bims-supasi Biomed News
on Sulfation pathways and signalling
Issue of 2023–05–14
nine papers selected by
Jonathan Wolf Mueller, University of Birmingham
  1. Structural requirements of Holothuria floridana fucosylated chondroitin sulfate oligosaccharides in anti-SARS-CoV-2 and anticoagulant activities.
  2. Enzymatic sulfation of coelenterazine by human cytosolic aryl sulfotransferase SULT1A1: identification of coelenterazine C2-benzyl monosulfate by LC/ESI-TOF-MS.
  3. The effect of chondroitin sulfate concentration and matrix stiffness on chondrogenic differentiation of mesenchymal stem cells.
  4. Enhancing effects of immobilized chondroitin sulfate on odontogenic differentiation of dental pulp stem cells and reparative dentin formation.
  5. Anti-aging biomaterial sturgeon chondroitin sulfate upregulating anti-oxidant and SIRT-1/c-fos gene expression to reprogram stem cell senescence and prolong longevity.
  6. Blended Heparin: A new Perspective to Guarantee the Supply of a Life-Saving Drug?
  7. Hemolysis is associated with altered heparan sulfate of the endothelial glycocalyx and with local complement activation in thrombotic microangiopathies.
  8. Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival.
  9. Activatable Near-Infrared Fluorescent and Photoacoustic Dual-Modal Probe for Highly Sensitive Imaging of Sulfatase In Vivo.
  1. PLoS One. 2023 ;18(5): e0285539
    Structural requirements of Holothuria floridana fucosylated chondroitin sulfate oligosaccharides in anti-SARS-CoV-2 and anticoagulant activities.
    Marwa Farrag, Rohini Dwivedi, Poonam Sharma, Deepak Kumar, Ritesh Tandon, Vitor H Pomin.
      Fucosylated chondroitin sulfate (FucCS) is a unique glycosaminoglycan found primarily in sea cucumbers. This marine sulfated glycan is composed of a chondroitin sulfate backbone decorated with fucosyl branches attached to the glucuronic acid. FucCS exhibits potential biological actions including inhibition of blood clotting and severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. These biological effects have been attributed to certain structural features, including molecular weight (MW), and/or those related to fucosylation, such as degrees of fucosyl branches, sulfation patterns and contents. In a previous work, we were able to generate oligosaccharides of the FucCS from Pentacta pygmaea (PpFucCS) with reduced anticoagulant effect but still retaining significant anti-SARS-CoV-2 activity against the delta strain. In this work, we extended our study to the FucCS extracted from the species Holothuria floridana (HfFucCS). The oligosaccharides were prepared by free-radical depolymerization of the HfFucCS via copper-based Fenton reaction. One-dimensional 1H nuclear magnetic resonance spectra were employed in structural analysis. Activated partial thromboplastin time and assays using protease (factors Xa and IIa) and serine protease inhibitors (antithrombin, and heparin cofactor II) in the presence of the sulfated carbohydrates were used to monitor anticoagulation. Anti-SARS-CoV-2 effects were measured using the concentration-response inhibitory curves of HEK-293T-human angiotensin-converting enzyme-2 cells infected with a baculovirus pseudotyped SARS-CoV-2 wild-type and delta variant spike (S)-proteins. Furthermore, the cytotoxicity of native HfFucCS and its oligosaccharides was also assessed. Like for PpFucCS, we were able to generate a HfFucCS oligosaccharide fraction devoid of high anticoagulant effect but still retaining considerable anti-SARS-CoV-2 actions against both variants. However, compared to the oligosaccharide fraction derived from PpFucCS, the average MW of the shortest active HfFucCS oligosaccharide fraction was significantly lower. This finding suggests that the specific structural feature in HfFucCS, the branching 3,4-di-sulfated fucoses together with the backbone 4,6-di-sulfated N-acetylgalactosamines, is relevant for the anti-SARS-CoV-2 activity of FucCS molecules.
    DOI:  https://doi.org/10.1371/journal.pone.0285539
  2. Biochem Biophys Res Commun. 2023 May 02. pii: S0006-291X(23)00563-6. [Epub ahead of print]665 133-140
    Enzymatic sulfation of coelenterazine by human cytosolic aryl sulfotransferase SULT1A1: identification of coelenterazine C2-benzyl monosulfate by LC/ESI-TOF-MS.
    Satoshi Inouye, Kazuo Matsuda, Mitsuhiro Nakamura.
      Coelenterazine (CTZ) is known as a light-emitting source for the bioluminescence reaction in marine organisms. CTZ has two phenolic hydroxy groups at the C2-benzyl and C6-phenyl positions, and a keto-enol type hydroxy group at the C3-position in the core structure of imidazopyrazinone (= 3,7-dihydroimidazopyrazin-3-one). These hydroxy groups in CTZ could be sulfated by sulfotransferase(s), and the sulfates of Watasenia luciferin (CTZ disulfate at the C2- and C6-positions) and Renilla pre-luciferin (CTZ 3-enol sulfate) have been identified in marine organisms. To characterize the sulfation process of CTZ, human cytosolic aryl sulfotransferase SULT1A1 (SUTase) was used as a model enzyme. The sulfated products catalyzed by SUTase with 3'-phosphoadenosine 5'-phosphosulfate (PAPS) were analyzed by LC/ESI-TOF-MS. The product was the monosulfate of CTZ and identified as the C2-benzyl sulfate of CTZ (CTZ C2-benzyl monosulfate), but CTZ disulfate, CTZ 3-enol sulfate, and CTZ C6-phenyl monosulfate were not detected. The non-enzymatic oxidation products of dehydrocoelenterazine (dCTZ, dehydrogenated derivative of CTZ), coelenteramide (CTMD), and coelenteramine (CTM) from CTZ were also identified as their monosulfates.
    Keywords:  Coelenteramide; Coelenteramine; Dehydrocoelenterazine; Renilla pre-luciferin; Sulfation; Watasenia luciferin
    DOI:  https://doi.org/10.1016/j.bbrc.2023.05.007
  3. Biomater Sci. 2023 May 09.
    The effect of chondroitin sulfate concentration and matrix stiffness on chondrogenic differentiation of mesenchymal stem cells.
    Chengchong Ai, Ling Liu, Kallista Wong, Xuan Hao Tan, James C H Goh.
      Chondroitin sulfate (CS), a glycosaminoglycan of native cartilage, has shown its potential in promoting chondrogenesis of mesenchymal stem cells (MSCs), whereas the effect of matrix stiffness in a CS-containing 3D environment on chondrogenesis is still poorly understood. Herein, this study aimed at assessing the effect of CS concentration and stiffness of CS-containing hydrogels on the chondrogenesis of MSCs. Hydrogels composed of 6% (w/v) gelatin methacryloyl (GelMA) and three concentrations, i.e., 4%, 6%, or 10% (w/v), of methacrylated chondroitin sulfate (CSMA) were prepared. The hydrogels of each composition were prepared with two stiffness values (33.36 ± 8.25 kPa vs. 8.42 ± 2.83 kPa). Physical characterization showed similar microporous structures among the six groups, higher swelling ratios and faster degradation in the soft hydrogel groups. MSCs were encapsulated in the six groups of hydrogels and they underwent 28-day chondrogenic differentiation. The cell viability in each group on day 1 was similar and most cells exhibited a round shape without spreading. Afterwards, cellular protrusions in soft hydrogels remained filopodium-like from day 14 to day 28, while most protrusions were lamellipodium-like in stiff hydrogels on day 14 and then transformed into a spherical shape on day 28. The expression of chondrogenic markers analysed by real-time qPCR and immunohistochemical staining demonstrated that the optimal CS concentration for chondrogenesis was 6% (w/v) regardless of the stiffness of hydrogels. In addition, with the same CSMA concentration, the trend was observed that the stiff hydrogels supported superior chondrogenesis of MSCs compared to the soft hydrogel. To summarize, this study presents an advancement in the optimization of CSMA concentration and stiffness of hydrogels for chondrogenesis. In the CSMA/GelMA hydrogel, 6% (w/v) CSMA with an initial Young's modulus around 33 kPa was recommended for cartilage tissue engineering.
    DOI:  https://doi.org/10.1039/d2bm01980a
  4. J Endod. 2023 May 05. pii: S0099-2399(23)00240-6. [Epub ahead of print]
    Enhancing effects of immobilized chondroitin sulfate on odontogenic differentiation of dental pulp stem cells and reparative dentin formation.
    Ruoman Xu, Ziyu Zhou, Danle Lin, Lingling Yuan, Siyu Wang, Meng Xu, Yanan Chen, Xiaoli Hu.
       OBJECTIVES: Chondroitin sulfate (CS) is a major proteoglycan involved in the mineralization of the organic matrix of dentin. In this study, the roles of CS immobilized in crosslinked collagen I hydrogels (CS-Col I) on odontogenic differentiation of dental pulp stem cells (DPSCs) and reparative dentin formation were investigated.
    METHODS: Different concentrations of CS were incorporated into the genipin- crosslinked Col I hydrogels (CS-0.05, CS-0.1, and CS-0.2 respectively). The influences of CS on proliferation and odontogenic differentiation of DPSCs were investigated. Finally, the effect of the functionalized hydrogel on the formation of reparative dentin was analyzed in a rat pulp capping model in vivo.
    RESULTS: CS improved the proliferation of DPSCs seeded on the hydrogels (p<0.05). CS also enhanced the mineralization activities and increased the expression levels of the odontogenic related proteins of DPSCs on day 7 and day 14 (p<0.05). In vivo, CS-0.1 hydrogel induced reparative dentin formation with higher quality compared to mineral trioxide aggregate (MTA).
    CONCLUSION: CS immobilized in Col I hydrogels could induce odontogenic differentiation of DPSCs in vitro and promote homogeneous mineralized barrier formation in vivo. CS-Col I hydrogel has the potential for reparative dentin formation of high quality in direct pulp capping.
    Keywords:  chondroitin sulfate; dental pulp stem cells; immobilization; odontogenic differentiation; reparative dentin formation
    DOI:  https://doi.org/10.1016/j.joen.2023.04.012
  5. Biomater Sci. 2023 May 09.
    Anti-aging biomaterial sturgeon chondroitin sulfate upregulating anti-oxidant and SIRT-1/c-fos gene expression to reprogram stem cell senescence and prolong longevity.
    Abhinay Kumar Singh, Bou-Yue Peng, Shaw-Ting Chien, Chun-Hao Chan, Yue-Hua Deng, Hsiao-Yu Pai, Hong-Jian Wei, Ming-Fu Wang, Shwu-Huey Wang, Chia-Yu Wu, Win-Ping Deng.
      Aging involves tissue and cell potential dysfunction characterized by stem cell senescence and extracellular matrix microenvironment (ECM) alteration. Chondroitin sulfate (CS), found in the ECM of normal cells and tissues, aids in maintaining tissue homeostasis. Here, CS-derived biomaterial (CSDB) from sturgeon is extracted to investigate its antiaging effect in senescence-accelerated mouse prone-8 (SAMP8) mice and elucidate the underlying mechanism of its action. Although CSDB has been widely extracted from different sources and used as a scaffold, hydrogel, or drug carrier for the treatment of various pathological diseases, CSDB has not yet been used as a biomaterial for the amelioration of senescence and aging features. In this study, the extracted sturgeon CSDB showed a low molecular weight and comprised 59% 4-sulfated CS and 23% 6-sulfated CS. In an in vitro study, sturgeon CSDB promoted cell proliferation and reduced oxidative stress to inhibit stem cell senescence. In an ex vivo study, after oral CSDB treatment of SAMP8 mice, the stem cells were extracted to analyze the p16Ink4a and p19Arf gene-related pathways, which were inhibited and then SIRT-1 gene expression was upregulated to reprogram stem cells from a senescence state for retarding aging. In an in vivo study, CSDB also restored the aging-phenotype-related bone mineral density and skin morphology to prolong longevity. Thus, sturgeon CSDB may be useful for prolonging healthy longevity as an anti-aging drug.
    DOI:  https://doi.org/10.1039/d2bm01997c
  6. Clin Appl Thromb Hemost. 2023 Jan-Dec;29:29 10760296231173965
    Blended Heparin: A new Perspective to Guarantee the Supply of a Life-Saving Drug?
    Marco Guerrini.
      The risk of heparin shortage opens up the possibility of diversifying the sources of heparin by introducing products of other animal/organ origins. In addition to bovine heparin, already used in the past in the United States and Europe, ovine heparin can become another alternative to the widely used pig source. It is therefore appropriate to compare the anticoagulant activity of pig heparin with that of products of different animal origin and to verify whether blended heparin obtained from different sources can give rise to anticoagulant effects comparable to those of heparin of a single origin.
    Keywords:  heparin; heparin origin; heparin shortage; low molecular weight heparin
    DOI:  https://doi.org/10.1177/10760296231173965
  7. Kidney Int. 2023 May 08. pii: S0085-2538(23)00327-7. [Epub ahead of print]
    Hemolysis is associated with altered heparan sulfate of the endothelial glycocalyx and with local complement activation in thrombotic microangiopathies.
    Timothée Laboux, Mehdi Maanaoui, Fabrice Allain, Eric Boulanger, Agnès Denys, Jean-Baptiste Gibier, François Glowacki, Gaëlle Grolaux, Anne Grunenwald, Mike Howsam, Steve Lancel, Céline Lebas, Benjamin Lopez, Lubka Roumenina, François Provôt, Viviane Gnemmi, Marie Frimat.
      
    Keywords:  complement system; glomerular endothelial cell; glycocalyx; heme; hemolytic uremic syndrome; heparan sulfate; thrombotic microangiopathy
    DOI:  https://doi.org/10.1016/j.kint.2023.03.039
  8. Proc Natl Acad Sci U S A. 2023 05 16. 120(20): e2214853120
    Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival.
    Juliana Poças, Catarina Marques, Catarina Gomes, Andreia Hanada Otake, Filipe Pinto, Mariana Ferreira, Tiago Silva, Isabel Faria-Ramos, Rita Matos, Ana Raquel Ribeiro, Emanuel Senra, Bruno Cavadas, Sílvia Batista, Joana Maia, Joana A Macedo, Luís Lima, Luís Pedro Afonso, José Alexandre Ferreira, Lúcio Lara Santos, António Polónia, Hugo Osório, Mattias Belting, Celso A Reis, Bruno Costa-Silva, Ana Magalhães.
      Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane proteoglycan, is highly expressed in intestinal subtype gastric tumors and that this signature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.
    Keywords:  cancer cell invasion; extracellular vesicles; gastric cancer; heparan sulfate proteoglycans; syndecan-4
    DOI:  https://doi.org/10.1073/pnas.2214853120
  9. ACS Sens. 2023 May 11.
    Activatable Near-Infrared Fluorescent and Photoacoustic Dual-Modal Probe for Highly Sensitive Imaging of Sulfatase In Vivo.
    Mei-Hao Xiang, Zhi-Yuan Jiang, Wen-Long Zhao, Ensheng Zhang, Lian Xia, Rong-Mei Kong, Yan Zhao, Weiheng Kong, Xianjun Liu, Fengli Qu, Weihong Tan.
      Sulfatase is an important biomarker closely associated with various diseases. However, the state-of-the-art sulfatase probes are plagued with a short absorption/emission wavelength and limited sensitivity. Developing highly sensitive fluorescent probes for in vivo imaging of sulfatase remains a grand challenge. Herein, for the first time, an activatable near-infrared fluorescence/photoacoustic (NIRF/PA) dual-modal probe (Hcy-SA) for visualizing sulfatase activity in living cells and animals is developed. Hcy-SA is composed of a sulfate ester moiety as the recognition unit and a NIR fluorophore hemicyanine (Hcy-OH) as the NIRF/PA reporter. The designed probe exhibits a rapid response, excellent sensitivity, and high specificity for sulfatase detection in vitro. More importantly, cells and in vivo experiments confirm that Hcy-SA can be successfully applied for PA/NIRF dual-modal imaging of sulfatase activity in living sulfatase-overexpressed tumor cells and tumor-bearing animals. This probe can serve as a promising tool for sulfatase-related pathological research and cancer diagnosis.
    Keywords:  activatable probe; dual-modal imaging; highly sensitive detection; living tumor; sulfatase
    DOI:  https://doi.org/10.1021/acssensors.3c00201
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