusively to C-6 OH groups of N-acetylgalactosamine units of the acceptor substrates. Maximal sulfate transfer occurs at 2mM chondroitin disaccharide units (100%), the transfer rates decreasing with decreasing chain length in the order deca (55%), octa (17%) and hexasaccharides (4%). Lineweaver-Burk plots revealed equal maximal velocities for chondroitin, deca-, octa- and hexasaccharide, but decreasing Km values. Chondroitin 4-sulfate has 21% of the acceptor potency exhibited by chondroitin, whereas dermatan sulfate, heparan sulfate and hyaluronate and the chondroitin tetrasaccharide showed no acceptor properties. Analysis of the reaction products formed by prolonged enzymatic sulfation of a reduced chondroitin hexasaccharide [GlcA-GalNAc]2-GlcA-GalNAc-ol revealed that the preterminal N-acetylgalactosamine from the non-reducing end and the internal N-acetylgalactosamine but not the N-acetylgalactosaminitol were sulfated and that no hexasaccharide disulfate was formed by the action of chondroitin 6-sulfotransferase. Chondroitin 6-sulfotransferase is considered to possess a binding region capable of accommodating a nonsulfated oligosaccharide sequence of at least six sugars and is believed to act in the course of chondroitin sulfate synthesis in cooperation with, but shortly after, the enzymes involved in the chain elongation reaction.

Characterization of Glycosaminoglycan (GAG) Sulfatases from the Human Gut Symbiont Bacteroides thetaiotaomicron Reveals the First GAG-specific Bacterial Endosulfatase*

PubMed Central

Ulmer, Jonathan E.; Vilén, Eric Morssing; Namburi, Ramesh Babu; Benjdia, Alhosna; Beneteau, Julie; Malleron, Annie; Bonnaffé, David; Driguez, Pierre-Alexandre; Descroix, Karine; Lassalle, Gilbert; Le Narvor, Christine; Sandström, Corine; Spillmann, Dorothe; Berteau, Olivier

2014-01-01

Despite the importance of the microbiota in human physiology, the molecular bases that govern the interactions between these commensal bacteria and their host remain poorly understood. We recently reported that sulfatases play a key role in the adaptation of a major human commensal bacterium, Bacteroides thetaiotaomicron, to its host (Benjdia, A., Martens, E. C., Gordon, J. I., and Berteau, O. (2011) J. Biol. Chem. 286, 25973–25982). We hypothesized that sulfatases are instrumental for this bacterium, and related Bacteroides species, to metabolize highly sulfated glycans (i.e. mucins and glycosaminoglycans (GAGs)) and to colonize the intestinal mucosal layer. Based on our previous study, we investigated 10 sulfatase genes induced in the presence of host glycans. Biochemical characterization of these potential sulfatases allowed the identification of GAG-specific sulfatases selective for the type of saccharide residue and the attachment position of the sulfate group. Although some GAG-specific bacterial sulfatase activities have been described in the literature, we report here for the first time the identity and the biochemical characterization of four GAG-specific sulfatases. Furthermore, contrary to the current paradigm, we discovered that B. thetaiotaomicron possesses an authentic GAG endosulfatase that is active at the polymer level. This type of sulfatase is the first one to be identified in a bacterium. Our study thus demonstrates that bacteria have evolved more sophisticated and diverse GAG sulfatases than anticipated and establishes how B. thetaiotaomicron, and other major human commensal bacteria, can metabolize and potentially tailor complex host glycans. PMID:25002587

Discovery of a novel iota carrageenan sulfatase isolated from the marine bacterium Pseudoalteromonas carrageenovora

NASA Astrophysics Data System (ADS)

Genicot, Sabine; Groisillier, Agnès; Rogniaux, Hélène; Meslet-Cladière, Laurence; Barbeyron, Tristan; Helbert, William

2014-08-01

Carrageenans are sulfated polysaccharides extracted from the cell wall of some marine red algae. These polysaccharides are widely used as gelling, stabilizing, and viscosifying agents in the food and pharmaceutical industries. Since the rheological properties of these polysaccharides depend on their sulfate content, we screened several isolated marine bacteria for carrageenan specific sulfatase activity, in the aim of developing enzymatic bioconversion of carrageenans. As a result of the screening, an iota-carrageenan sulfatase was detected in the cell-free lysate of the marine bacterium Pseudoalteromonas carrageenovora strain PscT. It was purified through Phenyl Sepharose and Diethylaminoethyl Sepharose chromatography. The pure enzyme, Psc ?-CgsA, was characterized. It had a molecular weight of 115.9 kDaltons and exhibited an optimal activity/stability at pH ~8.3 and at 40°C ± 5°C. It was inactivated by phenylmethylsulfonyl fluoride but not by ethylene diamine tetraacetic acid. Psc ?-CgsA specifically catalyzes the hydrolysis of the 4-S sulfate of iota-carrageenan. The purified enzyme could transform iota-carrageenan into hybrid iota-/alpha- or pure alpha-carrageenan under controlled conditions. The gene encoding Psc ?-CgsA, a protein of 1038 amino acids, was cloned into Escherichia coli, and the sequence analysis revealed that Psc ?-CgsA has more than 90% sequence identity with a putative uncharacterized protein Q3IKL4 from the marine strain Pseudoalteromonas haloplanktis TAC 125, but besides this did not share any homology to characterized sulfatases. Phylogenetic studies show that P. carrageenovora sulfatase thus represents the first characterized member of a new sulfatase family, with a C-terminal domain having strong similarity with the superfamily of amidohydrolases, highlighting the still unexplored diversity of marine polysaccharide modifying enzymes.

Discovery of a novel iota carrageenan sulfatase isolated from the marine bacterium Pseudoalteromonas carrageenovora.

PubMed

Genicot, Sabine M; Groisillier, Agnès; Rogniaux, Hélène; Meslet-Cladière, Laurence; Barbeyron, Tristan; Helbert, William

2014-01-01

Carrageenans are sulfated polysaccharides extracted from the cell wall of some marine red algae. These polysaccharides are widely used as gelling, stabilizing, and viscosifying agents in the food and pharmaceutical industries. Since the rheological properties of these polysaccharides depend on their sulfate content, we screened several isolated marine bacteria for carrageenan specific sulfatase activity, in the aim of developing enzymatic bioconversion of carrageenans. As a result of the screening, an iota-carrageenan sulfatase was detected in the cell-free lysate of the marine bacterium Pseudoalteromonas carrageenovora strain Psc(T). It was purified through Phenyl Sepharose and Diethylaminoethyl Sepharose chromatography. The pure enzyme, Psc ι-CgsA, was characterized. It had a molecular weight of 115.9 kDaltons and exhibited an optimal activity/stability at pH ~8.3 and at 40 ± 5°C. It was inactivated by phenylmethylsulfonyl fluoride but not by ethylene diamine tetraacetic acid. Psc ι-CgsA specifically catalyzes the hydrolysis of the 4-S sulfate of iota-carrageenan. The purified enzyme could transform iota-carrageenan into hybrid iota-/alpha- or pure alpha-carrageenan under controlled conditions. The gene encoding Psc ι-CgsA, a protein of 1038 amino acids, was cloned into Escherichia coli, and the sequence analysis revealed that Psc ι-CgsA has more than 90% sequence identity with a putative uncharacterized protein Q3IKL4 from the marine strain Pseudoalteromonas haloplanktis TAC 125, but besides this did not share any homology to characterized sulfatases. Phylogenetic studies show that P. carrageenovora sulfatase thus represents the first characterized member of a new sulfatase family, with a C-terminal domain having strong similarity with the superfamily of amidohydrolases, highlighting the still unexplored diversity of marine polysaccharide modifying enzymes.

Discovery of a novel iota carrageenan sulfatase isolated from the marine bacterium Pseudoalteromonas carrageenovora

PubMed Central

Genicot, Sabine M.; Groisillier, Agnès; Rogniaux, Hélène; Meslet-Cladière, Laurence; Barbeyron, Tristan; Helbert, William

2014-01-01

Carrageenans are sulfated polysaccharides extracted from the cell wall of some marine red algae. These polysaccharides are widely used as gelling, stabilizing, and viscosifying agents in the food and pharmaceutical industries. Since the rheological properties of these polysaccharides depend on their sulfate content, we screened several isolated marine bacteria for carrageenan specific sulfatase activity, in the aim of developing enzymatic bioconversion of carrageenans. As a result of the screening, an iota-carrageenan sulfatase was detected in the cell-free lysate of the marine bacterium Pseudoalteromonas carrageenovora strain PscT. It was purified through Phenyl Sepharose and Diethylaminoethyl Sepharose chromatography. The pure enzyme, Psc ι-CgsA, was characterized. It had a molecular weight of 115.9 kDaltons and exhibited an optimal activity/stability at pH ~8.3 and at 40 ± 5°C. It was inactivated by phenylmethylsulfonyl fluoride but not by ethylene diamine tetraacetic acid. Psc ι-CgsA specifically catalyzes the hydrolysis of the 4-S sulfate of iota-carrageenan. The purified enzyme could transform iota-carrageenan into hybrid iota-/alpha- or pure alpha-carrageenan under controlled conditions. The gene encoding Psc ι-CgsA, a protein of 1038 amino acids, was cloned into Escherichia coli, and the sequence analysis revealed that Psc ι-CgsA has more than 90% sequence identity with a putative uncharacterized protein Q3IKL4 from the marine strain Pseudoalteromonas haloplanktis TAC 125, but besides this did not share any homology to characterized sulfatases. Phylogenetic studies show that P. carrageenovora sulfatase thus represents the first characterized member of a new sulfatase family, with a C-terminal domain having strong similarity with the superfamily of amidohydrolases, highlighting the still unexplored diversity of marine polysaccharide modifying enzymes. PMID:25207269

Extraction and determination of chondroitin sulfate from fish processing byproducts

USDA-ARS?s Scientific Manuscript database

Chondroitin sulfate (CS) refers to a group of sulfated glycosaminoglycan containing a chain of alternating N-acetylgalactosamine and glucuronic acid sugars. It is a major component of the extracellular matrix of cartilage and attached to proteins. CS is usually an over the counter dietary supplement...

Impact of enzyme replacement therapy and hematopoietic stem cell transplantation in patients with Morquio A syndrome

PubMed Central

Tomatsu, Shunji; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Shimada, Tsutomu; Bober, Michael B; Chinen, Yasutsugu; Yabe, Hiromasa; Montaño, Adriana M; Giugliani, Roberto; Kubaski, Francyne; Yasuda, Eriko; Rodríguez-López, Alexander; Espejo-Mojica, Angela J; Sánchez, Oscar F; Mason, Robert W; Barrera, Luis A; Mackenzie, William G; Orii, Tadao

2015-01-01

Patients with mucopolysaccharidosis IVA (MPS IVA) can present with systemic skeletal dysplasia, leading to a need for multiple orthopedic surgical procedures, and often become wheelchair bound in their teenage years. Studies on patients with MPS IVA treated by enzyme replacement therapy (ERT) showed a sharp reduction on urinary keratan sulfate, but only modest improvement based on a 6-minute walk test and no significant improvement on a 3-minute climb-up test and lung function test compared with the placebo group, at least in the short-term. Surgical remnants from ERT-treated patients did not show reduction of storage materials in chondrocytes. The impact of ERT on bone lesions in patients with MPS IVA remains limited. ERT seems to be enhanced in a mouse model of MPS IVA by a novel form of the enzyme tagged with a bone-targeting moiety. The tagged enzyme remained in the circulation much longer than untagged native enzyme and was delivered to and retained in bone. Three-month-old MPS IVA mice treated with 23 weekly infusions of tagged enzyme showed marked clearance of the storage materials in bone, bone marrow, and heart valves. When treatment was initiated at birth, reduction of storage materials in tissues was even greater. These findings indicate that specific targeting of the enzyme to bone at an early stage may improve efficacy of ERT for MPS IVA. Recombinant N-acetylgalactosamine-6-sulfate sulfatase (GALNS) in Escherichia coli BL21 (DE3) (erGALNS) and in the methylotrophic yeast Pichia pastoris (prGALNS) has been produced as an alternative to the conventional production in Chinese hamster ovary cells. Recombinant GALNS produced in microorganisms may help to reduce the high cost of ERT and the introduction of modifications to enhance targeting. Although only a limited number of patients with MPS IVA have been treated with hematopoietic stem cell transplantation (HSCT), beneficial effects have been reported. A wheelchair-bound patient with a severe form of MPS

Steroid Sulfatase Inhibition by Aryl Sulfamates: Clinical Progress, Mechanism and Future Prospects.

PubMed

Potter, Barry V L

2018-04-04

Steroid sulfatase is an emerging drug target for the endocrine therapy of hormone-dependent diseases, catalyzing estrogen sulfate hydrolysis to estrogen. Drug discovery, developing the core aryl O-sulfamate pharmacophore, has led to steroidal and non-steroidal drugs entering numerous clinical trials, with promising results in oncology and women's health. Steroidal estrogen sulfamate derivatives were the first irreversible active-site-directed inhibitors and one was developed clinically as an oral estradiol pro-drug and for endometriosis applications. This review summarizes work leading to the therapeutic concept of sulfatase inhibition, clinical trials executed to date and new insights into the mechanism of inhibition of steroid sulfatase. To date the non-steroidal sulfatase inhibitor Irosustat has been evaluated clinically in breast cancer, alone and in combination, in endometrial cancer and in prostate cancer. The versatile core pharmacophore both imbues attractive pharmaceutical properties and functions via three distinct mechanisms of action, as a pro-drug, an enzyme active site-modifying motif, likely through direct sulfamoyl group transfer, and as a structural component augmenting activity, for example by enhancing interactions at the colchicine binding site of tubulin. Preliminary new structural data on the Pseudomonas aeruginosa arylsulfatase enzyme suggest two possible sulfamate-based adducts with active site hydrated formylglycine as candidates for the inhibition end product via sulfamoyl group transfer, and a speculative choice is suggested. The clinical status of sulfatase inhibition is surveyed and how it might develop in the future. Also discussed are dual-targeting approaches, development of 2-substituted steroidal sulfamates and nonsteroidal derivatives as multi-targeting agents for hormone-independent tumours with other emerging directions.

Structure and expression of sulfatase and sulfatase modifying factor genes in the diamondback moth, Plutella xylostella.

PubMed

Ma, Xiao-Li; He, Wei-Yi; Chen, Wei; Xu, Xue-Jiao; Qi, Wei-Ping; Zou, Ming-Min; You, Yan-Chun; Baxter, Simon W; Wang, Ping; You, Min-Sheng

2017-06-01

The diamondback moth, Plutella xylostella (L.), uses sulfatases (SULF) to counteract the glucosinolate-myrosinase defensive system that cruciferous plants have evolved to deter insect feeding. Sulfatase activity is regulated by post-translational modification of a cysteine residue by sulfatase modifying factor 1 (SUMF1). We identified 12 SULF genes (PxylSulfs) and two SUMF1 genes (PxylSumf1s) in the P. xylostella genome. Phylogenetic analysis of SULFs and SUMFs from P. xylostella, Bombyx mori, Manduca sexta, Heliconius melpomene, Danaus plexippus, Drosophila melanogaster, Tetranychus urticae and Homo sapiens showed that the SULFs were clustered into five groups, and the SUMFs could be divided into two groups. Profiling of the expression of PxylSulfs and PxylSumfs by RNA-seq and by quantitative real-time polymerase chain reaction showed that two glucosinolate sulfatase genes (GSS), PxylSulf2 and PxylSulf3, were primarily expressed in the midgut of 3rd- and 4th-instar larvae. Moreover, expression of sulfatases PxylSulf2, PxylSulf3 and PxylSulf4 were correlated with expression of the sulfatases modifying factor PxylSumf1a. The findings from this study provide new insights into the structure and expression of SUMF1 and PxylSulf genes that are considered to be key factors for the evolutionary success of P. xylostella as a specialist herbivore of cruciferous plants. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Sulfation pattern of fucose branches affects the anti-hyperlipidemic activities of fucosylated chondroitin sulfate.

PubMed

Wu, Nian; Zhang, Yu; Ye, Xingqian; Hu, Yaqin; Ding, Tian; Chen, Shiguo

2016-08-20

Fucosylated chondroitin sulfates (fCSs) are glycosaminoglycans extracted from sea cucumbers, consisting of chondroitin sulfate E (CSE) backbones and sulfated fucose branches. The biological properties of fCSs could be affected by the sulfation pattern of their fucose branches. In the present study, two fCSs were isolated from sea cucumbers Isostichopus badionotus (fCS-Ib) and Pearsonothuria graeffei (fCS-Pg). Their monosaccharide compositions of glucuronic acid (GlcA), N-acetylgalactosamine (GalNAc), fucose (Fuc) and sulfate were at similar molar ratio with 1.0/0.7/0.9/3.1 for fCS-Ib and 1.0/0.8/1.5/2.6 for fCS-Pg. The two fCSs have different sulfation patterns on their fucose branches, fCS-Pg with 3,4-O-disulfation while fCS-Ib with 2,4-O-disulfation. Their antihyperlipidemic effects were compared using a high-fat high-fructose diet (HFFD)-fed C57BL/6J mice model. Both fCS-Ib and fCS-Pg had significant effects on lipid profile improvement, liver protection, blood glucose diminution and hepatic glycogen synthesis. Specifically, fCS-Pg with 3,4-O-disulfation fucose branches was more effective in reduction of blood cholesterol (TC), low density lipoprotein (LDL) and atherogenic index (AI). Our results indicate that both fCSs, especially fCS-Pg, could be used as a potential anti-hyperlipidemic drug. Copyright © 2016. Published by Elsevier Ltd.

GlcNAc6ST-1 regulates sulfation of N-glycans and myelination in the peripheral nervous system

PubMed Central

Yoshimura, Takeshi; Hayashi, Akiko; Handa-Narumi, Mai; Yagi, Hirokazu; Ohno, Nobuhiko; Koike, Takako; Yamaguchi, Yoshihide; Uchimura, Kenji; Kadomatsu, Kenji; Sedzik, Jan; Kitamura, Kunio; Kato, Koichi; Trapp, Bruce D.; Baba, Hiroko; Ikenaka, Kazuhiro

2017-01-01

Highly specialized glial cells wrap axons with a multilayered myelin membrane in vertebrates. Myelin serves essential roles in the functioning of the nervous system. Axonal degeneration is the major cause of permanent neurological disability in primary myelin diseases. Many glycoproteins have been identified in myelin, and a lack of one myelin glycoprotein results in abnormal myelin structures in many cases. However, the roles of glycans on myelin glycoproteins remain poorly understood. Here, we report that sulfated N-glycans are involved in peripheral nervous system (PNS) myelination. PNS myelin glycoproteins contain highly abundant sulfated N-glycans. Major sulfated N-glycans were identified in both porcine and mouse PNS myelin, demonstrating that the 6-O-sulfation of N-acetylglucosamine (GlcNAc-6-O-sulfation) is highly conserved in PNS myelin between these species. P0 protein, the most abundant glycoprotein in PNS myelin and mutations in which at the glycosylation site cause Charcot-Marie-Tooth neuropathy, has abundant GlcNAc-6-O-sulfated N-glycans. Mice deficient in N-acetylglucosamine-6-O-sulfotransferase-1 (GlcNAc6ST-1) failed to synthesize sulfated N-glycans and exhibited abnormal myelination and axonal degeneration in the PNS. Taken together, this study demonstrates that GlcNAc6ST-1 modulates PNS myelination and myelinated axonal survival through the GlcNAc-6-O-sulfation of N-glycans on glycoproteins. These findings may provide novel insights into the pathogenesis of peripheral neuropathy. PMID:28186137

GlcNAc6ST-1 regulates sulfation of N-glycans and myelination in the peripheral nervous system.

PubMed

Yoshimura, Takeshi; Hayashi, Akiko; Handa-Narumi, Mai; Yagi, Hirokazu; Ohno, Nobuhiko; Koike, Takako; Yamaguchi, Yoshihide; Uchimura, Kenji; Kadomatsu, Kenji; Sedzik, Jan; Kitamura, Kunio; Kato, Koichi; Trapp, Bruce D; Baba, Hiroko; Ikenaka, Kazuhiro

2017-02-10

Highly specialized glial cells wrap axons with a multilayered myelin membrane in vertebrates. Myelin serves essential roles in the functioning of the nervous system. Axonal degeneration is the major cause of permanent neurological disability in primary myelin diseases. Many glycoproteins have been identified in myelin, and a lack of one myelin glycoprotein results in abnormal myelin structures in many cases. However, the roles of glycans on myelin glycoproteins remain poorly understood. Here, we report that sulfated N-glycans are involved in peripheral nervous system (PNS) myelination. PNS myelin glycoproteins contain highly abundant sulfated N-glycans. Major sulfated N-glycans were identified in both porcine and mouse PNS myelin, demonstrating that the 6-O-sulfation of N-acetylglucosamine (GlcNAc-6-O-sulfation) is highly conserved in PNS myelin between these species. P 0 protein, the most abundant glycoprotein in PNS myelin and mutations in which at the glycosylation site cause Charcot-Marie-Tooth neuropathy, has abundant GlcNAc-6-O-sulfated N-glycans. Mice deficient in N-acetylglucosamine-6-O-sulfotransferase-1 (GlcNAc6ST-1) failed to synthesize sulfated N-glycans and exhibited abnormal myelination and axonal degeneration in the PNS. Taken together, this study demonstrates that GlcNAc6ST-1 modulates PNS myelination and myelinated axonal survival through the GlcNAc-6-O-sulfation of N-glycans on glycoproteins. These findings may provide novel insights into the pathogenesis of peripheral neuropathy.

The Regulation of Steroid Action by Sulfation and Desulfation

PubMed Central

Mueller, Jonathan W.; Gilligan, Lorna C.; Idkowiak, Jan; Arlt, Wiebke

2015-01-01

Steroid sulfation and desulfation are fundamental pathways vital for a functional vertebrate endocrine system. After biosynthesis, hydrophobic steroids are sulfated to expedite circulatory transit. Target cells express transmembrane organic anion-transporting polypeptides that facilitate cellular uptake of sulfated steroids. Once intracellular, sulfatases hydrolyze these steroid sulfate esters to their unconjugated, and usually active, forms. Because most steroids can be sulfated, including cholesterol, pregnenolone, dehydroepiandrosterone, and estrone, understanding the function, tissue distribution, and regulation of sulfation and desulfation processes provides significant insights into normal endocrine function. Not surprisingly, dysregulation of these pathways is associated with numerous pathologies, including steroid-dependent cancers, polycystic ovary syndrome, and X-linked ichthyosis. Here we provide a comprehensive examination of our current knowledge of endocrine-related sulfation and desulfation pathways. We describe the interplay between sulfatases and sulfotransferases, showing how their expression and regulation influences steroid action. Furthermore, we address the role that organic anion-transporting polypeptides play in regulating intracellular steroid concentrations and how their expression patterns influence many pathologies, especially cancer. Finally, the recent advances in pharmacologically targeting steroidogenic pathways will be examined. PMID:26213785

Placental sulfatase deficiency: maternal and fetal expression of steroid sulfatase deficiency and X-linked ichthyosis.

PubMed

Bradshaw, K D; Carr, B R

1986-07-01

PSD-X-linked ichthyosis are manifestations of a similar disorder of an inborn error of metabolism characterized by a deficiency of steroid sulfatase. The decreased enzyme activity is due to the absence of the expression of enzyme (steroid sulfatase) protein. Affected individuals with this disorder are males (X-linked inheritance) with a frequency of 1/2000 to 1/6000 births. Homozygous females from cosanguineous marriages have been reported with this disorder. The diagnosis is suspected and confirmed by: Low estriol excretion; Negative DHEAS loading test Increased DHEAS in amnionic fluid; Normal DHEAS in cord plasma; Possible delayed or abnormal labor patterns; Decreased sulfatase activity in the placenta, fibroblast, erythrocytes, lymphocytes or leukocytes of affected individuals; Development of ichthyosis in male infants at 2 to 3 months of age.

Mucopolysaccharidosis IVA and glycosaminoglycans

PubMed Central

Khan, Shaukat; Alméciga-Díaz, Carlos J.; Sawamoto, Kazuki; Mackenzie, William G.; Theroux, Mary C; Pizarro, Christian; Mason, Robert W.; Orii, Tadao; Tomatsu, Shunji

2016-01-01

Mucopolysaccharidosis IVA (MPS IVA; Morquio A: OMIM 253000) is a lysosomal storage disease with an autosomal recessive trait caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of specific glycosaminoglycans (GAGs): chondroitin-6-sulfate (C6S) and keratan sulfate (KS). C6S and KS are mainly produced in the cartilage. Therefore, the undegraded substrates are stored primarily in cartilage and in its extracellular matrix (ECM), leading to a direct impact on cartilage and bone development, and successive systemic skeletal dysplasia. Chondrogenesis, the earliest phase of skeletal formation, is maintained by cellular interactions with the ECM, growth and differentiation factors, signaling pathways, and transcription factors in a temporal-spatial manner. In patients with MPS IVA, the cartilage is disrupted at birth as a consequence of abnormal chondrogenesis and/or endochondral ossification. The unique skeletal features are distinguished by a disproportional short stature, odontoid hypoplasia, spinal cord compression, tracheal obstruction, pectus carinatum, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. In spite of many descriptions of these unique clinical features, delay of diagnosis still happens. The pathogenesis and treatment of systemic skeletal dysplasia in MPS IVA remains an unmet challenge. In this review article, we comprehensively describe historical aspect, property of GAGs, diagnosis, screening, pathogenesis, and current and future therapies of MPS IVA. PMID:27979613

Steroid sulfatase inhibition success and limitation in breast cancer clinical assays: an underlying mechanism.

PubMed

Sang, Xiaoye; Han, Hui; Poirier, Donald; Lin, Sheng Xiang

2018-05-24

Steroid sulfatase is detectable in most hormone-dependent breast cancers. STX64, an STS inhibitor, induced tumor reduction in animal assay. Despite success in phase І clinical trial, the results of phase II trial were not that significant. Breast Cancer epithelial cells (MCF-7 and T47D) were treated with two STS inhibitors (STX64 and EM1913). Cell proliferation, cell cycle, and the concentrations of estradiol and 5α-dihydrotestosterone were measured to determine the endocrinological mechanism of sulfatase inhibition. Comparisons were made with inhibitions of reductive 17β-hydroxysteroid dehydrogenases (17β-HSDs). Proliferation studies showed that DNA synthesis in cancer cells was modestly decreased (approximately 20%), accompanied by an up to 6.5% in cells in the G0/G1 phase and cyclin D1 expression reduction. The concentrations of estradiol and 5α-dihydrotestosterone were decreased by 26% and 3% respectively. However, supplementation of 5α-dihydrotestosterone produced a significant increase (approximately 35.6%) in the anti-proliferative effect of sulfatase inhibition. This study has clarified sex-hormone control by sulfatase in BC, suggesting that the different roles of estradiol and 5α-dihydrotestosterone can lead to a reduction in the effect of sulfatase inhibition when compared with 17β-HSD7 inhibition. This suggests that combined treatment of sulfatase inhibitors with 17β-HSD inhibitors such as the type7 inhibitor could hold promise for hormone-dependent breast cancer. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of tibolone and its principal metabolites (3α- and 3β-hydroxy, 3α-sulfate, and 4-ene derivatives) on estrone sulfatase activity in normal and cancerous human breast tissue.

PubMed

Chetrite, Gérard S; Cortes-Prieto, Joaquin; Pasqualini, Jorge R

2011-12-01

Tibolone (Org-OD14) is the active substance of Livial®, a synthetic steroid with the structure 7α,17α-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one, possessing weak tissue-specific estrogenic, progestogenic, and androgenic properties, used to treat menopausal complaints. After oral administration, tibolone is extensively metabolized into the 3α-(Org-4904) and 3β-(Org-30126) hydroxy derivatives with estrogenic properties, its 4-ene (Org-OM38) isomer with progestogenic/androgenic activities, and the 3α-sulfate (Org-34322) derivative, a major biologically inactive circulating form. We compared the dose response of tibolone and its metabolites on estrone sulfatase activity [conversion of estrone sulfate (E1S) to estrone (E1)] in normal and cancerous human breast tissues. Tissue minces were incubated with physiological concentrations of [3H]-E1S (5×10-9M) alone or in the presence of tibolone and its metabolites (concentration range: 5×10-7to 5×10-5M) for 4 h. Tritiated E1, estradiol (E2), and E1S were separated and evaluated quantitatively by thin-layer chromatography. The sulfatase activity was significantly higher in cancerous breast but strongly inhibited by tibolone and the different metabolites, whereas 3α- and 3β-hydroxy derivatives were the most potent inhibitors. This very significant inhibitory effect of tibolone and its principal metabolites on the enzyme involved in E2biosynthesis in the human breast provides interesting perspectives to study the biological responses of these compounds in trials with breast cancer patients.

The Intrinsic Reactivity of ATP and the Catalytic Proficiencies of Kinases Acting on Glucose, N-Acetylgalactosamine, and Homoserine

PubMed Central

Stockbridge, Randy B.; Wolfenden, Richard

2009-01-01

To evaluate the rate enhancements produced by representative kinases and their thermodynamic basis, rate constants were determined as a function of changing temperature for 1) the spontaneous methanolysis of ATP and 2) reactions catalyzed by kinases to which different mechanisms of action have been ascribed. For each of these enzymes, the minor effects of changing viscosity indicate that kcat/Km is governed by the central chemical events in the enzyme-substrate complex rather than by enzyme-substrate encounter. Individual Arrhenius plots, obtained at intervals between pH 4.8 and 11.0, yielded ΔH‡ and TΔS‡ for the nonenzymatic methanolysis of ATP2−, ATP3−, and ATP4− in the absence of Mg2+. The addition of Mg2+ led to partly compensating changes in ΔH‡ and TΔS‡, accelerating the nonenzymatic methanolysis of ATP 11-fold at pH 7 and 25 °C. The rate enhancements produced by yeast hexokinase, homoserine kinase, and N-acetylgalactosamine kinase (obtained by comparison of their kcat/Km values in the presence of saturating phosphoryl acceptor with the second order rate constant for methanolysis of MgATP) ranged between 1012- and 1014-fold. Their nominal affinities for the altered substrates in the transition state were 2.1 × 10−16 m for N-acetylgalactosamine kinase, 7.4 × 10−17 m for homoserine kinase, and 6.4 × 10−18 m for hexokinase. Compared with nonenzymatic phosphoryl transfer, all three kinases were found to produce major reductions in the entropy of activation, in accord with the likelihood that substrate juxtaposition and desolvation play prominent roles in their catalytic action. PMID:19531469

Mucopolysaccharidosis IVA and glycosaminoglycans.

PubMed

Khan, Shaukat; Alméciga-Díaz, Carlos J; Sawamoto, Kazuki; Mackenzie, William G; Theroux, Mary C; Pizarro, Christian; Mason, Robert W; Orii, Tadao; Tomatsu, Shunji

Mucopolysaccharidosis IVA (MPS IVA; Morquio A: OMIM 253000) is a lysosomal storage disease with an autosomal recessive trait caused by the deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Deficiency of this enzyme leads to accumulation of specific glycosaminoglycans (GAGs): chondroitin-6-sulfate (C6S) and keratan sulfate (KS). C6S and KS are mainly produced in the cartilage. Therefore, the undegraded substrates are stored primarily in cartilage and in its extracellular matrix (ECM), leading to a direct impact on cartilage and bone development, and successive systemic skeletal dysplasia. Chondrogenesis, the earliest phase of skeletal formation, is maintained by cellular interactions with the ECM, growth and differentiation factors, signaling pathways, and transcription factors in a temporal-spatial manner. In patients with MPS IVA, the cartilage is disrupted at birth as a consequence of abnormal chondrogenesis and/or endochondral ossification. The unique skeletal features are distinguished by a disproportional short stature, odontoid hypoplasia, spinal cord compression, tracheal obstruction, pectus carinatum, kyphoscoliosis, platyspondyly, coxa valga, genu valgum, waddling gait, and laxity of joints. In spite of many descriptions of these unique clinical features, delay of diagnosis still happens. The pathogenesis and treatment of systemic skeletal dysplasia in MPS IVA remains an unmet challenge. In this review article, we comprehensively describe historical aspect, property of GAGs, diagnosis, screening, pathogenesis, and current and future therapies of MPS IVA. Copyright © 2016 Elsevier Inc. All rights reserved.

The effect of the steroid sulfatase inhibitor (p-O-sulfamoyl)-tetradecanoyl tyramine (DU-14) on learning and memory in rats with selective lesion of septal-hippocampal cholinergic tract.

PubMed

Babalola, P A; Fitz, N F; Gibbs, R B; Flaherty, P T; Li, P-K; Johnson, D A

2012-10-01

Dehydroepiandrosterone sulfate (DHEAS), is an excitatory neurosteroid synthesized within the CNS that modulates brain function. Effects associated with augmented DHEAS include learning and memory enhancement. Inhibitors of the steroid sulfatase enzyme increase brain DHEAS levels and can also facilitate learning and memory. This study investigated the effect of steroid sulfatase inhibition on learning and memory in rats with selective cholinergic lesion of the septo-hippocampal tract using passive avoidance and delayed matching to position T-maze (DMP) paradigms. The selective cholinergic immunotoxin 192 IgG-saporin (SAP) was infused into the medial septum of animals and then tested using a step-through passive avoidance paradigm or DMP paradigm. Peripheral administration of the steroid sulfatase inhibitor, DU-14, increased step-through latency following footshock in rats with SAP lesion compared to both vehicle treated control and lesioned animals (p<0.05). However, in the DMP task, steroid sulfatase inhibition impaired acquisition in lesioned rats while having no effect on intact animals. These results suggest that steroid sulfatase inhibition facilitates memory associated with contextual fear, but impairs acquisition of spatial memory tasks in rats with selective lesion of the septo-hippocampal tract. Copyright © 2012 Elsevier Inc. All rights reserved.

Melatonin affects the dynamic steady-state equilibrium of estrogen sulfates in human umbilical vein endothelial cells by regulating the balance between estrogen sulfatase and sulfotransferase.

PubMed

González, Alicia; Martínez-Campa, Carlos; Alonso-González, Carolina; Cos, Samuel

2015-12-01

Melatonin is known to reduce the growth of endocrine-responsive breast cancers by interacting with estrogen signaling pathways. Estrogens play an important role in breast cancer, but also in various types of tissues, including vascular tissue. Estrogen sulfatase (STS) converts inactive estrogen sulfates into active estrogens, whereas estrogen sulfotransferase (EST) sulfonates estrogens to estrogen sulfates. Therefore, STS and EST are considered to be involved in the regulation of local estrogen levels in hormone‑dependent tumors and in non-pathologic tissues, such as those of the vascular system. Estrogens have a major impact on the vasculature, influencing vascular function, the expression of adhesion proteins, angiogenesis and the inflammatory state. In this study, we investigated the status of STS and EST in human umbilical vein endothelial cells (HUVECs) and the modulatory effects of melatonin. Both STS and EST were highly expressed in the HUVECs. The enzymatic activity correlated with the expression levels in these cells. Our findings also demonstrated that melatonin, at physiological concentrations, modulated the synthesis and transformation of biologically active estrogens in HUVECs through the inhibition of STS activity and expression, and the stimulation of EST activity and expression. Since melatonin decreased the STS levels and increased the EST levels, it modified the dynamic steady‑state equilibrium of estrogen sulfates by increasing the inactive estrogen levels and decreasing the active estrogen levels. Therefore, melatonin may modulate the known different biological actions of estrogens in endothelial cells, as well as in estrogen-dependent tumors and non-pathologic tissues.

Estrone Sulfate Transport and Steroid Sulfatase Activity in Colorectal Cancer: Implications for Hormone Replacement Therapy.

PubMed

Gilligan, Lorna C; Gondal, Ali; Tang, Vivien; Hussain, Maryam T; Arvaniti, Anastasia; Hewitt, Anne-Marie; Foster, Paul A

2017-01-01

Hormone replacement therapy (HRT) affects the incidence and potential progression of colorectal cancer (CRC). As HRT primarily consists of estrone sulfate (E 1 S), understanding whether this conjugated estrogen is transported and metabolized in CRC will define its potential effect in this malignancy. Here, we show that a panel of CRC cell lines (Colo205, Caco2, HCT116, HT-29) have steroid sulfatase (STS) activity, and thus can hydrolyze E 1 S. STS activity is significantly higher in CRC cell lysate, suggesting the importance of E 1 S transport in intracellular STS substrate availability. As E 1 S transport is regulated by the expression pattern of certain solute carrier organic anion transporter polypeptides, we show that in CRC OATP4A1 is the most abundantly expressed transporter. All four CRC cell lines rapidly transported E 1 S into cells, with this effect significantly inhibited by the competitive OATP inhibitor BSP. Transient knockdown of OATP4A1 significantly disrupted E 1 S uptake. Examination of estrogen receptor status showed ERα was present in Colo205 and Caco2 cells. None of the cells expressed ERβ. Intriguingly, HCT116 and HT29 cells strongly expressed the G protein coupled estrogen receptor (GPER), and that stimulation of this receptor with estradiol (E 2 ) and G1, a GPER agonist, significantly ( p < 0.01) increased STS activity. Furthermore, tamoxifen and fulvestrant, known GPER agonist, also increased CRC STS activity, with this effect inhibited by the GPER antagonist G15. These results suggest that CRC can take up and hydrolyze E 1 S, and that subsequent GPER stimulation increases STS activity in a potentially novel positive feedback loop. As elevated STS expression is associated with poor prognosis in CRC, these results suggest HRT, tamoxifen and fulvestrant may negatively impact CRC patient outcomes.

Simultaneous quantification of cholesterol sulfate, androgen sulfates, and progestagen sulfates in human serum by LC-MS/MS[S

PubMed Central

Sánchez-Guijo, Alberto; Oji, Vinzenz; Hartmann, Michaela F.; Traupe, Heiko; Wudy, Stefan A.

2015-01-01

Steroids are primarily present in human fluids in their sulfated forms. Profiling of these compounds is important from both diagnostic and physiological points of view. Here, we present a novel method for the quantification of 11 intact steroid sulfates in human serum by LC-MS/MS. The compounds analyzed in our method, some of which are quantified for the first time in blood, include cholesterol sulfate, pregnenolone sulfate, 17-hydroxy-pregnenolone sulfate, 16-α-hydroxy-dehydroepiandrosterone sulfate, dehydroepiandrosterone sulfate, androstenediol sulfate, androsterone sulfate, epiandrosterone sulfate, testosterone sulfate, epitestosterone sulfate, and dihydrotestosterone sulfate. The assay was conceived to quantify sulfated steroids in a broad range of concentrations, requiring only 300 μl of serum. The method has been validated and its performance was studied at three quality controls, selected for each compound according to its physiological concentration. The assay showed good linearity (R2 > 0.99) and recovery for all the compounds, with limits of quantification ranging between 1 and 80 ng/ml. Averaged intra-day and between-day precisions (coefficient of variation) and accuracies (relative errors) were below 10%. The method has been successfully applied to study the sulfated steroidome in diseases such as steroid sulfatase deficiency, proving its diagnostic value. This is, to our best knowledge, the most comprehensive method available for the quantification of sulfated steroids in human blood. PMID:26239050

A characteristic chondroitin sulfate trisaccharide unit with a sulfated fucose branch exhibits neurite outgrowth-promoting activity: Novel biological roles of fucosylated chondroitin sulfates isolated from the sea cucumber Apostichopus japonicus.

PubMed

Shida, Miharu; Mikami, Tadahisa; Tamura, Jun-Ichi; Kitagawa, Hiroshi

2017-06-03

Chondroitin sulfate (CS) is a class of sulfated glycosaminoglycan (GAG) chains that consist of repeating disaccharide unit composed of glucuronic acid (GlcA) and N-acetylgalactosamine (GalNAc). CS chains are found throughout the pericellular and extracellular spaces and contribute to the formation of functional microenvironments for numerous biological events. However, their structure-function relations remain to be fully characterized. Here, a fucosylated CS (FCS) was isolated from the body wall of the sea cucumber Apostichopus japonicus. Its promotional effects on neurite outgrowth were assessed by using isolated polysaccharides and the chemically synthesized FCS trisaccharide β-D-GalNAc(4,6-O-disulfate) (1-4)[α-l-fucose (2,4-O-disulfate) (1-3)]-β-D-GlcA. FCS polysaccharides contained the E-type disaccharide unit GlcA-GalNAc(4,6-O-disulfate) as a CS major backbone structure and carried distinct sulfated fucose branches. Despite their relatively lower abundance of E unit, FCS polysaccharides exhibited neurite outgrowth-promoting activity comparable to squid cartilage-derived CS-E polysaccharides, which are characterized by their predominant E units, suggesting potential roles of the fucose branch in neurite outgrowth. Indeed, the chemically synthesized FCS trisaccharide was as effective as CS-E tetrasaccharide in stimulating neurite elongation in vitro. In conclusion, FCS trisaccharide units with 2,4-O-disulfated fucose branches may provide new insights into understanding the structure-function relations of CS chains. Copyright © 2017 Elsevier Inc. All rights reserved.

Simultaneous quantification of cholesterol sulfate, androgen sulfates, and progestagen sulfates in human serum by LC-MS/MS.

PubMed

Sánchez-Guijo, Alberto; Oji, Vinzenz; Hartmann, Michaela F; Traupe, Heiko; Wudy, Stefan A

2015-09-01

Steroids are primarily present in human fluids in their sulfated forms. Profiling of these compounds is important from both diagnostic and physiological points of view. Here, we present a novel method for the quantification of 11 intact steroid sulfates in human serum by LC-MS/MS. The compounds analyzed in our method, some of which are quantified for the first time in blood, include cholesterol sulfate, pregnenolone sulfate, 17-hydroxy-pregnenolone sulfate, 16-α-hydroxy-dehydroepiandrosterone sulfate, dehydroepiandrosterone sulfate, androstenediol sulfate, androsterone sulfate, epiandrosterone sulfate, testosterone sulfate, epitestosterone sulfate, and dihydrotestosterone sulfate. The assay was conceived to quantify sulfated steroids in a broad range of concentrations, requiring only 300 μl of serum. The method has been validated and its performance was studied at three quality controls, selected for each compound according to its physiological concentration. The assay showed good linearity (R(2) > 0.99) and recovery for all the compounds, with limits of quantification ranging between 1 and 80 ng/ml. Averaged intra-day and between-day precisions (coefficient of variation) and accuracies (relative errors) were below 10%. The method has been successfully applied to study the sulfated steroidome in diseases such as steroid sulfatase deficiency, proving its diagnostic value. This is, to our best knowledge, the most comprehensive method available for the quantification of sulfated steroids in human blood. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Loss of Dermatan-4-Sulfotransferase 1 Function Results in Adducted Thumb-Clubfoot Syndrome

PubMed Central

Dündar, Munis; Müller, Thomas; Zhang, Qi; Pan, Jing; Steinmann, Beat; Vodopiutz, Julia; Gruber, Robert; Sonoda, Tohru; Krabichler, Birgit; Utermann, Gerd; Baenziger, Jacques U.; Zhang, Lijuan; Janecke, Andreas R.

2009-01-01

Adducted thumb-clubfoot syndrome is an autosomal-recessive disorder characterized by typical facial appearance, wasted build, thin and translucent skin, congenital contractures of thumbs and feet, joint instability, facial clefting, and coagulopathy, as well as heart, kidney, or intestinal defects. We elucidated the molecular basis of the disease by using a SNP array-based genome-wide linkage approach that identified distinct homozygous nonsense and missense mutations in CHST14 in each of four consanguineous families with this disease. The CHST14 gene encodes N-acetylgalactosamine 4-O-sulfotransferase 1 (D4ST1), which catalyzes 4-O sulfation of N-acetylgalactosamine in the repeating iduronic acid-α1,3-N-acetylgalactosamine disaccharide sequence to form dermatan sulfate. Mass spectrometry of glycosaminoglycans from a patient's fibroblasts revealed absence of dermatan sulfate and excess of chondroitin sulfate, showing that 4-O sulfation by CHST14 is essential for dermatan sulfate formation in vivo. Our results indicate that adducted thumb-clubfoot syndrome is a disorder resulting from a defect specific to dermatan sulfate biosynthesis and emphasize roles for dermatan sulfate in human development and extracellular-matrix maintenance. PMID:20004762

N-acetylgalactosamine-functionalized dendrimers as hepatic cancer cell-targeted carriers.

PubMed

Medina, Scott H; Tekumalla, Venkatesh; Chevliakov, Maxim V; Shewach, Donna S; Ensminger, William D; El-Sayed, Mohamed E H

2011-06-01

There is an urgent need for novel polymeric carriers that can selectively deliver a large dose of chemotherapeutic agents into hepatic cancer cells to achieve high therapeutic activity with minimal systemic side effects. PAMAM dendrimers are characterized by a unique branching architecture and a large number of chemical surface groups suitable for coupling of chemotherapeutic agents. In this article, we report the coupling of N-acetylgalactosamine (NAcGal) to generation 5 (G5) of poly(amidoamine) (PAMAM-NH₂) dendrimers via peptide and thiourea linkages to prepare NAcGal-targeted carriers used for targeted delivery of chemotherapeutic agents into hepatic cancer cells. We describe the uptake of NAcGal-targeted and non-targeted G5 dendrimers into hepatic cancer cells (HepG2) as a function of G5 concentration and incubation time. We examine the contribution of the asialoglycoprotein receptor (ASGPR) to the internalization of NAcGal-targeted dendrimers into hepatic cancer cells through a competitive inhibition assay. Our results show that uptake of NAcGal-targeted G5 dendrimers into hepatic cancer cells occurs via ASGPR-mediated endocytosis. Internalization of these targeted carriers increased with the increase in G5 concentration and incubation time following Michaelis-Menten kinetics characteristic of receptor-mediated endocytosis. These results collectively indicate that G5-NAcGal conjugates function as targeted carriers for selective delivery of chemotherapeutic agents into hepatic cancer cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparative glycopattern analysis of mucins in the Brunner's glands of the guinea-pig and the house mouse (Rodentia).

PubMed

Scillitani, Giovanni; Mentino, Donatella

2015-09-01

The mucins secreted by the Brunner's glands and the duodenal goblet cells of the Guinea-pig and the house mouse were compared by conventional and FITC-conjugated lectin histochemistry. Methylation/saponification and sialidase digestion were performed prior to lectin binding to detect the residues subterminal to sulfated groups and sialic acid, respectively. In the Guinea-pig the Brunner's glands produce class-III stable sulfosialomucins. Sialic acid is mostly 2,6-linked to galactose or to N-acetylgalactosamine and is in part O-acetylated in C7, C8, and C9. Sulfated groups are probably linked to sialic acid and N-acetylgalactosamine. Terminal residuals of N-acetylglucosamine, galactose, N-acetylgalactosamine and fucose linked in α1,2, α1,3, and α1,4 are also present. Duodenal goblet cells of the Guinea-pig present a lower number of residuals in respect to the Brunner's glandular ones, with sialic acid and N-acetylgalactosamine subterminal to sulfated groups. In the house mouse the Brunner's glands produce class-III stable neutral mucins, binding to same lectins as in the Guinea-pig except for those specific to sialic acid. A diversity of fucosylated residuals higher than in the Guinea-pig is observed. The mouse duodenal goblet cells lack stable class-III mucins, have little sialic acid and present a lower number of residuals in respect to the correspondent Brunner's glands. Regulation of the acidic intestinal microenvironment, prevention of pathologies and hosting of microflora can explain the observed results and the differences observed between the two rodents. Copyright © 2015 Elsevier GmbH. All rights reserved.

Structural analysis of N-linked oligosaccharides from glycoproteins secreted by Dictyostelium discoideum: identification of mannose 6-sulfate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1986-01-05

The N-linked oligosaccharides found on the lysosomal enzymes from Dictyostelium discoideum are highly sulfated and contain methylphosphomannosyl residues. Here the authors report studies done on the structure of N-linked oligosaccharides found on proteins secreted during growth, a major portion of which are lysosomal enzymes. Cells were metabolically labeled with (2-/sup 3/H)Man and /sup 35/SO/sub 4/ and a portion of the oligosaccharides were released by a sequential digestion with endoglycosidase H followed by endoglycosidase/peptide N-glycosidase F preparations. The oligosaccharides were separated by anion exchange high performance liquid chromatography into fractions containing from one up to six negative charges. Some of themore » oligosaccharides contained only sulfate esters or phosphodiesters, but most contained both. Less than 2% of the oligosaccharides contained a phosphomonoester or an acid-sensitive phosphodiester typical of the mammalian lysosomal enzymes. A combination of acid and base hydrolysis suggested that most of the sulfate esters were linked to primary hydroxyl groups. The presence of Man-6-SO/sub 4/ was demonstrated by the appearance of 3,6-anhydromannose in acid hydrolysates of base-treated, reduced oligosaccharides.« less

Synthesis of N-oleyl O-sulfate chitosan from methyl oleate with O-sulfate chitosan as edible film material

NASA Astrophysics Data System (ADS)

Daniel; Sihaloho, O.; Saleh, C.; Magdaleni, A. R.

2018-04-01

The research on the synthesis of N-oleyl O-sulfate chitosan through sulfonation reaction on chitosan with ammonium sulfate and followed by amidation reaction using methyl oleate has been done. In this study, chitosan was chemically modified into N-oleyl O-sulfatechitosan as an edible film making material. N-oleyl O-sulfate chitosan was synthesized by reaction between methyl oleate and O-sulfate chitosan. Wherein the depleted chitosan of O-sulfate chitosan into O-sulfate chitosan was obtained by reaction of sulfonation between ammonium sulfate and chitosan aldimine. While chitosan aldimine was obtained through reaction between chitosan with acetaldehyde. The structure of N-oleyl O-sulfate chitosan was characterized by FT-IR analysis which showed vibration uptake of C-H sp3 group, S=O group, and carbonyl group C=O of the ester. The resulting of N-oleyl O-sulfate chitosan yielded a percentage of 93.52%. Hydrophilic-Lipophilic Balance (HLB) test results gave a value of 6.68. In the toxicity test results of N-oleyl O-sulfate chitosan obtained LC50 value of 3738.4732 ppm. In WVTR (Water Vapor Transmission Rate) test results for chitosan film was 407.625 gram/m2/24 hours and N-oleylO-sulfate chitosan film was 201.125 gram/m2/24 hours.

Chondroitin Sulfate N-Acetylgalactosaminyltransferase 1 Is Necessary for Normal Endochondral Ossification and Aggrecan Metabolism*

PubMed Central

Sato, Takashi; Kudo, Takashi; Ikehara, Yuzuru; Ogawa, Hiroyasu; Hirano, Tomoko; Kiyohara, Katsue; Hagiwara, Kozue; Togayachi, Akira; Ema, Masatsugu; Takahashi, Satoru; Kimata, Koji; Watanabe, Hideto; Narimatsu, Hisashi

2011-01-01

Chondroitin sulfate (CS) is a glycosaminoglycan, consisting of repeating disaccharide units of N-acetylgalactosamine and glucuronic acid residues, and plays important roles in development and homeostasis of organs and tissues. Here, we generated and analyzed mice lacking chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGalNAcT-1). Csgalnact1−/− mice were viable and fertile but exhibited slight dwarfism. Biochemically, the level of CS in Csgalnact1−/− cartilage was reduced to ∼50% that of wild-type cartilage, whereas its chain length was similar to wild-type mice, indicating that CSGalNAcT-1 participates in the CS chain initiation as suggested in the previous study (Sakai, K., Kimata, K., Sato, T., Gotoh, M., Narimatsu, H., Shinomiya, K., and Watanabe, H. (2007) J. Biol. Chem. 282, 4152–4161). Histologically, the growth plate of Csgalnact1−/− mice contained shorter and slightly disorganized chondrocyte columns with a reduced volume of the extracellular matrix principally in the proliferative layer. Immunohistochemical analysis revealed that the level of both aggrecan and link protein 1 were decreased in Csgalnact1−/− cartilage. Western blot analysis demonstrated an increase in processed forms of aggrecan core protein. These results suggest that CSGalNAcT-1 is required for normal levels of CS biosynthesis in cartilage. Our observations suggest that CSGalNAcT-1 is necessary for normal levels of endochondral ossification, and the decrease in CS amount in the growth plate by its absence causes a rapid catabolism of aggrecan. PMID:21148564

Characterizing the distribution of steroid sulfatase during embryonic development: when and where might metabolites of maternal steroids be reactivated?

PubMed

Paitz, Ryan T; Duffield, Kristin R; Bowden, Rachel M

2017-12-15

All vertebrate embryos are exposed to maternally derived steroids during development. In placental vertebrates, metabolism of maternal steroids by the placenta modulates embryonic exposure, but how exposure is regulated in oviparous vertebrates is less clear. Recent work in oviparous vertebrates has demonstrated that steroids are not static molecules, as they can be converted to more polar steroid sulfates by sulfotransferase enzymes. Importantly, these steroid sulfates can be converted back to the parent compound by the enzyme steroid sulfatase (STS). We investigated when and where STS was present during embryonic development in the red-eared slider turtle, Trachemys scripta We report that STS is present during all stages of development and in all tissues we examined. We conclude that STS activity may be particularly important for regulating maternal steroid exposure in oviparous vertebrates. © 2017. Published by The Company of Biologists Ltd.

Targeting hepatic cancer cells with pegylated dendrimers displaying N-acetylgalactosamine and SP94 peptide ligands.

PubMed

Medina, Scott H; Tiruchinapally, Gopinath; Chevliakov, Maxim V; Durmaz, Yasemin Yuksel; Stender, Rachell N; Ensminger, William D; Shewach, Donna S; Elsayed, Mohamed E H

2013-10-01

Poly(amidoamine) (PAMAM) dendrimers are branched water-soluble polymers defined by consecutive generation numbers (Gn) indicating a parallel increase in size, molecular weight, and number of surface groups available for conjugation of bioactive agents. In this article, we compare the biodistribution of N-acetylgalactosamine (NAcGal)-targeted [(14) C]1 -G5-(NH2 )5 -(Ac)108 -(NAcGal)14 particles to non-targeted [(14) C]1 -G5-(NH2 )127 and PEGylated [(14) C]1 -G5-(NH2 )44 -(Ac)73 -(PEG)10 particles in a mouse hepatic cancer model. Results show that both NAcGal-targeted and non-targeted particles are rapidly cleared from the systemic circulation with high distribution to the liver. However, NAcGal-targeted particles exhibited 2.5-fold higher accumulation in tumor tissue compared to non-targeted ones. In comparison, PEGylated particles showed a 16-fold increase in plasma residence time and a 5-fold reduction in liver accumulation. These results motivated us to engineer new PEGylated G5 particles with PEG chains anchored to the G5 surface via acid-labile cis-aconityl linkages where the free PEG tips are functionalized with NAcGal or SP94 peptide to investigate their potential as targeting ligands for hepatic cancer cells as a function of sugar conformation (α versus β), ligand concentration (100-4000 nM), and incubation time (2 and 24 hours) compared to fluorescently (Fl)-labeled and non-targeted G5-(Fl)6 -(NH2 )122 and G5-(Fl)6 -(Ac)107 -(cPEG)15 particles. Results show G5-(Fl)6 -(Ac)107 -(cPEG[NAcGalβ ])14 particles achieve faster uptake and higher intracellular concentrations in HepG2 cancer cells compared to other G5 particles while escaping the non-specific adsorption of serum protein and phagocytosis by Kupffer cells, which make these particles the ideal carrier for selective drug delivery into hepatic cancer cells. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Assessment of bone dysplasia by micro-CT and glycosaminoglycan levels in mouse models for mucopolysaccharidosis type I, IIIA, IVA, and VII

PubMed Central

Rowan, Daniel J.; Tomatsu, Shunji; Grubb, Jeffrey H.; Montaño, Adriana M.; Sly, William S.

2012-01-01

Summary Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases caused by mutations in lysosomal enzymes involved in degradation of glycosaminoglycans (GAGs). Patients with MPS grow poorly and become physically disabled due to systemic bone disease. While many of the major skeletal effects in mouse models for MPS have been described, no detailed analysis that compares GAGs levels and characteristics of bone by micro-CT has been done. The aims of this study were to assess severity of bone dysplasia among four MPS mouse models (MPS I, IIIA, IVA and VII), to determine the relationship between severity of bone dysplasia and serum keratan sulfate (KS) and heparan sulfate (HS) levels in those models, and to explore the mechanism of KS elevation in MPS I, IIIA, and VII mouse models. Clinically, MPS VII mice had the most severe bone pathology; however, MPS I and IVA mice also showed skeletal pathology. MPS I and VII mice showed severe bone dysplasia, higher bone mineral density, narrowed spinal canal, and shorter sclerotic bones by micro-CT and radiographs. Serum KS and HS levels were elevated in MPS I, IIIA, and VII mice. Severity of skeletal disease displayed by micro-CT, radiographs and histopathology correlated with the level of KS elevation. We showed that elevated HS levels in MPS mouse models could inhibit N-acetylgalactosamine-6-sulfate sulfatase enzyme. These studies suggest that KS could be released from chondrocytes affected by accumulation of other GAGs and that KS could be useful as a biomarker for severity of bone dysplasia in MPS disorders. PMID:22971960

Mannose-recognition mutant of the galactose/N-acetylgalactosamine-specific C-type lectin CEL-I engineered by site-directed mutagenesis.

PubMed

Moriuchi, Hiromi; Unno, Hideaki; Goda, Shuichiro; Tateno, Hiroaki; Hirabayashi, Jun; Hatakeyama, Tomomitsu

2015-07-01

CEL-I is a galactose/N-acetylgalactosamine-specific C-type lectin isolated from the sea cucumber Cucumaria echinata. Its carbohydrate-binding site contains a QPD (Gln-Pro-Asp) motif, which is generally recognized as the galactose specificity-determining motif in the C-type lectins. In our previous study, replacement of the QPD motif by an EPN (Glu-Pro-Asn) motif led to a weak binding affinity for mannose. Therefore, we examined the effects of an additional mutation in the carbohydrate-binding site on the specificity of the lectin. Trp105 of EPN-CEL-I was replaced by a histidine residue using site-directed mutagenesis, and the binding affinity of the resulting mutant, EPNH-CEL-I, was examined by sugar-polyamidoamine dendrimer assay, isothermal titration calorimetry, and glycoconjugate microarray analysis. Tertiary structure of the EPNH-CEL-I/mannose complex was determined by X-ray crystallographic analysis. Sugar-polyamidoamine dendrimer assay and glycoconjugate microarray analysis revealed a drastic change in the specificity of EPNH-CEL-I from galactose/N-acetylgalactosamine to mannose. The association constant of EPNH-CEL-I for mannose was determined to be 3.17×10(3) M(-1) at 25°C. Mannose specificity of EPNH-CEL-I was achieved by stabilization of the binding of mannose in a correct orientation, in which the EPN motif can form proper hydrogen bonds with 3- and 4-hydroxy groups of the bound mannose. Specificity of CEL-I can be engineered by mutating a limited number of amino acid residues in addition to the QPD/EPN motifs. Versatility of the C-type carbohydrate-recognition domain structure in the recognition of various carbohydrate chains could become a promising platform to develop novel molecular recognition proteins. Copyright © 2015 Elsevier B.V. All rights reserved.

The heparanome--the enigma of encoding and decoding heparan sulfate sulfation.

PubMed

Lamanna, William C; Kalus, Ina; Padva, Michael; Baldwin, Rebecca J; Merry, Catherine L R; Dierks, Thomas

2007-04-30

Heparan sulfate (HS) is a cell surface carbohydrate polymer modified with sulfate moieties whose highly ordered composition is central to directing specific cell signaling events. The ability of the cell to generate these information rich glycans with such specificity has opened up a new field of "heparanomics" which seeks to understand the systems involved in generating these cell type and developmental stage specific HS sulfation patterns. Unlike other instances where biological information is encrypted as linear sequences in molecules such as DNA, HS sulfation patterns are generated through a non-template driven process. Thus, deciphering the sulfation code and the dynamic nature of its generation has posed a new challenge to system biologists. The recent discovery of two sulfatases, Sulf1 and Sulf2, with the unique ability to edit sulfation patterns at the cell surface, has opened up a new dimension as to how we understand the regulation of HS sulfation patterning and pattern-dependent cell signaling events. This review will focus on the functional relationship between HS sulfation patterning and biological processes. Special attention will be given to Sulf1 and Sulf2 and how these key editing enzymes might act in concert with the HS biosynthetic enzymes to generate and regulate specific HS sulfation patterns in vivo. We will further explore the use of knock out mice as biological models for understanding the dynamic systems involved in generating HS sulfation patterns and their biological relevance. A brief overview of new technologies and innovations summarizes advances in the systems biology field for understanding non-template molecular networks and their influence on the "heparanome".

Effect of N-acetylgalactosamine ligand valency on targeting dendrimers to hepatic cancer cells.

PubMed

Kuruvilla, Sibu P; Tiruchinapally, Gopinath; Kaushal, Neha; ElSayed, Mohamed E H

2018-04-16

The display of N-acetylgalactosamine (NAcGal) ligands has shown great potential in improving the targeting of various therapeutic molecules to hepatocellular carcinoma (HCC), a severe disease whose clinical treatment is severely hindered by limitations in delivery of therapeutic cargo. We previously used the display of NAcGal on generation 5 (G5) polyamidoamine (PAMAM) dendrimers connected through a poly(ethylene glycol) (PEG) brush (i.e. G5-cPEG-NAcGal; monoGal) to effectively target hepatic cancer cells and deliver a loaded therapeutic cargo. In this study, we were interested to see if tri-valent NAcGal ligands (i.e. NAcGal 3 ) displayed on G5 dendrimers (i.e. G5-cPEG-NAcGal 3 ; triGal) could improve their ability to target hepatic cancer cells compared to their monoGal counterparts. We therefore synthesized a library of triGal particles, with either 2, 4, 6, 8, 11, or 14 targeting branches (i.e. cPEG-NAcGal 3 ) attached. Conventional flow cytometry studies showed that all particle formulations can label hepatic cancer cells in a concentration-dependent manner, reaching 90-100% of cells labeled at either 285 or 570 nM G5, but interestingly, monoGal labeled more cells at lower concentrations. To elucidate the difference in internalization of monoGal versus triGal conjugates, we turned to multi-spectral imaging flow cytometry and quantified the amount of internalized (I) versus surface-bound (I 0 ) conjugates to determine the ratio of internalization (I/I 0 ) in all treatment groups. Results show that regardless of NAcGal valency, or the density of targeting branches, all particles achieve full internalization and diffuse localization throughout the cell (I/I 0  ∼ 3.0 for all particle compositions). This indicates that while tri-valent NAcGal is a promising technique for targeting nanoparticles to hepatic cancer cells, mono-valent NAcGal is more efficient, contrary to what is observed with small molecules. Copyright © 2018 Elsevier B.V. All rights reserved.

Endothelial Heparan Sulfate 6-O-Sulfation Levels Regulate Angiogenic Responses of Endothelial Cells to Fibroblast Growth Factor 2 and Vascular Endothelial Growth Factor*

PubMed Central

Ferreras, Cristina; Rushton, Graham; Cole, Claire L.; Babur, Muhammad; Telfer, Brian A.; van Kuppevelt, Toin H.; Gardiner, John M.; Williams, Kaye J.; Jayson, Gordon C.; Avizienyte, Egle

2012-01-01

Fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor 165 (VEGF165) are potent pro-angiogenic growth factors that play a pivotal role in tumor angiogenesis. The activity of these growth factors is regulated by heparan sulfate (HS), which is essential for the formation of FGF2/FGF receptor (FGFR) and VEGF165/VEGF receptor signaling complexes. However, the structural characteristics of HS that determine activation or inhibition of such complexes are only partially defined. Here we show that ovarian tumor endothelium displays high levels of HS sequences that harbor glucosamine 6-O-sulfates when compared with normal ovarian vasculature where these sequences are also detected in perivascular area. Reduced HS 6-O-sulfotransferase 1 (HS6ST-1) or 6-O-sulfotransferase 2 (HS6ST-2) expression in endothelial cells impacts upon the prevalence of HS 6-O-sulfate moieties in HS sequences, which consist of repeating short, highly sulfated S domains interspersed by transitional N-acetylated/N-sulfated domains. 1–40% reduction in 6-O-sulfates significantly compromises FGF2- and VEGF165-induced endothelial cell sprouting and tube formation in vitro and FGF2-dependent angiogenesis in vivo. Moreover, HS on wild-type neighboring endothelial or smooth muscle cells fails to restore endothelial cell sprouting and tube formation. The affinity of FGF2 for HS with reduced 6-O-sulfation is preserved, although FGFR1 activation is inhibited correlating with reduced receptor internalization. These data show that 6-O-sulfate moieties in endothelial HS are of major importance in regulating FGF2- and VEGF165-dependent endothelial cell functions in vitro and in vivo and highlight HS6ST-1 and HS6ST-2 as potential targets of novel antiangiogenic agents. PMID:22927437

How members of the human gut microbiota overcome the sulfation problem posed by glycosaminoglycans.

PubMed

Cartmell, Alan; Lowe, Elisabeth C; Baslé, Arnaud; Firbank, Susan J; Ndeh, Didier A; Murray, Heath; Terrapon, Nicolas; Lombard, Vincent; Henrissat, Bernard; Turnbull, Jeremy E; Czjzek, Mirjam; Gilbert, Harry J; Bolam, David N

2017-07-03

The human microbiota, which plays an important role in health and disease, uses complex carbohydrates as a major source of nutrients. Utilization hierarchy indicates that the host glycosaminoglycans heparin (Hep) and heparan sulfate (HS) are high-priority carbohydrates for Bacteroides thetaiotaomicron , a prominent member of the human microbiota. The sulfation patterns of these glycosaminoglycans are highly variable, which presents a significant enzymatic challenge to the polysaccharide lyases and sulfatases that mediate degradation. It is possible that the bacterium recruits lyases with highly plastic specificities and expresses a repertoire of enzymes that target substructures of the glycosaminoglycans with variable sulfation or that the glycans are desulfated before cleavage by the lyases. To distinguish between these mechanisms, the components of the B. thetaiotaomicron Hep/HS degrading apparatus were analyzed. The data showed that the bacterium expressed a single-surface endo-acting lyase that cleaved HS, reflecting its higher molecular weight compared with Hep. Both Hep and HS oligosaccharides imported into the periplasm were degraded by a repertoire of lyases, with each enzyme displaying specificity for substructures within these glycosaminoglycans that display a different degree of sulfation. Furthermore, the crystal structures of a key surface glycan binding protein, which is able to bind both Hep and HS, and periplasmic sulfatases reveal the major specificity determinants for these proteins. The locus described here is highly conserved within the human gut Bacteroides , indicating that the model developed is of generic relevance to this important microbial community.

Structural distortions due to missense mutations in human formylglycine-generating enzyme leading to multiple sulfatase deficiency.

PubMed

Meshach Paul, D; Chadah, Tania; Senthilkumar, B; Sethumadhavan, Rao; Rajasekaran, R

2017-11-03

The major candidate for multiple sulfatase deficiency is a defective formylglycine-generating enzyme (FGE). Though adequately produced, mutations in FGE stall the activation of sulfatases and prevent their activity. Missense mutations, viz. E130D, S155P, A177P, W179S, C218Y, R224W, N259I, P266L, A279V, C336R, R345C, A348P, R349Q and R349W associated with multiple sulfatase deficiency are yet to be computationally studied. Aforementioned mutants were initially screened through ws-SNPs&GO 3D program. Mutant R345C acquired the highest score, and hence was studied in detail. Discrete molecular dynamics explored structural distortions due to amino acid substitution. Therein, comparative analyses of wild type and mutant were carried out. Changes in structural contours were observed between wild type and mutant. Mutant had low conformational fluctuation, high atomic mobility and more compactness than wild type. Moreover, free energy landscape showed mutant to vary in terms of its conformational space as compared to wild type. Subsequently, wild type and mutant were subjected to single-model analyses. Mutant had lesser intra molecular interactions than wild type suggesting variations pertaining to its secondary structure. Furthermore, simulated thermal denaturation showed dissimilar pattern of hydrogen bond dilution. Effects of these variations were observed as changes in elements of secondary structure. Docking studies of mutant revealed less favourable binding energy towards its substrate as compared to wild type. Therefore, theoretical explanations for structural distortions of mutant R345C leading to multiple sulfatase deficiency were revealed. The protocol of the study could be useful to examine the effectiveness of pharmacological chaperones prior to experimental studies.

Complex Actions of Estradiol-3-Sulfate in Late Gestation Fetal Brain

PubMed Central

Winikor, Jared; Schlaerth, Christine; Rabaglino, Maria Belen; Cousins, Roderick; Sutherland, Monique

2011-01-01

The most abundant form of estrogen circulating in fetal plasma is sulfo-conjugated estrogen; for example, estradiol-3-sulfate (E2SO4) is more highly abundant than estradiol (E2). The present study investigated the ontogeny of the deconjugating (steroid sulfatase [STS]) and conjugating (estrogen sulfotransferase [STF]) enzymes in ovine fetal brain and tested the hypothesis that treatment with E2SO4 would alter the expression of one or both enzymes. Steroid sulfatase was more highly expressed than STF, and both changed as a function of gestational age. Estradiol-3-sulfate infused intracerebroventricularly (icv) significantly increased plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations. Plasma E2 and E2SO4 were increased, and brain expression of estrogen receptor α was decreased. The proteins STS and STF were up- and downregulated, respectively. Pituitary proopiomelanocortin (POMC) and follicle-stimulating hormone (FSH) and hypothalamic corticotrophin-releasing hormone (CRH) messenger RNA (mRNA) was decreased. We conclude that E2SO4 has complex actions on the fetal brain, which might involve deconjugation by STS, but that the net result of direct E2SO4 icv infusion is more complex than can be accounted for by infusion of E2 alone. PMID:21273638

(C6N2H16)[Co(H2O)6](SO4)2.2H2O: A new hybrid material based on sulfate templated by diprotonated trans-1,4-diaminocyclohexane

NASA Astrophysics Data System (ADS)

Hamdi, N.; Ngopoh, F. A. I.; da Silva, I.; El Bali, B.; Lachkar, M.

2018-03-01

Employing trans-1,4-diaminocyclohexane (DACH) as template, the new hybrid sulphate (C6N2H16)[Co(H2O)6](SO4)2.2H2O was prepared in solution. Single-crystal X-ray diffraction analysis shows that it crystallizes in the monoclinic system (S.G.: P 21/n), with the following unit-cell parameters (Å,°): a = 6.2897(2), b = 12.3716(6), c = 13.1996(4), β = 98.091(3) V = 1016.89(7) Å3, Z = 4. Its 3D crystal structure is made upon isolated [Co(H2O)6] octahedra, regular [SO4] tetrahedra, protonated DACH and free H2O molecules, which interact through N-H···O and O-H···O hydrogen bonds. The Fourier transform infrared result exhibits bands corresponding to the vibrations of DACH, sulfate group and water molecules. The thermal decomposition of the phase consists mainly in the loss of the organic moiety and one sulfate group, leading thus to the formation of anhydrous cobalt sulfate.

Glucosamine Sulfate

MedlinePlus

... Glucosamine Sulphate KCl, Glucosamine-6-Phosphate, GS, Mono-Sulfated Saccharide, Poly-(1->3)-N-Acetyl-2-Amino- ... Sulfate de Glucosamine, Sulfate de Glucosamine 2KCl, SG, Sulfated Monosaccharide, Sulfated Saccharide, Sulfato de Glucosamina. Glucosamine Hydrochloride ...

Novel Alkylsulfatases Required for Biodegradation of the Branched Primary Alkyl Sulfate Surfactant 2-Butyloctyl Sulfate

PubMed Central

Ellis, Andrew J.; Hales, Stephen G.; Ur-Rehman, Naheed G. A.; White, Graham F.

2002-01-01

Recent reports show that contrary to common perception, branched alkyl sulfate surfactants are readily biodegradable in standard biodegradability tests. We report here the isolation of bacteria capable of biodegrading 2-butyloctyl sulfate and the identification of novel enzymes that initiate the process. Enrichment culturing from activated sewage sludge yielded several strains capable of growth on 2-butyloctyl sulfate. Of these, two were selected for further study and identified as members of the genus Pseudomonas. Strain AE-A was able to utilize either sodium dodecyl sulfate (SDS) or 2-butyloctyl sulfate as a carbon and energy source for growth, but strain AE-D utilized only the latter. Depending on growth conditions, strain AE-A produced up to three alkylsulfatases, as shown by polyacrylamide gel electrophoresis zymography. Growth on either SDS or 2-butyloctyl sulfate or in nutrient broth produced an apparently constitutive, nonspecific primary alkylsulfatase, AP1, weakly active on SDS and on 2-butyloctyl sulfate. Growth on 2-butyloctyl sulfate produced a second enzyme, AP2, active on 2-butyloctyl sulfate but not on SDS, and growth on SDS produced a third enzyme, AP3, active on SDS but not on 2-butyloctyl sulfate. In contrast, strain AE-D, when grown on 2-butyloctyl sulfate (no growth on SDS), produced a single enzyme, DP1, active on 2-butyloctyl sulfate but not on SDS. DP1 was not produced in broth cultures. DP1 was induced when residual 2-butyloctyl sulfate was present in the growth medium, but the enzyme disappeared when the substrate was exhausted. Gas chromatographic analysis of products of incubating 2-butyloctyl sulfate with DP1 in gels revealed the formation of 2-butyloctanol, showing the enzyme to be a true sulfatase. In contrast, Pseudomonas sp. strain C12B, well known for its ability to degrade linear SDS, was unable to grow on 2-butyloctyl sulfate, and its alkylsulfatases responsible for initiating the degradation of SDS by releasing the parent

Spatiotemporal expression of chondroitin sulfate sulfotransferases in the postnatal developing mouse cerebellum.

PubMed

Ishii, Maki; Maeda, Nobuaki

2008-08-01

Chondroitin sulfate (CS) proteoglycans are major components of the cell surface and the extracellular matrix in the developing brain and bind to various proteins via CS chains in a CS structure-dependent manner. This study demonstrated the expression pattern of three CS sulfotransferase genes, dermatan 4-O-sulfotransferase (D4ST), uronyl 2-O-sulfotransferase (UST), and N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase (GalNAc4S-6ST), in the mouse postnatal cerebellum. These sulfotransferases are responsible for the biosynthesis of oversulfated structures in CS chains such as B, D, and E units, which constitute the binding sites for various heparin-binding proteins. Real-time reverse transcription-polymerase chain reaction analysis indicated that the expression of UST increased remarkably during cerebellar development. The amounts of B and D units, which are generated by UST activity, in the cerebellar CS chains also increased during development. In contrast, the expression of GalNAc4S-6ST and its biosynthetic product, E unit, decreased during postnatal development. In situ hybridization experiments revealed the levels of UST and GalNAc4S-6ST mRNAs to correlate inversely in many cells including Purkinje cells, granule cells in the external granular layer, and inhibitory interneurons. In these neurons, the expression of UST increased and that of GalNAc4S-6ST decreased during development and/or maturation. D4ST was also expressed by many neurons, but its expression was not simply correlated with development, which might contribute to the diversification of CS structures expressed by distinct neurons. These results suggest that the CS structures of various cerebellar neurons change during development and such changes of CS are involved in the regulation of various signaling pathways.

N-linked oligosaccharides on chondroitin 6-sulfotransferase-1 are required for production of the active enzyme, Golgi localization, and sulfotransferase activity toward keratan sulfate.

PubMed

Yusa, Akiko; Kitajima, Ken; Habuchi, Osami

2006-07-21

We have shown previously that purified chondroitin 6-sulfotransferase-1 (C6ST-1) was a glycoprotein abundant in N-linked oligosaccharides and could sulfate both chondroitin (C6ST activity) and keratan sulfate (KSST activity); however, functional roles of the N-glycans have remained unclear. In the present study, we show essential roles of N-glycans attached to C6ST-1 in the generation of the active enzyme and in its KSST activity. Treatment with tunicamycin of COS-7 cells transfected with C6ST-1 cDNA totally abolished production of the active C6ST-1. A nearly complete removal of N-glycans of the recombinant C6ST-1 by peptide N-glycosidase F increased the C6ST activity but decreased the KSST activity. Among six potential N-glycosylation sites, deletion of the fourth or sixth site from the amino terminus inhibited production of the active C6ST-1, whereas deletion of the fifth site resulted in a marked loss of the KSST activity. Wild-type recombinant C6ST-1 showed a typical Golgi localization, whereas M-4 recombinant C6ST-1, in which the fourth N-glycosylation site was deleted, colocalized with calnexin, an endoplasmic reticulum-resident protein. Unlike wildtype recombinant C6ST-1, M-4 recombinant C6ST-1 showed a weak affinity toward wheat germ agglutinin and was converted completely to the nonglycosylated form by endoglycosidase H. These observations suggest that N-glycan attached to the fourth N-glycosylation site may function in the proper processing of N-glycans required for the Golgi localization, thereby causing the production of the active C6ST-1, and that N-glycan attached to the fifth N-glycosylation site may contribute to the KSST activity of C6ST-1.

Opiate receptor binding properties of morphine-, dihydromorphine-, and codeine 6-O-sulfate ester congeners.

PubMed

Crooks, Peter A; Kottayil, Santosh G; Al-Ghananeem, Abeer M; Byrn, Stephen R; Butterfield, D Allan

2006-08-15

A series of 3-O-acyl-6-O-sulfate esters of morphine, dihydromorphine, N-methylmorphinium iodide, codeine, and dihydrocodeine were prepared and evaluated for their ability to bind to mu-, delta-, kappa(1)-, kappa(2)-, and kappa(3)-opiate receptors. Several compounds exhibited good affinity for the mu-opiate receptor. Morphine-3-O-propionyl-6-O-sulfate had four times greater affinity than morphine at the mu-opiate receptor and was the most selective compound at this receptor subtype.

Synthesis, crystal structure and thermal study of the hybrid nickel sulfate: C6N2H16[Ni(H2O)6(SO4)2].2H2O

NASA Astrophysics Data System (ADS)

Ngopoh, F. A. I.; Hamdi, N.; Chaouch, S.; Lachkar, M.; da Silva, I.; El Bali, B.

2018-03-01

A new inorganic-organic hybrid open framework nickel sulfate C6N2H16[Ni(H2O)6(SO4)2].2H2O has been synthesized by slow evaporation in aqueous solution using trans-1,4-diaminocyclohexane as structure-directing agent. It was characterized by single-crystal X-ray diffraction, infrared spectroscopy and analyzed by TGA-DSC. The compound crystallizes in the monoclinic space group P21/n, with the unit cell parameters of a = 6.2586 Å, b = 12.3009 Å, c = 13.2451 Å, β = 98,047°, Z = 4. Its crystal structure consists of isolated polyhedrons [Ni(H2O)6]2+ and [SO4]2- and free water which connects through hydrogen bonds. This association results in the porous framework where the protonated organic molecule trans-1,4-diaminocyclohexane is located as a counter ion. The IR spectra Shows the bands corresponding to the sulfate anion, water molecule and diprotonated trans-1-4-diaminocyclohexane. Thermal study indicates the loss of water molecules and the degradation of trans-1-4-diaminocyclohexane.

40 CFR 721.10595 - Octadecen-1-aminium, N-ethyl-N,N-dimethy-, ethyl sulfate (1:1).

Code of Federal Regulations, 2013 CFR

2013-07-01

...-dimethy-, ethyl sulfate (1:1). 721.10595 Section 721.10595 Protection of Environment ENVIRONMENTAL...-, ethyl sulfate (1:1). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as octadecen-1-aminium, N-ethyl-N,N-dimethy-, ethyl sulfate (1:1) (PMN P-11...

40 CFR 721.10595 - Octadecen-1-aminium, N-ethyl-N,N-dimethy-, ethyl sulfate (1:1).

Code of Federal Regulations, 2014 CFR

2014-07-01

...-dimethy-, ethyl sulfate (1:1). 721.10595 Section 721.10595 Protection of Environment ENVIRONMENTAL...-, ethyl sulfate (1:1). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as octadecen-1-aminium, N-ethyl-N,N-dimethy-, ethyl sulfate (1:1) (PMN P-11...

Resveratrol-sulfates provide an intracellular reservoir for generation of parent resveratrol, which induces autophagy in cancer cells.

PubMed

Andreadi, Catherine; Britton, Robert G; Patel, Ketan R; Brown, Karen

2014-03-01

Resveratrol has many proposed health benefits, including the prevention of cancers, but its low bioavailability is considered a limiting factor in translating these effects to humans. Based on in vivo and clinical studies we have shown that resveratrol is indeed rapidly metabolized by phase II enzymes, and that resveratrol sulfates are deconjugated by steroid sulfatases to afford free resveratrol in vitro and in vivo and hence act as an intracellular reservoir for resveratrol. Further, we have demonstrated that at clinically achievable concentrations of resveratrol sulfate, parent resveratrol is regenerated within human colorectal cancer, but not normal epithelial cells, and is responsible for inducing autophagy with senescence selectively in cancer cells.

Asialoglycoprotein receptor 1 mediates productive uptake of N-acetylgalactosamine-conjugated and unconjugated phosphorothioate antisense oligonucleotides into liver hepatocytes

PubMed Central

Hettrick, Lisa; Revenko, Alexey; Kinberger, Garth A.; Prakash, Thazha P.; Seth, Punit P.

2017-01-01

Abstract Antisense oligonucleotide (ASO) therapeutics show tremendous promise for the treatment of previously intractable human diseases but to exert their effects on cellular RNA processing they must first cross the plasma membrane by endocytosis. The conjugation of ASOs to a receptor ligand can dramatically increase their entry into certain cells and tissues, as demonstrated by the implementation of N-acetylgalactosamine (GalNAc)-conjugated ASOs for Asialoglycoprotein Receptor (ASGR)-mediated uptake into liver hepatocytes. We compared the internalization and activity of GalNAc-conjugated ASOs and their parents in endogenous ASGR-expressing cells and were able to recapitulate hepatocyte ASO uptake and activity in cells engineered to heterologously express the receptor. We found that the minor receptor subunit, ASGR2, is not required for effective in vitro or in vivo uptake of GalNAc-conjugated ASO and that the major subunit, ASGR1, plays a small but significant role in the uptake of unconjugated phosphorothioate ASOs into hepatocytes. Moreover, our data demonstrates there is a large excess capacity of liver ASGR for the effective uptake of GalNAc–ASO conjugates, suggesting broad opportunities to exploit receptors with relatively moderate levels of expression. PMID:29069408

Hepatic overexpression of steroid sulfatase ameliorates mouse models of obesity and type 2 diabetes through sex-specific mechanisms.

PubMed

Jiang, Mengxi; He, Jinhan; Kucera, Heidi; Gaikwad, Nilesh W; Zhang, Bin; Xu, Meishu; O'Doherty, Robert M; Selcer, Kyle W; Xie, Wen

2014-03-21

The steroid sulfatase (STS)-mediated desulfation is a critical metabolic mechanism that regulates the chemical and functional homeostasis of endogenous and exogenous molecules. In this report, we first showed that the liver expression of Sts was induced in both the high fat diet (HFD) and ob/ob models of obesity and type 2 diabetes and during the fed to fasting transition. In defining the functional relevance of STS induction in metabolic disease, we showed that overexpression of STS in the liver of transgenic mice alleviated HFD and ob/ob models of obesity and type 2 diabetes, including reduced body weight, improved insulin sensitivity, and decreased hepatic steatosis and inflammation. Interestingly, STS exerted its metabolic benefit through sex-specific mechanisms. In female mice, STS may have increased hepatic estrogen activity by converting biologically inactive estrogen sulfates to active estrogens and consequently improved the metabolic functions, whereas ovariectomy abolished this protective effect. In contrast, the metabolic benefit of STS in males may have been accounted for by the male-specific decrease of inflammation in white adipose tissue and skeletal muscle as well as a pattern of skeletal muscle gene expression that favors energy expenditure. The metabolic benefit in male STS transgenic mice was retained after castration. Treatment with the STS substrate estrone sulfate also improved metabolic functions in both the HFD and ob/ob models. Our results have uncovered a novel function of STS in energy metabolism and type 2 diabetes. Liver-specific STS induction or estrogen/estrogen sulfate delivery may represent a novel approach to manage metabolic syndrome.

Validated high-performance anion-exchange chromatography with pulsed amperometric detection method for the determination of residual keratan sulfate and other glucosamine impurities in sodium chondroitin sulfate.

PubMed

Bottelli, Susanna; Grillo, Gianluca; Barindelli, Edoardo; Nencioni, Alessandro; Di Maria, Alessandro; Fossati, Tiziano

2017-07-07

An efficient and sensitive analytical method based on high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) was devised for the determination of glucosamine (GlcN) in sodium chondroitin sulfate (CS). Glucosamine (GlcN) is intended as marker of residual keratan sulfate (KS) and other impurities generating glucosamine by acidic hydrolyzation. The latter brings CS and KS to their respective monomers. Since GlcN is present only in KS we developed a method that separates GlcN from GalN, the principal hydrolytic product of CS, and then we validated it in order to quantify GlcN. Method validation was performed by spiking CS raw material with known amounts of KS. Detection limit was 0.5% of KS in CS (corresponding to 0.1μg/ml), and the linear range was 0.5-5% of KS in CS (corresponding to 0.1-1μg/ml). The optimized analysis was carried out on an ICS-5000 system (Dionex, Sunnyvale, CA, USA) equipped with a Dionex Amino Trap guard column (3mm×30mm), Dionex CarboPac-PA20 (3mm×30mm) and a Dionex CarboPac-PA20 analytical column (3mm×150mm) using gradient elution at a 0.5ml/min flow rate. Regression equations revealed good linear relationship (R 2 =0.99, n=5) within the test ranges. Quality parameters, including precision and accuracy, were fully validated and found to be satisfactory. The fully validated HPAEC-PAD method was readily applied for the quantification of residual KS in CS in several raw materials and USP/EP reference substance. Results confirmed that the HPAEC-PAD method is more specific than the electrophoretic method for related substance reported in EP and provides sensitive determination of KS in acid-hydrolyzed CS samples, enabling the quantitation of KS and other impurities (generating glucosamine) in CS. Copyright © 2017 Elsevier B.V. All rights reserved.

Sulfated steroids as natural ligands of mouse pheromone-sensing neurons.

PubMed

Nodari, Francesco; Hsu, Fong-Fu; Fu, Xiaoyan; Holekamp, Terrence F; Kao, Lung-Fa; Turk, John; Holy, Timothy E

2008-06-18

Among mice, pheromones and other social odor cues convey information about sex, social status, and identity; however, the molecular nature of these cues is essentially unknown. To identify these cues, we screened chromatographic fractions of female mouse urine for their ability to cause reproducible firing rate increases in the pheromone-detecting vomeronasal sensory neurons (VSNs) using multielectrode array (MEA) recording. Active compounds were found to be remarkably homogenous in their basic properties, with most being of low molecular weight, moderate hydrophobicity, low volatility, and possessing a negative electric charge. Purification and structural analysis of active compounds revealed multiple sulfated steroids, of which two were identified as sulfated glucocorticoids, including corticosterone 21-sulfate. Sulfatase-treated urine extracts lost >80% of their activity, indicating that sulfated compounds are the predominant VSN ligands in female mouse urine. As measured by MEA recording, a collection of 31 synthetic sulfated steroids triggered responses 30-fold more frequently than did a similarly sized stimulus set containing the majority of all previously reported VSN ligands. Collectively, VSNs detected all major classes of sulfated steroids, but individual neurons were sensitive to small variations in chemical structure. VSNs from both males and females detected sulfated steroids, but knock-outs for the sensory transduction channel TRPC2 did not detect these compounds. Urine concentrations of the two sulfated glucocorticoids increased many fold in stressed animals, indicating that information about physiological status is encoded by the urine concentration of particular sulfated steroids. These results provide an unprecedented characterization of the signals available for chemical communication among mice.

Sulfated steroids as natural ligands of mouse pheromone-sensing neurons

PubMed Central

Nodari, Francesco; Hsu, Fong-Fu; Fu, Xiaoyan; Holekamp, Terrence F.; Kao, Lung-Fa; Turk, John; Holy, Timothy E.

2009-01-01

Among mice, pheromones and other social odor cues convey information about sex, social status, and identity; however, the molecular nature of these cues is largely unknown. To identify these cues, we screened chromatographic fractions of female mouse urine for their ability to cause reproducible firing rate increases in the pheromone-detecting vomeronasal sensory neurons (VSNs) using multielectrode array (MEA) recording. Active compounds were found to be remarkably homogenous in their basic properties, with most being of low molecular weight, moderate hydrophobicity, low volatility, and possessing a negative electric charge. Purification and structural analysis of active compounds revealed multiple sulfated steroids, of which two were identified as sulfated glucocorticoids, including corticosterone 21-sulfate. Sulfatase-treated urine extracts lost more than 80% of their activity, indicating that sulfated compounds are the predominant VSN ligands in female mouse urine. As measured by MEA recording, a collection of 31 synthetic sulfated steroids triggered responses 30-fold more frequently than did a similarly-sized stimulus set containing the majority of all previously-reported VSN ligands. Collectively, VSNs detected all major classes of sulfated steroids, but individual neurons were sensitive to small variations in chemical structure. VSNs from both males and females detected sulfated steroids, but knockouts for the sensory transduction channel TRPC2 did not detect these compounds. Urine concentrations of the two sulfated glucocorticoids increased many-fold in stressed animals, indicating that information about physiological status is encoded by the urine concentration of particular sulfated steroids. These results provide an unprecedented characterization of the signals available for chemical communication among mice. PMID:18562612

Preparation and anticoagulant activity of N-succinyl chitosan sulfates.

PubMed

Wang, Tan; Zhou, Yue; Xie, Weiguo; Chen, Lingyun; Zheng, Hua; Fan, Lihong

2012-12-01

In order to develop a promising substitute for heparin, N-succinyl chitosan (NSC) was chemically modified by sulfating agent N(SO(3)Na)(3), which were synthesized with sodium bisulfite and sodium nitrite in aqueous solution. The N-succinyl chitosan sulfates (NSCS) products were characterized by infrared spectroscopy (FT-IR) and (13)C NMR. The degree of substitution (DS) of NSCS depended on the ratio of sulfating agent to N-succinyl chitosan, reaction temperature, reaction time and pH of sulfation agent. N-succinyl chitosan sulfates with DS of 1.97 were obtained under optimal conditions. The in vitro coagulation assay of NSCS was determined by activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) assays. The results showed that NSCS obviously prolonged APTT. The anticoagulant activity strongly depended on DS, molecular weight (M(w)) and concentration of NSCS. The anticoagulant activity of NSCS promoted with the increase of DS and concentration, and NSCS exhibited the best anticoagulant activity with the M(w) of 1.37×10(4). Copyright © 2012. Published by Elsevier B.V.

Structural analysis of isomeric chondroitin sulfate oligosaccharides using regioselective 6-O-desulfation method and tandem mass spectrometry.

PubMed

Chen, Shu-Ting; Her, Guor-Rong

2014-09-16

A strategy based on a regioselective 6-O-desulfation reaction and negative ion electrospray ionization tandem mass spectrometry (ESI-MS(n)) was developed for the structural delineation of isomeric chondroitin sulfate oligosaccharides. Product ions resulting from the glycosidic cleavage provided information about the number of sulfate groups in each sugar residue. After the regioselective 6-O-desulfation reaction, the number of sulfate groups on each residue was obtained using a tandem mass spectrometry analysis of the reaction product. The sulfation pattern could be obtained based on the product ions of analytes before and after the desulfation reaction. The strategy was demonstrated using a series of tetrasaccharides prepared from shark cartilage chondroitin sulfate D. Among the 12 identified tetrasaccharides, six structures had not been reported before. Copyright © 2014 Elsevier B.V. All rights reserved.

Resveratrol-sulfates provide an intracellular reservoir for generation of parent resveratrol, which induces autophagy in cancer cells

PubMed Central

Andreadi, Catherine; Britton, Robert G; Patel, Ketan R; Brown, Karen

2014-01-01

Resveratrol has many proposed health benefits, including the prevention of cancers, but its low bioavailability is considered a limiting factor in translating these effects to humans. Based on in vivo and clinical studies we have shown that resveratrol is indeed rapidly metabolized by phase II enzymes, and that resveratrol sulfates are deconjugated by steroid sulfatases to afford free resveratrol in vitro and in vivo and hence act as an intracellular reservoir for resveratrol. Further, we have demonstrated that at clinically achievable concentrations of resveratrol sulfate, parent resveratrol is regenerated within human colorectal cancer, but not normal epithelial cells, and is responsible for inducing autophagy with senescence selectively in cancer cells. PMID:24419144

Sulfation of 6-Gingerol by the Human Cytosolic Sulfotransferases: A Systematic Analysis.

PubMed

Luo, Lijun; Mei, Xue; Xi, Yuecheng; Zhou, Chunyang; Hui, Ying; Kurogi, Katsuhisa; Sakakibara, Yoichi; Suiko, Masahito; Liu, Ming-Cheh

2016-02-01

Previous studies have demonstrated the presence of the sulfated form of 6-gingerol, a major pharmacologically active component of ginger, in plasma samples of normal human subjects who were administered 6-gingerol. The current study was designed to systematically identify the major human cytosolic sulfotransferase enzyme(s) capable of mediating the sulfation of 6-gingerol. Of the 13 known human cytosolic sulfotransferases examined, six (SULT1A1, SULT1A2, SULT1A3, SULT1B1, SULT1C4, SULT1E1) displayed significant sulfating activity toward 6-gingerol. Kinetic parameters of SULT1A1, SULT1A3, SULT1C4, and SULT1E1 that showed stronger 6-gingerol-sulfating activity were determined. Of the four human organ samples tested, small intestine and liver cytosols displayed considerably higher 6-gingerol-sulfating activity than those of the lung and kidney. Moreover, sulfation of 6-gingerol was shown to occur in HepG2 human hepatoma cells and Caco-2 human colon adenocarcinoma cells under the metabolic setting. Collectively, these results provided useful information relevant to the metabolism of 6-gingerol through sulfation both in vitro and in vivo. Georg Thieme Verlag KG Stuttgart · New York.

Identifying the need for a multidisciplinary approach for early recognition of mucopolysaccharidosis VI (MPS VI).

PubMed

Choy, Yew Sing; Bhattacharya, Kaustuv; Balasubramaniam, Shanti; Fietz, Michael; Fu, Antony; Inwood, Anita; Jin, Dong-Kyu; Kim, Ok-Hwa; Kosuga, Motomichi; Kwun, Young Hee; Lin, Hsiang-Yu; Lin, Shuan-Pei; Mendelsohn, Nancy J; Okuyama, Torayuki; Samion, Hasri; Tan, Adeline; Tanaka, Akemi; Thamkunanon, Verasak; Thong, Meow-Keong; Toh, Teck-Hock; Yang, Albert D; McGill, Jim

2015-05-01

Mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome) is caused by deficient activity of the enzyme, N-acetylgalactosamine-4-sulfatase, resulting in impaired degradation of the glycosaminoglycan dermatan sulfate. Patients experience a range of manifestations including joint contractures, short stature, dysostosis multiplex, coarse facial features, decreased pulmonary function, cardiac abnormalities, corneal clouding and shortened life span. Recently, clinicians from institutions in the Asia-Pacific region met to discuss the occurrence and implications of delayed diagnosis and misdiagnosis of MPS VI in the patients they have managed. Eighteen patients (44% female) were diagnosed. The most common sign presented by the patients was bone deformities in 11 patients (65%). Delays to diagnosis occurred due to the lack of or distance to diagnostic facilities for four patients (31%), alternative diagnoses for two patients (15%), and misleading symptoms experienced by two patients (15%). Several patients experienced manifestations that were subtler than would be expected and were subsequently overlooked. Several cases highlighted the unique challenges associated with diagnosing MPS VI from the perspective of different specialties and provide insights into how these patients initially present, which may help to elucidate strategies to improve the diagnosis of MPS VI. Copyright © 2015 Elsevier Inc. All rights reserved.

The chondroitin sulfate/dermatan sulfate 4-O-endosulfatase from marine bacterium Vibrio sp FC509 is a dimeric species: Biophysical characterization of an endosulfatase.

PubMed

Neira, José L; Medina-Carmona, Encarnación; Hernández-Cifre, José G; Montoliu-Gaya, Laia; Cámara-Artigás, Ana; Seffouh, Ilham; Gonnet, Florence; Daniel, Régis; Villegas, Sandra; de la Torre, José García; Pey, Angel L; Li, Fuchuan

2016-12-01

Sulfatases catalyze hydrolysis of sulfate groups. They have a key role in regulating the sulfation states that determine the function of several scaffold molecules. Currently, there are no studies of the conformational stability of endosulfatases. In this work, we describe the structural features and conformational stability of a 4-O-endosulfatase (EndoV) from a marine bacterium, which removes specifically the 4-O-sulfate from chondroitin sulfate/dermatan sulfate. For that purpose, we have used several biophysical techniques, namely, fluorescence, circular dichroism (CD), FTIR spectroscopy, analytical ultracentrifugation (AUC), differential scanning calorimetry (DSC), mass spectrometry (MS), dynamic light scattering (DLS) and size exclusion chromatography (SEC). The protein was a dimer with an elongated shape. EndoV acquired a native-like structure in a narrow pH range (7.0-9.0); it is within this range where the protein shows the maximum of enzymatic activity. The dimerization did not involve the presence of disulphide-bridges as suggested by AUC, SEC and DLS experiments in the presence of β-mercaptoethanol (β-ME). EndoV secondary structure is formed by a mixture of α and β-sheet topology, as judged by deconvolution of CD and FTIR spectra. Thermal and chemical denaturations showed irreversibility and the former indicates that protein did not unfold completely during heating. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Differential involvement of the extracellular 6-O-endosulfatases Sulf1 and Sulf2 in brain development and neuronal and behavioural plasticity

PubMed Central

Kalus, Ina; Salmen, Benedikt; Viebahn, Christoph; von Figura, Kurt; Schmitz, Dietmar; D'Hooge, Rudi; Dierks, Thomas

2009-01-01

The extracellular sulfatases Sulf1 and Sulf2 remove specific 6-O-sulfate groups from heparan sulfate, thereby modulating numerous signalling pathways underlying development and homeostasis. In vitro data have suggested that the two enzymes show functional redundancy. To elucidate their in vivo functions and to further address the question of a putative redundancy, we have generated Sulf1- and Sulf2-deficient mice. Phenotypic analysis of these animals revealed higher embryonic lethality of Sulf2 knockout mice, which can be associated with neuroanatomical malformations during embryogenesis. Sulf1 seems not to be essential for developmental or postnatal viability, as mice deficient in this sulfatase show no overt phenotype. However, neurite outgrowth deficits were observed in hippocampal and cerebellar neurons of both mutant mouse lines, suggesting that not only Sulf2 but also Sulf1 function plays a role in the developing nervous system. Behavioural analysis revealed differential deficits with regard to cage activity and spatial learning for Sulf1- and Sulf2-deficient mouse lines. In addition, Sulf1-specific deficits were shown for synaptic plasticity in the CA1 region of the hippocampus, associated with a reduced spine density. These results reveal that Sulf1 and Sulf2 fulfil non-redundant functions in vivo in the development and maintenance of the murine nervous system. PMID:20394677

Pseudomonas aeruginosa arylsulfatase: a purified enzyme for the mild hydrolysis of steroid sulfates.

PubMed

Stevenson, Bradley J; Waller, Christopher C; Ma, Paul; Li, Kunkun; Cawley, Adam T; Ollis, David L; McLeod, Malcolm D

2015-10-01

The hydrolysis of sulfate ester conjugates is frequently required prior to analysis for a range of analytical techniques including gas chromatography-mass spectrometry (GC-MS). Sulfate hydrolysis may be achieved with commercial crude arylsulfatase enzyme preparations such as that derived from Helix pomatia but these contain additional enzyme activities such as glucuronidase, oxidase, and reductase that make them unsuitable for many analytical applications. Strong acid can also be used to hydrolyze sulfate esters but this can lead to analyte degradation or increased matrix interference. In this work, the heterologously expressed and purified arylsulfatase from Pseudomonas aeruginosa is shown to promote the mild enzyme-catalyzed hydrolysis of a range of steroid sulfates. The substrate scope of this P. aeruginosa arylsulfatase hydrolysis is compared with commercial crude enzyme preparations such as that derived from H. pomatia. A detailed kinetic comparison is reported for selected examples. Hydrolysis in a urine matrix is demonstrated for dehydroepiandrosterone 3-sulfate and epiandrosterone 3-sulfate. The purified P. aeruginosa arylsulfatase contains only sulfatase activity allowing for the selective hydrolysis of sulfate esters in the presence of glucuronide conjugates as demonstrated in the short three-step chemoenzymatic synthesis of 5α-androstane-3β,17β-diol 17-glucuronide (ADG, 1) from epiandrosterone 3-sulfate. The P. aeruginosa arylsulfatase is readily expressed and purified (0.9 g per L of culture) and thus provides a new and selective method for the hydrolysis of steroid sulfate esters in analytical sample preparation. Copyright © 2015 John Wiley & Sons, Ltd.

The heparin/heparan sulfate sequence that interacts with cyclophilin B contains a 3-O-sulfated N-unsubstituted glucosamine residue.

PubMed

Vanpouille, Christophe; Deligny, Audrey; Delehedde, Maryse; Denys, Agnès; Melchior, Aurélie; Liénard, Xavier; Lyon, Malcolm; Mazurier, Joël; Fernig, David G; Allain, Fabrice

2007-08-17

Many of the biological functions of heparan sulfate (HS) proteoglycans can be attributed to specialized structures within HS moieties, which are thought to modulate binding and function of various effector proteins. Cyclophilin B (CyPB), which was initially identified as a cyclosporin A-binding protein, triggers migration and integrin-mediated adhesion of peripheral blood T lymphocytes by a mechanism dependent on interaction with cell surface HS. Here we determined the structural features of HS that are responsible for the specific binding of CyPB. In addition to the involvement of 2-O,6-O, and N-sulfate groups, we also demonstrated that binding of CyPB was dependent on the presence of N-unsubstituted glucosamine residues (GlcNH2), which have been reported to be precursors for sulfation by 3-O-sulfotransferases-3 (3-OST-3). Interestingly, 3-OST-3B isoform was found to be the main 3-OST isoenzyme expressed in peripheral blood T lymphocytes and Jurkat T cells. Moreover, down-regulation of the expression of 3-OST-3 by RNA interference potently reduced CyPB binding and consequent activation of p44/42 mitogen-activated protein kinases. Altogether, our results strongly support the hypothesis that 3-O-sulfation of GlcNH2 residues could be a key modification that provides specialized HS structures for CyPB binding to responsive cells. Given that 3-O-sulfation of GlcNH2-containing HS by 3-OST-3 also provides binding sites for glycoprotein gD of herpes simplex virus type I, these findings suggest an intriguing structural linkage between the HS sequences involved in CyPB binding and viral infection.

Metabolic niche of a prominent sulfate-reducing human gut bacterium

PubMed Central

Rey, Federico E.; Gonzalez, Mark D.; Cheng, Jiye; Ahern, Philip P.; Gordon, Jeffrey I.

2013-01-01

Sulfate-reducing bacteria (SRB) colonize the guts of ∼50% of humans. We used genome-wide transposon mutagenesis and insertion-site sequencing, RNA-Seq, plus mass spectrometry to characterize genetic and environmental factors that impact the niche of Desulfovibrio piger, the most common SRB in a surveyed cohort of healthy US adults. Gnotobiotic mice were colonized with an assemblage of sequenced human gut bacterial species with or without D. piger and fed diets with different levels and types of carbohydrates and sulfur sources. Diet was a major determinant of functions expressed by this artificial nine-member community and of the genes that impact D. piger fitness; the latter includes high- and low-affinity systems for using ammonia, a limiting resource for D. piger in mice consuming a polysaccharide-rich diet. Although genes involved in hydrogen consumption and sulfate reduction are necessary for its colonization, varying dietary-free sulfate levels did not significantly alter levels of D. piger, which can obtain sulfate from the host in part via cross-feeding mediated by Bacteroides-encoded sulfatases. Chondroitin sulfate, a common dietary supplement, increased D. piger and H2S levels without compromising gut barrier integrity. A chondroitin sulfate-supplemented diet together with D. piger impacted the assemblage’s substrate utilization preferences, allowing consumption of more reduced carbon sources and increasing the abundance of the H2-producing Actinobacterium, Collinsella aerofaciens. Our findings provide genetic and metabolic details of how this H2-consuming SRB shapes the responses of a microbiota to diet ingredients and a framework for examining how individuals lacking D. piger differ from those who harbor it. PMID:23898195

Metabolic niche of a prominent sulfate-reducing human gut bacterium.

PubMed

Rey, Federico E; Gonzalez, Mark D; Cheng, Jiye; Wu, Meng; Ahern, Philip P; Gordon, Jeffrey I

2013-08-13

Sulfate-reducing bacteria (SRB) colonize the guts of ∼50% of humans. We used genome-wide transposon mutagenesis and insertion-site sequencing, RNA-Seq, plus mass spectrometry to characterize genetic and environmental factors that impact the niche of Desulfovibrio piger, the most common SRB in a surveyed cohort of healthy US adults. Gnotobiotic mice were colonized with an assemblage of sequenced human gut bacterial species with or without D. piger and fed diets with different levels and types of carbohydrates and sulfur sources. Diet was a major determinant of functions expressed by this artificial nine-member community and of the genes that impact D. piger fitness; the latter includes high- and low-affinity systems for using ammonia, a limiting resource for D. piger in mice consuming a polysaccharide-rich diet. Although genes involved in hydrogen consumption and sulfate reduction are necessary for its colonization, varying dietary-free sulfate levels did not significantly alter levels of D. piger, which can obtain sulfate from the host in part via cross-feeding mediated by Bacteroides-encoded sulfatases. Chondroitin sulfate, a common dietary supplement, increased D. piger and H2S levels without compromising gut barrier integrity. A chondroitin sulfate-supplemented diet together with D. piger impacted the assemblage's substrate utilization preferences, allowing consumption of more reduced carbon sources and increasing the abundance of the H2-producing Actinobacterium, Collinsella aerofaciens. Our findings provide genetic and metabolic details of how this H2-consuming SRB shapes the responses of a microbiota to diet ingredients and a framework for examining how individuals lacking D. piger differ from those who harbor it.

Enzyme replacement therapy for mucopolysaccharidosis VI: Growth and pubertal development in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase

PubMed Central

Decker, Celeste; Yu, Zi-Fan; Giugliani, Roberto; Schwartz, Ida Vanessa D.; Guffon, Nathalie; Teles, Elisa Leão; Miranda, M. Clara Sá; Wraith, J. Edmond; Beck, Michael; Arash, Laila; Scarpa, Maurizio; Ketteridge, David; Hopwood, John J.; Plecko, Barbara; Steiner, Robert; Whitley, Chester B.; Kaplan, Paige; Swiedler, Stuart J.; Conrad, Susan; Harmatz, Paul

2010-01-01

Background and Methods Growth failure is characteristic of untreated mucopolysaccharidosis type VI (MPS VI: Maroteaux-Lamy syndrome). Growth was studied in fifty-six MPS VI patients (5 to 29 years old) prior to and for up to 240 weeks of weekly infusions of recombinant human arylsulfatase B (rhASB) at 1 mg/kg during Phase 1/2, Phase 2, Phase 3 or Phase 3 Extension clinical trials. Height, weight, and Tanner stage data were collected. Pooled data were analyzed to determine mean height increase by treatment week, growth impacts of pubertal status, baseline urinary GAG, and age at treatment initiation. Growth rate for approximately 2 years prior to and following treatment initiation was analyzed using longitudinal modeling. Results Mean height increased by 2.9 cm after 48 weeks and 4.3 cm after 96 weeks on enzyme replacement therapy (ERT). Growth on ERT was not correlated with baseline urinary GAG. Patients under 16 years of age showed greatest increases in height on treatment. Model results based on pooled data showed significant improvement in growth rate during 96 weeks of ERT when compared to the equivalent pretreatment time period. Delayed pubertal onset or progression was noted in 10 patients entering the clinical trials; all of whom showed progression of at least one Tanner stage during 2 years on ERT, and 6 of whom (60%) completed puberty. Conclusion Analysis of mean height by treatment week and longitudinal modeling demonstrate significant increase in height and growth rate in MPS VI patients receiving long-term ERT. This impact was greatest in patients aged below 16 years. Height increase may result from bone growth and/or reduction in joint contractures. Bone growth and resolution of delayed puberty may be related to improvements in general health, bone cell health, nutrition, endocrine gland function and reduced inflammation. PMID:20634905

Enhancement of VEGF-Mediated Angiogenesis by 2-N,6-O-Sulfated Chitosan-Coated Hierarchical PLGA Scaffolds.

PubMed

Yu, Yuanman; Chen, Jie; Chen, Rui; Cao, Lingyan; Tang, Wei; Lin, Dan; Wang, Jing; Liu, Changsheng

2015-05-13

Rapid and controlled vascularization within scaffolds remains one of the key limitations in tissue engineering applications. This study describes the fabrication and characterization of 2-N,6-O-sulfated chitosan (26SCS)-coated hierarchical scaffold composed of poly(lactic-co-glycolic acid) (PLGA) microspheres, as a desirable vehicle for vascular endothelial growth factor (VEGF) delivery and consequent angiogenic boosting in vitro. Owing to the hierarchical porous structure and high affinity between VEGF and 26SCS, the 26SCS-modified PLGA (S-PLGA) scaffold possesses excellent entrapment and sustained release of VEGF. Using human umbilical vein endothelial cells (HUVECs) as a cell model, the VEGF-loaded S-PLGA scaffold shows desirable cell viability and attachment. The bioactivity of released VEGF is validated by intracellular nitric oxide secretion and capillary tube formation, demonstrating the improved capacity of VEGF-mediated pro-angiogenesis ascribed to 26SCS incorporation. Such a strategy will afford an effective method to prepare a scaffold with promoted angiogenesis.

Identification of Sulfated Metabolites of 4-Chlorobiphenyl (PCB3) in the Serum and Urine of Male Rats

PubMed Central

Dhakal, Kiran; He, Xianran; Lehmler, Hans-Joachim; Teesch, Lynn M.; Duffel, Michael W.; Robertson, Larry W.

2012-01-01

Polychlorinated biphenyls (PCBs) are legacy pollutants that exert toxicities through various mechanisms. In the recent years exposure to PCBs via inhalation has been recognized as a hazard. Those PCBs with lower numbers of chlorine atoms (LC-PCBs) are semi-volatile, and have been reported in the urban air, as well as in the indoor air of older buildings. LC-PCBs are bioactivated to phenols and further to quinone electrophiles with genotoxic/carcinogenic potential. We hypothesized that phenolic LC-PCBs are subject to conjugation and excretion in the urine. PCB3, often present in high concentrations in air, is a prototypical congener for the study of the metabolism and toxicity of LC-PCBs. Our objective was to identify metabolites of PCB3 in urine that could be potentially employed in the estimation of exposure to LC-PCBs. Male Sprague Dawley rats (150–175 g) were housed in metabolism cages and received a single intraperitoneal injection of 600 µmol/kg body weight of PCB3. Urine was collected every four hours; rats were euthanized at 36 h and serum was collected. LC-MS analysis of urine before and after incubation with β-glucuronidase and sulfatase showed that sulfate conjugates were in higher concentrations than glucuronide conjugates and free phenolic forms. At least two major metabolites, and two minor metabolites were identified in urine that could be attributed to mercapturic acid metabolites of PCB3. Quantitation by authentic standards confirmed that approximately 3% of the dose was excreted in the urine as sulfates over 36 hours; with peak excretion occurring at 10–20 h after exposure. The major metabolites were 4’PCB3 sulfate, 3’PCB3 sulfate, 2’PCB3 sulfate, and presumably a catechol sulfate. The serum concentration of 4’PCB3 sulfate was 6.18±2.16 µg/mL. This is the first report that sulfated metabolites of PCBs are formed in vivo. These findings suggest a prospective approach for exposure assessment of LC- PCBs by analysis of phase II

Sulfated alpha-L-galactans from the sea urchin ovary: selective 6-desulfation as eggs are spawned.

PubMed

Cinelli, Leonardo P; Andrade, Leonardo; Valente, Ana Paula; Mourão, Paulo A S

2010-06-01

The sea urchin eggs are surrounded by a jelly coat, which contains sulfated polysaccharides with unique structures. These molecules are responsible for inducing the species-specific acrosome reaction, an obligatory event for the binding of sperm and fusion with the egg. The mechanism of biosynthesis of these sulfated polysaccharides is virtually unknown. The egg jelly of the sea urchin Echinometra lucunter contains a simple 2-sulfated, 3-linked alpha-L-galactan. Here, we pulse labeled the sea urchin ovary in vitro with (35)S-sulfate to follow the biosynthesis of the sulfated alpha-L-galactan. We found that the ovary contains a 2,6-disulfated, 3-linked alpha-L-galactan, which incorporates (35)S-sulfate more avidly than the 2-sulfated isoform. The 2,6-disulfated alpha-L-galactan was purified by anion exchange chromatography, analyzed by electrophoresis and characterized by 1D and 2D nuclear magnetic resonance spectra. We also investigated the location of the sulfated polysaccharides on the oocytes using histochemical procedures. The stain revealed high amounts of sulfated polysaccharide in mature oocytes and accessory cells. The amount of intracellular sulfated polysaccharides decreased as oocytes are spawned. We speculate that 2,6-disulfated galactan is initially synthesized in the ovary and that 6-sulfate ester is removed when the polysaccharide is secreted into the egg jelly. Similar events related to remodeling of sulfated polysaccharides have been reported in other biological systems.

Improved Reagents for Newborn Screening of Mucopolysaccharidosis Types I, II, and VI by Tandem Mass Spectrometry

PubMed Central

2015-01-01

Tandem mass spectrometry for the multiplex and quantitative analysis of enzyme activities in dried blood spots on newborn screening cards has emerged as a powerful technique for early assessment of lysosomal storage diseases. Here we report the design and process-scale synthesis of substrates for the enzymes α-l-iduronidase, iduronate-2-sulfatase, and N-acetylgalactosamine-4-sulfatase that are used for newborn screening of mucopolysaccharidosis types I, II, and VI. The products contain a bisamide unit that is hypothesized to readily protonate in the gas phase, which improves detection sensitivity by tandem mass spectrometry. The products contain a benzoyl group, which provides a useful site for inexpensive deuteration, thus facilitating the preparation of internal standards for the accurate quantification of enzymatic products. Finally, the reagents are designed with ease of synthesis in mind, thus permitting scale-up preparation to support worldwide newborn screening of lysosomal storage diseases. The new reagents provide the most sensitive assay for the three lysosomal enzymes reported to date as shown by their performance in reactions using dried blood spots as the enzyme source. Also, the ratio of assay signal to that measured in the absence of blood (background) is superior to all previously reported mucopolysaccharidosis types I, II, and VI assays. PMID:24694010

Fetal Hypothalamus-Pituitary-Adrenal Responses to Estradiol Sulfate

PubMed Central

2011-01-01

Estradiol (E2) is an important modifier of the activity of the fetal hypothalamus-pituitary-adrenal axis. We have reported that estradiol-3-sulfate (E2SO4) circulates in fetal blood in far higher concentrations than E2 and that the fetal brain expresses steroid sulfatase, required for local deconjugation of E2SO4. We performed the present study to test the hypothesis that chronic infusion of E2SO4 chronically increases ACTH and cortisol secretion and that it shortens gestation. Chronically catheterized fetal sheep were treated with E2SO4 intracerebroventricular (n = 5), E2SO4 iv (n = 4), or no steroid infusion (control group, n = 5). Fetuses were subjected to arterial blood sampling every other day until spontaneous birth for plasma hormone analysis. Treatment with E2SO4 attenuated preparturient increases in ACTH secretion near term without affecting the ontogenetic rise in plasma cortisol. Infusion of E2SO4 intracerebroventricularly significantly increased plasma E2, plasma E2SO4, and plasma progesterone and shortened gestation compared with all other groups. These results are consistent with the conclusion that E2SO4: 1) interacts with the hypothalamus-pituitary-adrenal axis primarily by stimulating cortisol secretion and inhibiting ACTH and pro-ACTH secretion by negative feedback; and 2) stimulates the secretion of E2 and E2SO4. We conclude that the endocrine response to E2SO4 in the fetus is not identical with the response to E2. PMID:21952234

LC-MS n Analysis of Isomeric Chondroitin Sulfate Oligosaccharides Using a Chemical Derivatization Strategy

NASA Astrophysics Data System (ADS)

Huang, Rongrong; Pomin, Vitor H.; Sharp, Joshua S.

2011-09-01

Improved methods for structural analyses of glycosaminoglycans (GAGs) are required to understand their functional roles in various biological processes. Major challenges in structural characterization of complex GAG oligosaccharides using liquid chromatography-mass spectrometry (LC-MS) include the accurate determination of the patterns of sulfation due to gas-phase losses of the sulfate groups upon collisional activation and inefficient on-line separation of positional sulfation isomers prior to MS/MS analyses. Here, a sequential chemical derivatization procedure including permethylation, desulfation, and acetylation was demonstrated to enable both on-line LC separation of isomeric mixtures of chondroitin sulfate (CS) oligosaccharides and accurate determination of sites of sulfation by MS n . The derivatized oligosaccharides have sulfate groups replaced with acetyl groups, which are sufficiently stable to survive MS n fragmentation and reflect the original sulfation patterns. A standard reversed-phase LC-MS system with a capillary C18 column was used for separation, and MS n experiments using collision-induced dissociation (CID) were performed. Our results indicate that the combination of this derivatization strategy and MS n methodology enables accurate identification of the sulfation isomers of CS hexasaccharides with either saturated or unsaturated nonreducing ends. Moreover, derivatized CS hexasaccharide isomer mixtures become separable by LC-MS method due to different positions of acetyl modifications.

Partial replacement of dietary linoleic acid with long chain n-3 polyunsaturated fatty acids protects against dextran sulfate sodium-induced colitis in rats.

PubMed

Tyagi, Anupama; Kumar, Uday; Santosh, Vadakattu Sai; Reddy, Suryam; Mohammed, Saazida Bhanu; Ibrahim, Ahamed

2014-12-01

Imbalances in the dietary n-6 and n-3 polyunsaturated fatty acids have been implicated in the increased prevalence of inflammatory bowel disease. This study investigated the effects of substitution of linoleic acid with long chain n-3 polyunsaturated fatty acids and hence decreasing n-6:n-3 fatty acid ratio on inflammatory response in dextran sulfate sodium induced colitis. Male weanling Sprague Dawley rats were fed diets with n-6:n-3 fatty acid in the ratios of 215,50,10 or 5 for 3 months and colitis was induced by administration of dextran sulfate sodium in drinking water during last 11 days. Decreasing the dietary n-6:n-3 fatty acid ratio to 10 and 5 significantly attenuated the severity of colitis as evidenced by improvements in clinical symptoms, reversal of shortening of colon length, reduced severity of anemia, preservation of colonic architecture as well as reduced colonic mucosal myeloperoxidase activity. This protection was associated with suppression of colonic mucosal proinflammatory mediators such as TNFα, IL-1β and nitric oxide. These findings suggest that long chain n-3 polyunsaturated fatty acids at a level of 3.0 g/kg diet (n-6:n-3 ratio of 10) prevents dextran sulfate sodium induced colitis by suppressing the proinflammatory mediators. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neurosteroid-like Inhibitors of N-Methyl-d-aspartate Receptor: Substituted 2-Sulfates and 2-Hemisuccinates of Perhydrophenanthrene.

PubMed

Slavikova, Barbora; Chodounska, Hana; Nekardova, Michaela; Vyklicky, Vojtech; Ladislav, Marek; Hubalkova, Pavla; Krausova, Barbora; Vyklicky, Ladislav; Kudova, Eva

2016-05-26

N-Methyl-d-aspartate receptors (NMDARs) display a critical role in various diseases of the central nervous system. The activity of NMDARs can be modulated by neurosteroids. Herein, we report a structure-activity relationship study for perhydrophenanthrene analogues possessing a framework that mimics the steroidal ring system. This study comprises the design, synthesis, and assessment of the biological activity of a library of perhydrophenanthrene 2-sulfates and 2-hemisuccinates (1-10). Their ability to modulate NMDAR-induced currents was tested on recombinant GluN1/GluN2B receptors. Our results demonstrate that such structural optimization leads to compounds that are inhibitors of NMDARs. Notably, compound 9 (IC50 = 15.6 μM) was assessed as a more potent inhibitor of NMDAR-induced currents than the known endogenous neurosteroid, pregnanolone sulfate (IC50 = 24.6 μM).

Histochemical Characterization of Oocytes in the Pink Cuskeel (Genypterus blacodes).

PubMed

Cohen, Stefanía; Petcoff, Gladys; Freijo, Roberto O; Portiansky, Enrique L; Barbeito, Claudio G; Macchi, Gustavo J; Díaz, Alcira O

2015-08-01

In the present study we histochemically and lectinhistochemically characterized the growing oocytes of the pink cuskeel (Genypterus blacodes). We used histochemical methods for the localization and characterization of glycoconjugates (GCs) and lectin histochemical techniques for the identification of specific sugar residues. We analyzed presence and distribution of GCs in the different structures of the growing follicles (cortical alveoli, globules, yolk granules and zona radiata). During the initial stage of vitellogenesis, the oocytes presented small yolk granules composed of GCs that gradually increased during exogenous vitellogenesis. These GCs contained moderate quantities of α-D-mannose, D-glucose, N-acetylglucosamine and N-acetyl-neuraminic acid. The cortical alveoli contained both neutral and carboxylated GCs, and lectin techniques detected N-acetylgalactosamine, galactose and L-fucose. The zona radiata showed a strong positive reaction to PAS and it reacted weakly with more specific techniques, such as KOH/PA*S and PA/Bh/KOH/PAS. This structure showed GCs with oxidizable vicinal diols, O-acyl sugars and sialic acid residues with different substitution types and presented N-acetylgalactosamine and L-fucose specific residues. The oocytes follicular envelope evidenced neutral and acidic non-sulfated GCs and high concentrations of α-D-mannose, D-glucose, galactose and N-acetylgalactosamine. The intergranular cytoplasmic GCs were mainly rich in α-D-mannose, D-glucose, N-acetylgalactosamine, N-acetylglucosamine and N-acetyl-neuraminic acid. These results enhance the comprehension of the structure and functionality of the pink cuskeel ovarian follicles, and provide a useful tool for the study of this tissue in other teleost species.

Is enzymatic hydrolysis a reliable analytical strategy to quantify glucuronidated and sulfated polyphenol metabolites in human fluids?

PubMed

Quifer-Rada, Paola; Martínez-Huélamo, Miriam; Lamuela-Raventos, Rosa M

2017-07-19

Phenolic compounds are present in human fluids (plasma and urine) mainly as glucuronidated and sulfated metabolites. Up to now, due to the unavailability of standards, enzymatic hydrolysis has been the method of choice in analytical chemistry to quantify these phase II phenolic metabolites. Enzymatic hydrolysis procedures vary in enzyme concentration, pH and temperature; however, there is a lack of knowledge about the stability of polyphenols in their free form during the process. In this study, we evaluated the stability of 7 phenolic acids, 2 flavonoids and 3 prenylflavanoids in urine during enzymatic hydrolysis to assess the suitability of this analytical procedure, using three different concentrations of β-glucuronidase/sulfatase enzymes from Helix pomatia. The results indicate that enzymatic hydrolysis negatively affected the recovery of the precursor and free-form polyphenols present in the sample. Thus, enzymatic hydrolysis does not seem an ideal analytical strategy to quantify glucuronidated and sulfated polyphenol metabolites.

Cooperative alpha-helix formation of beta-lactoglobulin induced by sodium n-alkyl sulfates.

PubMed

Chamani, J; Moosavi-Movahedi, A A; Rajabi, O; Gharanfoli, M; Momen-Heravi, M; Hakimelahi, G H; Neamati-Baghsiah, A; Varasteh, A R

2006-01-01

It is generally assumed that folding intermediates contain partially formed native-like secondary structures. However, if we consider the fact that the conformational stability of the intermediate state is simpler than that of the native state, it would be expected that the secondary structures in a folding intermediate would not necessarily be similar to those of the native state. beta-Lactoglobulin is a predominantly beta-sheet protein, although it has a markedly high intrinsic preference for alpha-helical structure. The formation of non-native alpha-helical intermediate of beta-lactoglobulin was induced by n-alkyl sulfates including sodium octyl sulfate, SOS; sodium decyl sulfate, SDeS; sodium dodecyl sulfate, SDS; and sodium tetradecyl sulfate, STS at special condition. The effect of n-alkyl sulfates on the structure of native beta-lactoglobulin at pH 2 was utilized to investigate the contribution of hydrophobic interactions to the stability of non-native alpha-helical intermediate. The addition of various concentrations of n-alkyl sulfates to the native state of beta-lactoglobulin (pH 2) appears to support the stabilized form of non-native alpha-helical intermediate at pH 2. The m values of the intermediate state of beta-lactoglobulin by SOS, SDeS, SDS and STS showed substantial variation. The enhancement of m values as the stability criterion of non-native alpha-helical intermediate state corresponded with increasing chain length of the cited n-alkyl sulfates. The present results suggest that the folding reaction of beta-lactoglobulin follows a non-hierarchical mechanism and hydrophobic interactions play important roles in stabilizing the non-native alpha-helical intermediate state.

Electron spin resonance and electron spin echo modulation of n-doxylstearic acid and N,N,N',N'-tetramethylbenzidine photoionization in sodium versus lithium dodecyl sulfate micellar solutions: effect of 15-crown-5 and 18-crown-6 ether addition

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baglioni, P.; Rivara-Minten, E.; Kevan, L.

1988-08-11

Electron spin echo modulation and electron spin resonance spectra of photogenerated N,N,N',N'-tetramethylbenzidine (TMB) cation radical and n-doxylstearic acids (n-DSA) in frozen micellar solutions of sodium and lithium dodecyl sulfate containing 15-crown-5 and 18-crown-6 ethers in D/sub 2/O have been studied as a function of crown ether concentration. Modulation effects due to N-DSA with water deuteriums give direct evidence that both crown ethers are mainly located at the micellar interface and that this causes a decrease of the hydration of the micellar interface. Crown ether complexation constants for sodium and lithium micellar counterions are reported and show that 18-crown-6 > 15-crown-5more » for sodium counterion and 15-crown-5 > 18-crown-6 for lithium counterion. Modulation effects from TMB/sup +/ interaction with water deuteriums indicate that the TMB molecule moves toward the micelle interfacial region when sodium or lithium cations are complexed by crown ethers. The TMB/sup +/ yield upon TMB photoionization increases by about 10% with crown ether addition for SDS and LDS micellar systems, but it is greater if the absolute values for the LDS system are compared to those for the SDS micellar system. This behavior correlates with the strength of TMB/sup +/-water interactions and suggests that the main factor in the photoionization efficiency is the photocation-water interaction.« less

Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part II: combination with external radiation improves survival

PubMed Central

Kushchayev, Sergiy V; Sankar, Tejas; Eggink, Laura L; Kushchayeva, Yevgeniya S; Wiener, Philip C; Hoober, J Kenneth; Eschbacher, Jennifer; Liu, Ruolan; Shi, Fu-Dong; Abdelwahab, Mohammed G; Scheck, Adrienne C; Preul, Mark C

2012-01-01

Background A peptide mimetic of a ligand for the galactose/N-acetylgalactosamine-specific C-type lectin receptors (GCLR) exhibited monocyte-stimulating activity, but did not extend survival when applied alone against a syngeneic murine malignant glioma. In this study, the combined effect of GCLRP with radiation was investigated. Methods C57BL/6 mice underwent stereotactic intracranial implantation of GL261 glioma cells. Animals were grouped based on randomized tumor size by magnetic resonance imaging on day seven. One group that received cranial radiation (4 Gy on days seven and nine) only were compared with animals treated with radiation and GCLRP (4 Gy on days seven and nine combined with subcutaneous injection of 1 nmol/g on alternative days beginning on day seven). Magnetic resonance imaging was used to assess tumor growth and correlated with survival rate. Blood and brain tissues were analyzed with regard to tumor and contralateral hemisphere using fluorescence-activated cell sorting analysis, histology, and enzyme-linked immunosorbent assay. Results GCLRP activated peripheral monocytes and was associated with increased blood precursors of dendritic cells. Mean survival increased (P < 0.001) and tumor size was smaller (P < 0.02) in the GCLRP + radiation group compared to the radiation-only group. Accumulation of dendritic cells in both the tumoral hemisphere (P < 0.005) and contralateral tumor-free hemisphere (P < 0.01) was associated with treatment. Conclusion Specific populations of monocyte-derived brain cells develop critical relationships with malignant gliomas. The biological effect of GCLRP in combination with radiation may be more successful because of the damage incurred by tumor cells by radiation and the enhanced or preserved presentation of tumor cell antigens by GCLRP-activated immune cells. Monocyte-derived brain cells may be important targets for creating effective immunological modalities such as employing the receptor system described in this

Monocyte galactose/N-acetylgalactosamine-specific C-type lectin receptor stimulant immunotherapy of an experimental glioma. Part II: combination with external radiation improves survival.

PubMed

Kushchayev, Sergiy V; Sankar, Tejas; Eggink, Laura L; Kushchayeva, Yevgeniya S; Wiener, Philip C; Hoober, J Kenneth; Eschbacher, Jennifer; Liu, Ruolan; Shi, Fu-Dong; Abdelwahab, Mohammed G; Scheck, Adrienne C; Preul, Mark C

2012-01-01

A peptide mimetic of a ligand for the galactose/N-acetylgalactosamine-specific C-type lectin receptors (GCLR) exhibited monocyte-stimulating activity, but did not extend survival when applied alone against a syngeneic murine malignant glioma. In this study, the combined effect of GCLRP with radiation was investigated. C57BL/6 mice underwent stereotactic intracranial implantation of GL261 glioma cells. Animals were grouped based on randomized tumor size by magnetic resonance imaging on day seven. One group that received cranial radiation (4 Gy on days seven and nine) only were compared with animals treated with radiation and GCLRP (4 Gy on days seven and nine combined with subcutaneous injection of 1 nmol/g on alternative days beginning on day seven). Magnetic resonance imaging was used to assess tumor growth and correlated with survival rate. Blood and brain tissues were analyzed with regard to tumor and contralateral hemisphere using fluorescence-activated cell sorting analysis, histology, and enzyme-linked immunosorbent assay. GCLRP activated peripheral monocytes and was associated with increased blood precursors of dendritic cells. Mean survival increased (P < 0.001) and tumor size was smaller (P < 0.02) in the GCLRP + radiation group compared to the radiation-only group. Accumulation of dendritic cells in both the tumoral hemisphere (P < 0.005) and contralateral tumor-free hemisphere (P < 0.01) was associated with treatment. Specific populations of monocyte-derived brain cells develop critical relationships with malignant gliomas. The biological effect of GCLRP in combination with radiation may be more successful because of the damage incurred by tumor cells by radiation and the enhanced or preserved presentation of tumor cell antigens by GCLRP-activated immune cells. Monocyte-derived brain cells may be important targets for creating effective immunological modalities such as employing the receptor system described in this study.

Effect of sulfate fertilization on soil biota in grassland columns

NASA Astrophysics Data System (ADS)

Ikoyi, Israel; Donohue, John; Fowler, Andrew; Schmalenberger, Achim

2017-04-01

Sulfur (S) is an important macronutrient element in plant nutrition as a component of protein, enzymes, enzyme cofactors as well as being the major constituent of the amino acids cysteine and methionine. Organically bound S is the predominant form of S in the soil constituting up to 95% of S in agricultural soils. The most important form of S in terms of plant nutrition is inorganic sulfate which forms only about 5% of the total soil S content. Air pollution was the major source of S (as SO2) for plants, with up to 80% of the S obtained from this source. However, common effects of S limitation on crops such as chlorosis, yield reduction, and decrease in crop quality are becoming increasingly evident as atmospheric S supply has decreased in recent years. Recent research has shown that organically-bound S in soils is also plant-bioavailable, likely due to interconversion of organic S forms to inorganic sulfate by soil microbes. In this study, soil columns were setup in a greenhouse using moderate S (equivalent to Wisconsin S soil availability index of below 30) soils. The columns were planted with Lolium perenne and fertilized with 0 (control), 5 (low), 10 (medium) and 20 (high) kg/ha sulfate S alongside a full complement of other nutrients. Results after 14 weeks of management show a significant decrease (P<0.05) in aryl sulfatase activity, mycorrhizal hyphal and arbuscular colonization rates in the high and medium S treatments but no significant effect on bacterial abundance of heterotrophs and aromatic sulfonate-utilizing bacteria upon S fertilization. In addition, soil from the top 20 cm of the column had significantly higher sulfatase activity compared to the bottom 20 cm. The medium and high S treatments had significantly higher grass dry matter yield compared to the control and low S treatments. All S treatments significantly shifted the bacterial community structure compared to the control. Overall, our preliminary results suggest that applying 5 kg/ ha S had

Oncogenic BRAFV600E drives expression of MGL ligands in the colorectal cancer cell line HT29 through N-acetylgalactosamine-transferase 3.

PubMed

Sahasrabudhe, Neha M; Lenos, Kristiaan; van der Horst, Joost C; Rodríguez, Ernesto; van Vliet, Sandra J

2018-06-27

Colorectal cancer is the third most common cancer type worldwide. It is characterized by a high expression of aberrantly glycosylated ligands, such as the Tn antigen (GalNAcα1-Ser/Thr), which is a major ligand for the C-type lectin macrophage galactose-type lectin (MGL). We have previously determined that a high level of MGL ligands in colorectal tumors is associated with lower disease-free survival in patients with late stage disease, which we could attribute to the presence of oncogenic BRAFV600E mutations. Here we aimed to elucidate the downstream pathway of BRAFV600E governing high MGL ligand and Tn antigen expression. We focused on glycosylation-related enzymes involved in the synthesis or elongation of Tn antigen, N-acetylgalactosamine-transferases (GALNTs) and C1GalT1/COSMC, respectively. Both the activity and expression of C1GalT1 and COSMC were unrelated to the BRAF mutational status. In contrast, GALNT3, GALNT7 and GALNT12 were increased in colorectal cancer cells harboring the BRAFV600E mutation. Through CRISPR-Cas9 gene knockouts we could establish that GALNT3 increased MGL ligand synthesis in the HT29 cell line, while GALNT7 and GALNT12 appeared to have redundant roles. Together our results highlight a novel mechanistic pathway connecting BRAFV600E to aberrant glycosylation in colorectal cancer through GALNT3.

Purification of N-Acetylgalactosaminidase by Isoelectric Focusing.

DTIC Science & Technology

1983-04-02

aminocaproic acid and histidyl glycine were tried. Focusing in his tidyl glycine separated the galactosidase activity into 2 peaks but did not separate...under acidic conditions. N-acetylgalactosamine was shown to be a competitive inhibitor with a K of 10.1 mM. The KM for p-NP- a-GALNAc was 6.6 mM. In...ampholyte was prepared by the copolymerization of acrylic acid with pentaethylene hexamine (PEHA) as described by Vinogradov et al. (Biochem. Biophys. Res

Highly sulfated hexasaccharide sequences isolated from chondroitin sulfate of shark fin cartilage: insights into the sugar sequences with bioactivities.

PubMed

Mizumoto, Shuji; Murakoshi, Saori; Kalayanamitra, Kittiwan; Deepa, Sarama Sathyaseelan; Fukui, Shigeyuki; Kongtawelert, Prachya; Yamada, Shuhei; Sugahara, Kazuyuki

2013-02-01

Chondroitin sulfate (CS) chains regulate the development of the central nervous system in vertebrates and are linear polysaccharides consisting of variously sulfated repeating disaccharides, [-4GlcUAβ1-3GalNAcβ1-](n), where GlcUA and GalNAc represent D-glucuronic acid and N-acetyl-D-galactosamine, respectively. CS chains containing D-disaccharide units [GlcUA(2-O-sulfate)-GalNAc(6-O-sulfate)] are involved in the development of cerebellar Purkinje cells and neurite outgrowth-promoting activity through interaction with a neurotrophic factor, pleiotrophin, resulting in the regulation of signaling. In this study, to obtain further structural information on the CS chains containing d-disaccharide units involved in brain development, oligosaccharides containing D-units were isolated from a shark fin cartilage. Seven novel hexasaccharide sequences, ΔO-D-D, ΔA-D-D, ΔC-D-D, ΔE-A-D, ΔD-D-C, ΔE-D-D and ΔA-B-D, in addition to three previously reported sequences, ΔC-A-D, ΔC-D-C and ΔA-D-A, were isolated from a CS preparation of shark fin cartilage after exhaustive digestion with chondroitinase AC-I, which cannot act on the galactosaminidic linkages bound to D-units. The symbol Δ stands for a 4,5-unsaturated bond of uronic acids, whereas A, B, C, D, E and O represent [GlcUA-GalNAc(4-O-sulfate)], [GlcUA(2-O-sulfate)-GalNAc(4-O-sulfate)], [GlcUA-GalNAc(6-O-sulfate)], [GlcUA(2-O-sulfate)-GalNAc(6-O-sulfate)], [GlcUA-GalNAc(4-O-, 6-O-sulfate)] and [GlcUA-GalNAc], respectively. In binding studies using an anti-CS monoclonal antibody, MO-225, the epitopes of which are involved in cerebellar development in mammals, novel epitope structures, ΔA-D-A, ΔA-D-D and ΔA-B-D, were revealed. Hexasaccharides containing two consecutive D-units or a B-unit will be useful for the structural and functional analyses of CS chains particularly in the neuroglycobiological fields.

Inter vs. intraglycosidic acetal linkages control sulfation pattern in semi-synthetic chondroitin sulfate.

PubMed

Laezza, Antonio; De Castro, Cristina; Parrilli, Michelangelo; Bedini, Emiliano

2014-11-04

Microbial-sourced unsulfated chondroitin could be converted into chondroitin sulfate (CS) polysaccharide by a multi-step strategy relying upon benzylidenation and acetylation reactions as key-steps for its regioselective protection. By conducting the two reactions one- or two-pots, CSs with different sulfation patterns could be obtained at the end of the semi-synthesis. In particular, a CS polysaccharide possessing sulfate groups randomly distributed between positions 4 and 6 of N-acetyl-galactosamine (GalNAc) units could be obtained through the two-pots route, whereas the one-pot pathway allowed an additional sulfation at position 3 of some glucuronic acid (GlcA) units. This difference was ascribed to the stabilization of a labile interglycosidic benzylidene acetal involving positions O-3 and O-6 of some GlcA and GalNAc, respectively, when the benzylidene-acetylation reactions were conducted in a one-pot fashion. Isolation and characterization of a polysaccharide intermediate showing interglycosidic acetal moieties was accomplished. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genetic and Pharmacological Modulation of the Steroid Sulfatase Axis Improves Response Control; Comparison with Drugs Used in ADHD

PubMed Central

Davies, William; Humby, Trevor; Trent, Simon; Eddy, Jessica B; Ojarikre, Obah A; Wilkinson, Lawrence S

2014-01-01

Maladaptive response control is a feature of many neuropsychiatric conditions, including attention deficit hyperactivity disorder (ADHD). As ADHD is more commonly diagnosed in males than females, a pathogenic role for sex-linked genes has been suggested. Deletion or point mutation of the X-linked STS gene, encoding the enzyme steroid sulfatase (STS) influences risk for ADHD. We examined whether deletion of the Sts gene in the 39,XY*O mouse model, or pharmacological manipulation of the STS axis, via administration of the enzyme substrate dehydroepiandrosterone sulfate or the enzyme inhibitor COUMATE, influenced behavior in a novel murine analog of the stop-signal reaction time task used to detect inhibitory deficits in individuals with ADHD. Unexpectedly, both the genetic and pharmacological treatments resulted in enhanced response control, manifest as highly specific effects in the ability to cancel a prepotent action. For all three manipulations, the effect size was comparable to that seen with the commonly used ADHD therapeutics methylphenidate and atomoxetine. Hence, converging genetic and pharmacological evidence indicates that the STS axis is involved in inhibitory processes and can be manipulated to give rise to improvements in response control. While the precise neurobiological mechanism(s) underlying the effects remain to be established, there is the potential for exploiting this pathway in the treatment of disorders where failures in behavioral inhibition are prominent. PMID:24842408

40 CFR 721.2465 - Xanthylium, 9-(2-(ethoxycarbonyl)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate.

Code of Federal Regulations, 2013 CFR

2013-07-01

...)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate. 721.2465 Section 721.2465 Protection of...-(ethoxycarbonyl)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate. (a) Chemical substance and significant...-(ethoxycarbonyl)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate (PMN P-00-1195; CAS No. 26694-69-9) is...

40 CFR 721.2465 - Xanthylium, 9-(2-(ethoxycarbonyl)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate.

Code of Federal Regulations, 2012 CFR

2012-07-01

...)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate. 721.2465 Section 721.2465 Protection of...-(ethoxycarbonyl)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate. (a) Chemical substance and significant...-(ethoxycarbonyl)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate (PMN P-00-1195; CAS No. 26694-69-9) is...

40 CFR 721.2465 - Xanthylium, 9-(2-(ethoxycarbonyl)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate.

Code of Federal Regulations, 2011 CFR

2011-07-01

...)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate. 721.2465 Section 721.2465 Protection of...-(ethoxycarbonyl)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate. (a) Chemical substance and significant...-(ethoxycarbonyl)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate (PMN P-00-1195; CAS No. 26694-69-9) is...

40 CFR 721.2465 - Xanthylium, 9-(2-(ethoxycarbonyl)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate.

Code of Federal Regulations, 2014 CFR

2014-07-01

...)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate. 721.2465 Section 721.2465 Protection of...-(ethoxycarbonyl)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate. (a) Chemical substance and significant...-(ethoxycarbonyl)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate (PMN P-00-1195; CAS No. 26694-69-9) is...

Effect of sulfation on the surface activity of CaO for N2O decomposition

NASA Astrophysics Data System (ADS)

Wu, Lingnan; Hu, Xiaoying; Qin, Wu; Dong, Changqing; Yang, Yongping

2015-12-01

Limestone addition to circulating fluidized bed boilers for sulfur removal affects nitrous oxide (N2O) emission at the same time, but mechanism of how sulfation process influences the surface activity of CaO for N2O decomposition remains unclear. In this paper, we investigated the effect of sulfation on the surface properties and catalytic activity of CaO for N2O decomposition using density functional theory calculations. Sulfation of CaO (1 0 0) surface by the adsorption of a single gaseous SO2 or SO3 molecule forms stable local CaSO3 or CaSO4 on the CaO (1 0 0) surface with strong hybridization between the S atom of SOx and the surface O anion. The formed local CaSO3 increases the barrier energy of N2O decomposition from 0.989 eV (on the CaO (1 0 0) surface) to 1.340 eV, and further sulfation into local CaSO4 remarkably increases the barrier energy to 2.967 eV. Sulfation from CaSO3 into CaSO4 is therefore the crucial step for deactivating the surface activity for N2O decomposition. Completely sulfated CaSO4 (0 0 1) and (0 1 0) surfaces further validate the negligible catalytic ability of CaSO4 for N2O decomposition.

Reduced Sulfation of Chondroitin Sulfate but Not Heparan Sulfate in Kidneys of Diabetic db/db Mice

PubMed Central

Reine, Trine M.; Grøndahl, Frøy; Jenssen, Trond G.; Hadler-Olsen, Elin; Prydz, Kristian

2013-01-01

Heparan sulfate proteoglycans are hypothesized to contribute to the filtration barrier in kidney glomeruli and the glycocalyx of endothelial cells. To investigate potential changes in proteoglycans in diabetic kidney, we isolated glycosaminoglycans from kidney cortex from healthy db/+ and diabetic db/db mice. Disaccharide analysis of chondroitin sulfate revealed a significant decrease in the 4-O-sulfated disaccharides (D0a4) from 65% to 40%, whereas 6-O-sulfated disaccharides (D0a6) were reduced from 11% to 6%, with a corresponding increase in unsulfated disaccharides. In contrast, no structural differences were observed in heparan sulfate. Furthermore, no difference was found in the molar amount of glycosaminoglycans, or in the ratio of hyaluronan/heparan sulfate/chondroitin sulfate. Immunohistochemical staining for the heparan sulfate proteoglycan perlecan was similar in both types of material but reduced staining of 4-O-sulfated chondroitin and dermatan was observed in kidney sections from diabetic mice. In support of this, using qRT-PCR, a 53.5% decrease in the expression level of Chst-11 (chondroitin 4-O sulfotransferase) was demonstrated in diabetic kidney. These results suggest that changes in the sulfation of chondroitin need to be addressed in future studies on proteoglycans and kidney function in diabetes. PMID:23757342

Reduced sulfation of chondroitin sulfate but not heparan sulfate in kidneys of diabetic db/db mice.

PubMed

Reine, Trine M; Grøndahl, Frøy; Jenssen, Trond G; Hadler-Olsen, Elin; Prydz, Kristian; Kolset, Svein O

2013-08-01

Heparan sulfate proteoglycans are hypothesized to contribute to the filtration barrier in kidney glomeruli and the glycocalyx of endothelial cells. To investigate potential changes in proteoglycans in diabetic kidney, we isolated glycosaminoglycans from kidney cortex from healthy db/+ and diabetic db/db mice. Disaccharide analysis of chondroitin sulfate revealed a significant decrease in the 4-O-sulfated disaccharides (D0a4) from 65% to 40%, whereas 6-O-sulfated disaccharides (D0a6) were reduced from 11% to 6%, with a corresponding increase in unsulfated disaccharides. In contrast, no structural differences were observed in heparan sulfate. Furthermore, no difference was found in the molar amount of glycosaminoglycans, or in the ratio of hyaluronan/heparan sulfate/chondroitin sulfate. Immunohistochemical staining for the heparan sulfate proteoglycan perlecan was similar in both types of material but reduced staining of 4-O-sulfated chondroitin and dermatan was observed in kidney sections from diabetic mice. In support of this, using qRT-PCR, a 53.5% decrease in the expression level of Chst-11 (chondroitin 4-O sulfotransferase) was demonstrated in diabetic kidney. These results suggest that changes in the sulfation of chondroitin need to be addressed in future studies on proteoglycans and kidney function in diabetes.

Synthesis of disulfated peptides corresponding to the N-terminus of chemokines receptors CXCR6 (CXCR6 1-20) and DARC (DARC 8-42) using a sulfate-protecting group strategy.

PubMed

Ali, Ahmed M; Taylor, Scott D

2010-04-01

Tyrosine sulfation is a post translational modification that occurs on integral membrane and secreted proteins, and is required for mediating crucial biological processes. Until recently the synthesis of sTyr peptides, especially those containing multiple sTyr residues, were among the most challenging peptides to prepare. We recently described an efficient strategy for Fmoc-based solid phase synthesis of sTyr peptides in which the sulfate group in the sTyr residue(s) is protected with a DCV group (FmocTyr(SO(3)DCV)OH, 1). After cleavage of the peptide from the support the DCV group is removed by hydrogenolysis. Here we demonstrate that sTyr peptides containing Met or Trp residues can be prepared using our sulfate-protecting group strategy by preparing peptides corresponding to residues 1-20 of chemokine receptor CXCR6 and 8-42 of chemokine receptor DARC. Removing the DCV groups at the end of the syntheses was readily achieved, without any reduction of the indole ring in Trp, by performing the hydrogenolysis in the presence of triethylamine. These conditions were found to be particularly efficient for removing the DCV group and superiour to our original conditions using H(2), ammonium formate, Pd/C. The presence of Met was found not to interfere with the removal of the DCV group. The use of pseudoproline dipeptides and N-backbone protection with the 2,4-dimethoxybenzyl group were found to be very effective tactics for preventing aggregation and aspartimide formation during the synthesis of these peptides. We also report an alternative and more cost effective synthesis of amino acid 1. Copyright (c) 2010 European Peptide Society and John Wiley & Sons, Ltd.

Structure of sulfamidase provides insight into the molecular pathology of mucopolysaccharidosis IIIA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sidhu, Navdeep S.; University of Göttingen, Tammannstrasse 4, 37077 Göttingen; Schreiber, Kathrin

2014-05-01

Mucopolysaccharidosis IIIA is a fatal neurodegenerative disease that typically manifests itself in childhood and is caused by mutations in the gene for the lysosomal enzyme sulfamidase. The first structure of this enzyme is presented, which provides insight into the molecular basis of disease-causing mutations, and the enzymatic mechanism is proposed. Mucopolysaccharidosis type IIIA (Sanfilippo A syndrome), a fatal childhood-onset neurodegenerative disease with mild facial, visceral and skeletal abnormalities, is caused by an inherited deficiency of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH; sulfamidase). More than 100 mutations in the SGSH gene have been found to reduce or eliminate its enzymatic activity. However,more » the molecular understanding of the effect of these mutations has been confined by a lack of structural data for this enzyme. Here, the crystal structure of glycosylated SGSH is presented at 2 Å resolution. Despite the low sequence identity between this unique N-sulfatase and the group of O-sulfatases, they share a similar overall fold and active-site architecture, including a catalytic formylglycine, a divalent metal-binding site and a sulfate-binding site. However, a highly conserved lysine in O-sulfatases is replaced in SGSH by an arginine (Arg282) that is positioned to bind the N-linked sulfate substrate. The structure also provides insight into the diverse effects of pathogenic mutations on SGSH function in mucopolysaccharidosis type IIIA and convincing evidence for the molecular consequences of many missense mutations. Further, the molecular characterization of SGSH mutations will lay the groundwork for the development of structure-based drug design for this devastating neurodegenerative disorder.« less

Purification and Characterization of an Inverting Stereo- and Enantioselective sec-Alkylsulfatase from the Gram-Positive Bacterium Rhodococcus ruber DSM 44541

PubMed Central

Pogorevc, Mateja; Faber, Kurt

2003-01-01

Whole cells of Rhodococcus ruber DSM 44541 were found to hydrolyze (±)-2-octyl sulfate in a stereo- and enantiospecific fashion. When growing on a complex medium, the cells produced two sec-alkylsulfatases and (at least) one prim-alkylsulfatase in the absence of an inducer, such as a sec-alkyl sulfate or a sec-alcohol. From the crude cell-free lysate, two proteins responsible for sulfate ester hydrolysis (designated RS1 and RS2) were separated from each other based on their different hydrophobicities and were subjected to further chromatographic purification. In contrast to sulfatase RS1, enzyme RS2 proved to be reasonably stable and thus could be purified to homogeneity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a single band at a molecular mass of 43 kDa. Maximal enzyme activity was observed at 30°C and at pH 7.5. Sulfatase RS2 showed a clear preference for the hydrolysis of linear secondary alkyl sulfates, such as 2-, 3-, or 4-octyl sulfate, with remarkable enantioselectivity (an enantiomeric ratio of up to 21 [23]). Enzymatic hydrolysis of (R)-2-octyl sulfate furnished (S)-2-octanol without racemization, which revealed that the enzymatic hydrolysis proceeded through inversion of the configuration at the stereogenic carbon atom. Screening of a broad palette of potential substrates showed that the enzyme exhibited limited substrate tolerance; while simple linear sec-alkyl sulfates (C7 to C10) were freely accepted, no activity was found with branched and mixed aryl-alkyl sec-sulfates. Due to the fact that prim-sulfates were not accepted, the enzyme was classified as sec-alkylsulfatase (EC 3.1.6.X). PMID:12732552

Mechanism of free radical generation in platelets and primary hepatocytes: A novel electron spin resonance study.

PubMed

Wang, Chiun-Lang; Yang, Po-Sheng; Tsao, Jeng-Ting; Jayakumar, Thanasekaran; Wang, Meng-Jiy; Sheu, Joen-Rong; Chou, Duen-Suey

2018-01-01

Oxygen free radicals have been implicated in the pathogenesis of toxic liver injury and are thought to be involved in cardiac dysfunction in the cirrhotic heart. Therefore, direct evidence for the electron spin resonance (ESR) detection of how D‑galactosamine (GalN), an established experimental hepatotoxic substance, induced free radicals formation in platelets and primary hepatocytes is presented in the present study. ESR results demonstrated that GalN induced hydroxyl radicals (OH•) in a resting human platelet suspension; however, radicals were not produced in a cell free Fenton reaction system. The GalN‑induced OH• formation was significantly inhibited by the cyclooxygenase (COX) inhibitor indomethasin, though it was not affected by the lipoxygenase (LOX) or cytochrome P450 inhibitors, AA861 and 1‑aminobenzotriazole (ABT), in platelets. In addition, the present study demonstrated that baicalein induced semiquinone free radicals in platelets, which were significantly reduced by the COX inhibitor without affecting the formed OH•. In the mouse primary hepatocytes, the formation of arachidonic acid (AA) induced carbon‑centered radicals that were concentration dependently enhanced by GalN. These radicals were inhibited by AA861, though not affected by indomethasin or ABT. In addition, GalN did not induce platelet aggregation prior to or following collagen pretreatment in human platelets. The results of the present study indicated that GalN and baicalein may induce OH• by COX and LOX in human platelets. GalN also potentiated AA induced carbon‑centered radicals in hepatocytes via cytochrome P450. The present study presented the role of free radicals in the pathophysiological association between platelets and hepatocytes.

Isolation, N-glycosylations and Function of a Hyaluronidase-Like Enzyme from the Venom of the Spider Cupiennius salei.

PubMed

Biner, Olivier; Trachsel, Christian; Moser, Aline; Kopp, Lukas; Langenegger, Nicolas; Kämpfer, Urs; von Ballmoos, Christoph; Nentwig, Wolfgang; Schürch, Stefan; Schaller, Johann; Kuhn-Nentwig, Lucia

2015-01-01

Hyaluronidases are important venom components acting as spreading factor of toxic compounds. In several studies this spreading effect was tested on vertebrate tissue. However, data about the spreading activity on invertebrates, the main prey organisms of spiders, are lacking. Here, a hyaluronidase-like enzyme was isolated from the venom of the spider Cupiennius salei. The amino acid sequence of the enzyme was determined by cDNA analysis of the venom gland transcriptome and confirmed by protein analysis. Two complex N-linked glycans akin to honey bee hyaluronidase glycosylations, were identified by tandem mass spectrometry. A C-terminal EGF-like domain was identified in spider hyaluronidase using InterPro. The spider hyaluronidase-like enzyme showed maximal activity at acidic pH, between 40-60°C, and 0.2 M KCl. Divalent ions did not enhance HA degradation activity, indicating that they are not recruited for catalysis. Besides hyaluronan, the enzyme degrades chondroitin sulfate A, whereas heparan sulfate and dermatan sulfate are not affected. The end products of hyaluronan degradation are tetramers, whereas chondroitin sulfate A is mainly degraded to hexamers. Identification of terminal N-acetylglucosamine or N-acetylgalactosamine at the reducing end of the oligomers identified the enzyme as an endo-β-N-acetyl-D-hexosaminidase hydrolase. The spreading effect of the hyaluronidase-like enzyme on invertebrate tissue was studied by coinjection of the enzyme with the Cupiennius salei main neurotoxin CsTx-1 into Drosophila flies. The enzyme significantly enhances the neurotoxic activity of CsTx-1. Comparative substrate degradation tests with hyaluronan, chondroitin sulfate A, dermatan sulfate, and heparan sulfate with venoms from 39 spider species from 21 families identified some spider families (Atypidae, Eresidae, Araneidae and Nephilidae) without activity of hyaluronidase-like enzymes. This is interpreted as a loss of this enzyme and fits quite well the current

Some structural features of the teichuronic acid of Bacillus licheniformis N.C.T.C. 6346 cell walls

PubMed Central

Hughes, R. C.; Thurman, P. F.

1970-01-01

A teichuronic acid, containing glucuronic acid and N-acetylgalactosamine, was purified from acid extracts of Bacillus licheniformis 6346 cell walls as described by Janczura, Perkins & Rogers (1961). After reduction of the carboxyl function of glucuronic acid residues in the polysaccharide the reduced polymer contains equimolar amounts of N-acetylgalactosamine and glucose. Methylation of the reduced polysaccharide by the Hakamori (1964) technique showed the glucose residues to be substituted on C-4. A disaccharide, 3-O-glucuronosylgalactosamine, was isolated from partial acid hydrolysates of teichuronic acid. After N-acetylation the disaccharide produces chromogen readily on heating at pH7, in agreement with C-3 substitution of the reducing N-acetylamino sugar. Teichuronic acid also produces chromogen under the same conditions, with concurrent elimination of a modified polysaccharide from C-3 of reducing terminal N-acetylgalactosamine residues of the teichuronic acid chains. The number-average chain lengths of several preparations of teichuronic acid were estimated from the amounts of chromogen produced in comparison with the N-acetylated disaccharide. The values obtained are in good agreement with the weight-average molecular weight determined by ultracentrifugal analysis. The reducing terminals of teichuronic acid are shown to be exclusively N-acetylgalactosamine by reduction with sodium boro[3H]hydride. The number-average chain lengths of the teichuronic acid preparations were estimated by the extent of in corporation of tritium and are in agreement with values obtained by the other methods. PMID:5419741

The Effect of Multiple Sulfatase Deficiency (MSD) on Dental Development: Can We Use the Teeth as an Early Diagnostic Tool?

PubMed

Zilberman, Uri; Bibi, Haim

2016-01-01

Multiple sulfatase deficiency (MSD) is a rare autosomal recessive inborn error of metabolism due to reduced catalytic activity of the different sulfatase. Affected individuals show neurologic deterioration with mental retardation, skeletal anomalies, organomegaly, and skin changes as in X-linked ichthyosis. The only organ that was not examined in MSD patients is the dentition. To evaluate the effect of the metabolic error on dental development in a patient with the intermediate severe late-infantile form of MSD (S155P). Histological and chemical study were performed on three deciduous and five permanent teeth from MSD patient and pair-matched normal patients. Tooth germ size and enamel thickness were reduced in both deciduous and permanent MSD teeth, and the scalloping feature of the DEJ was missing in MSD teeth causing enamel to break off from the dentin. The mineral components in the enamel and dentin were different. The metabolic error insults the teeth in the stage of organogenesis in both the deciduous and permanent dentition. The end result is teeth with very sharp cusp tips, thin hypomineralized enamel, and exposed dentin due to the break off of enamel. These findings are different from all other types of MPS syndromes.Clinically the phenotype of intermediate severe late-infantile form of MSD appeared during the third year of life. In children of parents that are carriers, we can diagnose the disease as early as birth using X-ray radiograph of the anterior upper region or as early as 6-8 months when the first deciduous tooth erupt and consider very early treatment to ameliorate the symptoms.

Synthesis of chondroitin sulfate CC and DD tetrasaccharides and interactions with 2H6 and LY111.

PubMed

Matsushita, Kenya; Nakata, Tomomi; Takeda-Okuda, Naoko; Nadanaka, Satomi; Kitagawa, Hiroshi; Tamura, Jun-Ichi

2018-03-01

We synthesized the biotinylated chondroitin sulfate tetrasaccharides CS-CC [-3)βGalNAc6S(1-4)βGlcA(1-] 2 and CS-DD [-3)βGalNAc6S(1-4)βGlcA2S(1-] 2 which possess sulfate groups at O-6 of GalNAc and an additional sulfate group at O-2 of GlcA, respectively. We also analyzed interactions among CS-CC and CS-DD and the antibodies 2H6 and LY111, both of which are known to bind with CS-A, while CS-DD was shown for the first time to bind with both antibodies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Functional Exploration of the Polysaccharide Lyase Family PL6

PubMed Central

Mathieu, Sophie; Henrissat, Bernard; Labre, Flavien; Skjåk-Bræk, Gudmund; Helbert, William

2016-01-01

Alginate, the main cell-wall polysaccharide of brown algae, is composed of two residues: mannuronic acid (M-residues) and, its C5-epimer, guluronic acid (G-residues). Alginate lyases define a class of enzymes that cleave the glycosidic bond of alginate by β-elimination. They are classified according to their ability to recognize the distribution of M- and G-residues and are named M-, G- or MG-lyases. In the CAZy database, alginate lyases have been grouped by sequence similarity into seven distinct polysaccharide lyase families. The polysaccharide lyase family PL6 is subdivided into three subfamilies. Subfamily PL6_1 includes three biochemically characterized enzymes (two alginate lyases and one dermatan sulfatase lyase). No characterized enzymes have been described in the two other subfamilies (PL6_2 and PL6_3). To improve the prediction of polysaccharide-lyase activity in the PL6 family, we re-examined the classification of the PL6 family and biochemically characterized a set of enzymes reflecting the diversity of the protein sequences. Our results show that subfamily PL6_1 includes two dermatan sulfates lyases and several alginate lyases that have various substrate specificities and modes of action. In contrast, subfamilies PL6_2 and PL6_3 were found to contain only endo-poly-MG-lyases. PMID:27438604

Metabolism of dehydroepiandrosterone sulfate and estrone-sulfate by human platelets.

PubMed

Garrido, A; Munoz, Y; Sierralta, W; Valladares, L

2012-01-01

The aim of the present research was to study the uptake of DHEAS, and to establish the intracrine capacity of human platelets to produce sex steroid hormones. The DHEAS transport was evaluated through the uptake of [(3)H]-DHEAS in the presence or absence of different substrates through the organic anion transporting polypeptide (OATP) family. The activity of sulfatase enzyme was evaluated, and the metabolism of DHEAS was measured by the conversion of [(3)H]-DHEAS to [(3)H]-androstenedione, [(3)H]-testosterone, [(3)H]-estrone and [(3)H]-17beta-estradiol. Results indicated the existence in the plasma membrane of an OATP with high affinity for DHEAS and estrone sulphate (E(1)S). The platelets showed the capacity to convert DHEAS to active DHEA by the steroid-sulfatase activity. The cells resulted to be a potential site for androgens production, since they have the capacity to produce androstenedione and testosterone; in addition, they reduced [(3)H]-estrone to [(3)H]-17beta-estradiol. This is the first demonstration that human platelets are able to import DHEAS and E(1)S using the OATP family and to convert DHEAS to active DHEA, and to transform E(1)S to 17beta-estradiol.

Evaluation of antioxidant activities and chemical analysis of sulfated chitosan from Sepia prashadi.

PubMed

Seedevi, Palaniappan; Moovendhan, Meivelu; Vairamani, Shanmugam; Shanmugam, Annaian

2017-06-01

The chitin and chitosan of S. prashadi was prepared through demineralization, deproteinzation, deacetylation process and sulfation were carried by chlorosulfonic acid in N,N-dimethylformamide. The sulfate content in chitosan was found to be 18.9%. The carbon, hydrogen and nitrogen composition of the sulfated chitosan were recorded 39.09%, 6.95% and 6.58% respectively. The structural analysis was done by using FT-IR and NMR spectroscopy technique. The DSC curves of sulfated chitosan showed a large endothermic peak resolved with T o value of 54.57°C and T P value of 97.46°C. The morphology of sulfated chitin and sulfated chitosan were studied by SEM. The Further in vitro antioxidant activity of sulfated chitosan was screened by scavenging activity of superoxide radical assay, hydroxyl radical scavenging assay, metal-ion chelating effect and reducing power. Its anticoagulant activity was tested for human plasma with respect to Activated Partial Thromboplastin Time (APTT) and Prothrombin Time (PT). Results prove that sulfated chitosan has potent antioxidant and anticoagulant activity. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis and NMR analysis of model compounds related to fucosylated chondroitin sulfates: GalNAc and Fuc(1 → 6)GalNAc derivatives.

PubMed

Vinnitskiy, Dmitry Z; Ustyuzhanina, Nadezhda E; Dmitrenok, Andrey S; Shashkov, Alexander S; Nifantiev, Nikolay E

2017-01-13

Unsubstituted and 6-O-α-L-fucosylated propyl 2-acetamido-2-deoxy-β-D-galactopyranosides and their selectively O-sulfated (both in GalNAc and Fuc units) derivatives were synthesized as model compounds representing the fragments of fucosylated chondroitin sulfates (FCS) from sea cucumbers. Per-O-acetylated 2-deoxy-2-N-phthalimido-D-glucopyranose was used as a key precursor for the preparation of all 2-acetamido-2-deoxy-D-galactopyranoside containing products. Attempts at 6-O-glycosylation of propyl 3-O-benzoyl-2-deoxy-2-N-phthalimido-D-galactoside by 2-O-benzyl-3,4-di-O-chloracetyl-L-fucosyl trichloracetimidate in the presence of TMSOTf gave a 1:1 mixture of the corresponding α- and β-isomeric disaccharides, while the use of structurally related fucosyl bromide donor with promotion by Bu 4 NBr led to the formation of desired α-isomeric disaccharide exclusively. Selective removal of orthogonal O-protections permitted subsequent O-sulfation both at the GalNAc and Fuc units. Further removal of blocking groups yielded the target products which were systematically studied by 1 H and 13 C NMR spectroscopy in order to determine the spectral effects of O-sulfation and α-L-fucosylation needed for the development of computer assisted structural analysis of natural FCS. Copyright © 2016 Elsevier Ltd. All rights reserved.

The crystal structures of iron and cobalt pyridine (py)–sulfates, [Fe(SO4)(py)4]n and [Co3(SO4)3(py)11]n

PubMed Central

Pham, Duyen N. K.; Roy, Mrittika; Kreider-Mueller, Ava; Golen, James A.; Manke, David R.

2018-01-01

The solid-state structures of two metal–pyridine–sulfate compounds, namely catena-poly[[tetra­kis­(pyridine-κN)iron(II)]-μ-sulfato-κ2 O:O′], [Fe(SO4)(C5H5N)4]n, (1), and catena-poly[[tetra­kis­(pyridine-κN)cobalt(II)]-μ-sulfato-κ2 O:O′-[tetra­kis­(pyridine-κN)cobalt(II)]-μ-sulfato-κ3 O,O′:O′′-[tris­(pyridine-κN)cobalt(II)]-μ-sulfato-κ2 O:O′], [Co3(SO4)3(C5H5N)11]n, (2), are reported. The iron compound (1) displays a polymeric structure, with infinite chains of FeII atoms adopting octa­hedral N4O2 coordination environments that involve four pyridine ligands and two bridging sulfate ligands. The cobalt compound (2) displays a polymeric structure, with infinite chains of CoII atoms. Two of the three Co centers have an octa­hedral N4O2 coordination environment that involves four pyridine ligands and two bridging sulfate ligands. The third Co center has an octa­hedral N3O3 coordination environment that involves three pyridine ligands, and two bridging sulfate ligands with one sulfate chelating the cobalt atom.

Transport of steroid 3-sulfates and steroid 17-sulfates by the sodium-dependent organic anion transporter SOAT (SLC10A6).

PubMed

Grosser, Gary; Bennien, Josefine; Sánchez-Guijo, Alberto; Bakhaus, Katharina; Döring, Barbara; Hartmann, Michaela; Wudy, Stefan A; Geyer, Joachim

2018-05-01

The sodium-dependent organic anion transporter SOAT/Soat shows highly specific transport activity for sulfated steroids. SOAT substrates identified so far include dehydroepiandrosterone sulfate, 16α-hydroxydehydroepiandrosterone sulfate, estrone-3-sulfate, pregnenolone sulfate, 17β-estradiol-3-sulfate, and androstenediol sulfate. Apart from these compounds, many other sulfated steroids occur in mammals. Therefore, we aimed to expand the substrate spectrum of SOAT and analyzed the SOAT-mediated transport of eight different sulfated steroids by combining in vitro transport experiments in SOAT-transfected HEK293 cells with LC-MS/MS analytics of cell lysates. In addition, we aimed to better understand the structural requirements for SOAT substrates and so selected structural pairs varying only at specific positions: 3α/3β-sulfate, 17α/17β-sulfate, mono-sulfate/di-sulfate, and 17α-hydroxylation. We found significant and sodium-dependent SOAT-mediated transport of 17α-hydroxypregnenolone sulfate, 17β-estradiol-17-sulfate, androsterone sulfate, epiandrosterone sulfate, testosterone sulfate, epitestosterone sulfate, and 5α-dihydrotestosterone sulfate. However, 17β-estradiol-3,17-disulfate was not transported by SOAT. SOAT substrates from the group of sulfated steroids are characterized by a planar and lipophilic steroid backbone in trans-trans-trans conformation of the rings and a negatively charged mono-sulfate group at positions 3' or 17' with flexibility for α- or β- orientation. Furthermore, 5α-reduction, 16α-hydroxylation, and 17α-hydroxylation are acceptable for SOAT substrate recognition, whereas addition of a second negatively charged sulfate group seems to abolish substrate binding to SOAT, and so 17β-estradiol-3,17-disulfate is not transported by SOAT. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genomic organization of the human heparan sulfate-N-deacetylase/N-sulfotransferase gene: Exclusion from a causative role in the pathogenesis of Treacher Collins syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gladwin, A.J.; Dixon, J.; Loftus, S.K.

Heparan sulfate-N-deacetylase/N-sulfotransferase (HSST) catalyzes both the N-deacetylation and the N-sulfation of heparan sulfate. Previous studies have resulted in the isolation of the human HSST gene from within the Treacher Collins syndrome locus (TCOF1) critical region on 5q. In the present study, the genomic organization of the HSST gene has been elucidated, and the 14 exons identified have been tested for TCOF1-specific mutations. As a result of these studies, mutations within the coding sequence and adjacent splice junctions of HSST can be excluded from a causative role in the pathogenesis of Treacher Collins syndrome. 13 refs., 1 fig., 2 tabs.

Mechanism for stabilization of the molten globule state of papain by sodium n-alkyl sulfates: spectroscopic and calorimetric approaches.

PubMed

Chamani, J; Heshmati, M

2008-06-01

Papain exists in a molten globule (MG) state at pH 2 and in this state protein tends to aggregate in the presence of lower concentrations of guanidine hydrochloride (GuHCl). Such aggregation is prevented if low concentrations of sodium n-alkyl sulfates are also present in the buffer; in addition, stabilization of the protein is also induced. The guanidine hydrochloride and temperature-induced unfolding of papain, in the presence of n-alkyl sulfates, indicate stabilization of the protein as seen from the higher transition midpoints when monitored by fluorescence, circular dichroism, and differential scanning calorimetry. However, a similar phenomenon is not seen under neutral conditions in the presence of n-alkyl sulfate concentrations. The effect of n-alkyl sulfates on the structure of the MG state of papain was utilized to investigate the contribution of hydrophobic interaction to the stability of the MG state. The Td values of the MG states of papain in the presence of n-alkyl sulfates at different concentrations showed substantial variation. The enhancement of Td values at the stability criterion of MG states corresponded with increasing chain length of the cited n-alkyl sulfates. The present results suggest that the hydrophobic interactions play important roles in stabilizing and preventing the aggregation of the MG state of papain.

Structural characterization and biological implications of sulfated N-glycans in a serine protease from the neotropical moth Hylesia metabus (Cramer [1775]) (Lepidoptera: Saturniidae).

PubMed

Cabrera, Gleysin; Salazar, Víctor; Montesino, Raquel; Támbara, Yanet; Struwe, Weston B; Leon, Evelyn; Harvey, David J; Lesur, Antoine; Rincón, Mónica; Domon, Bruno; Méndez, Milagros; Portela, Madelón; González-Hernández, Annia; Triguero, Ada; Durán, Rosario; Lundberg, Ulf; Vonasek, Eva; González, Luis Javier

2016-03-01

Contact with the urticating setae from the abdomen of adult females of the neo-tropical moth Hylesia metabus gives rise to an urticating dermatitis, characterized by intense pruritus, generalized malaise and occasionally ocular lesions (lepidopterism). The setae contain a pro-inflammatory glycosylated protease homologous to other S1A serine proteases of insects. Deglycosylation with PNGase F in the presence of a buffer prepared with 40% H2 (18)O allowed the assignment of an N-glycosylation site. Five main paucimannosidic N-glycans were identified, three of which were exclusively α(1-6)-fucosylated at the proximal GlcNAc. A considerable portion of these N-glycans are anionic species sulfated on either the 4- or the 6-position of the α(1-6)-mannose residue of the core. The application of chemically and enzymatically modified variants of the toxin in an animal model in guinea pigs showed that the pro-inflammatory and immunological reactions, e.g. disseminated fibrin deposition and activation of neutrophils, are due to the presence of sulfate-linked groups and not on disulfide bonds, as demonstrated by the reduction and S-alkylation of the toxin. On the other hand, the hemorrhagic vascular lesions observed are attributed to the proteolytic activity of the toxin. Thus, N-glycan sulfation may constitute a defense mechanism against predators. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

21 CFR 524.1484e - Neomycin sulfate and polymyxin B sulfate ophthalmic solution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Neomycin sulfate and polymyxin B sulfate... DOSAGE FORM NEW ANIMAL DRUGS § 524.1484e Neomycin sulfate and polymyxin B sulfate ophthalmic solution. (a) Specifications. Each milliliter of the ophthalmic preparation contains 5.0 milligrams neomycin sulfate (3.5...

21 CFR 524.1484e - Neomycin sulfate and polymyxin B sulfate ophthalmic solution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Neomycin sulfate and polymyxin B sulfate... DOSAGE FORM NEW ANIMAL DRUGS § 524.1484e Neomycin sulfate and polymyxin B sulfate ophthalmic solution. (a) Specifications. Each milliliter of the ophthalmic preparation contains 5.0 milligrams neomycin sulfate (3.5...

21 CFR 524.1484e - Neomycin sulfate and polymyxin B sulfate ophthalmic solution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Neomycin sulfate and polymyxin B sulfate... DOSAGE FORM NEW ANIMAL DRUGS § 524.1484e Neomycin sulfate and polymyxin B sulfate ophthalmic solution. (a) Specifications. Each milliliter of the ophthalmic preparation contains 5.0 milligrams neomycin sulfate (3.5...

21 CFR 524.1484e - Neomycin sulfate and polymyxin B sulfate ophthalmic solution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin sulfate and polymyxin B sulfate... DOSAGE FORM NEW ANIMAL DRUGS § 524.1484e Neomycin sulfate and polymyxin B sulfate ophthalmic solution. (a) Specifications. Each milliliter of the ophthalmic preparation contains 5.0 milligrams neomycin sulfate (3.5...

In vitro and in vivo immunomodulatory activity of sulfated polysaccharides from red seaweed Nemalion helminthoides.

PubMed

Pérez-Recalde, Mercedes; Matulewicz, María C; Pujol, Carlos A; Carlucci, María J

2014-02-01

Water-soluble sulfated polysaccharides from the red seaweed Nemalion helminthoides: two xylomannan fractions (N3 and N4) and a mannan fraction (N6) were investigated to determine their in vitro and in vivo immunomodulatory activities. N3 and N4 induced in vitro proliferation of macrophages of the murine cell line RAW 264.7 and significantly stimulated the production of nitric oxide (NO) and cytokines (IL-6 and TNF-α) in the same cells, whereas this response was not observed with the mannan N6. The cytokine production was also stimulated by sulfated xylomannans in vivo in BALB/c mice inoculated intravenously with these polysaccharides. Remarkably, when mice were treated with N3 and N4 for 1 h before being infected with Herpes simplex virus type 2, they remained asymptomatic with no signs of disease. The in vitro and in vivo results suggest that sulfated xylomannans could be strong immunomodulators. Copyright © 2013 Elsevier B.V. All rights reserved.

Release of chromaffin granule glycoproteins and proteoglycans from potassium-stimulated PC12 pheochromocytoma cells.

PubMed

Salton, S R; Margolis, R U; Margolis, R K

1983-10-01

Cultured PC12 pheochromocytoma cells were labeled with [3H]glucosamine, and the glycoproteins and proteoglycans released following potassium-induced depolarization were fractionated and characterized. Exposure of PC12 cells for 20 min to a high concentration of potassium (51.5 mM in Krebs-Ringers-HEPES buffer) results in an approximately sixfold increase in the release of labeled glycoproteins and proteoglycans, compared to incubation in physiological levels of potassium (6 mM). The released complex carbohydrates include chromogranins, dopamine beta-hydroxylase, and two chondroitin sulfate/heparan sulfate proteoglycan fractions, which together account for 7.4% of the soluble cell radioactivity. The chromogranins contained galactosyl(beta 1 leads to 3)N-acetylgalactosamine, as well as several mono- and disialyl O-glycosidically-linked oligosaccharides, and the tetrasaccharide AcNeu(alpha 2 leads to 3)Gal(beta 1 leads to 3)[AcNeu(alpha 2 leads to 6)] GalNAcol, obtained by alkaline borohydride treatment of the chromogranin glycopeptides, accounted for almost half of the total chromogranin labeling. The proteoglycan fractions varied in their relative proportions of chondroitin sulfate (23-68%), heparan sulfate (16-23%), and glycoprotein oligosaccharides (16-54%), which are of the tri- and tetraantennary and O-glycosidic types. As previously found in the case of proteoglycans from bovine chromaffin granules, the more acidic species has a considerably higher proportion of carbohydrate in the form of sulfated glycosaminoglycans.

NTP Toxicology and Carcinogenesis Studies of Cobalt Sulfate Heptahydrate (CAS No. 10026-24-1) in F344/N Rats and B6C3F1 Mice (Inhalation Studies).

PubMed

1998-08-01

Cobalt sulfate is used in the electroplating and electro chemical industries. It is also used as a coloring agent for ceramics and as a drying agent in inks, paints, varnishes, and linoleum. Cobalt sulfate may be added to animal feed as a mineral supplement and has been used as a top dressing on pasture lands. Cobalt sulfate was nominated by the National Cancer Institute for study based on a lack of information on the toxicity of soluble salts. Male and female F344/N rats and B6C3F1 mice were exposed to cobalt sulfate heptahydrate (approximately 99% pure) by inhalation for 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium. The results of prechronic inhalation toxicity studies were reported previously (Bucher et al., 1990; NTP, 1991). 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female rats were exposed to aerosols containing 0, 0.3, 1.0, or 3.0 mg/m3 cobalt sulfate heptahydrate 6 hours per day, 5 days per week, for 105 weeks. Survival and Body Weights Survival of exposed males and females was similar to that of the chamber controls. Mean body weights of exposed male and female rats were similar to those of the chamber controls throughout the study. Pathology Findings The incidences and severities of proteinosis, alveolar epithelial metaplasia, granulomatous alveolar inflammation, and interstitial fibrosis were markedly greater in all exposed groups of male and female rats than in the chamber controls. The incidences of alveolar epithelial hyperplasia in all groups of exposed males and in females exposed to 3.0 mg/m3 were significantly greater than those in the chamber control groups, as were the incidences of squamous metaplasia in 1.0 mg/m3 females and atypical alveolar epithelial hyperplasia in 3.0 mg/m3 females. In 3.0 mg/m3 males, the combined incidence of alveolar/ bronchiolar neoplasms (adenoma and/or carcinoma) was significantly greater than in the chamber controls. In female rats exposed to 1.0 or 3.0 mg/m3, the incidences of

Negative Electron Transfer Dissociation Sequencing of 3-O-Sulfation-Containing Heparan Sulfate Oligosaccharides

NASA Astrophysics Data System (ADS)

Wu, Jiandong; Wei, Juan; Hogan, John D.; Chopra, Pradeep; Joshi, Apoorva; Lu, Weigang; Klein, Joshua; Boons, Geert-Jan; Lin, Cheng; Zaia, Joseph

2018-03-01

Among dissociation methods, negative electron transfer dissociation (NETD) has been proven the most useful for glycosaminoglycan (GAG) sequencing because it produces informative fragmentation, a low degree of sulfate losses, high sensitivity, and translatability to multiple instrument types. The challenge, however, is to distinguish positional sulfation. In particular, NETD has been reported to fail to differentiate 4-O- versus 6-O-sulfation in chondroitin sulfate decasaccharide. This raised the concern of whether NETD is able to differentiate the rare 3-O-sulfation from predominant 6-O-sulfation in heparan sulfate (HS) oligosaccharides. Here, we report that NETD generates highly informative spectra that differentiate sites of O-sulfation on glucosamine residues, enabling structural characterizations of synthetic HS isomers containing 3-O-sulfation. Further, lyase-resistant 3-O-sulfated tetrasaccharides from natural sources were successfully sequenced. Notably, for all of the oligosaccharides in this study, the successful sequencing is based on NETD tandem mass spectra of commonly observed deprotonated precursor ions without derivatization or metal cation adduction, simplifying the experimental workflow and data interpretation. These results demonstrate the potential of NETD as a sensitive analytical tool for detailed, high-throughput structural analysis of highly sulfated GAGs. [Figure not available: see fulltext.

Mammalian sex chromosomes. III. Activity of pseudoautosomal steroid sulfatase enzyme during spermatogenesis in Mus musculus.

PubMed

Raman, R; Das, P

1991-09-01

Parallel to the inactivation of the X chromosome in somatic cells of female, the male X in mammals is rendered inactive during spermatogenesis. Pseudoautosomal genes, those present on the X-Y meiotically pairable region of male, escape inactivation in female soma. It is suggested, but not demonstrated, that they may also be refractory to the inactivation signal in male germ cells. We have assayed activity of the enzyme steroid sulfatase, product of a pseudoautosomal gene, in testicular cells of the mouse and shown its presence in premeiotic, meiotic (pachytene), and postmeiotic (spermatid) cell types. It appears that, as in females, pseudoautosomal genes may escape inactivation in male germ cells also.

21 CFR 524.960 - Flumethasone, neomycin sulfate, and polymyxin B sulfate ophthalmic solutions.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Flumethasone, neomycin sulfate, and polymyxin B sulfate ophthalmic solutions. 524.960 Section 524.960 Food and Drugs FOOD AND DRUG ADMINISTRATION... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.960 Flumethasone, neomycin sulfate, and polymyxin B sulfate...

21 CFR 524.960 - Flumethasone, neomycin sulfate, and polymyxin B sulfate ophthalmic solutions.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Flumethasone, neomycin sulfate, and polymyxin B sulfate ophthalmic solutions. 524.960 Section 524.960 Food and Drugs FOOD AND DRUG ADMINISTRATION... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.960 Flumethasone, neomycin sulfate, and polymyxin B sulfate...

Genetic manipulation of murine embryonic stem cells with enhanced green fluorescence protein and sulfatase-modifying factor I genes.

PubMed

Zhao, Guoying; Karageorgos, Litsa; Hutchinson, Rhonda G; Hopwood, John J; Hemsley, Kim

2010-05-01

Mucopolysaccharidosis type IIIA (MPS IIIA) is a lysosomal storage disorder (LSD) in which an absence of sulfamidase results in incomplete degradation and subsequent accumulation of its substrate, heparan sulfate. Most neurodegenerative LSD remain untreatable. However, therapy options, such as gene, enzyme end cell therapy, are under investigation. Previously, we have constructed an embryonic stem (ES) cell line (NS21) that over-expresses human sulphamidase as a potential treatment for murine MPS IIIA. In the present study the sulfatase-modifying factor I (SUMF1) and enhanced green fluorescence protein (eGFP) genes were co-introduced under a cytomegalovirus (CMV) promoter into NS21 cells, to enhance further sulfamidase activity and provide a marker for in vivo cell tracking, respectively. eGFP was also introduced under the control of the human elongation factor-1alpha (hEF-1alpha) promoter to compare the stability of transgene expression. During differentiation of ES cells into glial precursors, SUMF1 was down-regulated and was hardly detectable by day 18 of differentiation. Likewise, eGFP expression was heterogeneous and highly unstable. Use of a human EF-1alpha promoter resulted in more homogeneous eGFP expression, with approximately 50% of cells eGFP positive following differentiation into glial precursors. Compared with NS21 cells, the outgrowth of eGFP-expressing cells was not as confluent when differentiated into glial precursors. Our data suggest that SUMF1 enhances sulfamidase activity in ES cells, hEF-1alpha is a stronger promoter than CMV for ES cells and over-expression of eGFP may affect cell growth and contribute to unstable gene expression.

[Newly leaching method of copper from waste print circuit board using hydrochloric acid/n-butylamine/copper sulfate].

PubMed

Wang, Hong-Yan; Cui, Zhao-Jie; Yao, Ya-Wei

2010-12-01

A newly leaching method of copper from waste print circuit board was established by using hydrochloric acid-n-butylamine-copper sulfate mixed solution. The conditions of leaching were optimized by changing the hydrochloric acid, n-butylamine, copper sulfate,temperature and other conditions using copper as target mimics. The results indicated that copper could be leached completely after 8 h at 50 degrees C, hydrochloric acid concentration of 1.75 mol/L, n-butylamine concentration of 0.25 mol/L, and copper sulfate mass of 0.96 g. Under the conditions, copper leaching rates in waste print circuit board samples was up to 95.31% after 9 h. It has many advantages such as better effects, low cost, mild reaction conditions, leaching solution recycling.

Promiscuity in the Enzymatic Catalysis of Phosphate and Sulfate Transfer

PubMed Central

2016-01-01

The enzymes that facilitate phosphate and sulfate hydrolysis are among the most proficient natural catalysts known to date. Interestingly, a large number of these enzymes are promiscuous catalysts that exhibit both phosphatase and sulfatase activities in the same active site and, on top of that, have also been demonstrated to efficiently catalyze the hydrolysis of other additional substrates with varying degrees of efficiency. Understanding the factors that underlie such multifunctionality is crucial both for understanding functional evolution in enzyme superfamilies and for the development of artificial enzymes. In this Current Topic, we have primarily focused on the structural and mechanistic basis for catalytic promiscuity among enzymes that facilitate both phosphoryl and sulfuryl transfer in the same active site, while comparing this to how catalytic promiscuity manifests in other promiscuous phosphatases. We have also drawn on the large number of experimental and computational studies of selected model systems in the literature to explore the different features driving the catalytic promiscuity of such enzymes. Finally, on the basis of this comparative analysis, we probe the plausible origins and determinants of catalytic promiscuity in enzymes that catalyze phosphoryl and sulfuryl transfer. PMID:27187273

Rapid transport of ash and sulfate from the 2011 Puyehue-Cordón Caulle (Chile) eruption to West Antarctica

NASA Astrophysics Data System (ADS)

Koffman, Bess G.; Dowd, Eleanor G.; Osterberg, Erich C.; Ferris, David G.; Hartman, Laura H.; Wheatley, Sarah D.; Kurbatov, Andrei V.; Wong, Gifford J.; Markle, Bradley R.; Dunbar, Nelia W.; Kreutz, Karl J.; Yates, Martin

2017-08-01

The Volcanic Explosivity Index 5 eruption of the Puyehue-Cordón Caulle volcanic complex (PCC) in central Chile, which began 4 June 2011, provides a rare opportunity to assess the rapid transport and deposition of sulfate and ash from a midlatitude volcano to the Antarctic ice sheet. We present sulfate, microparticle concentrations of fine-grained ( 5 μm diameter) tephra, and major oxide geochemistry, which document the depositional sequence of volcanic products from the PCC eruption in West Antarctic snow and shallow firn. From the depositional phasing and duration of ash and sulfate peaks, we infer that transport occurred primarily through the troposphere but that ash and sulfate transport were decoupled. We use Hybrid Single-Particle Lagrangian Integrated Trajectory back trajectory modeling to assess atmospheric circulation conditions in the weeks following the eruption and find that conditions favored southward air parcel transport during 6-14 June and 4-18 July 2011. We suggest that two discrete pulses of cryptotephra deposition relate to these intervals, and as such, constrain the sulfate transport and deposition lifespan to the 2-3 weeks following the eruption. Finally, we compare PCC depositional patterns to those of prominent low- and high-latitude eruptions in order to improve multiparameter-based efforts to identify "unknown source" eruptions in the ice core record. Our observations suggest that midlatitude eruptions such as PCC can be distinguished from explosive tropical eruptions by differences in ash/sulfate phasing and in the duration of sulfate deposition, and from high-latitude eruptions by differences in particle size distribution and in cryptotephra geochemical composition.

O-sulfated bacterial polysaccharides with low anticoagulant activity inhibit metastasis.

PubMed

Borgenström, Marjut; Wärri, Anni; Hiilesvuo, Katri; Käkönen, Rami; Käkönen, Sanna; Nissinen, Liisa; Pihlavisto, Marjo; Marjamäki, Anne; Vlodavsky, Israel; Naggi, Annamaria; Torri, Giangiacomo; Casu, Benito; Veromaa, Timo; Salmivirta, Markku; Elenius, Klaus

2007-07-01

Heparin-like polysaccharides possess the capacity to inhibit cancer cell proliferation, angiogenesis, heparanase-mediated cancer cell invasion, and cancer cell adhesion to vascular endothelia via adhesion receptors, such as selectins. The clinical applicability of the antitumor effect of such polysaccharides, however, is compromised by their anticoagulant activity. We have compared the potential of chemically O-sulfated and N,O-sulfated bacterial polysaccharide (capsular polysaccharide from E. COLI K5 [K5PS]) species to inhibit metastasis of mouse B16-BL6 melanoma cells and human MDA-MB-231 breast cancer cells in two in vivo models. We demonstrate that in both settings, O-sulfated K5PS was a potent inhibitor of metastasis. Reducing the molecular weight of the polysaccharide, however, resulted in lower antimetastatic capacity. Furthermore, we show that O-sulfated K5PS efficiently inhibited the invasion of B16-BL6 cells through Matrigel and also inhibited the in vitro activity of heparanase. Moreover, treatment with O-sulfated K5PS lowered the ability of B16-BL6 cells to adhere to endothelial cells, intercellular adhesion molecule-1, and P-selectin, but not to E-selectin. Importantly, O-sulfated K5PSs were largely devoid of anticoagulant activity. These findings indicate that O-sulfated K5PS polysaccharide should be considered as a potential antimetastatic agent.

Loss of the anion exchanger DRA (Slc26a3), or PAT1 (Slc26a6), alters sulfate transport by the distal ileum and overall sulfate homeostasis.

PubMed

Whittamore, Jonathan M; Hatch, Marguerite

2017-09-01

The ileum is considered the primary site of inorganic sulfate ([Formula: see text]) absorption. In the present study, we explored the contributions of the apical chloride/bicarbonate (Cl - /[Formula: see text]) exchangers downregulated in adenoma (DRA; Slc26a3), and putative anion transporter 1 (PAT1; Slc26a6), to the underlying transport mechanism. Transepithelial 35 [Formula: see text] and 36 Cl - fluxes were determined across isolated, short-circuited segments of the distal ileum from wild-type (WT), DRA-knockout (KO), and PAT1-KO mice, together with measurements of urine and plasma sulfate. The WT distal ileum supported net sulfate absorption [197.37 ± 13.61 (SE) nmol·cm -2 ·h -1 ], but neither DRA nor PAT1 directly contributed to the unidirectional mucosal-to-serosal flux ([Formula: see text]), which was sensitive to serosal (but not mucosal) DIDS, dependent on Cl - , and regulated by cAMP. However, the absence of DRA significantly enhanced net sulfate absorption by one-third via a simultaneous rise in [Formula: see text] and a 30% reduction to the secretory serosal-to-mucosal flux ([Formula: see text]). We propose that DRA, together with PAT1, contributes to [Formula: see text] by mediating sulfate efflux across the apical membrane. Associated with increased ileal sulfate absorption in vitro, plasma sulfate was 61% greater, and urinary sulfate excretion ( U SO4 ) 2.2-fold higher, in DRA-KO mice compared with WT controls, whereas U SO4 was increased 1.8-fold in PAT1-KO mice. These alterations to sulfate homeostasis could not be accounted for by any changes to renal sulfate handling suggesting that the source of this additional sulfate was intestinal. In summary, we characterized transepithelial sulfate fluxes across the mouse distal ileum demonstrating that DRA (and to a lesser extent, PAT1) secretes sulfate with significant implications for intestinal sulfate absorption and overall homeostasis. NEW & NOTEWORTHY Sulfate is an essential anion that is

Amine templating effect absent in uranyl sulfates synthesized with 1,4-n-butyldiamine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jouffret, Laurent J., E-mail: ljouffret@nd.edu; Wylie, Ernest M.; Burns, Peter C.

2013-01-15

Two new uranyl sulfates, (C{sub 4}H{sub 14}N{sub 2})[(UO{sub 2}){sub 2}(SO{sub 4}){sub 3}(H{sub 2}O)]{center_dot}2H{sub 2}O (NDUS2) and (C{sub 4}H{sub 14}N{sub 2})[(UO{sub 2})(SO{sub 4}){sub 2}(H{sub 2}O)]{center_dot}2H{sub 2}O (NDUS3), were synthesized and their crystal structures determined. NDUS2 was obtained in highly acidic media heat-treated at 373 K and subsequently maintained at 278 K until crystals formed after two months. NDUS3 results from the degradation of NDUS2 over the course of a few days. NDUS2 and NDUS3 crystallize in the monoclinic space group P2{sub 1}/n, a=10.9075(4) A, b=10.4513(4) A, c=17.7881(7) A, {beta}=97.908(2) Degree-Sign , V=2008.52(13) A{sup 3}, Z=4, at 140 K and a=8.8570(4) A,more » b=7.3299(3) A, c=20.4260(9) A, {beta}=95.140(2) Degree-Sign , V=1320.74(10) A{sup 3}, Z=4, at 140 K, respectively. The compounds contain interlayer 1,4-n-butyldiammonium cations that charge-balance the anionic structural units. - Graphical abstract: Amine templating effect absent in uranyl sulfates synthesized with 1,4-diaminobutane, as shown by the synthesis of two new uranyl sulfates, (C{sub 4}H{sub 14}N{sub 2})[(UO{sub 2}){sub 2}(SO{sub 4}){sub 3}(H{sub 2}O)]{center_dot}2H{sub 2}O (NDUS2) and (C{sub 4}H{sub 14}N{sub 2})[(UO{sub 2})(SO{sub 4}){sub 2}(H{sub 2}O)]{center_dot}2H{sub 2}O (NDUS3). Highlights: Black-Right-Pointing-Pointer Two layered uranyl sulfates were synthesized. Black-Right-Pointing-Pointer Amine molecules are located in the interlayers of the compounds. Black-Right-Pointing-Pointer No templating effect of the amine was observed. Black-Right-Pointing-Pointer Amine molecules are only charge balancing cations in the structures.« less

A sperm-agglutinating lectin from seeds of Jack fruit (Artocarpus heterophyllus).

PubMed

Namjuntra, P; Muanwongyathi, P; Chulavatnatol, M

1985-04-30

A lectin specific for N-acetylgalactosamine was isolated from seed extract of Jack fruit (Artocarpus heterophyllus) by ammonium sulfate precipitation, followed by affinity chromatography on a Affigel-galactosamine-agarose column. The lectin possessed agglutinating activities for human and rat sperm as well as human red blood cells. It was found to have Mr = 62,000 consisting of two dissimilar subunits of Mr = 18,000 and 13,000. It also cross-reacted with an antibody against the lectin of Osage Orange (Maclura pomifera).

Variation of acharan sulfate and monosaccharide composition and analysis of neutral N-glycans in African giant snail (Achatina fulica).

PubMed

Park, Youmie; Zhang, Zhenqing; Laremore, Tatiana N; Li, Boyangzi; Sim, Joon-Soo; Im, A-Rang; Ahn, Mi Young; Kim, Yeong Shik; Linhardt, Robert J

2008-12-01

Acharan sulfate content from African giant snail (Achatina fulica) was compared in eggs and snails of different ages. Acharan sulfate was not found in egg. Acharan sulfate disaccharide -->4)-alpha-D-GlcNpAc (1-->4)-alpha-L-IdoAp2S(1-->, analyzed by SAX (strong-anion exchange)-HPLC was observed soon after hatching and increases as the snails grow. Monosaccharide compositional analysis showed that mole % of glucosamine, a major monosaccharide of acharan sulfate, increased with age while mole % of galactose decreased with age. These results suggest that galactans represent a major energy source during development, while acharan sulfate appearing immediately after hatching, is essential for the snail growth. The structures of neutral N-glycans released from eggs by peptide N-glycosidase F (PNGase F), were next elucidated using ESI-MS/MS, MALDI-MS/MS, enzyme digestion, and monosaccharide composition analysis. Three types of neutral N-glycan structures were observed, truncated (Hex(2-4)-HexNAc(2)), high mannose (Hex(5-9)-HexNAc(2)), and complex (Hex(3)-HexNAc(2-10)) types. None showed core fucosylation.

Evaluation of Extracellular Endosulfatase HSULF-2 in Breast Cancer Cell WNT Signaling and Its Inhibition by a Sulfate Ester Derivative of Synthetic Antioxidant

DTIC Science & Technology

2010-08-01

Breast Cancer, Balb/c nude mice, hydrogen peroxide, extracellular matrix, sulfatase, extracellular sulfatase, aryl sulfatase, PBN, nitrones , phenyl...previously made in studying the anti‐cancer activity of the PBN  nitrones  has helped us generate new novel and testable  ideas for future research in...cancer development appears to be still in question.    Anti‐cancer activity of the PBN‐ nitrones . PBN refers to α‐phenyl‐tert‐butylnitrone. Our

Oligosaccharide Substrate Preferences of Human Extracellular Sulfatase Sulf2 Using Liquid Chromatography-Mass Spectrometry Based Glycomics Approaches

PubMed Central

Huang, Yu; Mao, Yang; Buczek-Thomas, Jo Ann; Nugent, Matthew A.; Zaia, Joseph

2014-01-01

Sulfs are extracellular endosulfatases that selectively remove the 6-O-sulfate groups from cell surface heparan sulfate (HS) chain. By altering the sulfation at these particular sites, Sulfs function to remodel HS chains. As a result of the remodeling activity, HSulf2 regulates a multitude of cell-signaling events that depend on interactions between proteins and HS. Previous efforts to characterize the substrate specificity of human Sulfs (HSulfs) focused on the analysis of HS disaccharides and synthetic repeating units. In this study, we characterized the substrate preferences of human HSulf2 using HS oligosaccharides with various lengths and sulfation degrees from several naturally occurring HS sources by applying liquid chromatography mass spectrometry based glycomics methods. The results showed that HSulf2 preferentially digests highly sulfated HS oligosaccharides with zero acetyl groups and this preference is length dependent. In terms of length of oligosaccharides, HSulf2 digestion induced more sulfation decrease on DP6 (DP: degree of polymerization) compared to DP2, DP4 and DP8. In addition, the HSulf2 preferentially digests the oligosaccharide domain located at the non-reducing end (NRE) of the HS and heparin chain. In addition, the HSulf2 digestion products were altered only for specific isomers. HSulf2 treated NRE oligosaccharides also showed greater decrease in cell proliferation than those from internal domains of the HS chain. After further chromatographic separation, we identified the three most preferred unsaturated hexasaccharide for HSulf2. PMID:25127119

Heterogenous uptake of gaseous N(sub 2)O(sub 5) by sulfate aerosols

NASA Technical Reports Server (NTRS)

Leu, M. -T.; Kane, S. M.; Caloz, F.

2001-01-01

The heterogeneous uptake of gaseous N sub 2 O sub 5 by ammonium sulfate, ammonium bisulfate, and sulfuric acid aerosols as a function of relative humididty has been investigated at room temperature and atmsopheric pressure.

Aryl imidazylates and aryl sulfates as electrophiles in metal-free ArS(N)1 reactions.

PubMed

Qrareya, Hisham; Protti, Stefano; Fagnoni, Maurizio

2014-12-05

Some oxygen-bonded substituents were investigated as leaving groups in photoinduced ArS(N)1 reactions. Irradiation of aryl imidazylates and of the corresponding imidazolium salts mainly caused homolysis of the ArO-S bond. However, previously unexplored trifluoroethoxy aryl sulfates were found to undergo efficient metal-free arylation. The sulfates were conveniently generated in situ by dissolving the corresponding imidazolium salts in basic 2,2,2-trifluoroethanol.

Variation of acharan sulfate and monosaccharide composition and analysis of neutral N-glycans in African giant snail (Achatina fulica)

PubMed Central

Park, Youmie; Zhang, Zhenqing; Laremore, Tatiana N.; Li, Boyangzi; Sim, Joon-Soo; Im, A-Rang; Ahn, Mi Young

2009-01-01

Acharan sulfate content from African giant snail (Achatina fulica) was compared in eggs and snails of different ages. Acharan sulfate was not found in egg. Acharan sulfate disaccharide →4)-α-d-GlcNpAc (1→4)-α-l-IdoAp2S(1→, analyzed by SAX (strong-anion exchange)–HPLC was observed soon after hatching and increases as the snails grow. Monosaccharide compositional analysis showed that mole % of glucosamine, a major monosaccharide of acharan sulfate, increased with age while mole % of galactose decreased with age. These results suggest that galactans represent a major energy source during development, while acharan sulfate appearing immediately after hatching, is essential for the snail growth. The structures of neutral N-glycans released from eggs by peptide N-glycosidase F (PNGase F), were next elucidated using ESI-MS/MS, MALDI-MS/MS, enzyme digestion, and monosaccharide composition analysis. Three types of neutral N-glycan structures were observed, truncated (Hex2–4-Hex-NAc2), high mannose (Hex5–9-HexNAc2), and complex (Hex3-HexNAc2–10) types. None showed core fucosylation. PMID:18670878

Shikonin, an ingredient of Lithospermum erythrorhizon, down-regulates the expression of steroid sulfatase genes in breast cancer cells.

PubMed

Zhang, Yi; Qian, Rui-Qin; Li, Ping-Ping

2009-10-18

Steroid sulfatase (STS) has an important role in regulating the biosynthesis of estrogen within breast tumors. We aimed to investigate whether shikonin, an ingredient of Lithospermum erythrorhizon, could modulate STS expression in breast cancer cells. By MTT assay, shikonin inhibited the cell proliferation of breast cancer cells MCF-7 and SK-BR-3. Moreover, by semi-quantitative/quantitative reverse transcription polymerase chain reaction and dual-luciferase reporter based bioluminescent measurements, the mRNA and enzymatic activity levels of STS were decreased after shikonin treatment. Concluding, shikonin could act as a selective estrogen enzyme modulator by down-regulating the STS expression.

Analysis of N-acetylaminosugars by CE: a comparative derivatization study.

PubMed

Rustighi, Isabella; Campa, Cristiana; Rossi, Marco; Semeraro, Sabrina; Vetere, Amedeo; Gamini, Amelia

2009-08-01

N-linked or O-linked glycans derived from glycoprotein processing carry, an N-acetylglucosamine or an N-acetylgalactosamine respectively, at their reducing termini. The presence of the N-acetylamino group on C-2 of reducing sugar residues has been reported to hamper the derivatization reaction with a chromophore at the anomeric centre. In this paper N-acetyllactosamine, N-acetylglucosamine, N-acetylgalactosamine and several other neutral monosaccharides are coupled to three different dyes (4-aminobenzonitrile, 2-aminopyridine, 2-aminobenzoic acid (2-AA)) by reductive amination and analysed by CE with UV detection. The 2-AA derivatives showed the lowest concentration detection limits, varying approximately in the 2-3 muM range for the saccharides tested including the N-acetamido ones. The possibility to separate and detect with the same sensitivity ten 2-AA-labelled monosaccharides mainly found in mammalian or plant glycoproteins in a single CE run is highlighted. The analysis has been carried out in less than 25 min using the borate-complexation method in CZE mode. The influence of the strength of the acid used as catalyst in the chemical modification of the sugars with 2-AA is also shortly addressed.

Separation of pharmacologically active nitrogen-containing compounds on silica gels modified with 6,10-ionene, dextran sulfate, and gold nanoparticles

NASA Astrophysics Data System (ADS)

Ioutsi, A. N.; Shapovalova, E. N.; Ioutsi, V. A.; Mazhuga, A. G.; Shpigun, O. A.

2017-12-01

New stationary phases for HPLC are obtained via layer-by-layer deposition of polyelectrolytes and studied: (1) silica gel modified layer-by-layer with 6,10-ionene and dextran sulfate (Sorbent 1); (2) silica gel twice subjected to the above modification (Sorbent 2); and (3) silica gel modified with 6,10-ionene, gold nanoparticles, and dextran sulfate (Sorbent 3). The effect the content of the organic solvent in the mobile phase and the concentration and pH of the buffer solution have on the chromatographic behavior of several pharmacologically active nitrogen-containing compounds is studied. The sorbents are stable during the process and allow the effective separation of beta-blockers, calcium channel blockers, alpha-agonists, and antihistamines. A mixture of caffeine, nadolol, tetrahydrozoline, pindolol, orphenadrine, doxylamine, carbinoxamine, and chlorphenamine is separated in 6.5 min on the silica gel modified with 6,10-ionene, gold nanoparticles, and dextran sulfate.

Epitaxial growth of aligned AlGalnN nanowires by metal-organic chemical vapor deposition

DOEpatents

Han, Jung; Su, Jie

2008-08-05

Highly ordered and aligned epitaxy of III-Nitride nanowires is demonstrated in this work. <1010> M-axis is identified as a preferential nanowire growth direction through a detailed study of GaN/AlN trunk/branch nanostructures by transmission electron microscopy. Crystallographic selectivity can be used to achieve spatial and orientational control of nanowire growth. Vertically aligned (Al)GaN nanowires are prepared on M-plane AlN substrates. Horizontally ordered nanowires, extending from the M-plane sidewalls of GaN hexagonal mesas or islands demonstrate new opportunities for self-aligned nanowire devices, interconnects, and networks.

21 CFR 558.364 - Neomycin sulfate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Neomycin sulfate. 558.364 Section 558.364 Food and... in Animal Feeds § 558.364 Neomycin sulfate. (a) Approvals. Type A medicated article: 325 grams per.... (c) [Reserved] (d) Conditions of use. Neomycin sulfate is used as follows: Neomycin Sulfate...

21 CFR 558.364 - Neomycin sulfate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Neomycin sulfate. 558.364 Section 558.364 Food and... in Animal Feeds § 558.364 Neomycin sulfate. (a) Approvals. Type A medicated article: 325 grams per.... (c) [Reserved] (d) Conditions of use. Neomycin sulfate is used as follows: Neomycin Sulfate...

21 CFR 558.364 - Neomycin sulfate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Neomycin sulfate. 558.364 Section 558.364 Food and... in Animal Feeds § 558.364 Neomycin sulfate. (a) Approvals. Type A medicated article: 325 grams per.... (c) [Reserved] (d) Conditions of use. Neomycin sulfate is used as follows: Neomycin Sulfate...

21 CFR 558.364 - Neomycin sulfate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin sulfate. 558.364 Section 558.364 Food and... in Animal Feeds § 558.364 Neomycin sulfate. (a) Approvals. Type A medicated article: 325 grams per.... (c) [Reserved] (d) Conditions of use. Neomycin sulfate is used as follows: Neomycin Sulfate...

21 CFR 558.364 - Neomycin sulfate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Neomycin sulfate. 558.364 Section 558.364 Food and... in Animal Feeds § 558.364 Neomycin sulfate. (a) Approvals. Type A medicated article: 325 grams per.... (c) [Reserved] (d) Conditions of use. Neomycin sulfate is used as follows: Neomycin Sulfate...

Acute Exacerbations of COPD Are Associated With Increased Expression of Heparan Sulfate and Chondroitin Sulfate in BAL.

PubMed

Papakonstantinou, Eleni; Klagas, Ioannis; Roth, Michael; Tamm, Michael; Stolz, Daiana

2016-03-01

Acute exacerbations of COPD (AECOPDs) are associated with accelerated aggravation of clinical symptoms and deterioration of pulmonary function. The mechanisms by which exacerbations may contribute to airway remodeling and declined lung function are poorly understood. We investigated whether AECOPDs are associated with differential expression of glycosaminoglycans in BAL in a cohort of 97 patients with COPD. Patients with COPD with either stable disease (n = 53) or AECOPD (n = 44) and undergoing diagnostic bronchoscopy were matched for demographics and lung function parameters. Levels of heparan sulfate, chondroitin sulfate, dermatan sulfate, and matrix metalloproteinases (MMPs) in BAL were measured by enzyme-linked immunosorbent assay. Heparan sulfate and chondroitin sulfate were significantly increased in BAL of patients during exacerbations. Levels of heparan sulfate were higher in the BAL of patients with microbial infections. Chondroitin sulfate was negatively correlated with FEV1 % predicted but not with diffusing capacity of lung for carbon monoxide % predicted, indicating that chondroitin sulfate is associated with airway remodeling, leading to obstruction rather than to emphysema. Furthermore, heparan sulfate and chondroitin sulfate were significantly correlated with MMP-9, MMP-2, and MMP-12 in BAL, indicating that they were cleaved from their respective proteoglycans by MMPs and subsequently washed out in BAL. During AECOPD, there is increased expression of heparan sulfate and chondroitin sulfate in BAL. These molecules are significantly correlated with MMPs in BAL, indicating that they may be associated with airway remodeling and may lead to lung function decline during exacerbations of COPD. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Pharmacokinetics of 6-, 8-, 10-Gingerols and 6-Shogaol and Conjugate Metabolites in Healthy Human Subjects

PubMed Central

Zick, Suzanna M.; Djuric, Zora; Ruffin, Mack T.; Litzinger, Amie J.; Normolle, Daniel P.; Feng, Meihua Rose; Brenner, Dean E.

2009-01-01

Background Ginger demonstrates promising anticancer properties. No research has examined the pharmacokinetics of the ginger constituents 6-, 8-, 10-gingerol and 6-shogaol in humans. We conducted a clinical trial with 6-, 8-, 10-gingerol and 6-shogaol examining the pharmacokinetics and tolerability of these analytes and their conjugate metabolites Methods Human volunteers were given ginger at doses from 100 mg, to 2.0 g (N=27), and blood samples were obtained at 15 minutes to 72 hours after a single oral dose. Participants were allocated in a dose-escalation manner starting with 100 mg. There was a total of three participants at each dose except for 1.0 g (N=6) and 2.0 g (N=9). Results No participant had detectable free 6-, 8-, 10-gingerol or 6-shogaol, but 6-, 8-, 10-gingerol and 6-shogaol glucuronides were detected. The 6-gingerol sulfate conjugate was detected above the 1.0 g dose but there were no detectable 10-gingerol or 6-shogaol sulfates except for one participant with detectable 8-gingerol sulfate. The Cmax and AUC values (Mean±SE) estimated for the 2.0 g dose are 0.85±0.43, 0.23±0.16, 0.53±0.40, and 0.15±0.12 μg/mL ; and 65.6.33±44.4, 18.1±20.3, 50.1±49.3, and 10.9±13.0 μg·hr/mL for 6-, 8-, 10-gingerol, and 6-shogaol. The corresponding tmax values are 65.6±44.4, 73.1±29.4, 75.0±27.8, and 65.6±22.6 minutes and the analytes had elimination half-lives < 2hr. The 8-, 10-gingerol and 6-shogaol conjugates were present as either glucuronide or sulfate conjugates, not as mixed conjugates, although 6-, 10-gingerol were an exception. Conclusion Six-, 8-, 10-gingerol and 6-shogaol is absorbed after oral dosing and can be detected as glucuronide and sulfate conjugates. PMID:18708382

Tandem Mass Spectrometry of Heparan Sulfate Negative Ions: Sulfate Loss Patterns and Chemical Modification Methods for Improvement of Product Ion Profiles

NASA Astrophysics Data System (ADS)

Shi, Xiaofeng; Huang, Yu; Mao, Yang; Naimy, Hicham; Zaia, Joseph

2012-09-01

Heparan sulfate (HS) is a polysaccharide modified with sulfation, acetylation, and epimerization that enable its binding with protein ligands and regulation of important biological processes. Tandem mass spectrometry has been employed to sequence linear biomolecules e.g., proteins and peptides. However, its application in structural characterization of HS is limited due to the neutral loss of sulfate (SO3) during collisional induced dissociation (CID). In this report, we studied the dissociation patterns of HS disaccharides and demonstrate that the N-sulfate (N-S) bond is especially facile during CID. We identified factors that influence the propensities of such losses from precursor ions and proposed a Free Proton Index (FPI) to help select ions that are able to produce meaningful backbone dissociations. We then investigated the thermodynamics and kinetics of SO3 loss from sulfates that are protonated, deprotonated, and metal-adducted using density functional theory computations. The calculations showed that sulfate loss from a protonated site was much more facile than that from a deprotonated or metal-adducted site. Further, the loss of SO3 from N-sulfate was energetically favored by 3-8 kcal/mol in transition states relative to O-sulfates, making it more prone to this process by a substantial factor. In order to reduce the FPI, representing the number of labile sulfates in HS native chains and oligosaccharides, we developed a series of chemical modifications to selectively replace the N-sulfates of the glucosamine with deuterated acetyl group. These modifications effectively reduced the sulfate density on the HS oligosaccharides and generated considerably more backbone dissociation using on-line LC/tandem MS.

21 CFR 524.154 - Bacitracin or bacitracin zinc-neomycin sulfate-polymyxin B sulfate ophthalmic ointment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Bacitracin or bacitracin zinc-neomycin sulfate-polymyxin B sulfate ophthalmic ointment. 524.154 Section 524.154 Food and Drugs FOOD AND DRUG ADMINISTRATION... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.154 Bacitracin or bacitracin zinc-neomycin sulfate-polymyxin B...

21 CFR 524.154 - Bacitracin or bacitracin zinc-neomycin sulfate-polymyxin B sulfate ophthalmic ointment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Bacitracin or bacitracin zinc-neomycin sulfate-polymyxin B sulfate ophthalmic ointment. 524.154 Section 524.154 Food and Drugs FOOD AND DRUG ADMINISTRATION... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.154 Bacitracin or bacitracin zinc-neomycin sulfate-polymyxin B...

Sulfation of LH Does Not Affect Intracellular Trafficking

PubMed Central

Pearl, Christopher A.; Boime, Irving

2009-01-01

LH and FSH are produced by the same gonadotrope cells of the anterior pituitary but differ in their mode of secretion. LH secretion is primarily episodic, or regulated, while FSH secretion is primarily basal, or constitutive. The asparagine (N)-linked oligosaccharides of LH and FSH terminate with sulfate and sialic acid, respectively. TSH also contains sulfated N-linked oligosaccharides and is secreted through the regulated pathway. It has been hypothesized that sulfate plays a role in segregating LH to the regulated pathway. Using a mouse pituitary model, we tested this hypothesis by examining the secretory fate of LH from pituitaries treated with sodium chlorate, a known inhibitor of sulfation. Here we show that mouse LH is sulfated and secreted through the regulated pathway, while FSH is secreted constitutively. LH secretion from chlorate treated pituitaries, which showed complete inhibition of sulfation, was similar to untreated pituitaries. These data suggest that the metabolic role for sulfated N-linked oligosaccharides is not for intracellular trafficking but for the extracellular bioactivity of LH. PMID:19647136

Heparan sulfate niche for cell proliferation in the adult brain.

PubMed

Mercier, Frederic; Arikawa-Hirasawa, Eri

2012-02-29

In adulthood, new neurons and glial cells are generated from stem cells in restricted zones of the brain, namely the olfactory bulb (OB), rostral migratory stream (RMS), subventricular zone (SVZ) of the lateral ventricle, sub-callosum zone (SCZ) and sub-granular layer (SGL) of the dentate gyrus. What makes these zones germinal? We previously reported that N-sulfated heparan sulfates (N-sulfated HS) present in specialized extracellular matrix structures (fractones) and vascular basement membranes bind the neurogenic factor FGF-2 (fibroblast growth factor-2) next to stem cells in the anterior SVZ of the lateral ventricle, the most neurogenic zone in adulthood. To determine to which extent cell proliferation is associated with N-sulfated HS, we mapped N-sulfated HS and proliferating cells by immunohistochemistry throughout the adult mouse brain. We found that cell proliferation is associated with N-sulfated HS in the OB, RMS, the whole germinal SVZ, and the SCZ. Cell proliferation was weakly associated with N-sulfated HS in the SGL, but the SGL was directly connected to a sub-cortical N-sulfated HS+ extension of the meninges. The NS-sulfated HS+ structures were blood vessels in the OB, RMS and SCZ, and primarily fractones in the SVZ. N-sulfated HS+ fractones, blood vessels and meninges formed a continuum that coursed along the OB, SVZ, RMS, SCZ and SGL, challenging the view that these structures are independent germinal entities. These results support the possibility that a single anatomical system might be globally responsible for mitogenesis and ultimately the production of new neurons and glial cells in the adult brain. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Minimal sulfated carbohydrates for recognition by L-selectin and the MECA-79 antibody.

PubMed

Bruehl, R E; Bertozzi, C R; Rosen, S D

2000-10-20

Sulfated forms of sialyl-Le(X) containing Gal-6-SO(4) or GlcNAc-6-SO(4) have been implicated as potential recognition determinants on high endothelial venule ligands for L-selectin. The optimal configuration of sulfate esters on the N-acetyllactosamine (Galbeta1-->4GlcNAc) core of sulfosialyl-Le(X), however, remains unsettled. Using a panel of sulfated lactose (Galbeta1-->4Glc) neoglycolipids as substrates in direct binding assays, we found that 6',6-disulfolactose was the preferred structure for L-selectin, although significant binding to 6'- and 6-sulfolactose was observed as well. Binding was EDTA-sensitive and blocked by L-selectin-specific monoclonal antibodies. Surprisingly, 6', 6-disulfolactose was poorly recognized by MECA-79, a carbohydrate- and sulfate-dependent monoclonal antibody that binds competitively to L-selectin ligands. Instead, MECA-79 bound preferentially to 6-sulfolactose. The difference in preferred substrates between L-selectin and MECA-79 may explain the variable activity of MECA-79 as an inhibitor of lymphocyte adhesion to high endothelial venules in lymphoid organs. Our results suggest that both Gal-6-SO(4) and GlcNAc-6-SO(4) may contribute to L-selectin recognition, either as components of sulfosialyl-Le(X) capping groups or in internal structures. By contrast, only GlcNAc-6-SO(4) appears to contribute to MECA-79 binding.

Sulfate reduction in freshwater wetland soils and the effects of sulfate and substrate loading

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, J.; Hsieh, Y.P.

1998-07-01

Elevated sulfate and organic C loadings in freshwater wetlands could stimulate dissimilatory sulfate reduction that oxidizes organic C, produces hydrogen sulfide and alkalinity, and sequesters trace metals. The authors determined the extent of sulfate reduction in two freshwater wetland soils, that is black gum (Nyssa biflona) swamp soils and titi (Cliftonia monophylla) swamp soils, in northern Florida. They also investigated the potential of sulfate reduction in the wetland soils by adding sulfate, organic substrate, and lime. Sulfate reduction was found to be an active process in both swamp soils without any amendment, where the pore water pH was as lowmore » as 3.6 and sulfate concentration was as low as 5 mg L{sup {minus}1}. Without amendment, 11 to 14% of organic C was oxidized through sulfate reduction in the swamp soils. Sulfate loading, liming, and substrate addition significantly increased sulfate reduction in the black gum swamp soil, but none of those treatments increase sulfate reduction in the titi swamp soil. The limiting factor for sulfate reduction in the titi swamp soil were likely texture and soil aggregate related properties. The results suggested that wastewater loading may increase sulfate reduction in some freshwater wetlands such as the black swamps while it has no stimulating effect on other wetlands such as the titi swamps.« less

A rat osteogenic cell line (UMR 106-01) synthesizes a highly sulfated form of bone sialoprotein.

PubMed

Midura, R J; McQuillan, D J; Benham, K J; Fisher, L W; Hascall, V C

1990-03-25

The rat osteosarcoma cell line (UMR 106-01) synthesizes and secretes relatively large amounts of a sulfated glycoprotein into its culture medium (approximately 240 ng/10(6) cells/day). This glycoprotein was purified, and amino-terminal sequence analysis identified it as bone sialoprotein (BSP). [35S]Sulfate, [3H]glucosamine, and [3H]tyrosine were used as metabolic precursors to label the BSP. Sulfate esters were found on N- and O-linked oligosaccharides and on tyrosine residues, with about half of the total tyrosines in the BSP being sulfated. The proportion of 35S activity in tyrosine-O-sulfate (approximately 70%) was greater than that in N-linked (approximately 20%) and O-linked (approximately 10%) oligosaccharides. From the deduced amino acid sequence for rat BSP (Oldberg, A., Franzén, A., and Heinegård, D. (1988) J. Biol. Chem. 263, 19430-19432), the results indicate that on average approximately 12 tyrosine residues, approximately 3 N-linked, and approximately 2 O-linked oligosaccharides are sulfated/molecule. The carboxyl-terminal quarter of the BSP probably contains most, if not all, of the sulfated tyrosine residues because this region of the polypeptide contains the necessary requirements for tyrosine sulfation. Oligosaccharide analyses indicated that for every N-linked oligosaccharide on the BSP, there are also approximately 2 hexa-, approximately 5 tetra-, and approximately 2 trisaccharides O-linked to serine and threonine residues. On average, the BSP synthesized by UMR 106-01 cells would contain a total of approximately 3 N-linked and approximately 25 of the above O-linked oligosaccharides. This large number of oligosaccharides is in agreement with the known carbohydrate content (approximately 50%) of the BSP.

Effective Synthesis of Sulfate Metabolites of Chlorinated Phenols

PubMed Central

Lehmler, Hans-Joachim; He, Xianran; Li, Xueshu; Duffel, Michael W.; Parkin, Sean

2013-01-01

Chlorophenols are an important class of persistent environmental contaminants and have been implicated in a range of adverse health effects, including cancer. They are readily conjugated and excreted as the corresponding glucuronides and sulfates in the urine of humans and other species. Here we report the synthesis and characterization of a series of ten chlorophenol sulfates by sulfation of the corresponding chlorophenols with 2,2,2-trichloroethyl (TCE) chlorosulfate using N,N-dimethylaminopyridine (DMAP) as base. Deprotection of the chlorophenol diesters with zinc powder/ammonium formate yielded the respective chlorophenol sulfate ammonium salts in good yield. The molecular structure of three TCE-protected chlorophenol sulfate diesters and one chlorophenol sulfate monoester were confirmed by X-ray crystal structure analysis. The chlorophenol sulfates were stable for several months if stored at −20 °C and, thus, are useful for future toxicological, environmental and human biomonitoring studies. PMID:23906814

Isolation, purification, and characterization of glucosamine-6-phosphate-N-acetylase from pig liver.

PubMed

Porowski, T S; Porowska, H; Gałasiński, W

1990-08-01

The procedure of isolation, purification, and characterization of glucosamine-6-phosphate acetylase from the pig liver is described. The steps of purification were as follows: adsorption on hydroxylapatite, fractionation with ammonium sulfate, chromatography on cellulose phosphate, electrofocusing, and preparative gel electrophoresis. A highly purified (about 3000-fold) preparation of GlcN-6-P acetylase, with a yield of 23%, was obtained. It was found that GlcN-6-P acetylase from pig liver is heterogeneous and exists in two active forms. The characteristic features of the preparation were established: Mr, about 24 kDa; temperature optimum at 37 degrees; pH optimum at 7.45; and Km (GlcN-6-P) 3.7 x 10(-3) M and Km (AcCoA) 1.4 x 10(-3) M. The ions K+, Na+, NH4+, Mg2+, Mn2+, and CH3COO- do not stimulate the acetylase activity. The product of acetylase reaction (GlcNAc-6-P) inhibits this reaction according to the feedback process. The highly purified preparation of GlcN-6-P acetylase is unstable during storage and it is protected by ampholine or glycine from enzyme inactivation, but it is not protected by 2-mercaptoethanol.

Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol and conjugate metabolites in healthy human subjects.

PubMed

Zick, Suzanna M; Djuric, Zora; Ruffin, Mack T; Litzinger, Amie J; Normolle, Daniel P; Alrawi, Sara; Feng, Meihua Rose; Brenner, Dean E

2008-08-01

Ginger shows promising anticancer properties. No research has examined the pharmacokinetics of the ginger constituents 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol in humans. We conducted a clinical trial with 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol, examining the pharmacokinetics and tolerability of these analytes and their conjugate metabolites. Human volunteers were given ginger at doses from 100 mg to 2.0 g (N = 27), and blood samples were obtained at 15 minutes to 72 hours after a single p.o. dose. The participants were allocated in a dose-escalation manner starting with 100 mg. There was a total of three participants at each dose except for 1.0 g (N = 6) and 2.0 g (N = 9). No participant had detectable free 6-gingerol, 8-gingerol, 10-gingerol, or 6-shogaol, but 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol glucuronides were detected. The 6-gingerol sulfate conjugate was detected above the 1.0-g dose, but there were no detectable 10-gingerol or 6-shogaol sulfates except for one participant with detectable 8-gingerol sulfate. The C(max) and area under the curve values (mean +/- SE) estimated for the 2.0-g dose are 0.85 +/- 0.43, 0.23 +/- 0.16, 0.53 +/- 0.40, and 0.15 +/- 0.12 microg/mL; and 65.6.33 +/- 44.4, 18.1 +/- 20.3, 50.1 +/- 49.3, and 10.9 +/- 13.0 microg x hr/mL for 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol. The corresponding t(max) values are 65.6 +/- 44.4, 73.1 +/- 29.4, 75.0 +/- 27.8, and 65.6 +/- 22.6 minutes, and the analytes had elimination half-lives <2 hours. The 8-gingerol, 10-gingerol, and 6-shogaol conjugates were present as either glucuronide or sulfate conjugates, not as mixed conjugates, although 6-gingerol and 10-gingerol were an exception. Six-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol are absorbed after p.o. dosing and can be detected as glucuronide and sulfate conjugates.

21 CFR 582.1643 - Potassium sulfate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Potassium sulfate. 582.1643 Section 582.1643 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1643 Potassium sulfate. (a) Product. Potassium sulfate. (b) Conditions of use. This...

21 CFR 582.1643 - Potassium sulfate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Potassium sulfate. 582.1643 Section 582.1643 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1643 Potassium sulfate. (a) Product. Potassium sulfate. (b) Conditions of use. This...

21 CFR 582.1643 - Potassium sulfate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Potassium sulfate. 582.1643 Section 582.1643 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1643 Potassium sulfate. (a) Product. Potassium sulfate. (b) Conditions of use. This...

21 CFR 582.1643 - Potassium sulfate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Potassium sulfate. 582.1643 Section 582.1643 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1643 Potassium sulfate. (a) Product. Potassium sulfate. (b) Conditions of use. This...

21 CFR 582.1643 - Potassium sulfate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Potassium sulfate. 582.1643 Section 582.1643 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1643 Potassium sulfate. (a) Product. Potassium sulfate. (b) Conditions of use. This...

The role of bacteria and mycorrhiza in plant sulfur supply

PubMed Central

Gahan, Jacinta; Schmalenberger, Achim

2014-01-01

Plant growth is highly dependent on bacteria, saprophytic, and mycorrhizal fungi which facilitate the cycling and mobilization of nutrients. Over 95% of the sulfur (S) in soil is present in an organic form. Sulfate-esters and sulfonates, the major forms of organo-S in soils, arise through deposition of biological material and are transformed through subsequent humification. Fungi and bacteria release S from sulfate-esters using sulfatases, however, release of S from sulfonates is catalyzed by a bacterial multi-component mono-oxygenase system. The asfA gene is used as a key marker in this desulfonation process to study sulfonatase activity in soil bacteria identified as Variovorax, Polaromonas, Acidovorax, and Rhodococcus. The rhizosphere is regarded as a hot spot for microbial activity and recent studies indicate that this is also the case for the mycorrhizosphere where bacteria may attach to the fungal hyphae capable of mobilizing organo-S. While current evidence is not showing sulfatase and sulfonatase activity in arbuscular mycorrhiza, their effect on the expression of plant host sulfate transporters is documented. A revision of the role of bacteria, fungi and the interactions between soil bacteria and mycorrhiza in plant S supply was conducted. PMID:25566295

21 CFR 582.1143 - Ammonium sulfate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Ammonium sulfate. 582.1143 Section 582.1143 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1143 Ammonium sulfate. (a) Product. Ammonium sulfate. (b) Conditions of use. This substance...

21 CFR 582.1125 - Aluminum sulfate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Aluminum sulfate. 582.1125 Section 582.1125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1125 Aluminum sulfate. (a) Product. Aluminum sulfate. (b) Conditions of use. This substance...

21 CFR 582.1143 - Ammonium sulfate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Ammonium sulfate. 582.1143 Section 582.1143 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1143 Ammonium sulfate. (a) Product. Ammonium sulfate. (b) Conditions of use. This substance...

21 CFR 582.1143 - Ammonium sulfate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Ammonium sulfate. 582.1143 Section 582.1143 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1143 Ammonium sulfate. (a) Product. Ammonium sulfate. (b) Conditions of use. This substance...

21 CFR 582.1125 - Aluminum sulfate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Aluminum sulfate. 582.1125 Section 582.1125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1125 Aluminum sulfate. (a) Product. Aluminum sulfate. (b) Conditions of use. This substance...

21 CFR 582.1125 - Aluminum sulfate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Aluminum sulfate. 582.1125 Section 582.1125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1125 Aluminum sulfate. (a) Product. Aluminum sulfate. (b) Conditions of use. This substance...

21 CFR 582.1125 - Aluminum sulfate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Aluminum sulfate. 582.1125 Section 582.1125 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1125 Aluminum sulfate. (a) Product. Aluminum sulfate. (b) Conditions of use. This substance...

21 CFR 582.1143 - Ammonium sulfate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ammonium sulfate. 582.1143 Section 582.1143 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1143 Ammonium sulfate. (a) Product. Ammonium sulfate. (b) Conditions of use. This substance...

Determination of genotypic and clinical characteristics of Colombian patients with mucopolysaccharidosis IVA

PubMed Central

Tapiero-Rodriguez, Sandra M; Acosta Guio, Johanna C; Porras-Hurtado, Gloria Liliana; García, Natalia; Solano, Martha; Pachajoa, Harry; Velasco, Harvy M

2018-01-01

Background As mucopolysaccharidosis IVA (MPS IVA) is the most frequent MPS in Colombia, this paper aims to describe its clinical and mutational characteristics in 32 diagnosed patients included in this study. Methods Genotyping was completed by amplification and Sanger sequencing of the GALNS gene. The SWISS-model platform was used for bioinformatic analysis, and mutant proteins were generated by homology from the wild-type GALNS code 4FDI template from the Protein Data Bank (PDB) database. Docking was performed using the GalNAc6S ligand (PubChem CID: 193456) by AutoDock Vina 1.0 and visualized in PyMOL and LigPlot+. Results Eleven variants were identified, and one new pathogenic variant was described in the heterozygous state, which is consistent with genotype c. 319 G> T or p.Ala107Ser. The pathogenic variant c.901G>T or p.Gly301Cys was the most frequent mutation with 51.6% of alleles. Docking revealed affinity energy of −5.9 Kcal/mol between wild-type GALNS and the G6S ligand. Some changes were evidenced at the intermolecular interaction level, and affinity energy for each mutant decreased. Conclusion Clinical variables and genotypic analysis were similar to those reported for other world populations. Genotypic data showed greater allelic heterogeneity than those previously reported. Bioinformatics tools showed differences in the binding interactions of mutant proteins with the G6S ligand, in regard the wild-type GALNS. PMID:29731656

Roles of Heparan Sulfate Sulfation in Dentinogenesis*

PubMed Central

Hayano, Satoru; Kurosaka, Hiroshi; Yanagita, Takeshi; Kalus, Ina; Milz, Fabian; Ishihara, Yoshihito; Islam, Md. Nurul; Kawanabe, Noriaki; Saito, Masahiro; Kamioka, Hiroshi; Adachi, Taiji; Dierks, Thomas; Yamashiro, Takashi

2012-01-01

Cell surface heparan sulfate (HS) is an essential regulator of cell signaling and development. HS traps signaling molecules, like Wnt in the glycosaminoglycan side chains of HS proteoglycans (HSPGs), and regulates their functions. Endosulfatases Sulf1 and Sulf2 are secreted at the cell surface to selectively remove 6-O-sulfate groups from HSPGs, thereby modifying the affinity of cell surface HSPGs for its ligands. This study provides molecular evidence for the functional roles of HSPG sulfation and desulfation in dentinogenesis. We show that odontogenic cells are highly sulfated on the cell surface and become desulfated during their differentiation to odontoblasts, which produce tooth dentin. Sulf1/Sulf2 double null mutant mice exhibit a thin dentin matrix and short roots combined with reduced expression of dentin sialophosphoprotein (Dspp) mRNA, encoding a dentin-specific extracellular matrix precursor protein, whereas single Sulf mutants do not show such defective phenotypes. In odontoblast cell lines, Dspp mRNA expression is potentiated by the activation of the Wnt canonical signaling pathway. In addition, pharmacological interference with HS sulfation promotes Dspp mRNA expression through activation of Wnt signaling. On the contrary, the silencing of Sulf suppresses the Wnt signaling pathway and subsequently Dspp mRNA expression. We also show that Wnt10a protein binds to cell surface HSPGs in odontoblasts, and interference with HS sulfation decreases the binding affinity of Wnt10a for HSPGs, which facilitates the binding of Wnt10a to its receptor and potentiates the Wnt signaling pathway, thereby up-regulating Dspp mRNA expression. These results demonstrate that Sulf-mediated desulfation of cellular HSPGs is an important modification that is critical for the activation of the Wnt signaling in odontoblasts and for production of the dentin matrix. PMID:22351753

21 CFR 582.5997 - Zinc sulfate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Zinc sulfate. 582.5997 Section 582.5997 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5997 Zinc sulfate. (a) Product. Zinc sulfate. (b) Conditions of use. This substance is...

21 CFR 582.5997 - Zinc sulfate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Zinc sulfate. 582.5997 Section 582.5997 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5997 Zinc sulfate. (a) Product. Zinc sulfate. (b) Conditions of use. This substance is...

21 CFR 582.5997 - Zinc sulfate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Zinc sulfate. 582.5997 Section 582.5997 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5997 Zinc sulfate. (a) Product. Zinc sulfate. (b) Conditions of use. This substance is...

21 CFR 582.5997 - Zinc sulfate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Zinc sulfate. 582.5997 Section 582.5997 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5997 Zinc sulfate. (a) Product. Zinc sulfate. (b) Conditions of use. This substance is...

Purification, structural characterization and antiproliferative properties of chondroitin sulfate/dermatan sulfate from tunisian fish skins.

PubMed

Krichen, Fatma; Volpi, Nicola; Sila, Assaâd; Maccari, Francesca; Mantovani, Veronica; Galeotti, Fabio; Ellouz-Chaabouni, Semia; Bougatef, Ali

2017-02-01

Chondroitin sulfate/dermatan sulfate GAGs were extracted and purified from the skins of grey triggerfish (GTSG) and smooth hound (SHSG). The disaccharide composition produced by chondroitinase ABC treatment showed the presence of nonsulfated disaccharide, monosulfated disaccharides ΔDi6S and ΔDi4S, and disulfated disaccharides in different percentages. In particular, the nonsulfated disaccharide ΔDi0S of GTSG and SHSG were 3.5% and 5.5%, respectively, while monosulfated disaccharides ΔDi6S and ΔDi4S were evaluated to be 18.2%, 59% and 14.6%, 47.0%, respectively. Capillary elecrophoresis analysis of GTSG and SHSG contained 99.2% and 95.4% of chondroitin sulfate/dermatan sulfate, respectively. PAGE analysis showed a GTSG and SHSG having molecular masses with average values of 41.72KDa and 23.8KDa, respectively. HCT116 cell proliferation was inhibited (p<0.05) by 70.6% and 72.65% at 200μg/mL of GTSG and SHSG respectively. Both GTSG and SHSG demonstrated promising antiproliferative potential, which may be used as a novel, effective agent. Copyright © 2016 Elsevier B.V. All rights reserved.

21 CFR 556.300 - Gentamicin sulfate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate. 556.300 Section 556.300 Food... Tolerances for Residues of New Animal Drugs § 556.300 Gentamicin sulfate. (a) A tolerance of 0.1 part per million is established for negligible residues of gentamicin sulfate in the uncooked edible tissues of...

21 CFR 556.300 - Gentamicin sulfate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate. 556.300 Section 556.300 Food... Tolerances for Residues of New Animal Drugs § 556.300 Gentamicin sulfate. (a) A tolerance of 0.1 part per million is established for negligible residues of gentamicin sulfate in the uncooked edible tissues of...

21 CFR 556.300 - Gentamicin sulfate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gentamicin sulfate. 556.300 Section 556.300 Food... Tolerances for Residues of New Animal Drugs § 556.300 Gentamicin sulfate. (a) A tolerance of 0.1 part per million is established for negligible residues of gentamicin sulfate in the uncooked edible tissues of...

21 CFR 522.650 - Dihydrostreptomycin sulfate injection.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Dihydrostreptomycin sulfate injection. 522.650... § 522.650 Dihydrostreptomycin sulfate injection. (a) Specifications. Each milliliter contains dihydrostreptomycin sulfate equivalent to 500 milligrams of dihydrostreptomycin. (b) Sponsors. See Nos. 054771 and...

21 CFR 186.1797 - Sodium sulfate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Sodium sulfate. 186.1797 Section 186.1797 Food and....1797 Sodium sulfate. (a) Sodium sulfate (Na2SO4, CAS Reg. No. 7757-82-6), also known as Glauber's salt... by the neutralization of sulfuric acid with sodium hydroxide. (b) The ingredient is used as a...

21 CFR 186.1797 - Sodium sulfate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Sodium sulfate. 186.1797 Section 186.1797 Food and... Substances Affirmed as GRAS § 186.1797 Sodium sulfate. (a) Sodium sulfate (Na2SO4, CAS Reg. No. 7757-82-6... crystalline powder. It is prepared by the neutralization of sulfuric acid with sodium hydroxide. (b) The...

21 CFR 186.1797 - Sodium sulfate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Sodium sulfate. 186.1797 Section 186.1797 Food and... Substances Affirmed as GRAS § 186.1797 Sodium sulfate. (a) Sodium sulfate (Na2SO4, CAS Reg. No. 7757-82-6... crystalline powder. It is prepared by the neutralization of sulfuric acid with sodium hydroxide. (b) The...

21 CFR 186.1797 - Sodium sulfate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Sodium sulfate. 186.1797 Section 186.1797 Food and... Substances Affirmed as GRAS § 186.1797 Sodium sulfate. (a) Sodium sulfate (Na2SO4, CAS Reg. No. 7757-82-6... crystalline powder. It is prepared by the neutralization of sulfuric acid with sodium hydroxide. (b) The...

21 CFR 186.1797 - Sodium sulfate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Sodium sulfate. 186.1797 Section 186.1797 Food and... Substances Affirmed as GRAS § 186.1797 Sodium sulfate. (a) Sodium sulfate (Na2SO4, CAS Reg. No. 7757-82-6... crystalline powder. It is prepared by the neutralization of sulfuric acid with sodium hydroxide. (b) The...

Low-temperature superacid catalysis: Reactions of n - butane and propane catalyzed by iron- and manganese-promoted sulfated zirconia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsz-Keung, Cheung; d`Itri, J.L.; Lange, F.C.

1995-12-31

The primary goal of this project is to evaluate the potential value of solid superacid catalysts of the sulfated zirconia type for light hydrocarbon conversion. The key experiments catalytic testing of the performance of such catalysts in a flow reactor fed with streams containing, for example, n-butane or propane. Fe- and Mn-promoted sulfated zirconia was used to catalyze the conversion of n-butane at atmospheric pressure, 225-450{degrees}C, and n-butane partial pressures in the range of 0.0025-0.01 atm. At temperatures <225{degrees}C, these reactions were accompanied by cracking; at temperatures >350{degrees}C, cracking and isomerization occurred. Catalyst deactivation, resulting at least in part frommore » coke formation, was rapid. The primary cracking products were methane, ethane, ethylene, and propylene. The observation of these products along with an ethane/ethylene molar ratio of nearly 1 at 450{degrees}C is consistent with cracking occurring, at least in part, by the Haag-Dessau mechanism, whereby the strongly acidic catalyst protonates n-butane to give carbonium ions. The rate of methane formation from n-butane cracking catalyzed by Fe- and Mn-promoted sulfated zirconia at 450{degrees}C was about 3 x 10{sup -8} mol/(g of catalyst {center_dot}s). The observation of butanes, pentanes, and methane as products is consistent with Olah superacid chemistry, whereby propane is first protonated by a very strong acid to form a carbonium ion. The carbonium ion then decomposes into methane and an ethyl cation which undergoes oligocondensation reactions with propane to form higher molecular weight alkanes. The results are consistent with the identification of iron- and manganese-promoted sulfated zirconia as a superacid.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jain, Nikhil; Oshima, Ryuji; France, Ryan

To advance the state-of-the-art in III-V multijunction solar cells towards high concentration efficiencies approaching 50%, development of a high-quality ~1.7 eV second junction solar cell is of key interest for integration in five or more junction devices. Quaternary GalnAsP solar cells grown lattice-matched on GaAs allows bandgap tunability in the range from 1.42 to 1.92 eV and offers an attractive Al-free alternative to conventional AlGaAs solar cells. In this work, we investigate the role of growth temperature towards understanding the optimal growth window for realizing high-quality GalnAsP alloys. We demonstrate bandgap tunability from 1.6 to 1.8 eV in GalnAsP alloysmore » for compositions close to the miscibility gap, while still maintaining lattice-matched condition to GaAs. We perform an in-depth investigation to understand the impact of varying base thickness and doping concentration on the carrier collection and performance of these 1.7 eV GalnAsP solar cells. The photo-response of these cells is found to be very sensitive to p-type zinc dopant incorporation in the base layer. We demonstrate prototype 1.7 eV GalnAsP solar cell designs that leverage enhanced depletion width as an effective method to overcome this issue and boost long-wavelength carrier collection. Short-circuit current density (JSC) measured in field-aided devices were as high as 17.25 m A/cm2. The best GalnAsP solar cell in this study achieved an efficiency of 17.2% with a JSC of 17 m A/cm2 and a fill-factor of 86.4%. The corresponding open-circuit voltage (VOC) 1.7 eV measured on this cell represents the highest Voc reported for a 1.7 eV GalnAsP solar cell. These initial cell results are encouraging and highlight the potential of Al-free GalnAsP solar cells for integration in the next generation of III-V multijunction solar cells.« less

21 CFR 522.1204 - Kanamycin sulfate injection.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Kanamycin sulfate injection. 522.1204 Section 522.1204 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....1204 Kanamycin sulfate injection. (a) Specifications. Each milliliter of kanamycin sulfate injection...

21 CFR 522.1204 - Kanamycin sulfate injection.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Kanamycin sulfate injection. 522.1204 Section 522.1204 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....1204 Kanamycin sulfate injection. (a) Specifications. Each milliliter of kanamycin sulfate injection...

21 CFR 522.1204 - Kanamycin sulfate injection.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Kanamycin sulfate injection. 522.1204 Section 522.1204 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....1204 Kanamycin sulfate injection. (a) Specifications. Each milliliter of kanamycin sulfate injection...

21 CFR 522.1204 - Kanamycin sulfate injection.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Kanamycin sulfate injection. 522.1204 Section 522.1204 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED....1204 Kanamycin sulfate injection. (a) Specifications. Each milliliter of kanamycin sulfate injection...

21 CFR 520.1044c - Gentamicin sulfate powder.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate powder. 520.1044c Section 520... sulfate powder. (a) Specifications. Each gram of powder contains gentamicin sulfate equivalent to: (1) 16... colibacillosis: Gentamicin sulfate equivalent to 25 mg of gentamicin per gallon of drinking water to provide 0.5...

21 CFR 520.1044c - Gentamicin sulfate powder.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gentamicin sulfate powder. 520.1044c Section 520... sulfate powder. (a) Specifications. Each gram of powder contains gentamicin sulfate equivalent to: (1) 16... colibacillosis: Gentamicin sulfate equivalent to 25 mg of gentamicin per gallon of drinking water to provide 0.5...

21 CFR 582.1127 - Aluminum ammonium sulfate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Aluminum ammonium sulfate. 582.1127 Section 582.1127 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Additives § 582.1127 Aluminum ammonium sulfate. (a) Product. Aluminum ammonium sulfate. (b) Conditions of...

21 CFR 582.1127 - Aluminum ammonium sulfate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Aluminum ammonium sulfate. 582.1127 Section 582.1127 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Additives § 582.1127 Aluminum ammonium sulfate. (a) Product. Aluminum ammonium sulfate. (b) Conditions of...

21 CFR 582.1127 - Aluminum ammonium sulfate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Aluminum ammonium sulfate. 582.1127 Section 582.1127 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Additives § 582.1127 Aluminum ammonium sulfate. (a) Product. Aluminum ammonium sulfate. (b) Conditions of...

21 CFR 582.1127 - Aluminum ammonium sulfate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Aluminum ammonium sulfate. 582.1127 Section 582.1127 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Additives § 582.1127 Aluminum ammonium sulfate. (a) Product. Aluminum ammonium sulfate. (b) Conditions of...

21 CFR 582.1129 - Aluminum potassium sulfate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Aluminum potassium sulfate. 582.1129 Section 582.1129 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Additives § 582.1129 Aluminum potassium sulfate. (a) Product. Aluminum potassium sulfate. (b) Conditions of...

21 CFR 582.1129 - Aluminum potassium sulfate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Aluminum potassium sulfate. 582.1129 Section 582.1129 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Additives § 582.1129 Aluminum potassium sulfate. (a) Product. Aluminum potassium sulfate. (b) Conditions of...

21 CFR 582.1129 - Aluminum potassium sulfate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Aluminum potassium sulfate. 582.1129 Section 582.1129 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Additives § 582.1129 Aluminum potassium sulfate. (a) Product. Aluminum potassium sulfate. (b) Conditions of...

21 CFR 582.1129 - Aluminum potassium sulfate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Aluminum potassium sulfate. 582.1129 Section 582.1129 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Additives § 582.1129 Aluminum potassium sulfate. (a) Product. Aluminum potassium sulfate. (b) Conditions of...

Gadolinium sulfate modified by formate to obtain optimized magneto-caloric effect.

PubMed

Xu, Long-Yang; Zhao, Jiong-Peng; Liu, Ting; Liu, Fu-Chen

2015-06-01

Three new Gd(III) based coordination polymers [Gd2(C2H6SO)(SO4)3(H2O)2]n (1), {[Gd4(HCOO)2(SO4)5(H2O)6]·H2O}n (2), and [Gd(HCOO)(SO4)(H2O)]n (3) were obtained by modifying gadolinium sulfate. With the gradual increase of the volume ratio of HCOOH and DMSO in synthesis, the formate anions begin to coordinate with metal centers; this results in the coordination numbers of sulfate anion increasing and the contents of water and DMSO molecules decreasing in target complexes. Accordingly, spin densities both per mass and per volume were enhanced step by step, which are beneficial for the magneto-caloric effect (MCE). Magnetic studies reveal that with the more formate anions present, the larger the negative value of magnetic entropy change (-ΔSm) is. Complex 3 exhibits the largest -ΔSm = 49.91 J kg(-1) K(-1) (189.51 mJ cm(-3) K(-1)) for T = 2 K and ΔH = 7 T among three new complexes.

Inhibition of B16-BL6 melanoma lung colonies by semisynthetic sulfaminoheparosan sulfates from E. coli K5 polysaccharide.

PubMed

Poggi, Andreina; Rossi, Cosmo; Casella, Nicola; Bruno, Cristiana; Sturiale, Luisella; Dossi, Carla; Naggi, Annamaria

2002-08-01

Heparin (H), heparan sulfate (HS), and related glycosaminoglycans can inhibit cancer cell invasion, possibly due to their ability to interact with vascular growth factors, adhesion molecules, endoglycosidases, and signaling proteins, in addition to the well-known effects on the clotting system. We evaluated the antitumor activity of a series of semisynthetic sulfaminoheparosan sulfates (SAHSs) with different degree and distribution of sulfates, obtained by chemical modifications of the E. coli K5 polysaccharide, namely type A, B, and C compounds. B16-BL6 melanoma cells (10 5 cells/mouse) were injected intravenously (i.v.) in a lateral tail vein of C57BL6 mice at a dose of 0.5 mg/ mouse together with test compounds. Tumor lung nodules were significantly reduced as compared with controls only by H (95.5 +/- 1.0% inhibition), SAHS-2 (84.2 +/- 5.0% inhibition), and SAHS-4 (91.1 +/- 4.2% inhibition), among compounds tested. SAHS-2 and SAHS-4 are type B compounds, with a sulfate/carboxylate ratio similar to that of H. A typical mammalian HS showed only 54.8% inhibition. Supersulfated low-molecular-weight heparin and heparan sulfate (ssLMWH and ssLMWHS) showed an activity similar to that of unfractionated compounds. H and SAHS-4 inhibited dose dependently B16-BL6 lung colonies, with IC-50 values of 0.05 and 0.1 mg/mouse, respectively. The relationship with ex vivo anticoagulant potency was evaluated by activated partial thromboplastin time (aPTT) on mouse plasma at different time intervals after i.v. injection (0.1 to 0.5 mg/mouse) of the compound. H showed a dose-dependent anticoagulant activity lasting up to 2 hours, whereas SAHS-4 showed a potent anticoagulant effect only at a dose of 0.5 mg/mouse. Accordingly, H but not SAHS-4 consistently inhibited B16-BL6 lung colonies when given 1 hour before tumor cells. SAHS-4 derivatives, with different size and/or affinity depleted of AT binding sites, showed an inhibitory effect on B16-BL6 melanoma similar to that of SAHS-4

21 CFR 582.1131 - Aluminum sodium sulfate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Aluminum sodium sulfate. 582.1131 Section 582.1131 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1131 Aluminum sodium sulfate. (a) Product. Aluminum sodium sulfate. (b) Conditions of use...

21 CFR 582.1131 - Aluminum sodium sulfate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Aluminum sodium sulfate. 582.1131 Section 582.1131 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1131 Aluminum sodium sulfate. (a) Product. Aluminum sodium sulfate. (b) Conditions of use...

21 CFR 582.1131 - Aluminum sodium sulfate.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Aluminum sodium sulfate. 582.1131 Section 582.1131 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1131 Aluminum sodium sulfate. (a) Product. Aluminum sodium sulfate. (b) Conditions of use...

21 CFR 582.1131 - Aluminum sodium sulfate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Aluminum sodium sulfate. 582.1131 Section 582.1131 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Additives § 582.1131 Aluminum sodium sulfate. (a) Product. Aluminum sodium sulfate. (b) Conditions of use...

The role of sulfate in aerobic granular sludge process for emerging sulfate-laden wastewater treatment.

PubMed

Xue, Weiqi; Hao, Tianwei; Mackey, Hamish R; Li, Xiling; Chan, Richard C; Chen, Guanghao

2017-11-01

Sulfate-rich wastewaters pose a major threat to mainstream wastewater treatment due to the unpreventable production of sulfide and associated shift in functional bacteria. Aerobic granular sludge could mitigate these challenges in view of its high tolerance and resilience against changes in various environmental conditions. This study aims to confirm the feasibility of aerobic granular sludge in the treatment of sulfate containing wastewater, investigate the impact of sulfate on nutrient removal and granulation, and reveal metabolic relationships in the above processes. Experiments were conducted using five sequencing batch reactors with different sulfate concentrations operated under alternating anoxic/aerobic condition. Results showed that effect of sulfate on chemical oxygen demand (COD) removal is negligible, while phosphate removal was enhanced from 12% to 87% with an increase in sulfate from 0 to 200 mg/L. However, a long acclimatization of the biomass (more than 70 days) is needed at a sulfate concentration of 500 mg/L and a total deterioration of phosphate removal at 1000 mg/L. Batch tests revealed that sulfide promoted volatile fatty acids (VFAs) uptake, producing more energy for phosphate uptake when sulfate concentrations were beneath 200 mg/L. However, sulfide detoxification became energy dominating, leaving insufficient energy for Polyhydroxyalkanoate (PHA) synthesis and phosphate uptake when sulfate content was further increased. Granulation accelerated with increasing sulfate levels by enhanced production of N-Acyl homoserine lactones (AHLs), a kind of quorum sensing (QS) auto-inducer, using S-Adenosyl Methionine (SAM) as primer. The current study demonstrates interactions among sulfate metabolism, nutrients removal and granulation, and confirms the feasibility of using the aerobic granular sludge process for sulfate-laden wastewaters treatment with low to medium sulfate content. Copyright © 2017 Elsevier Ltd. All rights reserved.

The molecular architecture of human N-acetylgalactosamine kinase.

PubMed

Thoden, James B; Holden, Hazel M

2005-09-23

Galactokinase plays a key role in normal galactose metabolism by catalyzing the conversion of alpha-d-galactose to galactose 1-phosphate. Within recent years, the three-dimensional structures of human galactokinase and two bacterial forms of the enzyme have been determined. Originally, the gene encoding galactokinase in humans was mapped to chromosome 17. An additional gene, encoding a protein with sequence similarity to galactokinase, was subsequently mapped to chromosome 15. Recent reports have shown that this second gene (GALK2) encodes an enzyme with greater activity against GalNAc than galactose. This enzyme, GalNAc kinase, has been implicated in a salvage pathway for the reutilization of free GalNAc derived from the degradation of complex carbohydrates. Here we report the first structural analysis of a GalNAc kinase. The structure of the human enzyme was solved in the presence of MnAMPPNP and GalNAc or MgATP and GalNAc (which resulted in bound products in the active site). The enzyme displays a distinctly bilobal appearance with its active site wedged between the two domains. The N-terminal region is dominated by a seven-stranded mixed beta-sheet, whereas the C-terminal motif contains two layers of anti-parallel beta-sheet. The overall topology displayed by GalNAc kinase places it into the GHMP superfamily of enzymes, which generally function as small molecule kinases. From this investigation, the geometry of the GalNAc kinase active site before and after catalysis has been revealed, and the determinants of substrate specificity have been defined on a molecular level.

Desulfobulbus mediterraneus sp. nov., a sulfate-reducing bacterium growing on mono- and disaccharides.

PubMed

Sass, Andrea; Rütters, Heike; Cypionka, Heribert; Sass, Henrik

2002-06-01

A new sulfate-reducing bacterium, strain 86FS1, was isolated from a deep-sea sediment in the western Mediterranean Sea with sodium lactate as electron and carbon source. Cells were ovoid, gram-negative and motile. Strain 86FS1 contained b- and c-type cytochromes. The organism was able to utilize propionate, pyruvate, lactate, succinate, fumarate, malate, alanine, primary alcohols (C(2)-C(5)), and mono- and disaccharides (glucose, fructose, galactose, ribose, sucrose, cellobiose, lactose) as electron donors for the reduction of sulfate, sulfite or thiosulfate. The major products of carbon metabolism were acetate and CO(2), with exception of n-butanol and n-pentanol, which were oxidized only to the corresponding fatty acids. The growth yield with sulfate and glucose or lactate was 8.3 and 15 g dry mass, respectively, per mol sulfate. The temperature limits for growth were 10 degrees C and 30 degrees C with an optimum at 25 degrees C. Growth was observed at salinities ranging from 10 to 70 g NaCl l(-1). Sulfide concentrations above 4 mmol l(-1) inhibited growth. The fatty acid pattern of strain 86FS1 resembled that of Desulfobulbus propionicus with n-14:0, n-16:1omega7, n-16:1 omega5, n-17:1 omega6 and n-18:1 omega7 as dominant fatty acids. On the basis of its phylogenetic position and its phenotypic properties, strain 86FS1 affiliates with the genus Desulfobulbus and is described as a new species, Desulfobulbus mediterraneus sp. nov.

3-O sulfation of heparin leads to hepatotropism and longer circulatory half-life.

PubMed

Miller, Colton M; Xu, Yongmei; Kudrna, Katrina M; Hass, Blake E; Kellar, Brianna M; Egger, Andrew W; Liu, Jian; Harris, Edward N

2018-05-17

Heparins are common blood anticoagulants that are critical for many surgical and biomedical procedures used in modern medicine. In contrast to natural heparin derived from porcine gut mucosa, synthetic heparins are homogenous by mass, polymer length, and chemistry. Stable cell lines expressing the human and mouse Stabilin receptors were used to evaluate endocytosis of natural and synthetic heparin. We chemoenzymatically produced synthetic heparin consisting of 12 sugars (dodecamers) containing 14 sulfate groups resulting in a non-3-O sulfated structure (n12mer). Half of the n12mer was modified with a 3-O sulfate on a single GlcNS sugar producing the 3-O sulfated heparin (12mer). Wildtype (WT), Stabilin-1 knock-out (KO), and Stabilin-2 KO C57BL/6 mice were developed and used for metabolic studies and provided as a source for primary liver sinusoidal endothelial cells. Human and mouse Stabilin-2 receptors had very similar endocytosis rates of both the 12mer and n12mer, suggesting that they are functionally similar in primary cells. Subcutaneous injections of the n12mer and 12mer revealed that the 12mer had a much longer half-life in circulation and a higher accumulation in liver. The n12mer never accumulated in circulation and was readily excreted by the kidneys before liver accumulation could occur. Liver sinusoidal endothelial cells from the Stabilin-2 KO mice had lower uptake rates for both dodecamers, whereas, the Stabilin-1 KO mice had lower endocytosis rates for the 12mer than the n12mer. 3-O sulfation of heparin is correlated to both a longer circulatory half-life and hepatotropism which is largely performed by the Stabilin receptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Cysteine-Rich Domain of the Macrophage Mannose Receptor Is a Multispecific Lectin That Recognizes Chondroitin Sulfates a and B and Sulfated Oligosaccharides of Blood Group Lewisa and Lewisx Types in Addition to the Sulfated N-Glycans of Lutropin

PubMed Central

Leteux, Christine; Chai, Wengang; Loveless, R. Wendy; Yuen, Chun-Ting; Uhlin-Hansen, Lars; Combarnous, Yves; Jankovic, Mila; Maric, Svetlana C.; Misulovin, Ziva; Nussenzweig, Michel C.; Ten Feizi

2000-01-01

The mannose receptor (MR) is an endocytic protein on macrophages and dendritic cells, as well as on hepatic endothelial, kidney mesangial, tracheal smooth muscle, and retinal pigment epithelial cells. The extracellular portion contains two types of carbohydrate-recognition domain (CRD): eight membrane-proximal C-type CRDs and a membrane-distal cysteine-rich domain (Cys-MR). The former bind mannose-, N-acetylglucosamine-, and fucose-terminating oligosaccharides, and may be important in innate immunity towards microbial pathogens, and in antigen trapping for processing and presentation in adaptive immunity. Cys-MR binds to the sulfated carbohydrate chains of pituitary hormones and may have a role in hormonal clearance. A second feature of Cys-MR is binding to macrophages in marginal zones of the spleen, and to B cell areas in germinal centers which may help direct MR-bearing cells toward germinal centers during the immune response. Here we describe two novel classes of carbohydrate ligand for Cys-MR: chondroitin-4 sulfate chains of the type found on proteoglycans produced by cells of the immune system, and sulfated blood group chains. We further demonstrate that Cys-MR interacts with cells in the spleen via the binding site for sulfated carbohydrates. Our data suggest that the three classes of sulfated carbohydrate ligands may variously regulate the trafficking and function of MR-bearing cells. PMID:10748230

Absorption of N-phenylpropenoyl-L-amino acids in healthy humans by oral administration of cocoa (Theobroma cacao).

PubMed

Stark, Timo; Lang, Roman; Keller, Daniela; Hensel, Andreas; Hofmann, Thomas

2008-10-01

Besides flavan-3-ols, a family of N-phenylpropenoyl-L-amino acids (NPAs) has been recently identified as polyphenol/amino acid conjugates in the seeds of Theobroma cacao as well as in a variety of herbal drugs. Stimulated by reports on their biological activity, the purpose of this study was to investigate if these amides are absorbed by healthy volunteers after administration of a cocoa drink. For the first time, 12 NPAs were quantified in human urine by means of a stable isotope dilution analysis with LC-MS/MS (MRM) detection. A maximum amount was found in the urine taken 2 h after the cocoa consumption. The highest absolute amount of NPAs excreted with the urine was found for N-[4'-hydroxy-(E)-cinnamoyl]-L-aspartic acid (5), but the highest recovery rate (57.3 and 22.8%), that means the percentage amount of ingested amides excreted with the urine, were determined for N-[4'-hydroxy-(E)-cinnamoyl]-L-glutamic acid (6) and N-[4'-hydroxy-3'-methoxy-(E)-cinnamoyl]-L-tyrosine (13). In order to gain first insights into the NPA metabolism in vivo, urine samples were analyzed by LC-MS/MS before and after beta-glucuronidase/sulfatase treatment. As independent of the enzyme treatment the same NPA amounts were found in urine, there is strong evidence that these amides are metabolized neither via their O-glucuronides nor their O-sulfates. In order to screen for caffeic acid O-glucuronides as potential NPA metabolites, urine samples were screened by means of LC-MS/MS for caffeic acid 3-O-beta-D-glucuronide and 4-O-beta-D-glucuronide. But not even trace amounts of one of these glucuronides were detectable, thus excluding them as major NPA metabolites and underlining the importance of future investigations on a potential O-methylation or reduction of the N-phenylpropenoyl moiety in NPAs.

Tyrosine sulfation in N-terminal domain of human C5a receptor is necessary for binding of chemotaxis inhibitory protein of Staphylococcus aureus

PubMed Central

Liu, Zhen-jia; Yang, Yan-juan; Jiang, Lei; Xu, Ying-chun; Wang, Ai-xia; Du, Guan-hua; Gao, Jin-ming

2011-01-01

Aim: Staphylococcus aureus evades host defense through releasing several virulence proteins, such as chemotaxis inhibitory protein of staphylococcus aureus (CHIPS). It has been shown that extracellular N terminus of C5a receptor (C5aR) forms the binding domain for CHIPS, and tyrosine sulfation is emerging as a key factor in determining protein-protein interaction. The aim of this study was to evaluate the role of tyrosine sulfation of N-terminal of C5aR in its binding with CHIPS. Methods: Expression plasmids encoding C5aR and its mutants were prepared using PCR and site-directed mutagenesis and were used to transfect HEK 293T cells using calcium phosphate. Recombinant CHIPS protein was purified. Western blotting was used to examine the binding efficiency of CHIPS to C5aR or its mutants. Results: CHIPS exclusively binds to C5aR, but not to C5L2 or C3aR. A nonspecific sulfation inhibitor, sodium chlorate (50 nmol/L), diminishes the binding ability of C5aR with CHIPS. Blocking sulfation by mutation of tyrosine to phenylalanine at positions 11 and 14 of C5aR N terminus, which blocked sulfation, completely abrogates CHIPS binding. When tyrosine 14 alone was mutated to phenylalanine, the binding efficiency of recombinant CHIPS was substantially decreased. Conclusion: The results demonstrate a structural basis of C5aR-CHIPS association, in which tyrosine sulfation of N-terminal C5aR plays an important role. Our data may have potential significance in development of novel drugs for therapeutic intervention. PMID:21706042

Semi-synthesis of unusual chondroitin sulfate polysaccharides containing GlcA(3-O-sulfate) or GlcA(2,3-di-O-sulfate) units.

PubMed

Bedini, Emiliano; De Castro, Cristina; De Rosa, Mario; Di Nola, Annalida; Restaino, Odile F; Schiraldi, Chiara; Parrilli, Michelangelo

2012-02-13

The extraction from natural sources of Chondroitin sulfate (CS), a polysaccharide used for management of osteoarthritis, leads to very complex mixtures. The synthesis of CS by chemical modification of other polysaccharides has seldom been reported due to the intrinsic complexity that arises from fine chemical modifications of the polysaccharide structure. In view of the growing interest in expanding the application of CS to pharmacological fields other than osteoarthritis treatment, we launched a program to find new sources of known or even unprecedented CS polysaccharides. As part of this program, we report herein on an investigation of the use of a cyclic orthoester group to selectively protect the 4,6-diol of N-acetyl-galactosamine residues in chondroitin (obtained from a microbial source), thereby facilitating its transformation into CSs. In particular, three CS polysaccharides were obtained and demonstrated to possess rare or hitherto unprecedented sulfation patterns by 2D NMR spectroscopy characterization. Two of them contained disaccharide subunits characterized by glucuronic acid residues selectively sulfated at position 3 (GlcA(3S)), the biological functions of which are known but have yet to be fully investigated. This first semi-synthetic access to GlcA(3S)-containing CS could greatly expedite such studies, since it can easily furnish considerable amounts of these polysaccharides, which are usually isolated with difficulty and in very low quantity from natural sources. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Preparation, characterization and in vitro anticoagulant activity of corn stover xylan sulfates.

PubMed

Cheng, He-Li; Liu, Hao; Feng, Qing-Hua; Xie, Yi-Min; Zhan, Huai-Yu

2017-02-01

A new anticoagulant agent was prepared by introducing sulfate groups into corn stover xylan through homogeneous reactions. Three organic solvents, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO) and formamide (FA), were adopted as reaction media, with the assistance of LiCl. Structural characterization by FT-IR and 13 CNMR showed that xylan sulfate (XS) could be successfully synthesized with SO 3 ∙Pyridine (SO 3 ∙Py) complexes sulfation reagent in the three media. The effect of sulfation temperature, sulfation time, media type and molar ratio of -SO 3 /-OH on the degree of substitution (DS) and degree of the polymerization (DP) were studied. DMF/LiCl were more effective than DMSO/LiCl and FA/LiCl in preparation of xylan sulfate with high DS. The optimal conditions for sulfation were obtained when SO 3 ∙Py complex was added to DMF/LiCl with -SO 3 /-OH ratio of 1.5:1 and maintained at 50 °C for 3 h. Degree of polymerization of xylan was decreased during the sulfation process and DMF/LiCl offered the least xylan degradation as compared with DMSO/LiCl or FA/LiCl. Anticoagulant activities of the resultant xylan sulfates with different DS were evaluated by using activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). Results indicated that the introducing of sulfate groups into xylan did endow the polysaccharides with anticoagulant activity. The APTT and TT of XS with DS of 1.20 reached 141 and 45.3 s at a dosage of 20 μg/mL, while the APTT and TT values for the blank sample were only 35.5 and 15.6 s. Furthermore, coagulation time was prolonged with the increase of DS and the concentration of XS. Our findings provide new insights into the value-added utilization of agricultural biomass.

Estrogen-Mediated Breast Carcinogenesis: The Role of Sulfation Pharmacogenetics

DTIC Science & Technology

2002-05-01

Final (1 May 99 - 30 Apr 02) 4. TITLE AND SUBTITLE 5 . FUNDING NUMBERS Estrogen-Mediated Breast Carcinogenesis: The DAMD17-99-1-9281 Role of Sulfation...Pharmacogenetics 6 . AUTHOR(S) Araba Adjei, Ph.D. 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER Mayo...4 IN TR O D U CTIO N ................................................................................................... 5 B O D Y

Studies on the mucin derived from human colloid breast carcinoma

PubMed Central

Adams, J. B.

1965-01-01

1. A non-diffusible mucoid, showing a single peak in the ultracentrifuge, was isolated from human colloid breast carcinoma by treatment with trypsin and pepsin. The material contained threonine, leucine (isoleucine), valine, proline, glycine and glutamic acid in the approximate molar proportions 5:1:1:2:1:1. Smaller amounts of aspartic acid and serine were also found. For each 5 threonine residues, 6 N-acetylgalactosamine and 3–4 galactose residues were present. 2. The mucoid possessed reducing properties by the Park & Johnson (1949) procedure; these were attributable to the action of mild alkali, as employed in this procedure. Mild alkaline treatment by the Aminoff, Morgan & Watkins (1952) procedure gave rise to a diffusible N-acetylgalactosamine chromophore that gave an enhanced colour with Ehrlich's reagent. That galactosyl-(1→3)-N-acetylgalactosamine residues were liberated was supported by periodate studies. 3. Alkaline liberation of hexosamine residues was accompanied by a specific destruction of threonine. After 40 min. at 100° in 0·18 n-lithium hydroxide, both moieties had almost completely disappeared from the ninhydrin-positive components formed on subsequent acid hydrolysis. Glycine and α-oxobutyric acid were present in the acid hydrolysate, showing that both possible pathways of a β-elimination reaction were involved. Formation of diffusible peptide on very mild alkaline treatment was attributable to the rupture of the original peptide core, necessitated by the second of these two pathways. 4. Hydroxamate formation on treatment with hydroxylamine showed the presence of carbohydrate linkage to glutamic acid or aspartic acid residues or both. This could account for the single N-acetylgalactosamine residue not linked to threonine. 5. The native mucin contained sialic acid, which was cleaved by the acid environment used in the treatment with pepsin. A statistical model of the mucin would require each prosthetic group to be linked, via N-acetylgalactosamine

Reaction of 2-acetylaminofluorene-N-sulfate with RNA and glutathione: evidence for the generation of two reactive intermediates with different reactivities towards RNA and glutathione.

PubMed

van den Goorbergh, J A; Meerman, J H; de Wit, H; Mulder, G J

1985-11-01

The sulfate ester of N-hydroxy-2-acetylaminofluorene (AAF-N-sulfate) is one of the reactive intermediates of this carcinogen. This ester breaks down spontaneously to a very reactive nitrenium ion, which reacts with nucleophilic groups in protein, DNA, RNA and glutathione (GSH). Reactions involving the nitrenium ion with several nucleophiles under various conditions were studied. The adduct formation to RNA was much higher in Tris-HCI buffer than in phosphate buffer (at pH 7.4), while adduct formation to deoxy-guanosine monomers was the same in both buffers. The presence of 150 mM KCI had the same decreasing effect in both cases. Ionic strength effects may be involved in these phenomena. GSH decreased RNA adduct formation by 20-45%, while other thiols were much more effective. On the other hand, RNA did not decrease the formation of GSH conjugates from AAF-N-sulfate. The decrease in RNA adduct formation by thiols corresponded with an increase in the formation of 2-acetylaminofluorene (AAF) from AAF-N-sulfate, while no N-hydroxy-AAF was formed. These results suggest that two independent reactive intermediates are formed from AAF-N-sulfate, with different reactivities towards RNA and glutathione. Possibly these intermediates are the 'hard' triplet state nitrenium ion and the 'soft' singlet state nitrenium ion. Cysteine, cysteamine and penicillamine were most effective in the inhibition of RNA adduct formation; the extent of inhibition correlated with the extent of AAF formation. The mechanisms involved are discussed.

21 CFR 520.1044c - Gentamicin sulfate soluble powder.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate soluble powder. 520.1044c... Gentamicin sulfate soluble powder. (a) Specifications. Each gram of gentamicin sulfate soluble powder contains gentamicin sulfate equivalent to 16.7, 66.7, or 333.3 milligrams of gentamicin. (b) Sponsor. See...

21 CFR 520.1044c - Gentamicin sulfate soluble powder.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate soluble powder. 520.1044c... Gentamicin sulfate soluble powder. (a) Specifications. Each gram of gentamicin sulfate soluble powder contains gentamicin sulfate equivalent to 16.7, 66.7, or 333.3 milligrams of gentamicin. (b) Sponsor. See...

Sulfated Pentagalloylglucoside is a Potent, Allosteric, and Selective Inhibitor of Factor XIa

PubMed Central

Al-Horani, Rami A.; Ponnusamy, Pooja; Mehta, Akul Y.; Gailani, David; Desai, Umesh R.

2013-01-01

Inhibition of factor XIa (FXIa) is a novel paradigm for developing anticoagulants without major bleeding consequences. We present the discovery of sulfated pentagalloylglucoside (6) as a highly selective inhibitor of human FXIa. Biochemical screening of a focused library led to the identification of 6, a sulfated aromatic mimetic of heparin. Inhibitor 6 displayed a potency of 551 nM against FXIa, which was at least 200-fold more selective than other relevant enzymes. It also prevented activation of factor IX and prolonged human plasma and whole blood clotting. Inhibitor 6 reduced VMAX of FXIa hydrolysis of chromogenic substrate without affecting the KM suggesting an allosteric mechanism. Competitive studies showed that 6 bound in the heparin-binding site of FXIa. No allosteric small molecule has been discovered to date that exhibits equivalent potency against FXIa. Inhibitor 6 is expected to open up a major route to allosteric FXIa anticoagulants with clinical relevance. PMID:23316863

The selective estrogen enzyme modulators in breast cancer: a review.

PubMed

Pasqualini, Jorge R

2004-06-07

It is well established that increased exposure to estradiol (E(2)) is an important risk factor for the genesis and evolution of breast tumors, most of which (approximately 95-97%) in their early stage are estrogen-sensitive. However, two thirds of breast cancers occur during the postmenopausal period when the ovaries have ceased to be functional. Despite the low levels of circulating estrogens, the tissular concentrations of these hormones are significantly higher than those found in the plasma or in the area of the breast considered as normal tissue, suggesting a specific tumoral biosynthesis and accumulation of these hormones. Several factors could be implicated in this process, including higher uptake of steroids from plasma and local formation of the potent E(2) by the breast cancer tissue itself. This information extends the concept of 'intracrinology' where a hormone can have its biological response in the same organ where it is produced. There is substantial information that mammary cancer tissue contains all the enzymes responsible for the local biosynthesis of E(2) from circulating precursors. Two principal pathways are implicated in the last steps of E(2) formation in breast cancer tissues: the 'aromatase pathway' which transforms androgens into estrogens, and the 'sulfatase pathway' which converts estrone sulfate (E(1)S) into E(1) by the estrone-sulfatase. The final step of steroidogenesis is the conversion of the weak E(1) to the potent biologically active E(2) by the action of a reductive 17beta-hydroxysteroid dehydrogenase type 1 activity (17beta-HSD-1). Quantitative evaluation indicates that in human breast tumor E(1)S 'via sulfatase' is a much more likely precursor for E(2) than is androgens 'via aromatase'. Human breast cancer tissue contains all the enzymes (estrone sulfatase, 17beta-hydroxysteroid dehydrogenase, aromatase) involved in the last steps of E(2) biosynthesis. This tissue also contains sulfotransferase for the formation of the

Polyguluronate sulfate, polymannuronate sulfate, and their oligosaccharides have antithrombin III- and heparin cofactor II-independent anticoagulant activity

NASA Astrophysics Data System (ADS)

Zeng, Xuan; Lan, Ying; Zeng, Pengjiao; Guo, Zhihua; Hao, Cui; Zhang, Lijuan

2017-04-01

Cardiovascular disease is the leading causes of death. However, the complications can be treated with heparin and heparinoids, such as heparin pentasaccharide Fondaparinux, dermatan sulfate, and PSS made from alginate extracted from brown seaweeds by chemical sulfation. Alginate is composed of a linear backbone of polymannuronate (PM), polyguluronate (PG), and alternate residues of mannuronic acid and guluronic acid. It is unknown if heparin and sulfated PG (PGS)/PM (PMS) have the same or different anticoagulant molecular targets. In the current study, the anticoagulant activities of PGS, PMS, and their oligosaccharides were directly compared to that of heparin, Fondaparinux, and dermatan sulfate by the activated partial thrombinplastin time (aPTT) assay using normal, antithrombin III (ATIII)-deficient, heparin co-factor II (HCII)-deficient, and ATIII- and HCII-double deficient human plasmas. Our results showed that PGS, PMS, and their oligosaccharides had better anticoagulant activity than that of Fondaparinux in all four human plasmas tested. As expected, heparin was the best anticoagulant in normal plasma. Moreover, PGS, PGS6, PGS12, PGS25, PMS6, PMS12, and PMS25 were better anticoagulants than dermatan sulfate in HCII-deficient plasma. Most strikingly, PGS, PGS12, PGS25, PMS6, PMS12, and PMS25 were better anticoagulants than that of heparin in ATIII- and HCII-double deficient human plasma. The results revealed for the first time that sulfated alginate had ATIII- and HCII-independent anticoagulant activities. Therefore, developing PGS and PMS-based anticoagulants might require to discover their major molecular targets and to develop target-specific anticoagulant assays.

21 CFR 522.1484 - Neomycin sulfate sterile solution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Neomycin sulfate sterile solution. 522.1484... § 522.1484 Neomycin sulfate sterile solution. (a) Specifications. Each milliliter of sterile aqueous solution contains 50 milligrams of neomycin sulfate (equivalent to 35 milligrams of neomycin base).1 1...

21 CFR 522.1484 - Neomycin sulfate sterile solution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Neomycin sulfate sterile solution. 522.1484... § 522.1484 Neomycin sulfate sterile solution. (a) Specifications. Each milliliter of sterile aqueous solution contains 50 milligrams of neomycin sulfate (equivalent to 35 milligrams of neomycin base).1 1...

21 CFR 522.1484 - Neomycin sulfate sterile solution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin sulfate sterile solution. 522.1484... § 522.1484 Neomycin sulfate sterile solution. (a) Specifications. Each milliliter of sterile aqueous solution contains 50 milligrams of neomycin sulfate (equivalent to 35 milligrams of neomycin base).1 1...

21 CFR 522.1484 - Neomycin sulfate sterile solution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Neomycin sulfate sterile solution. 522.1484... § 522.1484 Neomycin sulfate sterile solution. (a) Specifications. Each milliliter of sterile aqueous solution contains 50 milligrams of neomycin sulfate (equivalent to 35 milligrams of neomycin base).1 1...

Modeling Reduction of Uranium U(VI) under Variable Sulfate Concentrations by Sulfate-Reducing Bacteria

PubMed Central

Spear, John R.; Figueroa, Linda A.; Honeyman, Bruce D.

2000-01-01

The kinetics for the reduction of sulfate alone and for concurrent uranium [U(VI)] and sulfate reduction, by mixed and pure cultures of sulfate-reducing bacteria (SRB) at 21 ± 3°C were studied. The mixed culture contained the SRB Desulfovibrio vulgaris along with a Clostridium sp. determined via 16S ribosomal DNA analysis. The pure culture was Desulfovibrio desulfuricans (ATCC 7757). A zero-order model best fit the data for the reduction of sulfate from 0.1 to 10 mM. A lag time occurred below cell concentrations of 0.1 mg (dry weight) of cells/ml. For the mixed culture, average values for the maximum specific reaction rate, Vmax, ranged from 2.4 ± 0.2 μmol of sulfate/mg (dry weight) of SRB · h−1) at 0.25 mM sulfate to 5.0 ± 1.1 μmol of sulfate/mg (dry weight) of SRB · h−1 at 10 mM sulfate (average cell concentration, 0.52 mg [dry weight]/ml). For the pure culture, Vmax was 1.6 ± 0.2 μmol of sulfate/mg (dry weight) of SRB · h−1 at 1 mM sulfate (0.29 mg [dry weight] of cells/ml). When both electron acceptors were present, sulfate reduction remained zero order for both cultures, while uranium reduction was first order, with rate constants of 0.071 ± 0.003 mg (dry weight) of cells/ml · min−1 for the mixed culture and 0.137 ± 0.016 mg (dry weight) of cells/ml · min−1 (U0 = 1 mM) for the D. desulfuricans culture. Both cultures exhibited a faster rate of uranium reduction in the presence of sulfate and no lag time until the onset of U reduction in contrast to U alone. This kinetics information can be used to design an SRB-dominated biotreatment scheme for the removal of U(VI) from an aqueous source. PMID:10966381

21 CFR 529.50 - Amikacin sulfate intrauterine solution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Amikacin sulfate intrauterine solution. 529.50... Amikacin sulfate intrauterine solution. (a) Specifications. Each milliliter of sterile aqueous solution contains 250 milligrams of amikacin (as the sulfate). (b) Sponsor. See No. 000856 and 059130 in § 510.600(c...

Distinctive and Complementary MS2 Fragmentation Characteristics for Identification of Sulfated Sialylated N-Glycopeptides by nanoLC-MS/MS Workflow

NASA Astrophysics Data System (ADS)

Kuo, Chu-Wei; Guu, Shih-Yun; Khoo, Kay-Hooi

2018-04-01

High sensitivity identification of sulfated glycans carried on specific sites of glycoproteins is an important requisite for investigation of molecular recognition events involved in diverse biological processes. However, aiming for resolving site-specific glycosylation of sulfated glycopeptides by direct LC-MS2 sequencing is technically most challenging. Other than the usual limiting factors such as lower abundance and ionization efficiency compared to analysis of non-glycosylated peptides, confident identification of sulfated glycopeptides among the more abundant non-sulfated glycopeptides requires additional considerations in the selective enrichment and detection strategies. Metal oxide has been applied to enrich phosphopeptides and sialylated glycopeptides, but its use to capture sulfated glycopeptides has not been investigated. Likewise, various complementary MS2 fragmentation modes have yet to be tested against sialylated and non-sialylated sulfoglycopeptides due to limited appropriate sample availability. In this study, we have investigated the feasibility of sequencing tryptic sulfated N-glycopeptide and its MS2 fragmentation characteristics by first optimizing the enrichment methods to allow efficient LC-MS detection and MS2 analysis by a combination of CID, HCD, ETD, and EThcD on hybrid and tribrid Orbitrap instruments. Characteristic sulfated glyco-oxonium ions and direct loss of sulfite from precursors were detected as evidences of sulfate modification. It is anticipated that the technical advances demonstrated in this study would allow a feasible extension of our sulfoglycomic analysis to sulfoglycoproteomics. [Figure not available: see fulltext.

40 CFR 721.2465 - Xanthylium, 9-(2-(ethoxycarbonyl)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.2465 Xanthylium, 9-(2-(ethoxycarbonyl)phenyl)-3,6-bis(ethylamino)-2,7-dimethyl-, ethyl sulfate. (a) Chemical substance and significant...

Activation barriers for methylation of DNA bases by dimethyl sulfate

NASA Astrophysics Data System (ADS)

Eichler, Daniel R.; Papadantonakis, George A.

2017-12-01

The SN2 transition states of the methylation reaction of DNA bases with dimethyl sulfate were examined employing DFT/ M06-2X/6-31+G∗ and DFT/B3LYP-D3/6-311+G (2df, 2p) levels of theory. Solvation effects were examined using the conductor-like polarizable continuum model (CPCM). Calculation results and feedback from electrostatic potential maps show that in water, charge separation lowers the activation barriers relative to the gas phase for the reactions at N7 of guanine, N3 of adenine and cytosine. Also, the reaction at the O6 site of guanine is governed by steric interference and exhibits a higher activation barrier in water.

Chondroitin-6-sulfate attenuates inflammatory responses in murine macrophages via suppression of NF-κB nuclear translocation.

PubMed

Tan, Guak-Kim; Tabata, Yasuhiko

2014-06-01

Inflammation is a host protective response to noxious stimuli, and excessive production of pro-inflammatory mediators by macrophages (mφ) can lead to numerous pathological conditions. In this study, immunomodulatory effects of immobilized and soluble glycosaminoglycans (GAGs) on mouse-bone-marrow-derived mφ were compared by measuring nitric oxide (NO). We demonstrate here that all GAGs studied except for heparin were able to modulate interferon-γ/lipopolysaccharide (IFN-γ/LPS)-induced NO release by mφ to varying extents after 24h of incubation. In particular, the modulatory activities of soluble chondroitin-6-sulfate (C6S), hyaluronic acid and heparan sulfate altered markedly after covalent immobilization. Of these, soluble C6S exhibited the strongest NO inhibitory activity, and the inhibition was dose- and time-dependent. Moreover, C6S significantly reduced pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α production by IFN-γ/LPS- or LPS-activated mφ. Specifically, the C6S-mediated suppression of mφ pro-inflammatory phenotype was accompanied by an increase in the IL-10 level, suggesting a possible switch towards anti-inflammatory/wound healing M2 state. In addition, the highest magnitude of inhibitory effects was obtained when cells were pre-treated with C6S prior to IFN-γ/LPS or LPS challenge, suggesting an additional role for C6S in protection against microbial infection. Further investigations reveal that the anti-inflammatory effects of C6S on activated mφ may be ascribed at least in part to suppression of NF-κB nuclear translocation. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Hemocytes and Plasma of the Eastern Oyster (Crassostrea virginica) Display a Diverse Repertoire of Sulfated and Blood Group A-modified N-Glycans*

PubMed Central

Kurz, Simone; Jin, Chunsheng; Hykollari, Alba; Gregorich, Daniel; Giomarelli, Barbara; Vasta, Gerardo R.; Wilson, Iain B. H.; Paschinger, Katharina

2013-01-01

The eastern oyster (Crassostrea virginica) has become a useful model system for glycan-dependent host-parasite interactions due to the hijacking of the oyster galectin CvGal1 for host entry by the protozoan parasite Perkinsus marinus, the causative agent of Dermo disease. In this study, we examined the N-glycans of both the hemocytes, which via CvGal1 are the target of the parasite, and the plasma of the oyster. In combination with HPLC fractionation, exoglycosidase digestion, and fragmentation of the glycans, mass spectrometry revealed that the major N-glycans of plasma are simple hybrid structures, sometimes methylated and core α1,6-fucosylated, with terminal β1,3-linked galactose; a remarkable high degree of sulfation of such glycans was observed. Hemocytes express a larger range of glycans, including core-difucosylated paucimannosidic forms, whereas bi- and triantennary glycans were found in both sources, including structures carrying sulfated and methylated variants of the histo-blood group A epitope. The primary features of the oyster whole hemocyte N-glycome were also found in dominin, the major plasma glycoprotein, which had also been identified as a CvGal1 glycoprotein ligand associated with hemocytes. The occurrence of terminal blood group moieties on oyster dominin and on hemocyte surfaces can account in part for their affinity for the endogenous CvGal1. PMID:23824194

Fractionation of sulfur and oxygen isotopes in sulfate by soil sorption

NASA Astrophysics Data System (ADS)

Van Stempvoort, D. R.; Reardon, E. J.; Fritz, P.

1990-10-01

Both field and laboratory data indicate that there is no significant isotope fractionation of sulfate during sorption in upland forest Podzols. The dominant sulfate sorption process in these soils is adsorption onto mineral surfaces. In the Plastic Lake watershed, Dorset, Ontario, Canada, fractions of sulfate from Podzol B-horizons have the following mean isotope (%.) compositions: water soluble sulfate, δ34S = +6.4; δ18O = -5.3; bicarbonate-exchanged sulfate by two methods, δ34S = + 4.5 and + 3.4; δ18O =-6.2 and -5.6; dissolved sulfate in B-horizon soilwater seepage, δ34S = + 4.8; δ18O = -5.4. These data indicate that soil sorption enriches dissolved sulfate in 34S by approximately 1 ± 1%. and in 18O by 0 +- 1 %. relative to sorbed sulfate. Similar results were obtained by laboratory sorption of sulfate by prepared goethite, which is a mineral representative of soil sorption sites in acidic Podzols like the one at Plastic Lake. The mean fractionation between sorbed and dissolved sulfate was found to be - 0.3%. for 34S and 0.1 %. for 18O. Earlier literature has confused the term adsorption; in many cases the more general term sorption, or retention, should be used. Pronounced fractionation of S and O isotopes in sulfate by lake and ocean sediments has been attributed to "adsorption" or "retention" but is more likely the result of sulfate reduction. Apparently, at Earth-surface conditions the only substantial isotope shifts in sulfate occur during microbial processes.

21 CFR 529.1044a - Gentamicin sulfate intrauterine solution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate intrauterine solution. 529... § 529.1044a Gentamicin sulfate intrauterine solution. (a) Specifications. Each milliliter of solution contains 50 or 100 milligrams gentamicin sulfate. (b) Sponsors. See Nos. 000010, 000061, 000856, 057561...

21 CFR 529.1044a - Gentamicin sulfate intrauterine solution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate intrauterine solution. 529... § 529.1044a Gentamicin sulfate intrauterine solution. (a) Specifications. Each milliliter of solution contains 50 or 100 milligrams gentamicin sulfate. (b) Sponsors. See Nos. 000010, 000061, 000856, 057561...

21 CFR 529.1044a - Gentamicin sulfate intrauterine solution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate intrauterine solution. 529... § 529.1044a Gentamicin sulfate intrauterine solution. (a) Specifications. Each milliliter of solution contains 50 or 100 milligrams gentamicin sulfate. (b) Sponsors. See Nos. 000010, 000061, 000856, 057561...

21 CFR 529.1044a - Gentamicin sulfate intrauterine solution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate intrauterine solution. 529... § 529.1044a Gentamicin sulfate intrauterine solution. (a) Specifications. Each milliliter of solution contains 50 or 100 milligrams gentamicin sulfate. (b) Sponsors. See Nos. 000010, 000061, 000856, 000859...

Association of Indoxyl Sulfate with Heart Failure among Patients on Hemodialysis

PubMed Central

Cao, Xue-Sen; Chen, Jun; Zou, Jian-Zhou; Zhong, Yi-Hong; Teng, Jie; Ji, Jun; Chen, Zhang-Wei; Liu, Zhong-Hua; Shen, Bo; Nie, Yu-Xin; Lv, Wen-Lv; Xiang, Fang-Fang; Tan, Xiao

2015-01-01

Background and objectives Indoxyl sulfate, a protein-bound uremic toxin, may be associated with cardiovascular events and mortality in patients with CKD. This study aimed to investigate the relationship between indoxyl sulfate and heart failure in patients on hemodialysis. Design, setting, participants, & measurements Patients on hemodialysis for >6 months were enrolled within 6 months. Patients with congestive heart failure, angina pectoris, acute myocardial infarction, cerebral infarction, or cerebral hemorrhage within 3 months before the study or those <18 years old were excluded. The primary end point was first heart failure event during follow-up. Results In total, 258 patients (145 men) with a mean age of 57.0±14.6 years old were enrolled. Median plasma indoxyl sulfate level was used to categorize patients into two groups: the low-indoxyl sulfate group (indoxyl sulfate ≤32.35 μg/ml) and the high-indoxyl sulfate group (indoxyl sulfate >32.35 μg/ml). Then, patients were prospectively followed up for a median of 48.0 (interquartile range: 33.5–48.0) months. During follow-up, 68 patients experienced episodes of first heart failure. Kaplan–Meier analysis revealed the incidence of first heart failure event in the high–indoxyl sulfate group was significantly higher than in the low-indoxyl sulfate group (log rank P<0.001). Cox regression analysis showed indoxyl sulfate was significantly associated with first heart failure event (indoxyl sulfate as the continuous variable: hazard ratio, 1.02; 95% confidence interval [95% CI], 1.01 to 1.03; P=0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 3.49; 95% CI, 1.97 to 6.20; P<0.001). After adjustment for other confounding factors, the results remained significant (indoxyl sulfate as the continuous variable: hazard ratio, 1.04; 95% CI, 1.02 to 1.06; P<0.001; indoxyl sulfate as the dichotomous variable: hazard ratio, 5.31; 95% CI, 2.43 to 11.58; P<0.001). Conclusions Plasma indoxyl sulfate was

Intra-articular TSG-6 delivery from heparin-based microparticles reduces cartilage damage in a rat model of osteoarthritis.

PubMed

Tellier, Liane E; Treviño, Elda A; Brimeyer, Alexandra L; Reece, David S; Willett, Nick J; Guldberg, Robert E; Temenoff, Johnna S

2018-05-01

As a potential treatment for osteoarthritis (OA), we have developed injectable and hydrolytically degradable heparin-based biomaterials with tunable sulfation for the intra-articular delivery of tumor necrosis factor-alpha stimulated gene-6 (TSG-6), a protein known to inhibit plasmin which may degrade extracellular matrix within OA joints. We first assessed the effect of heparin sulfation on TSG-6 anti-plasmin activity and found that while fully sulfated (Hep) and heparin desulfated at only the N position (Hep-N) significantly enhanced TSG-6 bioactivity in vitro, fully desulfated heparin (Hep-) had no effect, indicating that heparin sulfation plays a significant role in modulating TSG-6 bioactivity. Next, TSG-6 loaded, degradable 10 wt% Hep-N microparticles (MPs) were delivered via intra-articular injection into the knee at 1, 7, and 15 days following medial meniscal transection (MMT) injury in a rat model. After 21 days, cartilage thickness, volume, and attenuation were significantly increased with soluble TSG-6, indicating degenerative changes. In contrast, no significant differences were observed with TSG-6 loaded MP treatment, demonstrating that TSG-6 loaded MPs reduced cartilage damage following MMT injury. Ultimately, our results indicate that Hep-N can enhance TSG-6 anti-plasmin activity and that Hep-N-based biomaterials may be an effective method for TSG-6 delivery to treat OA.

Antifouling potential of Nature-inspired sulfated compounds

NASA Astrophysics Data System (ADS)

Almeida, Joana R.; Correia-da-Silva, Marta; Sousa, Emília; Antunes, Jorge; Pinto, Madalena; Vasconcelos, Vitor; Cunha, Isabel

2017-02-01

Natural products with a sulfated scaffold have emerged as antifouling agents with low or nontoxic effects to the environment. In this study 13 sulfated polyphenols were synthesized and tested for antifouling potential using the anti-settlement activity of mussel (Mytilus galloprovincialis) plantigrade post-larvae and bacterial growth inhibition towards four biofilm-forming bacterial strains. Results show that some of these Nature-inspired compounds were bioactive, particularly rutin persulfate (2), 3,6-bis(β-D-glucopyranosyl) xanthone persulfate (6), and gallic acid persulfate (12) against the settlement of plantigrades. The chemical precursors of sulfated compounds 2 and 12 were also tested for anti-settlement activity and it was possible to conclude that bioactivity is associated with sulfation. While compound 12 showed the most promising anti-settlement activity (EC50 = 8.95 μg.mL-1), compound 2 also caused the higher level of growth inhibition in bacteria Vibrio harveyi (EC20 = 12.5 μg.mL-1). All the three bioactive compounds 2, 6, and 12 were also found to be nontoxic to the non target species Artemia salina (<10% mortality at 250 μM) and Vibrio fischeri (LC50 > 1000 μg.mL-1). This study put forward the relevance of synthesizing non-natural sulfated small molecules to generate new nontoxic antifouling agents.

Antifouling potential of Nature-inspired sulfated compounds

PubMed Central

Almeida, Joana R.; Correia-da-Silva, Marta; Sousa, Emília; Antunes, Jorge; Pinto, Madalena; Vasconcelos, Vitor; Cunha, Isabel

2017-01-01

Natural products with a sulfated scaffold have emerged as antifouling agents with low or nontoxic effects to the environment. In this study 13 sulfated polyphenols were synthesized and tested for antifouling potential using the anti-settlement activity of mussel (Mytilus galloprovincialis) plantigrade post-larvae and bacterial growth inhibition towards four biofilm-forming bacterial strains. Results show that some of these Nature-inspired compounds were bioactive, particularly rutin persulfate (2), 3,6-bis(β-D-glucopyranosyl) xanthone persulfate (6), and gallic acid persulfate (12) against the settlement of plantigrades. The chemical precursors of sulfated compounds 2 and 12 were also tested for anti-settlement activity and it was possible to conclude that bioactivity is associated with sulfation. While compound 12 showed the most promising anti-settlement activity (EC50 = 8.95 μg.mL−1), compound 2 also caused the higher level of growth inhibition in bacteria Vibrio harveyi (EC20 = 12.5 μg.mL−1). All the three bioactive compounds 2, 6, and 12 were also found to be nontoxic to the non target species Artemia salina (<10% mortality at 250 μM) and Vibrio fischeri (LC50 > 1000 μg.mL−1). This study put forward the relevance of synthesizing non-natural sulfated small molecules to generate new nontoxic antifouling agents. PMID:28205590

Purification of Keratan Sulfate-endogalactosidase and its action on keratan sulfates of different origin.

PubMed

Nakazawa, K; Suzuki, S

1975-02-10

A glycosidase which attacks corneal keratan sulfate was purified from extracts of Pseudomonas sp. IFO-13309. When corneal keratan sulfate was degraded by the purified enzyme, Sephadex G-50 chromatography indicated the presence of a number of oligosaccharides differing in size and sulfate content. The characterization of two major fractions of the oligosaccharides indicated that the point of enzyme attack is limited to the endo-beta-D-galactoside bonds in which nonsulfated D-galactose residues participate. The enzyme, unlike ordinary exo-beta-D-galactosidases, did not catalyze the hydrolysis of phenyl beta-D-galactoside. Moreover, beta-D-galactosyl-(1 leads to 3)-2-acetamido-2-deoxy-beta-D-glucosyl-(1 leads to 3)-beta-D-galactosyl-(1 leads to 4)-D-glucose ("lacto-N-tetraose") was completely refractory to the action of this enzyme, suggesting that a structure of the type, X-(1 leads to 3)-beta-D-galactosyl-(1 leads to 4)-Y, is not the only specificity-determining factor, i.e. neighboring sugars, X and Y, or even larger portions of substrate molecule must have an important effect. Compared with corneal keratan sulfate, keratan sulfates from human nucleus pulposus and shark cartilage were attacked at lower rates with a resultant production of oligosaccharides of relatively large size. The result is in agreement with the view that considerable variations exist in the structure of keratan sulfates of different origin, and further suggests that the enzyme may serve as a useful reagent in studying these variations.

21 CFR 520.1044a - Gentamicin sulfate oral solution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate oral solution. 520.1044a... Gentamicin sulfate oral solution. (a) Specifications. Each milliliter of aqueous solution contains gentamicin sulfate equivalent to 50 milligrams of gentamicin. (b) Sponsor. See Nos. 000061 and 054925 in § 510.600(c...

21 CFR 520.1044a - Gentamicin sulfate oral solution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate oral solution. 520.1044a... Gentamicin sulfate oral solution. (a) Specifications. Each milliliter of aqueous solution contains gentamicin sulfate equivalent to 50 milligrams of gentamicin. (b) Sponsor. See Nos. 000061 and 054925 in § 510.600(c...

21 CFR 524.1044c - Gentamicin sulfate ophthalmic ointment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate ophthalmic ointment. 524.1044c... § 524.1044c Gentamicin sulfate ophthalmic ointment. (a) Specifications. Each gram of ointment contains gentamicin sulfate equivalent to 3 milligrams of gentamicin. (b) Sponsors. See Nos. 000061 and 043264 in...

21 CFR 524.1044c - Gentamicin sulfate ophthalmic ointment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate ophthalmic ointment. 524.1044c... § 524.1044c Gentamicin sulfate ophthalmic ointment. (a) Specifications. Each gram of ointment contains gentamicin sulfate equivalent to 3 milligrams of gentamicin. (b) Sponsors. See Nos. 000061 and 025463 in...

21 CFR 520.1044a - Gentamicin sulfate oral solution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate oral solution. 520.1044a... Gentamicin sulfate oral solution. (a) Specifications. Each milliliter of aqueous solution contains gentamicin sulfate equivalent to 50 milligrams of gentamicin. (b) Sponsor. See Nos. 000061 and 054925 in § 510.600(c...

21 CFR 524.1044c - Gentamicin sulfate ophthalmic ointment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate ophthalmic ointment. 524.1044c... § 524.1044c Gentamicin sulfate ophthalmic ointment. (a) Specifications. Each gram of ointment contains gentamicin sulfate equivalent to 3 milligrams of gentamicin. (b) Sponsors. See Nos. 000061 and 025463 in...

21 CFR 520.1044a - Gentamicin sulfate oral solution.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gentamicin sulfate oral solution. 520.1044a... Gentamicin sulfate oral solution. (a) Specifications. Each milliliter of aqueous solution contains gentamicin sulfate equivalent to 50 milligrams of gentamicin. (b) Sponsor. See Nos. 000061 and 054925 in § 510.600(c...

21 CFR 524.1044c - Gentamicin sulfate ophthalmic ointment.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate ophthalmic ointment. 524.1044c... § 524.1044c Gentamicin sulfate ophthalmic ointment. (a) Specifications. Each gram of ointment contains gentamicin sulfate equivalent to 3 milligrams of gentamicin. (b) Sponsors. See Nos. 000061 and 025463 in...

The Tyrosine Sulfate Domain of Fibromodulin Binds Collagen and Enhances Fibril Formation.

PubMed

Tillgren, Viveka; Mörgelin, Matthias; Önnerfjord, Patrik; Kalamajski, Sebastian; Aspberg, Anders

2016-11-04

Small leucine-rich proteoglycans interact with other extracellular matrix proteins and are important regulators of matrix assembly. Fibromodulin has a key role in connective tissues, binding collagen through two identified binding sites in its leucine-rich repeat domain and regulating collagen fibril formation in vitro and in vivo Some nine tyrosine residues in the fibromodulin N-terminal domain are O-sulfated, a posttranslational modification often involved in protein interactions. The N-terminal domain mimics heparin, binding proteins with clustered basic amino acid residues. Because heparin affects collagen fibril formation, we investigated whether tyrosine sulfate is involved in fibromodulin interactions with collagen. Using full-length fibromodulin and its N-terminal tyrosine-sulfated domain purified from tissue, as well as recombinant fibromodulin fragments, we found that the N-terminal domain binds collagen. The tyrosine-sulfated domain and the leucine-rich repeat domain both bound to three specific sites along the collagen type I molecule, at the N terminus and at 100 and 220 nm from the N terminus. The N-terminal domain shortened the collagen fibril formation lag phase and tyrosine sulfation was required for this effect. The isolated leucine-rich repeat domain inhibited the fibril formation rate, and full-length fibromodulin showed a combination of these effects. The fibrils formed in the presence of fibromodulin or its fragments showed more organized structure. Fibromodulin and its tyrosine sulfate domain remained bound on the formed fiber. Taken together, this suggests a novel, regulatory function for tyrosine sulfation in collagen interaction and control of fibril formation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Alkylation of 6-mercaptopurine (6-MP) with N-alkyl-N-alkoxycarbonylaminomethyl chlorides: S6-(N-alkyl-N-alkoxycarbonyl)aminomethyl-6-MP prodrug structure effect on the dermal delivery of 6-MP.

PubMed

Siver, K G; Sloan, K B

1990-01-01

The S6-(N-alkyl-N-alkoxycarbonyl)aminomethyl-6-MP (6-CARB-6-MP) prodrugs 5-20 were synthesized from the reaction of 6-MP with N-alkyl-N-alkyoxycarbonylaminomethyl chlorides (4) in dimethyl sulfoxide in overall yields of 5-62%, depending on the N-alkyl and the alkoxy groups involved. The derivatives were fully characterized by spectral and microanalyses. The assignment of the substitution pattern as S6-alkyl was based on comparisons of the UV, 1H NMR and 13C NMR spectra with model compounds. A S6, 9-bis-alkyl derivative was obtained from the reaction of 2 equivalents of 4 with 6-MP but the product was unstable and decomposed on standing to a 9-alkyl derivative. The 6-CARB-6-MP prodrugs reverted to 6-MP in water by an SN1-type mechanism involving unimolecular charge separation in the transition state of the rate determining step. There was no effect of dermal enzymes on the rate of hydrolysis. The solubilities in isopropyl myristate (IPM) for all of the 6-CARB-6-MP prodrugs were significantly greater than the solubility of 6-MP in IPM but only one prodrug (5) was apparently even as soluble as 6-MP in water. Selected 6-CARB-6-MP prodrugs were examined in diffusion cell experiments. Only the N-methyl-N-methoxycarbonyl derivative 5 gave a steady-state rate of delivery of 6-MP from IPM that was significantly greater than the steady-state rate of delivery of 6-MP from 6-MP in IPM. All the other derivatives gave steady-state rates of delivery of 6-MP from IPM that were either not significantly different, or were significantly lower than the rate obtained from 6-MP in IPM. In all cases, the effect of the 6-CARB-6-MP:IPM suspensions on the permeability of the skin, as determined by the second application flux of theophylline:propylene glycol, was of the same magnitude as the effect of IPM alone.

Electron Capture Dissociation of Divalent Metal-adducted Sulfated N-Glycans Released from Bovine Thyroid Stimulating Hormone

NASA Astrophysics Data System (ADS)

Zhou, Wen; Håkansson, Kristina

2013-11-01

Sulfated N-glycans released from bovine thyroid stimulating hormone (bTSH) were ionized with the divalent metal cations Ca2+, Mg2+, and Co by electrospray ionization (ESI). These metal-adducted species were subjected to infrared multiphoton dissociation (IRMPD) and electron capture dissociation (ECD) and the corresponding fragmentation patterns were compared. IRMPD generated extensive glycosidic and cross-ring cleavages, but most product ions suffered from sulfonate loss. Internal fragments were also observed, which complicated the spectra. ECD provided complementary structural information compared with IRMPD, and all observed product ions retained the sulfonate group, allowing sulfonate localization. To our knowledge, this work represents the first application of ECD towards metal-adducted sulfated N-glycans released from a glycoprotein. Due to the ability of IRMPD and ECD to provide complementary structural information, the combination of the two strategies is a promising and valuable tool for glycan structural characterization. The influence of different metal ions was also examined. Calcium adducts appeared to be the most promising species because of high sensitivity and ability to provide extensive structural information.

Characterization and cytotoxic activity of sulfated derivatives of polysaccharides from Agaricus brasiliensis

PubMed Central

Cardozo, F. T. G. S.; Camelini, C. M.; Cordeiro, M. N. S.; Mascarello, A.; Malagoli, B. G.; Larsen, I.; Rossi, M. J.; Nunes, R. J.; Braga, F. C.; Brandt, C.R.; Simões, C. M. O.

2014-01-01

Agaricus brasiliensis cell-wall polysaccharides isolated from fruiting body (FR) and mycelium (MI) and their respective sulfated derivatives (FR-S and MI-S) were chemically characterized using elemental analysis, TLC, FT-IR, NMR, HPLC, and thermal analysis. Cytotoxic activity was evaluated against A549 tumor cells by MTT and sulforhodamine assays. The average molecular weight (Mw) of FR and MI was estimated to be 609 and 310 kDa, respectively. FR-S (127 kDa) and MI-S (86 kDa) had lower Mw, probably due to hydrolysis occurred during the sulfation reaction. FR-S and MI-S presented ~14 % sulfur content in elemental analysis. Sulfation of samples was characterized by the appearance of two new absorption bands at 1253 and 810 cm−1 in the infrared spectra, related to S=O and C-S-O sulfate groups, respectively. Through 1H and 13C NMR analysis FR-S was characterized as a (1→6)-(1→3)-β-D-glucan fully sulfated at C-4 and C-6 terminal and partially sulfated at C-6 of (1→3)-β-D-glucan moiety. MI-S was shown to be a (1→3)-β-D-gluco-(1→2)-β-D-mannan, partially sulfated at C-2, C-3, C-4, and C-6, and fully sulfated at C-6 of the terminal residues. The combination of high degree of sulfation and low molecular weight was correlated with the increased cytotoxic activity (48 h of treatment) of both FR-S (EC50=605.6 μg/mL) and MI-S (EC50=342.1 μg/mL) compared to the non-sulfated polysaccharides FR and MI (EC50>1500 μg/mL). PMID:23511057

The ammonium sulfate inhibition of human angiogenin.

PubMed

Chatzileontiadou, Demetra S M; Tsirkone, Vicky G; Dossi, Kyriaki; Kassouni, Aikaterini G; Liggri, Panagiota G V; Kantsadi, Anastassia L; Stravodimos, George A; Balatsos, Nikolaos A A; Skamnaki, Vassiliki T; Leonidas, Demetres D

2016-09-01

In this study, we investigate the inhibition of human angiogenin by ammonium sulfate. The inhibitory potency of ammonium sulfate for human angiogenin (IC50 = 123.5 ± 14.9 mm) is comparable to that previously reported for RNase A (119.0 ± 6.5 mm) and RNase 2 (95.7 ± 9.3 mm). However, analysis of two X-ray crystal structures of human angiogenin in complex with sulfate anions (in acidic and basic pH environments, respectively) indicates an entirely distinct mechanism of inhibition. While ammonium sulfate inhibits the ribonucleolytic activity of RNase A and RNase 2 by binding to the active site of these enzymes, sulfate anions bind only to peripheral substrate anion-binding subsites of human angiogenin, and not to the active site. © 2016 Federation of European Biochemical Societies.

21 CFR 524.1484g - Neomycin sulfate-thiabendazole-dexamethasone solution.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin sulfate-thiabendazole-dexamethasone... NEW ANIMAL DRUGS § 524.1484g Neomycin sulfate-thiabendazole-dexamethasone solution. (a) Specifications. Each cubic centimeter of neomycin sulfate-thiabendazole-dexamethasone solution contains: 40 milligrams...

21 CFR 524.1484g - Neomycin sulfate-thiabendazole-dexamethasone solution.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Neomycin sulfate-thiabendazole-dexamethasone... NEW ANIMAL DRUGS § 524.1484g Neomycin sulfate-thiabendazole-dexamethasone solution. (a) Specifications. Each cubic centimeter of neomycin sulfate-thiabendazole-dexamethasone solution contains: 40 milligrams...

21 CFR 524.1484g - Neomycin sulfate-thiabendazole-dexamethasone solution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Neomycin sulfate-thiabendazole-dexamethasone... NEW ANIMAL DRUGS § 524.1484g Neomycin sulfate-thiabendazole-dexamethasone solution. (a) Specifications. Each cubic centimeter of neomycin sulfate-thiabendazole-dexamethasone solution contains: 40 milligrams...

21 CFR 524.1484g - Neomycin sulfate-thiabendazole-dexamethasone solution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Neomycin sulfate-thiabendazole-dexamethasone... NEW ANIMAL DRUGS § 524.1484g Neomycin sulfate-thiabendazole-dexamethasone solution. (a) Specifications. Each cubic centimeter of neomycin sulfate-thiabendazole-dexamethasone solution contains: 40 milligrams...

Natural history and galsulfase treatment in mucopolysaccharidosis VI (MPS VI, Maroteaux-Lamy syndrome)--10-year follow-up of patients who previously participated in an MPS VI Survey Study.

PubMed

Giugliani, Roberto; Lampe, Christina; Guffon, Nathalie; Ketteridge, David; Leão-Teles, Elisa; Wraith, James E; Jones, Simon A; Piscia-Nichols, Cheri; Lin, Ping; Quartel, Adrian; Harmatz, Paul

2014-08-01

Mucopolysaccharidosis VI (MPS VI) is a clinically heterogeneous and progressive disorder with multiorgan manifestations caused by deficient N-acetylgalactosamine-4-sulfatase activity. A cross-sectional Survey Study in individuals (n = 121) affected with MPS VI was conducted between 2001 and 2002 to establish demographics, urinary glycosaminoglycan (GAG) levels, and clinical progression of disease. We conducted a Resurvey Study (ClinicalTrials.gov: NCT01387854) to obtain 10-year follow-up data, including medical histories and clinical assessments (n = 59), and survival status over 12 years (n = 117). Patients received a mean (SD) of 6.8 (2.2) years of galsulfase ERT between baseline (Survey Study) and follow-up. ERT patients increased in height by 20.4 cm in the 4-7-year-old baseline age group and by 16.8 cm in the 8-12-year-old baseline age group. ERT patients <13 years-old demonstrated improvement in forced vital capacity (FVC) by 68% and forced expiratory volume in 1 sec (FEV1) by 55%, and those ≥13 years-old increased FVC by 12.8% and maintained FEV1. Patients with >200 µg/mg baseline uGAG levels increased FVC by 48% in the <13-year-old baseline age group and by 15% in the ≥13-year-old baseline age group. ERT patients who completed the 6-min walk test demonstrated a mean (SD) increase of 65.7 (100.6) m. Cardiac outcomes did not significantly improve or worsen. Observed mortality rate among naïve patients was 50% (7/14) and 16.5% (17/103) in the ERT group (unadjusted hazard ratio, 0.24; 95% CI, 0.10-0.59). Long-term galsulfase ERT was associated with improvements in pulmonary function and endurance, stabilized cardiac function and increased survival. © 2014 Wiley Periodicals, Inc.

Heparan sulfates and the decrease of N-glycans promote early adipogenic differentiation rather than myogenesis of murine myogenic progenitor cells.

PubMed

Grassot, Vincent; Bouchatal, Amel; Da Silva, Anne; Chantepie, Sandrine; Papy-Garcia, Dulce; Maftah, Abderrahman; Gallet, Paul-François; Petit, Jean-Michel

In vitro, extracted muscle satellite cells, called myogenic progenitor cells, can differentiate either in myotubes or preadipocytes, depending on environmental factors and the medium. Transcriptomic analyses on glycosylation genes during satellite cells differentiation into myotubes showed that 31 genes present a significant variation of expression at the early stages of murine myogenic progenitor cells (MPC) differentiation. In the present study, we analyzed the expression of 383 glycosylation related genes during murine MPC differentiation into preadipocytes and compared the data to those previously obtained during their differentiation into myotubes. Fifty-six glycosylation related genes are specifically modified in their expression during early adipogenesis. The variations correspond mainly to: a decrease of N-glycans, and of alpha (2,3) and (2,6) linked sialic acids, and to a high level of heparan sulfates. A high amount of TGF-β1 in extracellular media during early adipogenesis was also observed. It seems that the increases of heparan sulfates and TGF-β1 favor pre-adipogenic differentition of MPC and possibly prevent their myogenic differentiation. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

Thermal Emission Spectroscopy of Sulfates: Possible Hydrous Iron-Sulfate in the Soil at the MER-A Gusev Crater Landing Site

NASA Technical Reports Server (NTRS)

Lane, Melissa D.

2004-01-01

Sulfates are likely to be present on Mars as indicated by the sulfur abundances measured at the Viking and Pathfinder landing sites (approx. 5-10% by weight SO3) [1-3] and because of Mars strongly oxidizing environment. Telescopic observations of Mars tentatively identified weak sulfate bands in near infrared [4] and thermal infrared [5] data. The currently orbiting midinfrared instruments (TES, THEMIS) and the Mini-TES on the Mars Exploration Rover landers may enable a positive identification [6] and determination of the chemistry of the sulfates. Critically important to the identification of these minerals is the presence of their spectra in a spectral library. There exist approximately 370 sulfate-mineral species [7]. Sulfate minerals occur in volcanic, hydrothermal, evaporitic, and chemical-weathering environments.

Separation and Precipitation of Nickel from Acidic Sulfate Leaching Solution of Molybdenum-Nickel Black Shale by Potassium Nickel Sulfate Hexahydrate Crystallization

NASA Astrophysics Data System (ADS)

Deng, Zhigan; Wei, Chang; Fan, Gang; Li, Xingbin; Li, Minting; Li, Cunxiong

2018-02-01

Nickel was separated and precipitated with potassium nickel sulfate hexahydrate [K2Ni(SO4)2·6H2O] from acidic sulfate solution, a leach solution from molybdenum-nickel black shale. The effects of the potassium sulfate (K2SO4) concentration, crystallization temperature, solution pH, and crystallization time on nickel(II) recovery and iron(III) precipitation were investigated, revealing that nickel and iron were separated effectively. The optimum parameters were K2SO4 concentration of 200 g/L, crystallization temperature of 10°C, solution pH of 0.5, and crystallization time of 24 h. Under these conditions, 97.6% nickel(II) was recovered as K2Ni(SO4)2·6H2O crystals while only 2.0% of the total iron(III) was precipitated. After recrystallization, 98.4% pure K2Ni(SO4)2·6H2O crystals were obtained in the solids. The mother liquor was purified by hydrolysis-precipitation followed by cooling, and more than 99.0% K2SO4 could be crystallized. A process flowsheet was developed to separate iron(III) and nickel(II) from acidic-sulfate solution.

N-glycolyl groups of nonhuman chondroitin sulfates survive in ancient fossils.

PubMed

Bergfeld, Anne K; Lawrence, Roger; Diaz, Sandra L; Pearce, Oliver M T; Ghaderi, Darius; Gagneux, Pascal; Leakey, Meave G; Varki, Ajit

2017-09-26

Biosynthesis of the common mammalian sialic acid N -glycolylneuraminic acid (Neu5Gc) was lost during human evolution due to inactivation of the CMAH gene, possibly expediting divergence of the Homo lineage, due to a partial fertility barrier. Neu5Gc catabolism generates N -glycolylhexosamines, which are potential precursors for glycoconjugate biosynthesis. We carried out metabolic labeling experiments and studies of mice with human-like Neu5Gc deficiency to show that Neu5Gc degradation is the metabolic source of UDP-GlcNGc and UDP-GalNGc and the latter allows an unexpectedly selective incorporation of N -glycolyl groups into chondroitin sulfate (CS) over other potential glycoconjugate products. Partially N -glycolylated-CS was chemically synthesized as a standard for mass spectrometry to confirm its natural occurrence. Much lower amounts of GalNGc in human CS can apparently be derived from Neu5Gc-containing foods, a finding confirmed by feeding Neu5Gc-rich chow to human-like Neu5Gc-deficient mice. Unlike the case with Neu5Gc, N -glycolyl-CS was also stable enough to be detectable in animal fossils as old as 4 My. This work opens the door for investigating the biological and immunological significance of this glycosaminoglycan modification and for an "ancient glycans" approach to dating of Neu5Gc loss during the evolution of Homo .

21 CFR 524.981c - Fluocinolone acetonide, neomycin sulfate cream.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Fluocinolone acetonide, neomycin sulfate cream... ANIMAL DRUGS § 524.981c Fluocinolone acetonide, neomycin sulfate cream. (a) Specifications. The drug contains 0.025 percent fluocinolone acetonide and 0.5 percent neomycin sulfate (0.35 percent neomycin base...

21 CFR 524.981c - Fluocinolone acetonide, neomycin sulfate cream.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fluocinolone acetonide, neomycin sulfate cream... ANIMAL DRUGS § 524.981c Fluocinolone acetonide, neomycin sulfate cream. (a) Specifications. The drug contains 0.025 percent fluocinolone acetonide and 0.5 percent neomycin sulfate (0.35 percent neomycin base...

21 CFR 524.981c - Fluocinolone acetonide, neomycin sulfate cream.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Fluocinolone acetonide, neomycin sulfate cream... ANIMAL DRUGS § 524.981c Fluocinolone acetonide, neomycin sulfate cream. (a) Specifications. The drug contains 0.025 percent fluocinolone acetonide and 0.5 percent neomycin sulfate (0.35 percent neomycin base...

21 CFR 524.981c - Fluocinolone acetonide, neomycin sulfate cream.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Fluocinolone acetonide, neomycin sulfate cream... ANIMAL DRUGS § 524.981c Fluocinolone acetonide, neomycin sulfate cream. (a) Specifications. The drug contains 0.025 percent fluocinolone acetonide and 0.5 percent neomycin sulfate (0.35 percent neomycin base...

Sulfation of melatonin: enzymatic characterization, differences of organs, species and genders, and bioactivity variation.

PubMed

Tian, Xiangge; Huo, Xiaokui; Dong, Peipei; Wu, Baojian; Wang, Xiaobo; Wang, Chao; Liu, Kexin; Ma, Xiaochi

2015-04-15

Exogenous melatonin (Mel) is widely used in clinic for multiple therapeutic purposes. In metabolism pathways of Mel, 6-hydroxymelatonin-sulfate (S-O-Mel) and N-acetylserotonin sulfate (S-NAS) are the most abundant metabolites account for over 90% of total Mel metabolites in humans, indicating that sulfation plays an important role in reflecting the functions and clearance of Mel in vivo. In the present study, we characterized Mel sulfation using various human organ cytosols (liver, lung, kidney, small intestine and brain), liver cytosols from five different animal species, and cDNA-expressed human sulfotransferase (SULT) for the first time. Our results demonstrated that liver, lung, kidney and small intestine of humans had high catalytic efficiency for Mel sulfation, however, brain contained a very low reaction rate. Interestingly, organ cytosols prepared from females exhibited higher sulfation activity than those of males. SULT isoforms 1A1, 1A2, 1A3, 1B1 and 1E1 exhibited metabolic activities toward Mel. According to kinetic parameters (Km and Vmax), chemical inhibition, correlation analysis, molecular docking and sulfation assays with recombinant human SULTs isoforms, SULT1A1 was determined as the major enzyme responsible for Mel sulfation. Furthermore, considerable species differences in Mel sulfation were observed, and the total intrinsic clearance rate of Mel sulfation was as follows: monkey>rat>dog>human>pig>mouse. Additionally, the anti-inflammatory effects of Mel and its sulfated metabolites were evaluated by inhibiting nitric oxide (NO) production in RAW264.7 cells, and S-O-Mel as a bioactive form, exhibited potent bioactivity. Our investigation provided a global view of the enzyme-dependent sulfation of Mel that can guide biomedical research on Mel. Copyright © 2015 Elsevier Inc. All rights reserved.

Distinguishing iron-reducing from sulfate-reducing conditions

USGS Publications Warehouse

Chapelle, F.H.; Bradley, P.M.; Thomas, M.A.; McMahon, P.B.

2009-01-01

Ground water systems dominated by iron- or sulfate-reducing conditions may be distinguished by observing concentrations of dissolved iron (Fe2+) and sulfide (sum of H2S, HS-, and S= species and denoted here as "H2S"). This approach is based on the observation that concentrations of Fe2+ and H2S in ground water systems tend to be inversely related according to a hyperbolic function. That is, when Fe2+ concentrations are high, H2S concentrations tend to be low and vice versa. This relation partly reflects the rapid reaction kinetics of Fe2+ with H2S to produce relatively insoluble ferrous sulfides (FeS). This relation also reflects competition for organic substrates between the iron- and the sulfate-reducing microorganisms that catalyze the production of Fe2+ and H 2S. These solubility and microbial constraints operate in tandem, resulting in the observed hyperbolic relation between Fe2+ and H 2S concentrations. Concentrations of redox indicators, including dissolved hydrogen (H2) measured in a shallow aquifer in Hanahan, South Carolina, suggest that if the Fe2+/H2S mass ratio (units of mg/L) exceeded 10, the screened interval being tapped was consistently iron reducing (H2 ???0.2 to 0.8 nM). Conversely, if the Fe 2+/H2S ratio was less than 0.30, consistent sulfate-reducing (H2 ???1 to 5 nM) conditions were observed over time. Concomitantly high Fe2+ and H2S concentrations were associated with H2 concentrations that varied between 0.2 and 5.0 nM over time, suggesting mixing of water from adjacent iron- and sulfate-reducing zones or concomitant iron and sulfate reduction under nonelectron donor-limited conditions. These observations suggest that Fe2+/H2S mass ratios may provide useful information concerning the occurrence and distribution of iron and sulfate reduction in ground water systems. ?? 2009 National Ground Water Association.

Differential inhibition of hepatic and duodenal sulfation of (-)-salbutamol and minoxidil by mefenamic acid.

PubMed

Vietri, M; Pietrabissa, A; Spisni, R; Mosca, F; Pacifici, G M

2000-09-01

The aim of this investigation was to determine whether mefenamic acid and salicylic acid inhibit the sulfation of (-)-salbutamol and minoxidil in the human liver and duodenum, and if so, to ascertain whether the 50% inhibitory concentration (IC50) estimates are different in the two tissues. Sulfotransferase activities were measured for 10 mM (-)-salbutamol and 5 mM minoxidil, and the concentration of 3'-phosphoadenosine-5'-phosphosulphate-[35S] was 0.4 microM. The IC50 estimates for (-)-salbutamol and minoxidil sulfation of mefenamic acid were 72 +/- 5.4 nM and 1.5 +/- 0.6 microM (liver), respectively, and 161 + 23 microM and 420 +/- 18 microM (duodenum), respectively. The figures for the liver were significantly lower (P < 0.0001) than those for the duodenum. The IC50 estimates for (-)-salbutamol sulfation of salicylic acid were 93 +/- 11 microM (liver) and 705 +/- 19 microM (duodenum, P < 0.0001). Salicylic acid was a poor inhibitor of minoxidil sulfation. The IC50 estimates for (-)-salbutamol sulfation of mefenamic acid and salicylic acid are lower than their unbound plasma concentrations after standard dosing, suggesting that mefenamic acid and salicylic acid should inhibit the hepatic sulfation of (-)-salbutamol in vivo.

The A{sup 2+}Mn{sub 5}(SO{sub 4}){sub 6} family of triangular lattice, ferrimagnetic sulfates

DOE Office of Scientific and Technical Information (OSTI.GOV)

West, D.V., E-mail: barelytone@gmail.co; McQueen, T.M.; Posen, I.D.

2009-06-15

A new family of anhydrous sulfates, A{sup 2+}Mn{sub 5}(SO{sub 4}){sub 6} (A=Pb, Ba, Sr) is reported. The crystal structures of PbMn{sub 5}(SO{sub 4}){sub 6} and SrMn{sub 5}(SO{sub 4}){sub 6} are solved by powder X-ray and neutron diffraction. BaMn{sub 5}(SO{sub 4}){sub 6} is isostructural. PbMn{sub 5}(SO{sub 4}){sub 6} crystallizes with P3-bar symmetry and unit cell parameters of a=14.551(1) A and c=7.535(1) A. The structure has rich features, including dimers of face-sharing MnO{sub 6} octahedra, and two complementary triangular layers of Mn atoms. All compounds undergo a magnetic ordering transition at 10 K, below which, the magnetic susceptibility of the compounds variesmore » systematically with the radius of the non-magnetic cation. Low temperature neutron diffraction shows that the complementary triangular layers result in a ferrimagnet with a net moment corresponding to one high spin Mn{sup 2+} per unit cell, correlating well with the magnetization data. The non-magnetic variant PbMg{sub 5}(SO{sub 4}){sub 6} is also reported. - Graphical abstract: A new family sulfates, A{sup 2+}Mn{sub 5}(SO{sub 4}){sub 6} (A=Pb, Ba, Sr) is reported. Structures are solved by powder neutron diffraction. PbMn{sub 5}(SO{sub 4}){sub 6} is trigonal with lattice parameters of a=14.551(1) A and c=7.535(1) A. The structure has dimers of face-sharing MnO{sub 6} octahedra, and two complementary triangular layers of Mn atoms that result in a ferrimagnet. All compounds magnetically order at 10 K. Low field susceptibility varies systematically with non-magnetic cation radius.« less

Crystallization of Chicken Egg White Lysozyme from Sulfate Salts

NASA Technical Reports Server (NTRS)

Forsythe, Elizabeth; Pusey, Marc

1998-01-01

It has been "known" that chicken egg white lysozyme does not crystallize from sulfate, particularly ammonium sulfate, salts, but instead gives amorphous precipitates. This has been the basis of several studies using lysozyme comparing macromolecule crystal nucleation and amorphous precipitation. Recently Ries-Kautt et al (Acta Cryst D50, (1994) 366) have shown that purified isoionic CEWL could be crystallized from low concentrations of sulfate at basic pH, and we subsequently showed that in fact CEWL could be purified in both the tetragonal and orthorhombic forms using ammonium sulfate over the pH range 4.0 to 7.8 (Acta Cryst D53, (1997) 795). We have now extended these observations to include a range of common sulfate salts, specifically sodium, potassium, rubidium, magnesium, and manganese sulfates. In all cases but the manganese sulfates both the familiar tetragonal and orthorhombic forms were obtained, with unit cell dimensions close to those known for the "classic" sodium chloride crystallized forms. Manganese sulfate has only yielded orthorhombic crystals to date. All crystallizations were carried out using low (typically less than or equal to 6 M) salt and high (greater than approximately 90 mg/ml) protein concentrations. As with ammonium sulfate, the tetragonal - orthorhombic phase shift appears to be a function of both the temperature and the protein concentration, with higher temperatures and concentrations favoring the orthorhombic and lower the tetragonal form. The phase change range is somewhat reduced for the sulfate salts, depending upon conditions being typically between approximately 15 - 20 C. Both the magnesium and manganese sulfates gave crystals at salt concentrations over 0.6 M as well, with magnesium sulfate giving a very slowly nucleating and growing hexagonal form. A triclinic crystal form, characterized by aggressively small crystals (typically 0.1 mm in size) has been occasionally obtained from ammonium sulfate. Finally, preliminary spot

Novel diffusive gradients in thin films technique to assess labile sulfate in soil.

PubMed

Hanousek, Ondrej; Mason, Sean; Santner, Jakob; Chowdhury, Md Mobaroqul Ahsan; Berger, Torsten W; Prohaska, Thomas

2016-09-01

A novel diffusive gradients in thin films (DGT) technique for sampling labile soil sulfate was developed, based on a strong basic anion exchange resin (Amberlite IRA-400) for sulfate immobilization on the binding gel. For reducing the sulfate background on the resin gels, photopolymerization was applied instead of ammonium persulfate-induced polymerization. Agarose cross-linked polyacrylamide (APA) hydrogels were used as diffusive layer. The sulfate diffusion coefficient in APA gel was determined as 9.83 × 10(-6) ± 0.35 × 10(-6) cm(2) s(-1) at 25 °C. The accumulated sulfate was eluted in 1 mol L(-1) HNO3 with a recovery of 90.9 ± 1.6 %. The developed method was tested against two standard extraction methods for soil sulfate measurement. The obtained low correlation coefficients indicate that DGT and conventional soil test methods assess differential soil sulfate pools, rendering DGT a potentially important tool for measuring labile soil sulfate.

21 CFR 524.1580e - Nitrofurazone ointment with butacaine sulfate.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Nitrofurazone ointment with butacaine sulfate. 524... ANIMAL DRUGS § 524.1580e Nitrofurazone ointment with butacaine sulfate. (a) Specifications. The drug contains 0.2 percent nitrofurazone and 0.5 percent butacaine sulfate in a water-soluble base. (b) Sponsor...

21 CFR 524.1580e - Nitrofurazone ointment with butacaine sulfate.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Nitrofurazone ointment with butacaine sulfate. 524... ANIMAL DRUGS § 524.1580e Nitrofurazone ointment with butacaine sulfate. (a) Specifications. The drug contains 0.2 percent nitrofurazone and 0.5 percent butacaine sulfate in a water-soluble base. (b) Sponsor...

Chondroitin-4-sulfation negatively regulates axonal guidance and growth

PubMed Central

Wang, Hang; Katagiri, Yasuhiro; McCann, Thomas E.; Unsworth, Edward; Goldsmith, Paul; Yu, Zu-Xi; Tan, Fei; Santiago, Lizzie; Mills, Edward M.; Wang, Yu; Symes, Aviva J.; Geller, Herbert M.

2008-01-01

Summary Glycosaminoglycan (GAG) side chains endow extracellular matrix proteoglycans with diversity and complexity based upon the length, composition, and charge distribution of the polysaccharide chain. Using cultured primary neurons, we show that specific sulfation in the GAG chains of chondroitin sulfate (CS) mediates neuronal guidance cues and axonal growth inhibition. Chondroitin-4-sulfate (CS-A), but not chondroitin-6-sulfate (CS-C), exhibits a strong negative guidance cue to mouse cerebellar granule neurons. Enzymatic and gene-based manipulations of 4-sulfation in the GAG side chains alter their ability to direct growing axons. Furthermore, 4-sulfated CS GAG chains are rapidly and significantly increased in regions that do not support axonal regeneration proximal to spinal cord lesions in mice. Thus, our findings provide the evidence showing that specific sulfation along the carbohydrate backbone carries instructions to regulate neuronal function. PMID:18768934

N6-Trimethyl-lysine metabolism. 3-Hydroxy-N6-trimethyl-lysine and carnitine biosynthesis.

PubMed Central

Hoppel, C L; Cox, R A; Novak, R F

1980-01-01

Rats injected with N6-[Me-3H]trimethyl-lysine excrete in the urine five radioactively labelled metabolites. Two of these identified metabolites are carnitine and 4-trimethylammoniobutyrate. A third metabolite, identified as 5-trimethylammoniopentanoate, is not an intermediate in the biosynthesis of carnitine; the fourth and major metabolite, N2-acetyl-N6-trimethyl-lysine, is not a precursor of carnitine. The remaining metabolite (3-hydroxy-N6-trimethyl-lysine) is converted into trimethylammoniobutyrate and carnitine by rat liver slices and into trimethylammoniobutyrate by rat kidney slices. In rat liver and kidney-slice experiments, radioactivity from DL-N6-trimethyl-[1-14C]lysine and DL-N6-trimethyl-[2-14C]lysine was incorporated into N2-acetyl-N6-trimethyl-lysine and 3-hydroxy-N6-trimethyl-lysine, but not into trimethylammoniobutyrate or carnitine. A procedure was devised to purify milligram quantities of 3-hydroxy-N6-trimethyl-lysine from the urine of rats injected chronically with N6-trimethyl-lysine (100 mg/kg body wt. per day). The structure of 3-hydroxy-N6-trimethyl-lysine was confirmed chemically and by nuclear-magnetic-resonance spectrometry [Novak, Swift & Hoppel (1980) Biochem. J. 188, 521--527]. The sequence for carnitine biosynthesis in liver is: N6-trimethyl-lysine leads to 3-hydryxy-N6-trimethyl-lysine leads to leads to 4-trimethylammoniobutyrate leads to carnitine. PMID:6772168

Characterization of bioactive chitosan and sulfated chitosan from Doryteuthis singhalensis (Ortmann, 1891).

PubMed

Ramasamy, Pasiyappazham; Subhapradha, Namasivayam; Thinesh, Thangadurai; Selvin, Joseph; Selvan, Kanagaraj Muthamizh; Shanmugam, Vairamani; Shanmugam, Annaian

2017-06-01

Chitosan was extracted from the pen of squid Doryteuthis singhalensis and characterized using FT-IR, NMR, CHN, SEM and DSC analysis. Purified chitosan was sulfated with chlorosulfonic acid in N,N-dimethylformamide and the added sulfate group was confirmed with FT-IR analysis. The molecular weight and degree of deacetylation (DDA) of chitosan was found 226.6kDa and 83.76% respectively. Chitosan exhibited potent antioxidant activity evidenced by reducing power, chelating ability on ferrous ions and scavenging activity on DPPH, superoxide and hydroxyl radicals. The anticoagulant assay using activated partial thromboplastin time (APTT) and prothrombin time (PT) showed chitosan as a strong anticoagulant. The results of this study showed possibility of using D. singhalensis pen as a non-conventional source of natural antioxidants and anticoagulant which can be incorporated in functional food formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis, structure and photoluminescence properties of amine-templated open-framework bismuth sulfates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marri, Subba R.; Behera, J.N., E-mail: jnbehera@niser.ac.in

2014-02-15

Two organically-templated bismuth sulfates of the compositions, [C{sub 6}N{sub 2}H{sub 14}] [Bi(SO{sub 4}){sub 2}(NO{sub 3})], (1) and [C{sub 4}N{sub 2}H{sub 12}]{sub 4}[Bi{sub 4}(SO{sub 4}){sub 10}(H{sub 2}O){sub 4}], (2), with open architecture have been synthesized and their structures determined by single crystal X-ray diffraction. 1 has a corrugated layered structure with 8-membered aperture wherein the SO{sub 4} tetrahedra and the BiO{sub 8} polyhedra join together to form (4, 4) net sheets of the metal centers while 2 has a three-dimensional structure possessing 8- and 12-membered channels. Both the compounds show good fluorescence properties exhibiting blue luminescence. Time-resolved fluorescence behavior of 1more » and 2 shows mean fluorescence life time of 0.9 and 1.0 ns, respectively. - Graphical abstract: Two open-framework bismuth sulfates with the layered and three-dimensional structures have been synthesized and characterized. Both the compounds show good fluorescence properties exhibiting blue luminescence. Display Omitted - Highlights: • Two organically-templated bismuth sulfates with open architecture have been synthesized and characterized. • One has a corrugated layered structure while the other one has a three-dimensional structure possessing channels. • They are novel in that open-framework three-dimensional main group metal sulfates are first to be reported. • They show good fluorescence properties exhibiting blue luminescence.« less

Production of a Pseudomonas lipase in n-alkane substrate and its isolation using an improved ammonium sulfate precipitation technique.

PubMed

Kanwar, Lambit; Gogoi, Binod Kumar; Goswami, Pranab

2002-09-01

Among the various lipidic and non-lipidic substances, normal alkanes within the chain lengths of C-12 to C-20 served as the best carbon substrates for the production of extracellular lipase by Pseudomonas species G6. Maximum lipase production of 25 U/ml of the culture broth was obtained by using n-hexadecane as the sole carbon substrate. The optimum pH of 8 and temperature of 34 + 1 degrees C were demonstrated for the production of lipase in n-hexadecane substrate. The optimum concentration of iron, which played a critical role on the lipase production, was found to be 0.25 mg/l. Lipase production could be enhanced to nearly 2.4-fold by using tributyrin at a concentration of 0.05% (v/v) in the culture medium. High recovery of the lipase protein (83%) from the culture broth was achieved by treating the culture supernatant with Silicone 21 Defoamer followed by ammonium sulfate (60% saturation) fractionation.

Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys

PubMed Central

Dorman, David C; Struve, Melanie F; Gross, Elizabeth A; Wong, Brian A; Howroyd, Paul C

2005-01-01

Background Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation. Methods Subchronic (6 hr/day, 5 days/week) inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration) was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3 for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point) was exposed to manganese sulfate at 1.5 mg Mn/m3 and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test. Results Animals exposed to manganese sulfate at ≥0.3 mg Mn/m3 for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3 for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure. Conclusion High-dose subchronic manganese sulfate inhalation is associated with increased

21 CFR 520.82b - Aminopropazine fumarate, neomycin sulfate tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Aminopropazine fumarate, neomycin sulfate tablets... Aminopropazine fumarate, neomycin sulfate tablets. (a) Specifications. The drug is in tablet form. Each tablet... sulfate equivalent to 50 milligrams of neomycin base. (b) Sponsor. See No. 000061 in § 510.600(c) of this...

Toxicity of copper sulfate and rotenone to Chinese mystery snail (Bellamya chinensis)

USGS Publications Warehouse

Haak, Danielle M.; Stephen, Bruce J.; Kill, Robert A.; Smeenk, Nicholas A.; Allen, Craig R.; Pope, Kevin L.

2014-01-01

The Chinese mystery snail (Bellamya chinensis) is a freshwater snail native to Southeast Asia, Japan, and Russia and is currently classified as an invasive species in at least 27 states in the USA. The species tolerates a wide range of environmental conditions, making management of established populations difficult. We tested the efficacy of two traditional chemical treatments, rotenone and copper sulfate, on the elimination of adult Chinese mystery snails in laboratory experiments. All snails (N=50) survived 72-hour exposure to rotenone-treated lake water, and 96% (N=25) survived 72-hour exposure to pre-determined rotenone concentrations of 0.25, 2.5, and 25.0 mg/L. All snails (N=10) survived exposure to 1.25 mg/L copper sulfate solution, 90% (N=10) survived exposure to 2.50 mg/L copper sulfate solution, and 80% (N=5) survived exposure to 5.0 mg/L copper sulfate solution. Neither rotenone nor copper sulfate effectively killed adult Chinese mystery snails in laboratory experiments, most likely due to their relatively large size, thick shell, and operculum. Therefore, it appears that populations will be very difficult to control once established, and management should focus on preventing additional spread or introductions of this species.

Adsorption and catalytic properties of sulfated aluminum oxide modified with cobalt ions

NASA Astrophysics Data System (ADS)

Lanin, S. N.; Bannykh, A. A.; Vlasenko, E. V.; Krotova, I. N.; Obrezkov, O. N.; Shilina, M. I.

2017-01-01

The adsorption properties of sulfated aluminum oxide (9% SO 4 2- /γ-Al2O3) and a cobalt-containing composite (0.5%Co/SO 4 2- /γ-Al2O3) based on it are studied via dynamic sorption. The adsorption isotherms of such test adsorbates as n-hydrocarbons (C6-C8), benzene, ethylbenzene, chloroform, and diethyl ether are measured, and their isosteric heats of adsorption are calculated. It is shown that the surface sulfation of aluminum oxide substantially improves its electron-accepting properties, and so the catalytic activity of SO 4 2- /γ-Al2O3 in the liquid-phase alkylation of benzene with octene-1 at temperatures of 25-120°C is one order of magnitude higher than for the initial aluminum oxide. It is established that additional modification of sulfated aluminum oxide with cobalt ions increases the activity of this catalyst by 2-4 times. It is shown that adsorption sites capable of strong specific adsorption with both donating (aromatics, diethyl ether chemosorption) and accepting molecules (chloroform) form on the surface of sulfated γ-Al2O3 promoted by cobalt salt.

Noncomparative contraceptive efficacy of cellulose sulfate gel.

PubMed

Mauck, Christine K; Freziers, Ron G; Walsh, Terri L; Peacock, Karen; Schwartz, Jill L; Callahan, Marianne M

2008-03-01

To estimate the 6-month cumulative probability of pregnancy, short-term adverse effects, and acceptability of cellulose sulfate vaginal contraceptive gel. Two hundred fertile heterosexual couples were enrolled in this single-center, phase II, 6-month noncomparative study conducted at the California Family Health Council in Los Angeles, California. Couples did not desire pregnancy, were at low risk for sexually transmitted diseases, and agreed to use 3.5 mL of cellulose sulfate gel intravaginally before each coital act as their primary means of contraception. Scheduled follow-up visits took place after one menstrual cycle and at study completion, which occurred after 6 months and six menstrual cycles had elapsed. In addition, participants were instructed to call the site at the onset of each menses to review their diary cards. The cumulative probabilities of pregnancy during 6 months and six cycles of typical use were 13.4% (95% confidence interval [CI] 7.5-19.4%) and 13.9% (95% CI 7.7-20.2%), respectively, and during 6 cycles of correct and consistent ("perfect") use: 3.9% (95% CI 0.0-9.2%). Slightly over one fourth of the women and one man reported experiencing gel-related adverse events, two thirds of which were mild and only possibly related to the gel. Three quarters of women and men reported that they would buy cellulose sulfate gel for contraception. Cellulose sulfate vaginal gel yields pregnancy rates comparable to nonoxynol-9 and few adverse events among couples at low risk for sexually transmitted diseases.

Flameless Atomic Absorption Spectroscopy: Effects of Nitrates and Sulfates.

DTIC Science & Technology

1980-05-01

ATTACHED DDJ~P 1413 EDITION 01 INO, 6 5 IabSoLEr J UjN!LbAa~ A- i SELU 0 IONOF I tG 651 J Flameless Atomic Absorption Spectroscopy: Effects of Nitrates...analytical techniques, flameless atomic absorption is subject to matrix or interference effects. Upon heating, nitrate and sulfate salts decompose to...Eklund and J.E. Smith, Anal Chem, 51, 1205 (1979) R.H. Eklund and J.A. Holcombe, Anal Chim. Acta, 109, 97 (1979) FLAMELESS ATOMIC ABSORPTION

Dietary Nanosized Lactobacillus plantarum Enhances the Anticancer Effect of Kimchi on Azoxymethane and Dextran Sulfate Sodium-Induced Colon Cancer in C57BL/6J Mice.

PubMed

Lee, Hyun Ah; Kim, Hyunung; Lee, Kwang-Won; Park, Kun-Young

2016-01-01

This study was undertaken to evaluate enhancement of the chemopreventive properties of kimchi by dietary nanosized Lactobacillus (Lab.)plantarum (nLp) in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated colorectal cancer C57BL/6J mouse model. nLp is a dead, shrunken, processed form of Lab. Plantarum isolated from kimchi that is 0.5-1.0 µm in size. The results obtained showed that animals fed kimchi with nLp (K-nLp) had longer colons and lower colon weights/length ratios and developed fewer tumors than mice fed kimchi alone (K). In addition, K-nLp administration reduced levels of proinflammatory cytokine serum levels and mediated the mRNA and protein expressions of inflammatory, apoptotic, and cell-cycle markers to suppress inflammation and induce tumor-cell apoptosis and cell-cycle arrest. Moreover, it elevated natural killer-cell cytotoxicity. The study suggests adding nLp to kimchi could improve the suppressive effect of kimchi on AOM/DSS-induced colorectal cancer. These findings indicate nLp has potential use as a functional chemopreventive ingredient in the food industry.

Impact of sulfate pollution on anaerobic biogeochemical cycles in a wetland sediment.

PubMed

Baldwin, Darren S; Mitchell, Alison

2012-03-15

The impact of sulfate pollution is increasingly being seen as an issue in the management of inland aquatic ecosystems. In this study we use sediment slurry experiments to explore the addition of sulfate, with or without added carbon, on the anaerobic biogeochemical cycles in a wetland sediment that previously had not been exposed to high levels of sulfate. Specifically we looked at the cycling of S (sulfate, dissolved and particulate sulfide--the latter measured as acid volatile sulfide; AVS), C (carbon dioxide, bicarbonate, methane and the short chain volatile fatty acids formate, acetate, butyrate and propionate), N (dinitrogen, ammonium, nitrate and nitrite) and redox active metals (Fe(II) and Mn(II)). Sulfate had the largest effects on the cycling of S and C. All the added S at lower loadings were converted to AVS over the course of the experiment (30 days). At the highest loading (8 mmol) less than 50% of consumed S was converted to AVS, however this is believed to be a kinetic effect. Although sulfate reduction was occurring in sediments with added sulfate, dissolved sulfide concentrations remained low throughout the study. Sulfate addition affected methanogenesis. In the absence of added carbon, addition of sulfate, even at a loading of 1 mmol, resulted in a halving of methane formation. The initial rate of formation of methane was not affected by sulfate if additional carbon was added to the sediment. However, there was evidence for anaerobic methane oxidation in those sediments with added sulfate and carbon, but not in those sediments treated only with carbon. Surprisingly, sulfate addition had little apparent impact on N dynamics; previous studies have shown that sulfide can inhibit denitrification and stimulate dissimilatory nitrate reduction to ammonia. We propose that because most of the reduced sulfur was in particulate form, levels of dissolved sulfide were too low to interfere with the N cycle. Crown Copyright © 2011. Published by Elsevier Ltd. All

Twinned low-temperature structures of tris(ethylenediamine)zinc(II) sulfate and tris(ethylenediamine)copper(II) sulfate.

PubMed

Lutz, Martin

2010-11-01

Tris(ethylenediamine)zinc(II) sulfate, [Zn(C(2)H(8)N(2))(3)]SO(4), (I), undergoes a reversible solid-solid phase transition during cooling, accompanied by a lowering of the symmetry from high-trigonal P31c to low-trigonal P3 and by merohedral twinning. The molecular symmetries of the cation and anion change from 32 (D(3)) to 3 (C(3)). This lower symmetry allows an ordered sulfate anion and generates in the complex cation two independent N atoms with significantly different geometries. The twinning is the same as in the corresponding Ni complex [Jameson et al. (1982). Acta Cryst. B38, 3016-3020]. The low-temperature phase of tris(ethylenediamine)copper(II) sulfate, [Cu(C(2)H(8)N(2))(3)]SO(4), (II), has only triclinic symmetry and the unit-cell volume is doubled with respect to the room-temperature structure in P31c. (II) was refined as a nonmerohedral twin with five twin domains. The asymmetric unit contains two independent formula units, and all cations and anions are located on general positions with 1 (C(1)) symmetry. Both molecules of the Cu complex are in elongated octahedral geometries because of the Jahn-Teller effect. This is in contrast to an earlier publication, which describes the complex as a compressed octahedron [Bertini et al. (1979). J. Chem. Soc. Dalton Trans. pp. 1409-1414].

21 CFR 524.1044b - Gentamicin sulfate, betamethasone valerate otic solution.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate, betamethasone valerate otic... NEW ANIMAL DRUGS § 524.1044b Gentamicin sulfate, betamethasone valerate otic solution. (a) Specifications. Each milliliter of solution contains gentamicin sulfate equivalent to 3 milligrams (mg...

21 CFR 524.1044g - Gentamicin sulfate, betamethasone valerate, clotrimazole ointment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate, betamethasone valerate... DOSAGE FORM NEW ANIMAL DRUGS § 524.1044g Gentamicin sulfate, betamethasone valerate, clotrimazole ointment. (a) Specifications. Each gram (g) of ointment contains gentamicin sulfate equivalent to 3...

21 CFR 524.1044b - Gentamicin sulfate, betamethasone valerate otic solution.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate, betamethasone valerate otic... NEW ANIMAL DRUGS § 524.1044b Gentamicin sulfate, betamethasone valerate otic solution. (a) Specifications. Each milliliter of solution contains gentamicin sulfate equivalent to 3 milligrams (mg...

21 CFR 524.1044g - Gentamicin sulfate, betamethasone valerate, clotrimazole ointment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate, betamethasone valerate... DOSAGE FORM NEW ANIMAL DRUGS § 524.1044g Gentamicin sulfate, betamethasone valerate, clotrimazole ointment. (a) Specifications. Each gram (g) of ointment contains gentamicin sulfate equivalent to 3...

21 CFR 524.1044g - Gentamicin sulfate, betamethasone valerate, clotrimazole ointment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate, betamethasone valerate... DOSAGE FORM NEW ANIMAL DRUGS § 524.1044g Gentamicin sulfate, betamethasone valerate, clotrimazole ointment. (a) Specifications. Each gram (g) of ointment contains gentamicin sulfate equivalent to 3...

21 CFR 524.1044g - Gentamicin sulfate, betamethasone valerate, clotrimazole ointment.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate, betamethasone valerate... DOSAGE FORM NEW ANIMAL DRUGS § 524.1044g Gentamicin sulfate, betamethasone valerate, clotrimazole ointment. (a) Specifications. Each gram (g) of ointment contains gentamicin sulfate equivalent to 3...

Electron spin resonance and proton matrix electron nuclear double resonance studies of N,N,N[prime],N[prime]-tetramethylbenzidine photoionization in sodium and lithium dodecyl sulfate micelles: Structural effects of crown ethers

DOE Office of Scientific and Technical Information (OSTI.GOV)

McManus, H.J.D.; Young Soo Kang; Kevan, L.

1993-01-07

The study of model membrane systems enjoys increasing attention within the area of solar energy research. An electron nuclear double resonance and electron spin resonance study of photogenerated N,N,N[prime],N[prime]-tetramethylbenzidine (TMB) cation in frozen suspensions of lithium (LDS) and sodium (SDS) dodecyl sulfate micelles containing various concentrations of cyclic polyethers was undertaken. The relative location of the TMB cation within the organic aggregate was determined from the proton matrix ENDOR line width at 142 K. A broader line width was observed in LDS compared to SDS micelles, which is due to the fact that the larger lithium cation opens the micellarmore » interface resulting in increased hydration and deeper solubilization of TMB. The proton matrix ENDOR line width decreased upon addition of crown ethers. This decrease may be explained by displacement of the TMB toward the interface as a result of the decrease in ionic strength caused by the complexation of the countercations. The photoyield shows a slight increase with addition of crown ethers. This increase is most likely caused by the increase in the effective anionic charge of the micelle effected by the complexation of the sodium or lithium ions by the crown ethers. This increase in the anionic charge mitigates the rate of thermal back electron transfer resulting in an increased photoyield. 54 refs., 6 figs., 2 tabs.« less

Tyrosine sulfation in precursors of collagen V.

PubMed

Fessler, L I; Brosh, S; Chapin, S; Fessler, J H

1986-04-15

Radioactive labeling of p-collagens V, collagens V, and, to a small extent, of procollagen V occurred when [35S]sulfate was incubated with tendons or primary tendon cell cultures, or blood vessels and crops of 17- to 19-day-old chick embryos, or with lung slices from neonatal rats. Most or all of this label is in the form of 1 or more sulfated tyrosine residues/chain of p alpha 1(V), alpha 1(V), p alpha 1'(V), alpha 1'(V), p alpha 2(V), and alpha 2(V), and it remains attached through purification by dialysis, ammonium sulfate precipitation, CsCl-GdnCl2 equilibrium buoyant density and velocity sedimentations, ion-exchange chromatography, and sodium dodecyl sulfate gel electrophoresis. Radioactive tyrosine sulfate was identified in alkaline hydrolysates of these collagen V chains, after labeling the tissues with either [35S]sulfate or [3H]tyrosine, by electrophoretic and chromatographic comigration with a tyrosine sulfate standard. Tunicamycin A1, which inhibits the attachment of N-linked complex carbohydrate, did not interfere with the sulfation process. The tyrosine sulfate is located in a noncollagenous domain, which is probably adjacent to the amino end of the collagen helix, and is retained throughout the physiological proteolytic processing of procollagens V. After digestion with Staphylococcus aureus V8 protease, 35S-labeled p alpha 1(V) and alpha 1(V) chains gave the same map of labeled peptides, and this differed from the map given by p alpha 1'(V) and alpha 1'(V) chains. Little sulfation of p alpha 2(V) and alpha 2(V) chains occurs. The implications of these observations for the structure and properties of procollagens V and their derivatives are considered.

21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

21 CFR 520.1044 - Gentamicin sulfate oral dosage forms.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate oral dosage forms. 520.1044 Section 520.1044 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... sulfate oral dosage forms. ...

In breast cancer subtypes steroid sulfatase (STS) is associated with less aggressive tumour characteristics.

PubMed

McNamara, Keely M; Guestini, Fouzia; Sauer, Torill; Touma, Joel; Bukholm, Ida Rashida; Lindstrøm, Jonas C; Sasano, Hironobu; Geisler, Jürgen

2018-05-01

The majority of breast cancer cases are steroid dependent neoplasms, with hormonal manipulation of either CYP19/aromatase or oestrogen receptor alpha axis being the most common therapy. Alternate pathways of steroid actions are documented, but their interconnections and correlations to BC subtypes and clinical outcome could be further explored. We evaluated selected steroid receptors (Androgen Receptor, Oestrogen Receptor alpha and Beta, Glucocorticoid Receptor) and oestrogen pathways (steroid sulfatase (STS), 17β-hydroxysteroid dehydrogenase 2 (17βHSD2) and aromatase) in a cohort of 139 BC cases from Norway. Using logistic and cox regression analysis, we examined interactions between these and clinical outcomes such as distant metastasis, local relapse and survival. Our principal finding is an impact of STS expression on the risk for distant metastasis (p<0.001) and local relapses (p <0.001), HER2 subtype (p<0.015), and survival (p<0.001). The suggestion of a beneficial effect of alternative oestrogen synthesis pathways was strengthened by inverted, but non-significant findings for 17βHSD2. Increased intratumoural metabolism of oestrogens through STS is associated with significantly lower incidence of relapse and/or distant metastasis and correspondingly improved prognosis. The enrichment of STS in the HER2 overexpressing subtype is intriguing, especially given the possible role of HER-2 over-expression in endocrine resistance.

Mono- and Polyhydrated Sulfates in Tithonium Chasma

NASA Technical Reports Server (NTRS)

2008-01-01

This image of sulfate-containing deposits in Tithonium Chasma was taken by the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) at 1538 UTC (11:38 a.m. EDT) on August 31, 2007 near 5.22 degrees south latitude, 270.48 degrees east longitude. CRISM's image was taken in 544 colors covering 0.36-3.92 micrometers, and shows features as small as 40 meters (132 feet) across. The region covered is just over 10 kilometers (6.2 miles) wide at its narrowest point.

Tithonium Chasma lies at the western end of the Valles Marineris canyon system. It extends approximately east-west for roughly 810 kilometers (503 miles), varies in width from approximately 10 to 110 kilometers (6 to 68 miles), and cuts into the Martian surface to a maximum depth of roughly 6 kilometers (4 miles).

The top panel in the montage above shows the location of the CRISM image on a mosaic taken by the Mars Odyssey spacecraft's Thermal Emission Imaging System (THEMIS). The CRISM data covers an area centered on a ridge of erosion-resistant rock.

The center left image, an infrared false color image, reveals banded, light-colored material draped on the ridge. The center right image unveils the mineralogical composition of the area, with yellow representing monohydrated sulfates (sulfates with one water molecule incorporated into each molecule of the mineral) and purple polyhydrated sulfates (sulfates with multiple waters per mineral molecule).

The lower two images are renderings of data draped over topography with 7 times vertical exaggeration. These images provide a view of the topography and reveal how the sulfate deposits both cover and flank the ridge. Brighter, monohydrated sulfate (yellow) deposits revealed in the lower right image lies along the ridge's northwest side and fall off into a small valley or depression, while darker polyhydrated sulfates (purple) lie along the ridge's northeast flank. A deposit of both mono- and polyhydrated sulfates spanning the ridge

Nocturnal 6-hydroxymelatonin sulfate excretion in female workers exposed to magnetic fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Juutilainen, J; Stevens, Richard G.; Anderson, Larry E.

The objective of this study was to determine whether daytime occupational exposure to extremely low frequency magnetic fields (MFs) suppresses nocturnal melatonin production. Sixty female volunteers were recruited. Thirty-nine worked in a garment factory, and 21 office workers served as a reference group. Exposure assessment was based on the type of sewing machine used and MF measurements around each type of machine. Eye-level MF flux density was used to classify the operators to higher (> 1 microT) and lower (0.3-1 microT) exposure categories. A third group of factory workers had diverse MF exposures from other sources. The reference group hadmore » average exposure of about 0.15 microT. Urine samples were collected on Friday and Monday for three consecutive weeks. Melatonin production was assessed as urinary 6-hydroxymelatonin sulfate (6-OHMS) excretion. The ratio of Friday morning/Monday morning 6-OHMS was used to test the hypothesis that melatonin production is suppressed after 4 days of occupational MF exposure with significant recovery during the weekend. Possible chronic suppression of melatonin production was evaluated by studying exposure-related differences in the Friday values by multivariate regression analysis. The Monday/Friday ratios were close to 1.0, suggesting that there is no increase in melatonin production over the weekend. The average 6-OHMS excretion on Friday was lower among the factory workers than in the reference group, but no monotonous dose-response was observed. Multivariate regression analysis identified MF exposure, smoking, and age as significant explanatory variables associated with decreased 6-OHMS excretion.« less

Identification of allantoin, uric acid, and indoxyl sulfate as biochemical indicators of filth in food packaging by LC.

PubMed

Carlson, M; Thompson, R D

2001-01-01

A liquid chromatographic (LC) method was developed for the determination of allantoin, uric acid, and indoxyl sulfate in mammalian urine contaminated packaging material including paper bagging, corrugated cardboard, grayboard, and burlap bagging. The procedure involves solvent extraction and isolation of the 3 analytes by reversed-phase LC with ultraviolet detection at 225 nm for allantoin and 286 nm for uric acid and indoxyl sulfate. The composition of authentic mammalian urine such as mouse, rat, cat, dog, and human were also determined with regard to the 3 compounds of interest. A linear concentration range of 0.11-20.4, 0.02-10.0, and 0.04-30.0 microg/mL was obtained for allantoin, uric acid, and indoxyl sulfate, respectively. Limits of detection (LOD) and quantitation (LOQ) were 0.0104 and 0.0345 microg/mL for allantoin; 0.0018 and 0.0060 microg/mL for uric acid; and 0.0049 and 0.0165 microg/mL for indoxyl sulfate, respectively. Interday relative standard deviation values for a mixture of standard allantoin, uric acid, and indoxyl sulfate (n = 5) were 0.97, 0.80, and 0.94%, respectively. Analyte composition for 5 types of authentic mammalian urine varied from 0.19-6.88 mg/mL allantoin; 0.08-0.57 mg/mL uric acid; and 0.03-0.78 mg/mL indoxyl sulfate. Analyte content for 8 samples including 2 samples each for paper, cardboard, grayboard, and burlap bagging each contaminated with mouse or rat urine ranged from sulfate. Recoveries of allantoin, uric acid, and indoxyl sulfate from 11 fortified samples (4 types) for both mouse and rat urine ranged from 28.2 to 114.1 % for allantoin; 32.6 to 123.4% for uric acid; and 52.6 to 118.2% for indoxyl sulfate.

Chondroitin sulfate effects on neural stem cell differentiation.

PubMed

Canning, David R; Brelsford, Natalie R; Lovett, Neil W

2016-01-01

We have investigated the role chondroitin sulfate has on cell interactions during neural plate formation in the early chick embryo. Using tissue culture isolates from the prospective neural plate, we have measured neural gene expression profiles associated with neural stem cell differentiation. Removal of chondroitin sulfate from stage 4 neural plate tissue leads to altered associations of N-cadherin-positive neural progenitors and causes changes in the normal sequence of neural marker gene expression. Absence of chondroitin sulfate in the neural plate leads to reduced Sox2 expression and is accompanied by an increase in the expression of anterior markers of neural regionalization. Results obtained in this study suggest that the presence of chondroitin sulfate in the anterior chick embryo is instrumental in maintaining cells in the neural precursor state.

Blood Plasma-Derived Anti-Glycan Antibodies to Sialylated and Sulfated Glycans Identify Ovarian Cancer Patients

PubMed Central

Pochechueva, Tatiana; Chinarev, Alexander; Schoetzau, Andreas; Fedier, André; Bovin, Nicolai V.; Hacker, Neville F.; Jacob, Francis; Heinzelmann-Schwarz, Viola

2016-01-01

Altered levels of naturally occurring anti-glycan antibodies (AGA) circulating in human blood plasma are found in different pathologies including cancer. Here the levels of AGA directed against 22 negatively charged (sialylated and sulfated) glycans were assessed in high-grade serous ovarian cancer (HGSOC, n = 22) patients and benign controls (n = 31) using our previously developed suspension glycan array (SGA). Specifically, the ability of AGA to differentiate between controls and HGSOC, the most common and aggressive type of ovarian cancer with a poor outcome was determined. Results were compared to CA125, the commonly used ovarian cancer biomarker. AGA to seven glycans that significantly (P<0.05) differentiated between HGSOC and control were identified: AGA to top candidates SiaTn and 6-OSulfo-TF (both IgM) differentiated comparably to CA125. The area under the curve (AUC) of a panel of AGA to 5 glycans (SiaTn, 6-OSulfo-TF, 6-OSulfo-LN, SiaLea, and GM2) (0.878) was comparable to CA125 (0.864), but it markedly increased (0.985) when combined with CA125. AGA to SiaTn and 6-OSulfo-TF were also valuable predictors for HGSOC when CA125 values appeared inconclusive, i.e. were below a certain threshold. AGA-glycan binding was in some cases isotype-dependent and sensitive to glycosidic linkage switch (α2–6 vs. α2–3), to sialylation, and to sulfation of the glycans. In conclusion, plasma-derived AGA to sialylated and sulfated glycans including SiaTn and 6-OSulfo-TF detected by SGA present a valuable alternative to CA125 for differentiating controls from HGSOC patients and for predicting the likelihood of HGSOC, and may be potential HGSOC tumor markers. PMID:27764122

Blood Plasma-Derived Anti-Glycan Antibodies to Sialylated and Sulfated Glycans Identify Ovarian Cancer Patients.

PubMed

Pochechueva, Tatiana; Chinarev, Alexander; Schoetzau, Andreas; Fedier, André; Bovin, Nicolai V; Hacker, Neville F; Jacob, Francis; Heinzelmann-Schwarz, Viola

2016-01-01

Altered levels of naturally occurring anti-glycan antibodies (AGA) circulating in human blood plasma are found in different pathologies including cancer. Here the levels of AGA directed against 22 negatively charged (sialylated and sulfated) glycans were assessed in high-grade serous ovarian cancer (HGSOC, n = 22) patients and benign controls (n = 31) using our previously developed suspension glycan array (SGA). Specifically, the ability of AGA to differentiate between controls and HGSOC, the most common and aggressive type of ovarian cancer with a poor outcome was determined. Results were compared to CA125, the commonly used ovarian cancer biomarker. AGA to seven glycans that significantly (P<0.05) differentiated between HGSOC and control were identified: AGA to top candidates SiaTn and 6-OSulfo-TF (both IgM) differentiated comparably to CA125. The area under the curve (AUC) of a panel of AGA to 5 glycans (SiaTn, 6-OSulfo-TF, 6-OSulfo-LN, SiaLea, and GM2) (0.878) was comparable to CA125 (0.864), but it markedly increased (0.985) when combined with CA125. AGA to SiaTn and 6-OSulfo-TF were also valuable predictors for HGSOC when CA125 values appeared inconclusive, i.e. were below a certain threshold. AGA-glycan binding was in some cases isotype-dependent and sensitive to glycosidic linkage switch (α2-6 vs. α2-3), to sialylation, and to sulfation of the glycans. In conclusion, plasma-derived AGA to sialylated and sulfated glycans including SiaTn and 6-OSulfo-TF detected by SGA present a valuable alternative to CA125 for differentiating controls from HGSOC patients and for predicting the likelihood of HGSOC, and may be potential HGSOC tumor markers.

Sulfated and pyruvylated disaccharide alditols obtained from a red seaweed galactan: ESIMS and NMR approaches.

PubMed

Gonçalves, Alan G; Ducatti, Diogo R B; Duarte, M Eugênia R; Noseda, Miguel D

2002-11-29

The water-soluble acid agaran isolated from Acanthophora spicifera (Rhodophyta) was submitted to alkaline treatment for the complete cyclization of alpha-L-Galp 6-sulfate to 3,6-An-alpha-L-Galp units. The modified agaran was then partially depolymerized using partial reductive hydrolysis. The resulting oligosaccharide mixture was fractionated by adsorption and ion-exchange chromatography. Fractions were purified by gel-filtration chromatography and studied by ESIMS and NMR spectroscopy, including 1D 1H, 13C, DEPT and 2D 1H, 1H COSY, TOCSY and 1H, 13C HMQC procedures. The following neutral, pyruvylated, sulfated and sulfated/pyruvylated disaccharide alditols were obtained: beta-D-Galp-(1-->4)-3,6-An-L-GalOH; 4,6-O-(1-carboxyethylidene)-beta-D-Galp-(1-->4)-3,6-An-L-GalOH; beta-D-Galp 2-sulfate-(1-->4)-3,6-An-L-GalOH and 4,6-O-(1-carboxyethylidene)-beta-D-Galp 2-sulfate-(1-->4)-3,6-An-L-GalOH.

Acidic Fluids Across Mars: Detections of Magnesium-Nickel Sulfates

NASA Technical Reports Server (NTRS)

Yen, A. S.; Ming, D. W.; Gellert, R.; Mittlefehldt, D. W.; Rampe, E. B.; Vaniman, D. T.; Thompson, L. M.; Morris, R. V.; Clark, B. C.; VanBommel, S. J.

2017-01-01

Calcium, magnesium and ferric iron sulfates have been detected by the instrument suites on the Mars rovers. A subset of the magnesium sulfates show clear associations with nickel. These associations indicate Ni(2+) co-precipitation with or substitution for Mg(2+) from sulfate-saturated solutions. Nickel is ex-tracted from primary rocks almost exclusively at pH values less than 6, constraining the formation of these Mg-Ni sulfates to mildly to strongly acidic conditions. There is clear evidence for aqueous alteration at the rim of Endeavour Crater (Meridiani Planum), in the Murray formation mudstone (Gale Crater), and near Home Plate (Gusev Crater). The discovery of Mg-Ni sulfates at these locations indicates a history of fluid-rock interactions at low pH.

Photoionization of N,N,N',N'-tetramethylbenzidine in anionic-cationic mixed micelles of sodium dodecyl sulfate-dodecyltrimethylammonium chloride: electron spin resonance and electron spin echo modulation studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rivara-Minten, E.; Baglioni, P.; Kevan, L.

1988-05-05

Electron spin echo modulation (ESEM) and electron spin resonance (ESR) spectra of the photogenerated N,N,N',N'-tetramethylbenzidine cation radical (TMB/sup +/) in frozen mixed micelles of dodecyltrimethylammonium chloride (DTAC) and sodium dodecyl sulfate (SDS) have been studied as a function of the mixed micelle composition. ESEM effects due to TMB/sup +/ interactions with deuterium in D/sub 2/O show a decrease of the TMB/sup +/-water interaction that depends on the SDS-DTAC mixed micelle composition and reaches a minimum for the equimolar mixed micelle. The efficiency of charge separation upon photoionization of TMB to produce TMB/sup +/ measured by ESR correlates with the degreemore » of water penetration into the micelle. ESEM effects due to interaction of x-doxylstearic acid nitroxide probes with deuterium in D/sub 2/O show that the decrease of water penetration is due to higher surface packing due to electrostatic attraction among the polar headgroups of the two surfactants.« less

AnSBBR applied to organic matter and sulfate removal: interaction effect between feed strategy and COD/sulfate ratio.

PubMed

Friedl, Gregor F; Mockaitis, Gustavo; Rodrigues, José A D; Ratusznei, Suzana M; Zaiat, Marcelo; Foresti, Eugênio

2009-10-01

A mechanically stirred anaerobic sequencing batch reactor containing anaerobic biomass immobilized on polyurethane foam cubes, treating low-strength synthetic wastewater (500 mg COD L(-1)), was operated under different operational conditions to assess the removal of organic matter and sulfate. These conditions were related to fill time, defined by the following feed strategies: batch mode of 10 min, fed-batch mode of 3 h and fed-batch mode of 6 h, and COD/[SO(4)(2-)] ratios of 1.34, 0.67, and 0.34 defined by organic matter concentration of 500 mg COD L(-1) and sulfate concentrations of 373, 746, and 1,493 mg SO(4)(2-) L(-1) in the influent. Thus, nine assays were performed to investigate the influence of each of these parameters, as well as the interaction effect, on the performance of the system. The reactor operated with agitation of 400 rpm, total volume of 4.0 L, and treated 2.0 L synthetic wastewater in 8-h cycles at 30 +/- 1 degrees C. During all assays, the reactor showed operational stability in relation to the monitored variables such as COD, sulfate, sulfide, sulfite, volatile acids, bicarbonate alkalinity, and solids, thus demonstrating the potential to apply this technology to the combined removal of organic matter and sulfate. In general, the results showed that the 3-h fed-batch operation with a COD/[SO(4)(2-)] ratio of 0.34 presented the best conditions for organic matter removal (89%). The best efficiency for sulfate removal (71%) was accomplished during the assay with a COD/[SO(4)(2-)] ratio of 1.34 and a fill time of 6 h. It was also observed that as fill time and sulfate concentration in the influent increased, the ratio between removed sulfate load and removed organic load also increased. However, it should be pointed out that the aim of this study was not to optimize the removal of organic matter and sulfate, but rather to analyze the behavior of the reactor during the different feed strategies and applied COD/[SO(4)(2-)] ratios, and mainly to

Separation of hydroxynorketamine stereoisomers using capillary electrophoresis with sulfated β-cyclodextrin and highly sulfated γ-cyclodextrin.

PubMed

Sandbaumhüter, Friederike A; Theurillat, Regula; Thormann, Wolfgang

2017-08-01

The racemic N-methyl-d-aspartate receptor antagonist ketamine is used in anesthesia, analgesia and the treatment of depressive disorders. It is known that interactions of hydroxylated norketamine metabolites and 5,6-dehydronorketamine (DHNK) with the α 7 -nicotinic acetylcholine receptor and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor are responsible for the antidepressive effects. Ketamine and its first metabolite norketamine are not active on these receptors. As stereoselectivity plays a role in ketamine metabolism, a cationic capillary electrophoresis based method capable of resolving and analyzing the stereoisomers of four hydroxylated norketamine metabolites, norketamine and DHNK was developed. The assay is based on liquid/liquid extraction of the analytes from the biological matrix, electrokinetic sample injection across a buffer plug and analysis of the stereoisomers in a phosphate background electrolyte (BGE) at pH 3 comprising a mixture of sulfated β-cyclodextrin (5 mg/mL) and highly sulfated γ-cyclodextrin (0.1%). The method was used to analyze samples of an in vitro study in which ketamine was incubated with equine liver microsomes and in plasma samples of dogs and horses that were collected after an i.v. bolus injection of racemic ketamine. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Isomer separation and effect of the degree of polymerization on the gas-phase structure of chondroitin sulfate oligosaccharides analyzed by ion mobility and tandem mass spectrometry.

PubMed

Poyer, Salomé; Lopin-Bon, Chrystel; Jacquinet, Jean-Claude; Salpin, Jean-Yves; Daniel, Régis

2017-12-15

Chondroitin sulfate (CS) glycosaminoglycans are bioactive sulfated polysaccharides comprising repeating units of uronic acid and N-acetyl galactose sulfated at various positions. The optimal length and sulfation pattern of the CS bioactive sequences remain elusive so that structure-activity relationships cannot be easily established. Development of efficient analytical methods allowing the differentiation of the various sulfation patterns of CS sequences is therefore of particular importance to correlate their biological functions to the sulfation pattern. Discrimination of different oligomers (dp2 to dp6) of synthetic chondroitin sulfate isomers was evaluated by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the negative-ion mode from deprotonated and alkali adduct species. In addition, ion mobility mass spectrometry (IMS-MS) was used to study the influence of both the degree of polymerization and sulfate group location on the gas-phase conformation of CS oligomers. ESI-MS/MS spectra of chondroitin sulfate isomers show characteristic product ions exclusively from alkali adduct species (Li, Na, K and Cs). Whatever the alkali adducts studied, MS/MS of chondroitin oligosaccharides sulfated at position 6 yields a specific product ion at m/z 139 while CS oligosaccharides sulfated at position 4 show a specific product ion at m/z 154. Being observed for the different CS oligomers di-, tetra- and hexasaccharides, these fragment ions are considered as diagnostic ions for chondroitin 6-O-sulfate and chondroitin 4-O-sulfate, respectively. IMS-MS experiments reveal that collision cross-sections (CCS) of CS oligomers with low charge states evolved linearly with degrees of polymerization indicating a similar gas-phase conformation. This study allows the fast and unambiguous differentiation of CS isomers sulfated at position 6 or 4 for both saturated and unsaturated analogues from MS/MS experiments. In addition, the CCS linear evolution of CS oligomers in

21 CFR 524.1044h - Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Gentamicin sulfate, mometasone furoate... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1044h Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension. (a) Specifications. Each gram contains gentamicin sulfate, United States Pharmacopeia (USP...

21 CFR 524.1044h - Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate, mometasone furoate... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1044h Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension. (a) Specifications. Each gram contains gentamicin sulfate, United States Pharmacopeia (USP...

21 CFR 524.1044h - Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Gentamicin sulfate, mometasone furoate... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1044h Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension. (a) Specifications. Each gram contains gentamicin sulfate, United States Pharmacopeia (USP...

21 CFR 524.1044h - Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Gentamicin sulfate, mometasone furoate... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1044h Gentamicin sulfate, mometasone furoate, clotrimazole otic suspension. (a) Specifications. Each gram contains gentamicin sulfate, United States Pharmacopeia (USP...

Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory.

PubMed

Foscarin, Simona; Raha-Chowdhury, Ruma; Fawcett, James W; Kwok, Jessica C F

2017-06-28

Chondroitin sulfate (CS) proteoglycans in perineuronal nets (PNNs) from the central nervous system (CNS) are involved in the control of plasticity and memory. Removing PNNs reactivates plasticity and restores memory in models of Alzheimer's disease and ageing. Their actions depend on the glycosaminoglycan (GAG) chains of CS proteoglycans, which are mainly sulfated in the 4 (C4S) or 6 (C6S) positions. While C4S is inhibitory, C6S is more permissive to axon growth, regeneration and plasticity. C6S decreases during critical period closure. We asked whether there is a late change in CS-GAG sulfation associated with memory loss in aged rats. Immunohistochemistry revealed a progressive increase in C4S and decrease in C6S from 3 to 18 months. GAGs extracted from brain PNNs showed a large reduction in C6S at 12 and 18 months, increasing the C4S/C6S ratio. There was no significant change in mRNA levels of the chondroitin sulfotransferases. PNN GAGs were more inhibitory to axon growth than those from the diffuse extracellular matrix. The 18-month PNN GAGs were more inhibitory than 3-month PNN GAGs. We suggest that the change in PNN GAG sulfation in aged brains renders the PNNs more inhibitory, which lead to a decrease in plasticity and adversely affect memory.

S-33 constraints on the seawater sulfate contribution in modern seafloor hydrothermal vent sulfides

USGS Publications Warehouse

Ono, Shuhei; Shanks, Wayne C.; Rouxel, O.J.; Rumble, D.

2007-01-01

Sulfide sulfur in mid-oceanic ridge hydrothermal vents is derived from leaching of basaltic-sulfide and seawater-derived sulfate that is reduced during high temperature water rock interaction. Conventional sulfur isotope studies, however, are inconclusive about the mass-balance between the two sources because 34S/32S ratios of vent fluid H2S and chimney sulfide minerals may reflect not only the mixing ratio but also isotope exchange between sulfate and sulfide. Here, we show that high-precision analysis of S-33 can provide a unique constraint because isotope mixing and isotope exchange result in different ??33S (?????33S-0.515 ??34S) values of up to 0.04??? even if ??34S values are identical. Detection of such small ??33S differences is technically feasible by using the SF6 dual-inlet mass-spectrometry protocol that has been improved to achieve a precision as good as 0.006??? (2??). Sulfide minerals (marcasite, pyrite, chalcopyrite, and sphalerite) and vent H2S collected from four active seafloor hydrothermal vent sites, East Pacific Rise (EPR) 9-10??N, 13??N, and 21??S and Mid-Atlantic Ridge (MAR) 37??N yield ??33S values ranging from -0.002 to 0.033 and ??34S from -0.5??? to 5.3???. The combined ??34S and ??33S systematics reveal that 73 to 89% of vent sulfides are derived from leaching from basaltic sulfide and only 11 to 27% from seawater-derived sulfate. Pyrite from EPR 13??N and marcasite from MAR 37??N are in isotope disequilibrium not only in ??34S but also in ??33S with respect to associated sphalerite and chalcopyrite, suggesting non-equilibrium sulfur isotope exchange between seawater sulfate and sulfide during pyrite precipitation. Seafloor hydrothermal vent sulfides are characterized by low ??33S values compared with biogenic sulfides, suggesting little or no contribution of sulfide from microbial sulfate reduction into hydrothermal sulfides at sediment-free mid-oceanic ridge systems. We conclude that 33S is an effective new tracer for interplay among

21 CFR 524.1484f - Neomycin sulfate, prednisolone acetate, tetracaine hydrochloride eardrops.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Neomycin sulfate, prednisolone acetate, tetracaine... DOSAGE FORM NEW ANIMAL DRUGS § 524.1484f Neomycin sulfate, prednisolone acetate, tetracaine hydrochloride eardrops. (a) Specifications. The product contains 5 milligrams of neomycin sulfate equivalent to 3.5...

21 CFR 524.1484c - Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride ointment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Neomycin sulfate, isoflupredone acetate... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1484c Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride ointment. (a) Specifications. The drug contains 5 milligrams of neomycin sulfate (equivalent to 3...

21 CFR 524.1484f - Neomycin sulfate, prednisolone acetate, tetracaine hydrochloride eardrops.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Neomycin sulfate, prednisolone acetate, tetracaine... DOSAGE FORM NEW ANIMAL DRUGS § 524.1484f Neomycin sulfate, prednisolone acetate, tetracaine hydrochloride eardrops. (a) Specifications. The product contains 5 milligrams of neomycin sulfate equivalent to 3.5...

21 CFR 524.1484f - Neomycin sulfate, prednisolone acetate, tetracaine hydrochloride eardrops.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Neomycin sulfate, prednisolone acetate, tetracaine... DOSAGE FORM NEW ANIMAL DRUGS § 524.1484f Neomycin sulfate, prednisolone acetate, tetracaine hydrochloride eardrops. (a) Specifications. The product contains 5 milligrams of neomycin sulfate equivalent to 3.5...

21 CFR 524.1484c - Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride ointment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Neomycin sulfate, isoflupredone acetate... TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1484c Neomycin sulfate, isoflupredone acetate, tetracaine hydrochloride ointment. (a) Specifications. The drug contains 5 milligrams of neomycin sulfate (equivalent to 3...

Reduction in Brain Heparan Sulfate with Systemic Administration of an IgG Trojan Horse-Sulfamidase Fusion Protein in the Mucopolysaccharidosis Type IIIA Mouse.

PubMed

Boado, Ruben J; Lu, Jeff Zhiqiang; Hui, Eric Ka-Wai; Pardridge, William M

2018-02-05

Mucopolysaccharidosis Type IIIA (MPSIIIA), also known as Sanfilippo A syndrome, is an inherited neurodegenerative disease caused by mutations in the lysosomal enzyme, N-sulfoglucosamine sulfohydrolase (SGSH), also known as sulfamidase. Mutations in the SGSH enzyme, the only mammalian heparan N-sulfatase, cause accumulation of lysosomal inclusion bodies in brain cells comprising heparan sulfate (HS) glycosaminoglycans (GAGs). Treatment of MPSIIIA with intravenous recombinant SGSH is not possible because this large molecule does not cross the blood-brain barrier (BBB). BBB penetration by SGSH was enabled in the present study by re-engineering this enzyme as an IgG-SGSH fusion protein, where the IgG domain is a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR), designated the cTfRMAb. The IgG domain of the fusion protein acts as a molecular Trojan horse to deliver the enzyme into brain via transport on the endogenous BBB TfR. The cTfRMAb-SGSH fusion protein bound to the mouse TfR with high affinity, ED 50 = 0.74 ± 0.07 nM, and retained high SGSH enzyme activity, 10 043 ± 1003 units/mg protein, which is comparable to recombinant human SGSH. Male and female MPSIIIA mice, null for the SGSH enzyme, were treated for 6 weeks with thrice-weekly intraperitoneal injections of vehicle, 5 mg/kg of the cTfRMAb alone, or 5 mg/kg of the cTfRMAb-SGSH fusion protein, starting at the age of 2 weeks, and were euthanized 1 week after the last injection. Brain and liver HS, as determined by liquid chromatography-mass spectrometry, were elevated 30-fold and 36-fold, respectively, in the MPSIIIA mouse. Treatment of the mice with the cTfRMAb-SGSH fusion protein caused a 70% and 85% reduction in brain and liver HS, respectively. The reduction in brain HS was associated with a 28% increase in latency on the rotarod test of motor activity in male mice. The mice exhibited no injection related reactions, and only a low titer end of study antidrug antibody

Therapeutic Effects of 6-Gingerol, 8-Gingerol, and 10-Gingerol on Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis in Rats.

PubMed

Zhang, Feng; Ma, Na; Gao, Yong-Feng; Sun, Li-Li; Zhang, Ji-Guo

2017-09-01

Ulcerative colitis is one of the most common types of inflammatory bowel disease and is multifactorial and relapsing. 6-Gingerol, a component of gingerols extracted from ginger (Zingiber officinale), has been reported to improve ulcerative colitis. The present study aims to investigate the therapeutic efficacy of two analogous forms of 6-gingerol, 8-gingerol, and 10-gingerol, on ulcerative colitis. Colitis was induced in rats through consumption of 5% (w/v) dextran sulfate sodium drinking water for 7 consecutive days. 6-Gingerol, 8-gingerol, and 10-gingerol were then given intraperitoneally at doses of 30 mg kg -1  d -1 for another 7 days, respectively. Body weight change, disease activity index, inflammatory cytokines, and oxidative stress indices were measured, and the colonic tissue injuries were assessed macroscopically and histopathologically. Results showed that all three gingerols attenuated colitic symptoms evoked by dextran sulfate sodium, significantly elevated superoxide dismutase activity, decreased malondialdehyde levels and myeloperoxidase activity in the colon tissue, and markedly reduced the content of tumor necrosis factor alpha and Interleukin 1 beta in the serum. Histological observations showed that all three gingerols obviously accelerated mucosal damage healing. It is concluded that 6-gingerol, 8-gingerol, and 10-gingerol, the three analogues, have a strong and relatively equal efficacy in the treatment of colitis. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

The impact of N,N-dimethyldodecylamine N-oxide (DDAO) concentration on the crystallisation of sodium dodecyl sulfate (SDS) systems and the resulting changes to crystal structure, shape and the kinetics of crystal growth.

PubMed

Summerton, Emily; Hollamby, Martin J; Zimbitas, Georgina; Snow, Tim; Smith, Andrew J; Sommertune, Jens; Bettiol, Jeanluc; Jones, Christopher; Britton, Melanie M; Bakalis, Serafim

2018-05-19

At low temperatures stability issues arise in commercial detergent products when surfactant crystallisation occurs, a process which is not currently well-understood. An understanding of the phase transition can be obtained using a simple binary SDS (sodium dodecyl sulfate) + DDAO (N,N-dimethyldodecylamine N-oxide) aqueous system. It expected that the crystallisation temperature of an SDS system can be lowered with addition of DDAO, thus providing a route to improve detergent stability. Detergent systems are typically comprised of anionic surfactants, non-ionic surfactants and water. This study explores the crystallisation of a three component system consisting of sodium dodecyl sulfate (SDS), N,N-dimethyldodecylamine N-oxide (DDAO), and water using wide-angle X-ray scattering (WAXS), differential scanning calorimetry (DSC) and confocal Raman microscopy. The presence of DDAO lowered the crystallisation temperature of a 20 wt% SDS system. For all aqueous mixtures of SDS + DDAO at low temperatures, SDS hydrated crystals, SDS.1/2H 2 O or SDS·H 2 O, formed. SDS hydrates comprising of layers of SDS separated by water layers. DDAO tended to reside in the vicinity of these SDS crystals. In the absence of DDAO an additional intermediary hydrate structure, SDS.1/8H 2 O, formed whereas for mixed SDS + DDAO systems no such structure was detected during crystallisation. Copyright © 2018. Published by Elsevier Inc.

Impacts of Stratospheric Sulfate Geoengineering on PM2.5

NASA Astrophysics Data System (ADS)

Robock, A.; Xia, L.; Tilmes, S.; Mills, M. J.; Richter, J.; Kravitz, B.; MacMartin, D.

2017-12-01

Particulate matter (PM) includes sulfate, nitrate, organic carbon, elemental carbon, soil dust, and sea salt. The first four components are mostly present near the ground as fine particulate matter with a diameter less than 2.5 µm (PM2.5), and these are of the most concern for human health. PM is efficiently scavenged by precipitation, which is its main atmospheric sink. Here we examine the impact of stratospheric climate engineering on this important pollutant and health risk, taking advantage of two sets of climate model simulations conducted at the National Center for Atmospheric Research. We use the full tropospheric and stratospheric chemistry version of the Community Earth System Model - Community Atmospheric Model 4 (CESM CAM4-chem) with a horizontal resolution of 0.9° x 1.25° lat-lon to simulate a stratospheric sulfate injection climate intervention of 8 Tg SO2 yr-1 combined with an RCP6.0 global warming forcing, the G4 Specified Stratospheric Aerosol (G4SSA) scenario. We also analyze the output from a 20-member ensemble of Community Earth System Model, version 1 with the Whole Atmosphere Community Climate Model as its atmospheric component (CESM1(WACCM)) simulations, also at 0.9° x 1.25° lat-lon resolution, with sulfur dioxide injection at 15°N, 15°S, 30°N, and 30°S varying in time to balance RCP8.5 forcing. While the CESM CAM4-chem model has full tropospheric and stratospheric chemistry, CESM1(WACCM) has an internally generated quasi-biennial oscillation and a comprehensive tropospheric and stratospheric sulfate aerosol treatment, but only stratospheric chemistry. For G4SSA, there are a global temperature reduction of 0.8 K and global averaged precipitation decrease of 3% relative to RCP6.0. The global averaged surface PM2.5 reduces about 1% compared with RCP6.0, mainly over Eurasian and East Asian regions in Northern Hemisphere winter. The PM2.5 concentration change is a combination of effects from tropospheric chemistry and precipitation

Sulfated N-linked oligosaccharides affect secretion but are not essential for the transport, proteolytic processing, and sorting of lysosomal enzymes in Dictyostelium discoideum.

PubMed

Cardelli, J A; Bush, J M; Ebert, D; Freeze, H H

1990-05-25

Although previous studies have indicated that N-linked oligosaccharides on lysosomal enzymes in Dictyostelium discoideum are extensively phosphorylated and sulfated, the role of these modifications in the sorting and function of these enzymes remains to be determined. We have used radiolabel pulse-chase, subcellular fractionation, and immunofluorescence microscopy to analyze the transport, processing, secretion, and sorting of two lysosomal enzymes in a mutant, HL244, which is almost completely defective in sulfation. [3H]Mannose-labeled N-linked oligosaccharides were released from immunoprecipitated alpha-mannosidase and beta-glucosidase of HL244 by digestion with peptide: N-glycosidase. The size, Man9-10GlcNAc2, and processing of the neutral species were similar to that found in the wild type, but the anionic oligosaccharides were less charged than those from the wild-type enzymes. All of the negative charges on the oligosaccharides for HL244 were due to the presence of 1, 2, or 3 phosphodiesters and not to sulfate esters. The rate of proteolytic processing of precursor forms of alpha-mannosidase and beta-glucosidase to mature forms in HL244 was identical to wild type. The precursor polypeptides in the mutant and the wild type were membrane associated until being processed to mature forms; therefore, sulfated sugars are not essential for this association. Furthermore, the rate of transport of alpha-mannosidase and beta-glucosidase from the endoplasmic reticulum to the Golgi complex was normal in the mutant as determined by the rate at which the newly synthesized proteins became resistant to the enzyme, endo-beta-N-acetylglucosaminidase H. There was no increase in the percentage of newly synthesized mutant precursors which escaped sorting and were secreted, and the intracellularly retained lysosomal enzymes were properly localized to lysosomes as determined by fractionation of cell organelles on Percoll gradients and immunofluorescence microscopy. However, the

Synthesis and anticoagulant activity of the quaternary ammonium chitosan sulfates.

PubMed

Fan, Lihong; Wu, Penghui; Zhang, Jinrong; Gao, Song; Wang, Libo; Li, Mingjia; Sha, Mingming; Xie, Weiguo; Nie, Min

2012-01-01

Quaternary ammonium chitosan sulfates with diverse degrees of substitution (DS) ascribed to sulfate groups between 0.52 and 1.55 were synthesized by reacting quaternary ammonium chitosan with an uncommon sulfating agent (N(SO(3)Na)(3)) that was prepared from sodium bisulfite (NaHSO(3)) through reaction with sodium nitrite (NaNO(2)) in the aqueous system homogeneous. The structures of the derivatives were characterized by FTIR, (1)H NMR and (13)C NMR. The factors affecting DS of quaternary ammonium chitosan sulfates which included the molar ratio of NaNO(2) to quaternary ammonium chitosan, sulfated temperature, sulfated time and pH of sulfated reaction solution were investigated in detail. Its anticoagulation activity in vitro was determined by an activated partial thromboplastin time (APTT) assay, a thrombin time (TT) assay and a prothrombin time (PT) assay. Results of anticoagulation assays showed quaternary ammonium chitosan sulfates significantly prolonged APTT and TT, but not PT, and demonstrated that the introduction of sulfate groups into the quaternary ammonium chitosan structure improved its anticoagulant activity obviously. The study showed its anticoagulant properties strongly depended on its DS, concentration and molecular weight. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

The Hemolymph of the ascidian Styela plicata (Chordata-Tunicata) contains heparin inside basophil-like cells and a unique sulfated galactoglucan in the plasma.

PubMed

de Barros, Cintia M; Andrade, Leonardo R; Allodi, Silvana; Viskov, Christian; Mourier, Pierre A; Cavalcante, Moisés C M; Straus, Anita H; Takahashi, Helio K; Pomin, Vitor H; Carvalho, Vinicius F; Martins, Marco A; Pavão, Mauro S G

2007-01-19

The hemolymph of ascidians (Chordata-Tunicata) contains different types of hemocytes embedded in a liquid plasma. In the present study, heparin and a sulfated heteropolysaccharide were purified from the hemolymph of the ascidian Styela plicata. The heteropolysaccharide occurs free in the plasma, is composed of glucose ( approximately 60%) and galactose ( approximately 40%), and is highly sulfated. Heparin, on the other hand, occurs in the hemocytes, and high performance liquid chromatography of the products formed by degradation with specific lyases revealed that it is composed mainly by the disaccharides DeltaUA(2SO(4))-1-->4-beta-d-GlcN(SO(4)) (39.7%) and DeltaUA(2SO(4))-1-->4-beta-d-GlcN(SO(4))(6SO(4)) (38.2%). Small amounts of the 3-O-sulfated disaccharides DeltaUA(2SO(4))-1-->4-beta-d-GlcN(SO(4))(3SO(4)) (9.8%) and DeltaUA(2SO(4))-1-->4-beta-d-GlcN(SO(4))(3SO(4))(6SO(4)) (3.8%) were also detected. These 3-O-sulfated disaccharides were demonstrated to be essential for the binding of the hemocyte heparin to antithrombin III. Electron microscopy techniques were used to characterize the ultrastructure of the hemocytes and to localize heparin and histamine in these cells. At least five cell types were recognized and classified as univacuolated and multivacuolated cells, amebocytes, hemoblasts, and granulocytes. Immunocytochemistry showed that heparin and histamine co-localize in intracellular granules of only one type of hemocyte, the granulocyte. These results show for the first time that in ascidians, a sulfated galactoglucan circulates free in the plasma, and heparin occurs as an intracellular product of a circulating basophil-like cell.

Significant role of organic sulfur in supporting sedimentary sulfate reduction in low-sulfate environments

NASA Astrophysics Data System (ADS)

Fakhraee, Mojtaba; Li, Jiying; Katsev, Sergei

2017-09-01

Dissimilatory sulfate reduction (DSR) is a major carbon mineralization pathway in aquatic sediments, soils, and groundwater, which regulates the production of hydrogen sulfide and the mobilization rates of biologically important elements such as phosphorus and mercury. It has been widely assumed that water-column sulfate is the main sulfur source to fuel this reaction in sediments. While this assumption may be justified in high-sulfate environments such as modern seawater, we argue that in low-sulfate environments mineralization of organic sulfur compounds can be an important source of sulfate. Using a reaction-transport model, we investigate the production of sulfate from sulfur-containing organic matter for a range of environments. The results show that in low sulfate environments (<500 μM) the in-sediment production of sulfate can support a substantial portion (>50%) of sulfate reduction. In well-oxygenated systems, porewater sulfate profiles often exhibit sub-interface peaks so that sulfate fluxes are directed out of the sediment. Our measurements in Lake Superior, the world's largest lake, corroborate this conclusion: offshore sediments act as sources rather than sinks of sulfate for the water column, and sediment DSR is supported entirely by the in-sediment production of sulfate. Sulfate reduction rates are correlated to the depth of oxygen penetration and strongly regulated by the supply of reactive organic matter; rate co-regulation by sulfate availability becomes appreciable below 500 μM level. The results indicate the need to consider the mineralization of organic sulfur in the biogeochemical cycling in low-sulfate environments, including several of the world's largest freshwater bodies, deep subsurface, and possibly the sulfate-poor oceans of the Early Earth.

Study of thermochemical sulfate reduction mechanism using compound specific sulfur isotope analysis

NASA Astrophysics Data System (ADS)

Meshoulam, Alexander; Ellis, Geoffrey S.; Said Ahmad, Ward; Deev, Andrei; Sessions, Alex L.; Tang, Yongchun; Adkins, Jess F.; Liu, Jinzhong; Gilhooly, William P.; Aizenshtat, Zeev; Amrani, Alon

2016-09-01

The sulfur isotopic fractionation associated with the formation of organic sulfur compounds (OSCs) during thermochemical sulfate reduction (TSR) was studied using gold-tube pyrolysis experiments to simulate TSR. The reactants used included n-hexadecane (n-C16) as a model organic compound with sulfate, sulfite, or elemental sulfur as the sulfur source. At the end of each experiment, the S-isotopic composition and concentration of remaining sulfate, H2S, benzothiophene, dibenzothiophene, and 2-phenylthiophene (PT) were measured. The observed S-isotopic fractionations between sulfate and BT, DBT, and H2S in experimental simulations of TSR correlate well with a multi-stage model of the overall TSR process. Large kinetic isotope fractionations occur during the first, uncatalyzed stage of TSR, 12.4‰ for H2S and as much as 22.2‰ for BT. The fractionations decrease as the H2S concentration increases and the reaction enters the second, catalyzed stage. Once all of the oxidizable hydrocarbons have been consumed, sulfate reduction ceases and equilibrium partitioning then dictates the fractionation between H2S and sulfate (∼17‰). Experiments involving sparingly soluble CaSO4 show that during the second catalytic phase of TSR the rate of sulfate reduction exceeds that of sulfate dissolution. In this case, there is no apparent isotopic fractionation between source sulfate and generated H2S, as all of the available sulfate is effectively reduced at all reaction times. When CaSO4 is replaced with fully soluble Na2SO4, sulfate dissolution is no longer rate limiting and significant S-isotopic fractionation is observed. This supports the notion that CaSO4 dissolution can lead to the apparent lack of fractionation between H2S and sulfate produced by TSR in nature. The S-isotopic composition of individual OSCs record information related to geochemical reactions that cannot be discerned from the δ34S values obtained from bulk phases such as H2S, oil, and sulfate minerals, and

Hydrothermal synthesis, crystal structure and properties of 2-D and 3-D lanthanide sulfates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu Yan; Ding Shaohua; Zheng Xuefang

2007-07-15

Two new lanthanum sulfates DySO{sub 4}(OH) 1 and Eu{sub 2}(SO{sub 4}){sub 3}(H{sub 2}O){sub 8} 2 have been hydrothermally synthesized. The colorless crystals were characterized by IR, TGA, ICP and XRD. The structure was determined by single-crystal X-ray diffraction. 1 crystallizes with monoclinic symmetry, space group P2(1)/n [a=7.995(4) A, b=10.945(5) A, c=8.164(4) A, {alpha}=90{sup o}, {beta}=93.619(6){sup o}, {gamma}=90{sup o}, V=713.0(5) A{sup 3}, Z=8]. It displays a three-dimensional framework, based on the novel Dy-O chains connected by the sulfate groups through helical chains. 2 crystallizes with monoclinic symmetry, space group C2/c, [a=13.5605(17) A, b=6.7676(8) A, c=18.318(2) A, {alpha}=90{sup o}, {beta}=102.265(2){sup o}, {gamma}=90{supmore » o}, V=1642.7 (4) A{sup 3}, Z=4]. Its layered framework is attained by the europium atoms connected by the sulfate groups arranged in a helical manner. - Graphical abstract: Two new lanthanum sulfates DySO{sub 4}(OH) 1 and Eu{sub 2} (SO{sub 4}){sub 3} (H{sub 2}O){sub 8} 2 have been hydrothermally synthesized. The colorless crystals were characterized by IR, TGA, ICP and XRD. The structure was determined by single-crystal X-ray diffraction. It displays a three dimensional framework, based on the novel Dy-O chains connected by the sulfate groups through helical chains.« less

Permeability of rosmarinic acid in Prunella vulgaris and ursolic acid in Salvia officinalis extracts across Caco-2 cell monolayers.

PubMed

Qiang, Zhiyi; Ye, Zhong; Hauck, Cathy; Murphy, Patricia A; McCoy, Joe-Ann; Widrlechner, Mark P; Reddy, Manju B; Hendrich, Suzanne

2011-10-11

Rosmarinic acid (RA), a caffeic acid-related compound found in high concentrations in Prunella vulgaris (self-heal), and ursolic acid (UA), a pentacyclic triterpene acid concentrated in Salvia officinalis (sage), have been traditionally used to treat inflammation in the mouth, and may also be beneficial for gastrointestinal health in general. To investigate the permeabilities of RA and UA as pure compounds and in Prunella vulgaris and Salvia officinalis ethanol extracts across human intestinal epithelial Caco-2 cell monolayers. The permeabilities and phase II biotransformation of RA and UA as pure compounds and in herbal extracts were compared using Caco-2 cells with HPLC detection. The apparent permeability coefficient (P(app)) for RA and RA in Prunella vulgaris extracts was 0.2 ± 0.05 × 10(-6)cm/s, significantly increased to 0.9 ± 0.2 × 10(-6)cm/s after β-glucuronidase/sulfatase treatment. P(app) for UA and UA in Salvia officinalis extract was 2.7 ± 0.3 × 10(-6)cm/s and 2.3 ± 0.5 × 10(-6)cm/s before and after β-glucuronidase/sulfatase treatment, respectively. Neither compound was affected in permeability by the herbal extract matrix. RA and UA in herbal extracts had similar uptake as that found using the pure compounds, which may simplify the prediction of compound efficacy, but the apparent lack of intestinal glucuronidation/sulfation of UA is likely to further enhance the bioavailability of that compound compared with RA. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Permeability of Rosmarinic acid in Prunella vulgaris and Ursolic acid in Salvia officinalis Extracts across Caco-2 Cell Monolayers

PubMed Central

Qiang, Zhiyi; Ye, Zhong; Hauck, Cathy; Murphy, Patricia A.; McCoy, Joe-Ann; Widrlechner, Mark P.; Reddy, Manju B.; Hendrich, Suzanne

2011-01-01

Ethnopharmacological relevance Rosmarinic acid (RA), a caffeic acid-related compound found in high concentrations in Prunella vulgaris (self-heal), and ursolic acid (UA), a pentacyclic triterpene acid concentrated in Salvia officinalis (sage), have been traditionally used to treat inflammation in the mouth, and may also be beneficial for gastrointestinal health in general. Aim of the study To investigate the permeabilities of RA and UA as pure compounds and in P. vulgaris and S. officinalis ethanol extracts across human intestinal epithelial Caco-2 cell monolayers. Materials and methods The permeabilities and Phase II biotransformation of RA and UA as pure compounds and in herbal extracts were compared using Caco-2 cells with HPLC detection. Results The apparent permeability coefficient (Papp) for RA and RA in P. vulgaris extracts was 0.2 ± 0.05 × 10−6 cm/s, significantly increased to 0.9 ± 0.2 × 10−6 cm/s after β-glucuronidase/sulfatase treatment. Papp for UA and UA in S. officinalis extract was 2.7 ± 0.3 × 10−6 cm/s and 2.3 ± 0.5 × 10−6 cm/s before and after β-glucuronidase/sulfatase treatment, respectively. Neither compound was affected in permeability by the herbal extract matrix. Conclusion RA and UA in herbal extracts had similar uptake as that found using the pure compounds, which may simplify the prediction of compound efficacy, but the apparent lack of intestinal glucuronidation/sulfation of UA is likely to further enhance the bioavailability of that compound compared with RA. PMID:21798330

Structural studies of sialylated oligosaccharides of human midcycle cervical mucin.

PubMed

Yurewicz, E C; Matsuura, F; Moghissi, K S

1987-04-05

It was previously shown that reductive alkali treatment of purified human cervical mucin releases a heterogeneous population of reduced neutral, sialylated, and sulfated oligosaccharides (Yurewicz, E. C., and Moghissi, K. S. (1981) J. Biol. Chem. 256, 11895-11904). Four major sialylated oligosaccharide fractions were isolated with approximate compositions of Fuc:GlcNac:Gal:NeuAc:N-acetylgalactosaminitol (GalNAcol) = 0:0:0:1:1 (B1a), 0:0:1:1:1 (B2b), 0:1:2:1:1 (B3a), and 1:1:2:1:1 (B4a), where Fuc is fucose. They comprised roughly 3, 11, 7, and 6% of recovered oligosaccharide chains, respectively. On the basis of periodate oxidations, methylation analyses, and sequential degradations with glycosidases, the following structures were determined. (Formula: see text) Oligosaccharides 1 and 2 are characterized by the presence of N-acetylneuraminic acid in alpha 2,6-linkage to N-acetylgalactosaminitol. The remaining oligosaccharides contain N-acetylneuraminic acid in alpha 2,3-linkage to galactose residues. Oligosaccharides 3 and 4 and oligosaccharides 5 and 6 were isolated as unresolved isomeric mixtures in fractions B3a and B4a, respectively. Oligosaccharides 3 and 4 were distinguished on the basis of susceptibility to digestion with Aspergillus niger beta-galactosidase whereas oligosaccharides 5 and 6 were distinguished on the basis of differential rates of digestion with beef kidney alpha-fucosidase. The structural data indicate the presence of at least two sialyltransferases in human cervical epithelium and further suggest a potential physiologically significant competition between sialyltransferase and beta-N-acetylglucosaminyltransferase for C-6 of the N-acetylgalactosamine residue O-glycosidically linked to serine/threonine of the polypeptide core.

The Role of Heparan Sulfate Proteoglycans in Optic Disc and Stalk Morphogenesis

PubMed Central

Cai, Zhigang; Grobe, Kay; Zhang, Xin

2014-01-01

Background Heparan sulfate proteoglycans (HSPG) are important for embryonic development via the regulation of gradient formation and signaling of multiple growth factors and morphogens. Previous studies have shown that Bmp/Shh/Fgf signaling are required for the regionalization of the optic vesicle (OV) and for the closure of the optic fissure (OF), the disturbance of which underlie ocular anomalies such as microphthalmia, coloboma and optic nerve hypoplasia. Results To study HSPG-dependent coordination of these signaling pathways during mammalian visual system development, we have generated a series of OV-specific mutations in the heparan sulfate (HS) N-sulfotransferase genes (Ndst1 and Ndst2) and HS O-sulfotransferase genes (Hs2st, Hs6st1 and Hs6st2) in mice. Interestingly, the resulting HS undersulfation still allowed for normal retinal neurogenesis and optic fissure closure, but led to defective optic disc and stalk development. The adult mutant animals further developed optic nerve aplasia/hypoplasia and displayed retinal degeneration. We observed that MAPK/ERK signaling was down-regulated in Ndst mutants, and consistent with this, HS-related optic nerve morphogenesis defects in mutant mice could partially be rescued by constitutive Kras activation. Conclusions These results suggest that HSPGs, depending on their HS sulfation pattern, regulate multiple signaling pathways in optic disc and stalk morphogenesis. PMID:24753163

Complex Sulfate Deposits in Coprates Chasma

NASA Technical Reports Server (NTRS)

2008-01-01

This image of layered sulfate-containing deposits in the Coprates Chasma region of Mars was taken by the Compact Reconnaissance Imaging Spectrometer for Mars (CRISM) at 1827UTC (1:27 p.m. EST) on December 12, 2006 near 10.2 degrees south latitude, 68.8 degrees west longitude. The image was taken in 544 colors covering 0.36-3.92 micrometers, and shows features as small as 40 meters (132 feet) across. The image is about 11 kilometers (6.8 miles) wide at its narrowest point.

Coprates Chasma forms part of the backbone of the Valles Marineris canyon system. It extends approximately east-west for roughly 966 kilometers (600 miles), and is one of the larger chasmata in the Valles Marineris system.

The top panel in the montage above shows the location of the CRISM image on a mosaic taken by the Mars Odyssey spacecraft's Thermal Emission Imaging System (THEMIS). The CRISM data covers an area centered on a knob near the chasma's northern wall.

The center left image, an infrared false color image, shows the knob's layered morphology. The center right image unveils the mineralogical signatures of some of those layers, with yellow representing monohydrated sulfates (sulfates with one water molecule incorporated into each molecule of the mineral) and purple representing polyhydrated sulfates (sulfates with multiple waters per mineral molecule).

The lower two images are renderings of data draped over topography with 3 times vertical exaggeration. These images provide a view of the topography and reveal how the sulfate deposits relate to that topography. Darker polyhydrated sulfates (purple) lie along the knob's western flank. Brighter, monohydrated sulfates (yellow) appear to be superimposed on polyhydrated sulfate deposits in the southwest corner of the image. These coarsely banded deposits continue along the southeast side of the knob.

There are two possible explanations for the compositional banding of these sulfates. The first is deposition of

NTP technical report on the toxicity studies of Cupric Sulfate (CAS No. 7758-99-8) Administered in Drinking Water and Feed to F344/N Rats and B6C3F1 Mice.

PubMed

Hebert, Charles

1993-07-01

Cupric sulfate is an inorganic salt which is widely used in industry, agriculture, and veterinary medicine. Its applications include use as an algicide in potable waters and as a feed additive and therapeutic agent in swine, sheep, and cattle. Because copper salts are found in human water supplies, toxicity studies of cupric sulfate pentahydrate were conducted in male and female F344/N rats and B6C3F1 mice by the drinking water (2-week studies only) and dosed feed routes (2-week and 13-week studies). Animals were evaluated for hematology, clinical chemistry, urinalysis, reproductive toxicity, tissue metal accumulation, and histopathology. In the 2-week drinking water studies, groups of five rats and five mice per sex received cupric sulfate at concentrations of 300 to 30,000 ppm for 15 days. One female rat, one male mouse, and three female mice in the 3000 ppm groups and all rats and mice in the 10,000 and 30,000 ppm groups died before the end of the studies. The remaining mice and rats in the 3000 ppm groups gained little or lost weight. Water consumption in the three highest dose groups of both species was reduced by more than 65%. Clinical signs observed in these groups were typical of those seen in moribund animals and were attributed to dehydration. The only gross or microscopic change specifically related to cupric sulfate toxicity was an increase in the size and number of cytoplasmic protein droplets in the epithelium of the renal proximal convoluted tubule in male rats from the 300 and 1000-ppm groups. In the 2-week feed studies, groups of five rats and five mice per sex were fed diets containing 1000 to 16,000 ppm cupric sulfate. No chemical-related deaths occurred in any dose group. Compared to the controls, rats and mice in the two highest dose groups had reduced body weight gains which were attributed to decreased feed consumption. Hyperplasia with hyperkeratosis of the squamous epithelium on the limiting ridge of the forestomach was seen in rats and

Sulfate Reduction and Sulfide Biomineralization By Deep-Sea Hydrothermal Vent Microorganisms

NASA Astrophysics Data System (ADS)

Picard, A.; Gartman, A.; Clarke, D. R.; Girguis, P. R.

2014-12-01

Deep-sea hydrothermal vents are characterized by steep temperature and chemical gradients and moderate pressures. At these sites, mesophilic sulfate-reducing bacteria thrive, however their significance for the formation of sulfide minerals is unknown. In this study we investigated sulfate reduction and sulfide biomineralization by the deep-sea bacterium Desulfovibrio hydrothermalis isolated from a deep-sea vent chimney at the Grandbonum vent site (13°N, East Pacific Rise, 2600 m water depth) [1]. Sulfate reduction rates were determined as a function of pressure and temperature. Biomineralization of sulfide minerals in the presence of various metal concentrations was characterized using light and electron microscopy and optical spectroscopy. We seek to better understand the significance of biological sulfate reduction in deep-sea hydrothermal environments, to characterize the steps in sulfide mineral nucleation and growth, and identify the interactions between cells and minerals. [1] D. Alazard, S. Dukan, A. Urios, F. Verhe, N. Bouabida, F. Morel, P. Thomas, J.L. Garcia and B. Ollivier, Desulfovibrio hydrothermalis sp. nov., a novel sulfate-reducing bacterium isolated from hydrothermal vents, Int. J. Syst. Evol. Microbiol., 53 (2003) 173-178.

Sulfate production depicts fed-state adaptation to protein restriction in humans.

PubMed

Hamadeh, M J; Schiffrin, A; Hoffer, L J

2001-08-01

One feature of the adaptation to dietary protein restriction is reduced urea production over the hours after consumption of a test meal of fixed composition. This adaptation is impaired in conventionally treated insulin-dependent diabetes mellitus (Hoffer LJ, Taveroff A, and Schiffrin A. Am J Physiol Endocrinol Metab 272: E59--E67, 1997). We have now tested the response to a test meal containing less protein and included as a main outcome variable the production of sulfate, a specific indicator of sulfur amino acid catabolism. Six normal men consumed a mixed test meal containing 0.25 g protein/kg and 10 kcal/kg while adapted to high (1.5 g x kg(-1) x day(-1)) and low (0.3 g. kg(-1) x day(-1)) protein intakes. They followed the identical protocol twice. Six subjects with insulin-dependent diabetes consumed the test meal while adapted to their customary high-protein diet. Adaptation to protein restriction reproducibly reduced 9-h cumulative postmeal urea N and S production by 22--29% and 49--52%, respectively (both P < 0.05). Similar results were obtained for a postmeal collection period of 6 h. The response of the diabetic subjects was normal. We conclude that reductions in postmeal urea and sulfate production after protein restriction are reproducible and are evident using a postmeal collection period as short as 6 h. Sulfate production effectively depicts fed-state adaptation to protein restriction.

Characterization of sulfate-reducing granular sludge in the SANI(®) process.

PubMed

Hao, Tianwei; Wei, Li; Lu, Hui; Chui, Hokwong; Mackey, Hamish R; van Loosdrecht, Mark C M; Chen, Guanghao

2013-12-01

Hong Kong practices seawater toilet flushing covering 80% of the population. A sulfur cycle-based biological nitrogen removal process, the Sulfate reduction, Autotrophic denitrification and Nitrification Integrated (SANI(®)) process, had been developed to close the loop between the hybrid water supply and saline sewage treatment. To enhance this novel process, granulation of a Sulfate-Reducing Up-flow Sludge Bed (SRUSB) reactor has recently been conducted for organic removal and provision of electron donors (sulfide) for subsequent autotrophic denitrification, with a view to minimizing footprint and maximizing operation resilience. This further study was focused on the biological and physicochemical characteristics of the granular sulfate-reducing sludge. A lab-scale SRUSB reactor seeded with anaerobic digester sludge was operated with synthetic saline sewage for 368 days. At 1 h nominal hydraulic retention time (HRT) and 6.4 kg COD/m(3)-d organic loading rate, the SRUSB reactor achieved 90% COD and 75% sulfate removal efficiencies. Granular sludge was observed within 30 days, and became stable after 4 months of operation with diameters of 400-500 μm, SVI5 of 30 ml/g, and extracellular polymeric substances of 23 mg carbohydrate/g VSS. Fluorescence in situ hybridization (FISH) analysis revealed that the granules were enriched with abundant sulfate-reducing bacteria (SRB) as compared with the seeding sludge. Pyrosequencing analysis of the 16S rRNA gene in the sulfate-reducing granules on day 90 indicated that the microbial community consisted of a diverse SRB genera, namely Desulfobulbus (18.1%), Desulfobacter (13.6%), Desulfomicrobium (5.6%), Desulfosarcina (0.73%) and Desulfovibrio (0.6%), accounting for 38.6% of total operational taxonomic units at genera level, with no methanogens detected. The microbial population and physicochemical properties of the granules well explained the excellent performance of the granular SRUSB reactor. Copyright © 2013 Elsevier

Partial characterization, antioxidant and antitumor activities of polysaccharides from Philomycusbilineatus.

PubMed

He, Rongjun; Ye, Jiaming; Zhao, Yuejun; Su, Weike

2014-04-01

Four polysaccharides (PBP60-A, PBP60-B, PBP60-C and PBP60-D) were purified from slug (Philomycusbilineatus) by ion-exchange chromatography. The antioxidant activities were studied by ABTS, DPPH, hydroxyl radical, superoxide radical and reducing power assay. In vitro antitumor activities were evaluated by MTT assay. Results demonstrated that PBP60-A was mainly composed of Man, Rha, Glc, Gal, Xyl and Fuc in a mole ratio of 6.13:3.08:8.97:5.22:2.46:1.13. PBP60-B was composed of Man, GlcN, Rha, GalN, GlcU, Glc, Gal, Xyl and Fuc in a mole ratio of 0.90:0.31:1.15:0.37:0.24:1.02:3.84:0.93:1.99. PBP60-C and PBP60-D were composed of Man, GlcN, Rha, GalN, GlcU, Glc, Gal, Xyl, Fuc and an unknown monosaccharide. Antioxidant tests indicated that four polysaccharides exhibited significant antioxidant activities in a dose-dependent manner. PBP60-D presented relative stronger antioxidant activity. PBP60-C showed higher antitumor activity against A549 and MCF-7 cells in vitro. At concentration of500 μg/mL, the antitumor activities of PBP60-C on theA549 and MCF-7 cells were 65.30% and 42.45%, respectively. These results indicated that polysaccharides from Philomycusbilineatus could be explored as potential natural antioxidants and cancer prevention agents. Copyright © 2014 Elsevier B.V. All rights reserved.

A VNTR element associated with steroid sulfatase gene deletions stimulates recombination in cultured cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gong, Y.; Li, X.M.; Shapiro, L.J.

1994-09-01

Steroid sulfatase deficiency is a common genetic disorder, with a prevalence of approximately one in every 3500 males world wide. About 90% of these patients have complete gene deletions, which appear to result from recombination between members of a low-copy repeat family (CRI-232 is the prototype) that flank the gene. RU1 and RU2 are two VNTR elements found within each of these family members. RU1 consists of 30 bp repeating units and its length shows minimal variation among individuals. The RU2 element consists of repeating sequences which are highly asymmetric, with about 90% purines and no C`s on one strand,more » and range from 0.6 kb to over 23 kb among different individuals. We conducted a study to determine if the RU1 or RU2 elements can promote recombination in an in vivo test system. We inserted these elements adjacent to the neo gene in each of two pSV2neo derivatives, one of which has a deletion in the 5{prime} portion of the neo gene and the other having a deletion in the 3{prime} portion. These plasmids were combined and used to transfect EJ cells. Survival of cells in G418 indicates restoration of a functional neo gene by recombination between two deletion constructs. Thus counting G418 resistant colonies gives a quantitative measure of the enhancement of recombination by the inserted VNTR elements. The results showed no effect on recombination by the inserted RU1 element (compared to the insertion of a nonspecific sequence), while the RU2 element stimulated recombination by 3.5-fold (P<0.01). A separate set of constructs placed RU1 or RU2 within the intron of an exon trapping vector. Following tranfection of cells, recombination events were monitored by a PCR assay that detected the approximation of primer binding sites (as a result of recombination). These studies showed that, as in the first set of experiments, the highly variable RU2 element is capable of stimulating somatic recombination in mammalian cells.« less

[Comparative studies on the characteristics of the Fourier-transform infrared spectra between sturgeon and shark chondroitin sulfates].

PubMed

Zheng, Jiang; Guan, Rui-Zhang; Huang, Shi-Yu

2008-01-01

The characteristics of the Fourier-transform infrared spectra of sturgeon and shark chondroitin sulfates (CHSs) were comparatively studied. The results show that sturgeon CHS exhibits special vibrations at the wavenumbers of 1 376, 1 344, 1 310, 1 157, 883 and 856 cm(-1). Further analysis shows that shark CHS contains 6-sulfated-CHS, while sturgeon CHS contains 4, 6-disulfated CHS, indicating that sturgeon CHS could have higher biological activities in decreasing the toxicity of medicine and in killing cancer cells. In general, the two kinds of CHSs have similar infrared spectra and groups of acylamino, carboxyl, sulfate, and saccharide ring. But the N-H variable-angle vibration of acylamino group of sturgeon CHS occurs at the higher wavenumber, and the vibration intensity of carboxyl group at 1 415 cm(-1) is also stronger than that of shark CHS. Chemical analysis shows that sturgeon CHS has a higher content of glucuronic acid, suggesting that it probably could be a better kind of medical materials for the bone mineralization.

Preparation of chondroitin sulfate libraries containing disulfated disaccharide units and inhibition of thrombin by these chondroitin sulfates.

PubMed

Numakura, Mario; Kusakabe, Noriko; Ishige, Kazuya; Ohtake-Niimi, Shiori; Habuchi, Hiroko; Habuchi, Osami

2010-07-01

Chondroitin sulfate (CS) containing GlcA-GalNAc(4,6-SO(4)) (E unit) and CS containing GlcA(2SO(4))-GalNAc(6SO(4)) (D unit) have been implicated in various physiological functions. However, it has been poorly understood how the structure and contents of disulfated disaccharide units in CS contribute to these functions. We prepared CS libraries containing E unit or D unit in various proportions by in vitro enzymatic reactions using recombinant GalNAc 4-sulfate 6-O-sulfotransferase and uronosyl 2-O-sulfotransferase, and examined their inhibitory activity toward thrombin. The in vitro sulfated CSs containing disulfated disaccharide units showed concentration-dependent direct inhibition of thrombin when the proportion of E unit or D unit in the CSs was above 15-17%. The CSs containing both E unit and D unit exhibited higher inhibitory activity toward thrombin than the CSs containing either E unit or D unit alone, if the proportion of the total disulfated disaccharide units of these CSs was comparable. The thrombin-catalyzed degradation of fibrinogen, a physiological substrate for thrombin, was also inhibited by the CS containing both E unit and D unit. These observations indicate that the enzymatically prepared CS libraries containing various amounts of disulfated disaccharide units appear to be useful for elucidating the physiological function of disulfated disaccharide units in CS.

Determination of parotid sulfate secretion in sheep by means of ultrasonic flow probes.

PubMed

Méot, F; Bonnet, J-M; Boivin, R; Cirio, A

2006-05-01

The bilateral output of sulfate in parotid saliva, the relationship with its plasma level and with parotid flow, and its variation according to feeding behavior were determined in ad libitum, normal-sulfate (0.28% DM)-fed sheep (n = 6) using a transit time ultrasonic flow meter system to measure salivary flow. Ultrasonic flow meter probes were bilaterally implanted, under general anesthesia, around parotid ducts previously fitted through their oral ends with nonobstructive sampling catheters. Salivary flows were continuously recorded during 24 h, and saliva and blood samples for sulfate determinations were obtained hourly. Jaw movements were monitored with the submandibular balloon technique. The sulfate concentration in parotid saliva (mean of the group = 4.9 +/- 3.7 microg/mL) showed high variability between sheep (individual means from 0.4 +/- 0.3 to 9.3 +/- 5.9 microg/mL) and averaged 12.3% of the more stable plasma level (41.2 +/- 8.1 microg/mL). Pronounced intraindividual variations were also evident (0.1 to 26.3 microg of sulphate/mL of parotid saliva), in strong association with the fluctuations of salivary output. In 4 sheep, a decreasing exponential relationship was observed between parotid sulfate concentration and salivary secretion rate (r2 = 0.36, P < 0.01). This fact and the absence of a relationship between sulfate levels in plasma and in saliva suggest a sulfate secretory process during the passage of primary saliva through the ductal tree of the gland. The greatest rates of bilateral salivary sulfate output were observed during feeding (14.1 +/- 14.0 microg/min) and rumination (12.7 +/- 11.0 microg/min). Nevertheless, 49% of the sulfate output in parotid saliva was present during rest, as a result of the length of the resting times. The contribution of parotid sulfate to the ruminal S pool was highly variable and averaged 13.2 mg/d, representing less than 1% of the S intake. In conclusion, the accurate, reliable, nonobstructive, and bilateral

Brittlestars contain highly sulfated chondroitin sulfates/dermatan sulfates that promote fibroblast growth factor 2-induced cell signaling.

PubMed

Ramachandra, Rashmi; Namburi, Ramesh B; Ortega-Martinez, Olga; Shi, Xiaofeng; Zaia, Joseph; Dupont, Sam T; Thorndyke, Michael C; Lindahl, Ulf; Spillmann, Dorothe

2014-02-01

Glycosaminoglycans (GAGs) isolated from brittlestars, Echinodermata class Ophiuroidea, were characterized, as part of attempts to understand the evolutionary development of these polysaccharides. A population of chondroitin sulfate/dermatan sulfate (CS/DS) chains with a high overall degree of sulfation and hexuronate epimerization was the major GAG found, whereas heparan sulfate (HS) was below detection level. Enzymatic digestion with different chondroitin lyases revealed exceptionally high proportions of di- and trisulfated CS/DS disaccharides. The latter unit appears much more abundant in one of four individual species of brittlestars, Amphiura filiformis, than reported earlier in other marine invertebrates. The brittlestar CS/DS was further shown to bind to growth factors such as fibroblast growth factor 2 and to promote FGF-stimulated cell signaling in GAG-deficient cell lines in a manner similar to that of heparin. These findings point to a potential biological role for the highly sulfated invertebrate GAGs, similar to those ascribed to HS in vertebrates.

21 CFR 524.1484d - Neomycin sulfate, hydrocortisone acetate, tetracaine hydrochloride ear ointment.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Neomycin sulfate, hydrocortisone acetate... OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1484d Neomycin sulfate, hydrocortisone acetate... sulfate, equivalent to 3.5 milligrams of neomycin base, 5 milligrams of hydrocortisone acetate, and 5...

21 CFR 524.1484d - Neomycin sulfate, hydrocortisone acetate, tetracaine hydrochloride ear ointment.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Neomycin sulfate, hydrocortisone acetate... OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1484d Neomycin sulfate, hydrocortisone acetate... sulfate, equivalent to 3.5 milligrams of neomycin base, 5 milligrams of hydrocortisone acetate, and 5...

21 CFR 524.1484d - Neomycin sulfate, hydrocortisone acetate, tetracaine hydrochloride ear ointment.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Neomycin sulfate, hydrocortisone acetate... OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1484d Neomycin sulfate, hydrocortisone acetate... sulfate, equivalent to 3.5 milligrams of neomycin base, 5 milligrams of hydrocortisone acetate, and 5...

21 CFR 524.1484d - Neomycin sulfate, hydrocortisone acetate, tetracaine hydrochloride ear ointment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Neomycin sulfate, hydrocortisone acetate... OPHTHALMIC AND TOPICAL DOSAGE FORM NEW ANIMAL DRUGS § 524.1484d Neomycin sulfate, hydrocortisone acetate... sulfate, equivalent to 3.5 milligrams of neomycin base, 5 milligrams of hydrocortisone acetate, and 5...

Biological Sulfate Reduction Rates in Hydrothermal Recharge Zones

NASA Astrophysics Data System (ADS)

Crowell, B.; Lowell, R. P.

2007-12-01

downwelling (u <n 10-9 m/s); however, anhydrite precipitation would seal pore on the order of thousands of years even in the absence of biogenic sulfate reduction. At these slower flow speeds, the biogenic sulfate reduction may provide an important mechanism for the removal of seawater sulfate from the deeper parts of the reaction zone. Bach, W. and K.J. Edwards (2003), Iron and sulfide oxidation within the basaltic ocean crust: Implications for chemolithoautotrophic microbial biomass production, Geochim.Cosmochim. Acta, 67, 3871-3887. Jorgensen, B.B., M.F. Isaksen and H.W. Jannasch (1992), Bacterial sulfate reduction above 100 degrees C in deep-sea hydrothermal vent sediments, Science, 258, 1756-1757. Lowell, R.P. and Y. Yao (2002), Anhydrite precipitation and the extent of hydrothermal recharge zones at ocean ridge crests, J. Geophys. Res., 107(B9), 2183, doi:10.1029/2001JB001289.

Magnesium sulfate accelerates the onset of low-dose rocuronium in patients undergoing laryngeal microsurgery.

PubMed

Choi, Eun-Su; Jeong, Woo-Jin; Ahn, Soon-Hyun; Oh, Ah-Young; Jeon, Young-Tae; Do, Sang-Hwan

2017-02-01

We evaluated the effect of magnesium sulfate-an enhancer of neuromuscular blockade-on onset and duration of low dose of rocuronium, and on operating conditions during laryngeal microsurgery. Randomized, prospective, double-blinded study. Eighty-four patients scheduled for elective laryngeal microsurgery. Patients were randomly allocated to receive different doses of rocuronium: 0.6 mg/kg (group C, n=28), 0.45 mg/kg (group LR, n=28), or 0.45 mg/kg plus magnesium sulfate 30 mg/kg (group LM, n=28). We measured the onset time and duration of action of rocuronium, and evaluated the surgeon's satisfaction with the operating conditions. Group LR showed significantly delayed onset time (group C: 87±22 seconds, group LR: 127±47 seconds, and group LM: 89±32 seconds; P=.001) and maximal suppression than did other groups (group C: 102±30 seconds, group LR: 155±66 seconds, and group LM: 105±36 seconds; P=.002). Duration of action of rocuronium was significantly longer in group C than in other groups (group C: 39±7 minutes, group LR: 28±8 minutes, group LRM: 31±8 minutes; P<.001). Laryngoscope placement score (P=.002), surgeon's satisfaction (P=.005), and sore throat (P=.035) were significantly worse in group LR. Magnesium sulfate 30 mg/kg accelerated the onset and improved operating conditions of low-dose rocuronium without prolongation of action. Copyright © 2016 Elsevier Inc. All rights reserved.

Whole-exome sequencing in a single proband reveals a mutation in the CHST8 gene in autosomal recessive peeling skin syndrome

PubMed Central

Cabral, Rita M.; Kurban, Mazen; Wajid, Muhammad; Shimomura, Yutaka; Petukhova, Lynn; Christiano, Angela M.

2015-01-01

Generalized peeling skin syndrome (PSS) is an autosomal recessive genodermatosis characterized by lifelong, continuous shedding of the upper epidermis. Using whole-genome homozygozity mapping and whole-exome sequencing, we identified a novel homozygous missense mutation (c.229C>T, R77W) within the CHST8 gene, in a large consanguineous family with non-inflammatory PSS type A. CHST8 encodes a Golgi transmembrane N-acetylgalactosamine-4-O-sulfotransferase (GalNAc4-ST1), which we show by immunofluorescence staining to be expressed throughout normal epidermis. A colorimetric assay for total sulfated glycosaminoglycan (GAG) quantification, comparing human keratinocytes (CCD1106 KERTr) expressing wild type and mutant recombinant GalNAc4-ST1, revealed decreased levels of total sulfated GAGs in cells expressing mutant GalNAc4-ST1, suggesting loss of function. Western blotting revealed lower expression levels of mutant recombinant GalNAc4-ST1 compared to wild type, suggesting that accelerated degradation may result in loss of function, leading to PSS type A. This is the first report describing a mutation as the cause of PSS type A. PMID:22289416

Progestins and breast cancer.

PubMed

Pasqualini, Jorge R

2007-10-01

Progestins exert their progestational activity by binding to the progesterone receptor (form A, the most active and form B, the less active) and may also interact with other steroid receptors (androgen, glucocorticoid, mineralocorticoid, estrogen). They can have important effects in other tissues besides the endometrium, including the breast, liver, bone and brain. The biological responses of progestins cover a very large domain: lipids, carbohydrates, proteins, water and electrolyte regulation, hemostasis, fibrinolysis, and cardiovascular and immunological systems. At present, more than 200 progestin compounds have been synthesized, but the biological response could be different from one to another depending on their structure, metabolism, receptor affinity, experimental conditions, target tissue or cell line, as well as the biological response considered. There is substantial evidence that mammary cancer tissue contains all the enzymes responsible for the local biosynthesis of estradiol (E(2)) from circulating precursors. Two principal pathways are implicated in the final steps of E(2) formation in breast cancer tissue: the 'aromatase pathway', which transforms androgens into estrogens, and the 'sulfatase pathway', which converts estrone sulfate (E(1)S) into estrone (E(1)) via estrone sulfatase. The final step is the conversion of weak E(1) to the potent biologically active E(2) via reductive 17beta-hydroxysteroid dehydrogenase type 1 activity. It is also well established that steroid sulfotransferases, which convert estrogens into their sulfates, are present in breast cancer tissues. It has been demonstrated that various progestins (e.g. nomegestrol acetate, medrogestone, promegestone) as well as tibolone and their metabolites can block the enzymes involved in E(2) bioformation (sulfatase, 17beta-hydroxysteroid dehydrogenase) in breast cancer cells. These substances can also stimulate the sulfotransferase activity which converts estrogens into the biologically

NKG2D and CD94 bind to heparin and sulfate-containing polysaccharides.

PubMed

Higai, Koji; Imaizumi, Yuzo; Suzuki, Chiho; Azuma, Yutaro; Matsumoto, Kojiro

2009-09-04

Killer lectin-like receptors NKG2D and CD94 on natural killer cells trigger cytotoxicity through binding of glycans on target cells including sialyl Lewis X antigen. We previously reported that NKG2D and CD94 recognize alpha2,3-linked NeuAc on multi-antennary N-glycans. Here we further investigated polysaccharide binding by these receptors, using glutathione-S-transferase-fused extracellular domains of NKG2D AA 73-216 (rNKG2Dlec) and CD94 AA 68-179 (rCD94lec). We found that rNKG2Dlec and rCD94lec bind in a dose-dependent manner to plates coated with heparin-conjugated bovine serum albumin (heparin-BSA). Binding to heparin-BSA was suppressed by soluble sulfate-containing polysaccharides, but minimally impacted by 2-O-, 6-O-, and 2-N-desulfated heparin. Mutagenesis revealed that (152)Y and (199)Y of NKG2D and (144)F, (160)N, and (166)C of CD94 were critical for binding to heparin-BSA. The present manuscript provides the first evidence that NKG2D and CD94 bind to heparin and sulfate-containing polysaccharides.

In vivo contribution of amino acid sulfur to cartilage proteoglycan sulfation

PubMed Central

Pecora, Fabio; Gualeni, Benedetta; Forlino, Antonella; Superti-Furga, Andrea; Tenni, Ruggero; Cetta, Giuseppe; Rossi, Antonio

2006-01-01

Cytoplasmic sulfate for sulfation reactions may be derived either from extracellular fluids or from catabolism of sulfur-containing amino acids and other thiols. In vitro studies have pointed out the potential relevance of sulfur-containing amino acids as sources for sulfation when extracellular sulfate concentration is low or when its transport is impaired such as in DTDST [DTD (diastrophic dysplasia) sulfate transporter] chondrodysplasias. In the present study, we have considered the contribution of cysteine and cysteine derivatives to in vivo macromolecular sulfation of cartilage by using the mouse model of DTD we have recently generated [Forlino, Piazza, Tiveron, Della Torre, Tatangelo, Bonafe, Gualeni, Romano, Pecora, Superti-Furga et al. (2005) Hum. Mol. Genet. 14, 859–871]. By intraperitoneal injection of [35S]cysteine in wild-type and mutant mice and determination of the specific activity of the chondroitin 4-sulfated disaccharide in cartilage, we demonstrated that the pathway by which sulfate is recruited from the intracellular oxidation of thiols is active in vivo. To check whether cysteine derivatives play a role, sulfation of cartilage proteoglycans was measured after treatment for 1 week of newborn mutant and wild-type mice with hypodermic NAC (N-acetyl-L-cysteine). The relative amount of sulfated disaccharides increased in mutant mice treated with NAC compared with the placebo group, indicating an increase in proteoglycan sulfation due to NAC catabolism, although pharmacokinetic studies demonstrated that the drug was rapidly removed from the bloodstream. In conclusion, cysteine contribution to cartilage proteoglycan sulfation in vivo is minimal under physiological conditions even if extracellular sulfate availability is low; however, the contribution of thiols to sulfation becomes significant by increasing their plasma concentration. PMID:16719839

40 CFR 721.3152 - Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

Code of Federal Regulations, 2013 CFR

2013-07-01

...-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates (salts). 721.3152 Section 721... Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates... ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates...

40 CFR 721.3152 - Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl...

Code of Federal Regulations, 2014 CFR

2014-07-01

...-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates (salts). 721.3152 Section 721... Ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates... ethanaminium, N-ethyl-2-hydroxy-N,N-bis(2-hydroxyethyl)-, diester with C12-18 fatty acids, ethyl sulfates...