bims-supasi 2024-04-28 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2024‒04‒28
twelve papers selected by
Jonathan Wolf Mueller, University of Birmingham

Chemical Synthesis of Fucosylated Chondroitin Sulfate Tetrasaccharide with Fucosyl Branch at the 6-OH of GalNAc Residue.
Marine sulfated glycans inhibit the interaction of heparin with S-protein of SARS-CoV-2 Omicron XBB variant.
Sulfated polysaccharide as biomimetic biopolymers for tissue engineering scaffolds fabrication: Challenges and opportunities.
Interactions of proteins with heparan sulfate.
Concentrations of dehydroepiandrosterone-sulphate (DHEA-S) in people with cystic fibrosis on and off elexacaftor-tezacaftor-ivacaftor.
Modified turbidometric microassay for the measurement of sulfate in plasma and urine.
Analysis of Endocrine and Inflammatory Markers in Preserved Ratio Impaired Spirometry.
Modular microgel-based bioassembly scaffold induced chondrogenic and osteogenic differentiation of BMSCs.
Syndecans, Exostosins and Sulfotransferases as Potential Synovial Inflammation Moderators in Patients with Hip Osteoarthritis.
Isolation of Adeno-associated Viral Vectors Through a Single-step and Semi-automated Heparin Affinity Chromatography Protocol.
Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in Dextran Sulfate Sodium-Induced Murine Model of Ulcerative Colitis.
Conjugated bisphenol S metabolites in human serum and whole blood.

Mar Drugs. 2024 Apr 19. pii: 184. [Epub ahead of print]22(4):

Chemical Synthesis of Fucosylated Chondroitin Sulfate Tetrasaccharide with Fucosyl Branch at the 6-OH of GalNAc Residue.

Changlun Lv, Xiaona Li, Guoqing Yang, Haijiao Chen, Chunxia Li.

  Fucosylated chondroitin sulfate is a unique glycosaminoglycan isolated from sea cucumbers, with excellent anticoagulant activity. The fucosyl branch in FCS is generally located at the 3-OH of D-glucuronic acid but, recently, a novel structure with α-L-fucose linked to the 6-OH of N-acetyl-galactosamine has been found. Here, using functionalized monosaccharide building blocks, we prepared novel FCS tetrasaccharides with fucosyl branches both at the 6-OH of GalNAc and 3-OH of GlcA. In the synthesis, the protective group strategy of selective O-sulfation, as well as stereoselective glycosylation, was established, which enabled the efficient synthesis of the specific tetrasaccharide compounds. This research enriches knowledge on the structural types of FCS oligosaccharides and facilitates the exploration of the structure-activity relationship in the future.

Keywords:  fucosyl branch; fucosylated chondroitin sulfate; synthesis; tetrasaccharide

DOI:  https://doi.org/10.3390/md22040184
Glycoconj J. 2024 Apr 20.

Marine sulfated glycans inhibit the interaction of heparin with S-protein of SARS-CoV-2 Omicron XBB variant.

Peng He, Yuefan Song, Weihua Jin, Yunran Li, Ke Xia, Seon Beom Kim, Rohini Dwivedi, Marwa Farrag, John Bates, Vitor H Pomin, Chunyu Wang, Robert J Linhardt, Jonathan S Dordick, Fuming Zhang.

  The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide COVID-19 pandemic, leading to 6.8 million deaths. Numerous variants have emerged since its outbreak, resulting in its significantly enhanced ability to spread among humans. As with many other viruses, SARS‑CoV‑2 utilizes heparan sulfate (HS) glycosaminoglycan (GAG) on the surface of host cells to facilitate viral attachment and initiate cellular entry through the ACE2 receptor. Therefore, interfering with virion-HS interactions represents a promising target to develop broad-spectrum antiviral therapeutics. Sulfated glycans derived from marine organisms have been proven to be exceptional reservoirs of naturally existing HS mimetics, which exhibit remarkable therapeutic properties encompassing antiviral/microbial, antitumor, anticoagulant, and anti-inflammatory activities. In the current study, the interactions between the receptor-binding domain (RBD) of S-protein of SARS-CoV-2 (both WT and XBB.1.5 variants) and heparin were applied to assess the inhibitory activity of 10 marine-sourced glycans including three sulfated fucans, three fucosylated chondroitin sulfates and two fucoidans derived from sea cucumbers, sea urchin and seaweed Saccharina japonica, respectively. The inhibitory activity of these marine derived sulfated glycans on the interactions between RBD of S-protein and heparin was evaluated using Surface Plasmon Resonance (SPR). The RBDs of S-proteins from both Omicrion XBB.1.5 and wild-type (WT) were found to bind to heparin, which is a highly sulfated form of HS. All the tested marine-sourced sulfated glycans exhibited strong inhibition of WT and XBB.1.5 S-protein binding to heparin. We believe the study on the molecular interactions between S-proteins and host cell glycosaminoglycans provides valuable insight for the development of marine-sourced, glycan-based inhibitors as potential anti-SARS-CoV-2 agents.

Keywords:  Heparin; Marine sulfated glycans; Omicron XBB.1.5; SARS-CoV-2; SPR; Spike Protein

DOI:  https://doi.org/10.1007/s10719-024-10150-1
Carbohydr Polym. 2024 Jul 15. pii: S0144-8617(24)00350-3. [Epub ahead of print]336 122124

Sulfated polysaccharide as biomimetic biopolymers for tissue engineering scaffolds fabrication: Challenges and opportunities.

Sanaz Alizadeh, Zahra Ameri, Hamed Daemi, Mohamad Pezeshki-Modaress.

  Sulfated polysaccharides play important roles in tissue engineering applications because of their high growth factor preservation ability and their native-like biological features. There are different sulfated polysaccharides based on different repeating units in the carbohydrate backbone, the position of the sulfate group, and the sulfation degree of the polysaccharide. These led to various sulfated polymers with different negative charge densities and resultant structure-property relationships. Since numerous reports are presented related to sulfated polysaccharide applications in tissue engineering, it is crucial to review the role of effective physicochemical and biological parameters in their usage; as well as their structure-property relationships. Within this review, we focused on the effect of naturally occurring and synthetic sulfated polysaccharides in tissue engineering applications reported in the last years, highlighting the challenges of the scaffold fabrication process, the position, and the degree of sulfate on biomedical activity. Additionally, we discussed their use in numerous in vitro and in vivo model systems.

Keywords:  Biomimetic; Scaffolds; Sulfated polysaccharide; Tissue engineering

DOI:  https://doi.org/10.1016/j.carbpol.2024.122124
Essays Biochem. 2024 Apr 22. pii: EBC20230093. [Epub ahead of print]

Interactions of proteins with heparan sulfate.

Faizah S Alotaibi, Marim M R Alsadun, Sarah A Alsaiari, Krithika Ramakrishnan, Edwin A Yates, David G Fernig.

  Heparan sulfate (HS) is a glycosaminoglycan, polysaccharides that are considered to have arisen in the last common unicellular ancestor of multicellular animals. In this light, the large interactome of HS and its myriad functions in relation to the regulation of cell communication are not surprising. The binding of proteins to HS determines their localisation and diffusion, essential for embryonic development and homeostasis. Following the biosynthesis of the initial heparosan polymer, the subsequent modifications comprise an established canonical pathway and a minor pathway. The more frequent former starts with N-deacetylation and N-sulfation of GlcNAc residues, the latter with C-5 epimerisation of a GlcA residue adjacent to a GlcNAc. The binding of proteins to HS is driven by ionic interactions. The multivalent effect arising from the many individual ionic bonds between a single protein and a polysaccharide chain results in a far stronger interaction than would be expected from an ion-exchange process. In many instances, upon binding, both parties undergo substantial conformational change, the resulting hydrogen and van der Waal bonds contributing significant free energy to the binding reaction. Nevertheless, ionic bonds dominate the protein-polysaccharide interaction kinetically. Together with the multivalent effect, this provides an explanation for the observed trapping of HS-binding proteins in extracellular matrix. Importantly, individual ionic bonds have been observed to be dynamic; breaking and reforming, while the protein remains bound to the polysaccharide. These considerations lead to a model for 1D diffusion of proteins in extracellular matrix on HS, involving mechanisms such as sliding, chain switching and rolling.

Keywords:  Protein diffusion; fibroblast growth factors; glycosaminoglycans; gradient; heparan sulphate

DOI:  https://doi.org/10.1042/EBC20230093
J Cyst Fibros. 2024 Apr 22. pii: S1569-1993(24)00052-3. [Epub ahead of print]

Concentrations of dehydroepiandrosterone-sulphate (DHEA-S) in people with cystic fibrosis on and off elexacaftor-tezacaftor-ivacaftor.

Shadaan Abid, Lauren Shaffer, Andrew Bayat, Minjae Lee, Ashley Keller, Raksha Jain.

  BACKGROUND: Levels of sulfated Dehydroepiandrosterone (DHEA-S) are unknown in people with Cystic Fibrosis (pwCF). DHEA-S is reported to have an inverse association with inflammation and warrants evaluation in pwCF.METHODS: We compared differences in DHEA-S and other hormones between pwCF (n = 180) and without CF (n = 180) and DHEA-S association with percent predicted forced expiratory volume in one second (ppFEV1). We also evaluated DHEA-S levels in people with CF on elexacaftor-tezacaftor-ivacaftor (ETI) (n = 145).
RESULTS: PwCF (not on ETI) had lower DHEA-S levels compared to healthy non-CF controls. DHEA-S levels in individuals with CF on ETI were similar to those without CF. Lower DHEA-S levels were associated with lower ppFEV1.
CONCLUSIONS: PwCF (not on ETI) have lower levels of DHEA-S than people without CF or people with CF on ETI. Additional studies are needed to investigate the impact of DHEA-S on the health of pwCF and mechanisms involved.

Keywords:  Adults; Cystic fibrosis; DHEA; Inflammation; Sex

DOI:  https://doi.org/10.1016/j.jcf.2024.04.007
MethodsX. 2024 Jun;12 102712

Modified turbidometric microassay for the measurement of sulfate in plasma and urine.

Prasidhee Vijayakumar, Avis McWhinney, Yvonne A Eiby, Paul A Dawson.

  Sulfate is the fourth most abundant anion in circulation. Despite being an essential nutrient for healthy growth and development, sulfate is not routinely measured in clinical settings. In research settings, animal studies have shown that hyposulfatemia and hypersulfaturia are associated with adverse developmental outcomes. Those findings have increased interest in measuring plasma and urine sulfate levels. In this study, we describe a modified assay to measure sulfate in low volumes of plasma and urine. •A streamlined microassay to measure sulfate levels using a microtiter plate format was developed.•To determine the robustness of the assay, this method assessed reagent stability and concentrations, as well as absorbance at different wavelengths and following a range of incubation times.•The optimized microassay was used to measure sulfate level in pig plasma and urine samples, which were compared to a validated ion chromatography method.

Keywords:  Barium chloride; Sulfate assay; Sulfatemia; Turbidometric microassay for measurement of inorganic sulfate

DOI:  https://doi.org/10.1016/j.mex.2024.102712
Med Sci (Basel). 2024 Mar 27. pii: 18. [Epub ahead of print]12(2):

Analysis of Endocrine and Inflammatory Markers in Preserved Ratio Impaired Spirometry.

Fabíola Ramos Jesus, Anna Clara Santiago Moraes, Ingrid Lorena Neves da Silva, Fabine Correia Passos, Cristina Salles, Margarida Célia Lima Costa Neves, Gyselle Chrystina Baccan.

  Chronic Obstructive Pulmonary Disease (COPD) is a disease of the lungs characterized by chronic airflow obstruction. Individuals with preserved ratio impaired spirometry (PRISm) may be at risk for developing COPD. This study aimed to characterize PRISm and COPD patients in terms of their immune response and endocrine profile to identify differences extending beyond lung function. The participants performed the clinical assessment, pulmonary function test, and blood collection to determine serum hormone levels and concentrations of cytokine. Differences were observed in the nutritional status, lung function, and comorbidity. There were no differences in IL-6, IL-8, IL-10, IL-12, and TNF levels between PRISm and COPD groups. Both PRISm and COPD patients have lower dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) levels than controls. Correlation analysis of PRISm and COPD patients revealed positive correlations between serum levels of DHEA-S and DHEA, with forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), which negatively correlated with IL-8 levels. The results indicated that despite differences in lung function parameters, the PRISm and COPD groups exhibited similarities in endocrine profile alterations. This study represents the first attempt to link endocrine with immune markers and lung function in individuals with PRISm.

Keywords:  COPD; DHEA; cytokines; disease pulmonary; lung function

DOI:  https://doi.org/10.3390/medsci12020018
Macromol Biosci. 2024 Apr 25. e2400051

Modular microgel-based bioassembly scaffold induced chondrogenic and osteogenic differentiation of BMSCs.

Yanyan Wang, Ruyu Yan, Hai Yang, Ying Liu, Xiupeng Zhong, Sa Liu, Renjian Xie, Li Ren.

  Bioactive scaffolds capable of simultaneously repairing osteochondral defects remain a big challenge due to the heterogeneity of bone and cartilage. Currently modular microgel-based bioassembly scaffolds are emerged as potential solution to this challenge. Here, microgels based on methacrylic anhydride and dopamine modified gelatin (GelMA-DA) were loaded with chondroitin sulfate (the obtained microgel named GC Ms) or bioactive glass (the obtained microgel named GB Ms), respectively. GC Ms and GB Ms showed good biocompatibility with BMSCs, which suggested by the adhesion and proliferation of BMSCs on their surfaces. Specially, GC Ms promoted chondrogenic differentiation of BMSCs, while GB Ms promoted osteogenic differentiation. Furthermore, the injectable GC Ms and GB Ms were assembled integrally by bottom-up in situ crosslinking to obtain modular microgel-based bioassembly scaffold (GC-GB/HM), which showed a distinct bilayer structure and good porous properties and swelling properties. Particularly, the results of in vivo and in vitro experiments showed that GC-GB/HM could simultaneously regulate the expression levels of chondrogenic- and osteogenesis-related genes and proteins. Therefore, modular microgel-based assembly scaffold in this work with the ability to promote bidirectional differentiation of BMSCs and has great potential for application in the minimally invasive treatment of osteochondral tissue defects. This article is protected by copyright. All rights reserved.

Keywords:  bidirectional differentiation; in situ crosslinking; modular microgel‐based bioassembly scaffold; osteochondral defects

DOI:  https://doi.org/10.1002/mabi.202400051
Int J Mol Sci. 2024 Apr 22. pii: 4557. [Epub ahead of print]25(8):

Syndecans, Exostosins and Sulfotransferases as Potential Synovial Inflammation Moderators in Patients with Hip Osteoarthritis.

Matko Rošin, Nela Kelam, Ivana Jurić, Anita Racetin, Marin Ogorevc, Brieuc Corre, Davor Čarić, Natalija Filipović, Katarina Vukojević.

  The gradual deterioration of articular cartilage was thought to be the central event in osteoarthritis (OA), but recent studies demonstrated the importance of low-grade synovitis in the progression of OA. The Syndecan (SDC) family of membrane proteoglycans is known to be involved in the regulation of inflammation, but there is limited evidence considering the role of syndecans in OA synovitis. Our study aimed to investigate the hip OA synovial membrane expression patterns of SDC1, SDC2 and SDC4, as well as exostosins and sulfotransferases (enzymes involved in the polymerisation and modification of syndecans' heparan sulphate chains). Synovial membrane samples of patients with OA (24) were divided into two groups according to their Krenn synovitis score severity. The immunohistochemical expressions of SDC1, SDC2, SDC4, EXT1, EXT2, NDST1 and NDST2 in synovial intima and subintima were then analysed and compared with the control group (patients with femoral neck fracture). According to our study, the immunoexpression of SDC1, NDST1 and EXT2 is significantly increased in the intimal cells of OA synovial membrane in patients with lower histological synovitis scores and SDC4 in patients with higher synovitis scores, in comparison with non-OA controls. The difference in the expression of SDC2 among the OA and non-OA groups was insignificant. SDC1, SDC4, NDST1 and EXT2 seem to be involved as inflammation moderators in low-grade OA synovitis and, therefore, should be further investigated as potential markers of disease progression and therapeutic goals.

Keywords:  exostosin; osteoarthritis; sulfotransferase; syndecan; synovial membrane

DOI:  https://doi.org/10.3390/ijms25084557
J Vis Exp. 2024 Apr 05.

Isolation of Adeno-associated Viral Vectors Through a Single-step and Semi-automated Heparin Affinity Chromatography Protocol.

Miguel M Lopes, Sara M Lopes, Rafael Baganha, Carina Henriques, Ana C Silva, Diana D Lobo, Luísa Cortes, Luís Pereira de Almeida, Rui Jorge Nobre.

Adeno-associated virus (AAV) has become an increasingly valuable vector for in vivo gene delivery and is currently undergoing human clinical trials. However, the commonly used methods to purify AAVs make use of cesium chloride or iodixanol density gradient ultracentrifugation. Despite their advantages, these methods are time-consuming, have limited scalability, and often result in vectors with low purity. To overcome these constraints, researchers are turning their attention to chromatography techniques. Here, we present an optimized heparin-based affinity chromatography protocol that serves as a universal capture step for the purification of AAVs. This method relies on the intrinsic affinity of AAV serotype 2 (AAV2) for heparan sulfate proteoglycans. Specifically, the protocol entails the co-transfection of plasmids encoding the desired AAV capsid proteins with those of AAV2, yielding mosaic AAV vectors that combine the properties of both parental serotypes. Briefly, after the lysis of producer cells, a mixture containing AAV particles is directly purified following an optimized single-step heparin affinity chromatography protocol using a standard fast protein liquid chromatography (FPLC) system. Purified AAV particles are subsequently concentrated and subjected to comprehensive characterization in terms of purity and biological activity. This protocol offers a simplified and scalable approach that can be performed without the need for ultracentrifugation and gradients, yielding clean and high viral titers.

DOI: https://doi.org/10.3791/66550
Medicina (Kaunas). 2024 Mar 26. pii: 539. [Epub ahead of print]60(4):

Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) Plays a Critical Role in Dextran Sulfate Sodium-Induced Murine Model of Ulcerative Colitis.

Akihito Nakajima, Tomoyoshi Shibuya, Takako Yao, Tsutomu Fujimura, Kimie Murayama, Ko Okumura, Akihito Nagahara, Yoshinori Seko.

  Oxidative stress is implicated in the pathogenesis of various acute disorders including ischemia/reperfusion injury, ultraviolet/radiation burn, as well as chronic disorders such as dyslipidemia, atherosclerosis, diabetes mellitus, chronic renal disease, and inflammatory bowel disease (IBD). However, the precise mechanism involved remains to be clarified. We formerly identified a novel apoptosis-inducing humoral protein, in a hypoxia/reoxygenation-conditioned medium of cardiac myocytes, which proved to be 69th tyrosine-sulfated eukaryotic translation initiation factor 5A (eIF5A). We named this novel tyrosine-sulfated secreted form of eIF5A Oxidative Stress-Responsive Apoptosis-Inducing Protein (ORAIP). To investigate the role of ORAIP in a dextran sulfate sodium (DSS)-induced murine model of ulcerative colitis (UC), we analyzed the effects of in vivo treatment with anti-ORAIP neutralizing monoclonal antibody (mAb) on the DSS-induced disease exacerbation. The body weight in anti-ORAIP mAb-treated group was significantly heavier than that in a mouse IgG-treated control group on day 8 of DSS-treatment ((85.21 ± 1.03%) vs. (77.38 ± 2.07%); (mean ± SE0, n = 5 each, p < 0.01, t-test). In vivo anti-ORAIP mAb-treatment also significantly suppressed the shortening of colon length as well as Disease Activity Index (DAI) score ((5.00 ± 0.44) vs. (8.20 ± 0.37); (mean ± SE), n = 5 each, p < 0.001, t-test) by suppressing inflammation of the rectal tissue and apoptosis of intestinal mucosal cells. These data reveal the pivotal role of ORAIP in DSS-induced oxidative stress involved in an animal model of UC.

Keywords:  Oxidative Stress-Responsive Apoptosis-Inducing Protein (ORAIP); apoptosis; dextran sulfate sodium (DSS); eukaryotic translation initiation factor 5A (eIF5A); ulcerative colitis (UC)

DOI:  https://doi.org/10.3390/medicina60040539
Chemosphere. 2024 Apr 18. pii: S0045-6535(24)00975-5. [Epub ahead of print]357 142082

Conjugated bisphenol S metabolites in human serum and whole blood.

Zhenling Fu, Hangbiao Jin, Weili Mao, Zefu Hu.

  Studies have shown that bisphenol S (BPS) is mainly present as its conjugated metabolites in human blood. However, the distribution of conjugated BPS metabolites in different human blood matrices has not been characterized. In this study, paired human serum and whole blood samples (n = 79) were collected from Chinese participants, and were measured for the occurrence of BPS and 4 BPS metabolites. BPS was detectable in 49% of human serum (<LOD-1.7 ng/mL) and 78% of whole blood (<LOD-2.1 ng/mL) samples. In both human serum and whole blood, BPS-sulfate (BPS-S; 74% and 86%, respectively) and BPS-glucuronide (BPS-G; 68% and 84%, respectively) had higher detection frequency than BPS. Consistently, BPS-S was the predominant BPS metabolite in human serum (mean 0.39 ng/mL) and whole blood (0.41 ng/mL), significantly higher than BPS-G (mean 0.13 and 0.13 ng/mL, respectively). This is contrary to the data from controlled oral exposure studies on model animals and humans, in which BPS-G was the dominant BPS metabolite in serum. BPS-S (mean ± SD, 0.99 ± 0.35) had the highest partitioning coefficient between human serum and whole blood, followed by BPS-G (0.89 ± 0.27) and BPS (0.81 ± 0.28), suggesting their preferential accumulation in the red blood cell fraction. These results represent the first human data on conjugated BPS metabolites in paired human serum and whole blood, which help to elucidate of the occurrence of conjugated BPS metabolites in humans.

Keywords:  BPS-G; BPS-S; Distribution; Serum; Whole blood

DOI:  https://doi.org/10.1016/j.chemosphere.2024.142082