bims-supasi Biomed News
on Sulfation pathways and signalling
Issue of 2023–11–05
seven papers selected by
Jonathan Wolf Mueller, University of Birmingham
  1. Potential Involvement of Sulfotransferase in the Mechanism of Lamotrigine-induced Skin Rash.
  2. Circulating Neuroactive Steroid Levels in a Patient With Schizophrenia Who Showed Periodic Catatonia.
  3. The novel HS-mimetic, Tet-29, regulates immune cell trafficking across barriers of the CNS during inflammation.
  4. Sulfated Polyglycerol-Modified Hydrogels for Binding HSV-1 and RSV.
  5. Glycosaminoglycan Replacement Therapy with Intravesical Instillations of Combined Hyaluronic Acid and Chondroitin Sulfate in Patients with Recurrent Cystitis, Post-radiation Cystitis and Bladder Pain Syndrome: A Narrative Review.
  6. High-resolution mass spectrometry imaging reveals skin lipid changes and the cholesterol sulfate cycle during keratinization.
  7. α-Tocopherol-loaded multi-layer nanoemulsion using chitosan, and dextran sulfate: Cellular uptake, antioxidant activity, and in vitro bioaccessibility.
  1. Chem Res Toxicol. 2023 Nov 03.
    Potential Involvement of Sulfotransferase in the Mechanism of Lamotrigine-induced Skin Rash.
    Yanshan Cao, Ahsan Bairam, Ming-Cheh Liu, Jack Uetrecht.
      The mechanism of drug-induced skin rash is not well understood. Circumstantial evidence suggests that the covalent binding of a reactive metabolite is involved in the mechanism of most idiosyncratic drug reactions. However, there is a limited quantity of drug metabolizing enzymes in the skin, except for sulfotransferases. It is possible that some drugs are metabolized to reactive sulfate metabolites that are responsible for skin rashes. For example, nevirapine-induced skin rash involves metabolism of nevirapine to 12-hydroxy-nevirapine, which is further metabolized by sulfotransferase in the skin to a reactive benzylic sulfate that covalently binds to proteins. The working hypothesis is that lamotrigine, valdecoxib, and sertraline skin rashes involve the formation of reactive sulfate in the skin. Lamotrigine-N-oxide, hydroxy-valdecoxib, and hydroxy-sertraline were tested as substrates with known human sulfotransferases. Hydroxy-valdecoxib and the benzylic alcohol metabolite of sertraline were not substrates for human sulfotransferases. Therefore, this pathway is presumably not involved in the mechanism by which they cause skin rashes. In contrast, lamotrigine-N-oxide is a substrate for several human sulfotransferases and the sulfate is chemically reactive. Furthermore, lamotrigine-N-sulfate not only alkylates proteins as we described previously but also forms the sulfate of tyrosine, suggesting another possible mechanism for protein modification. This study has further added to the understanding of the potential of the sulfotransferase pathways and protein sulfation to play a role in drug-induced skin rash.
    DOI:  https://doi.org/10.1021/acs.chemrestox.3c00187
  2. JCEM Case Rep. 2023 Jan;1(1): luad009
    Circulating Neuroactive Steroid Levels in a Patient With Schizophrenia Who Showed Periodic Catatonia.
    Katsumasa Muneoka, Yukihiko Shirayama, Hiroyuki Watanabe, Hiroshi Kimura.
      Catatonia is an abnormal psychological and behavioral state related to stress. The treatment strategy suggests the involvement of neuroactive steroids in its pathophysiology. We report a hospitalized patient with schizophrenia in whom a catatonic state occurred 7 times in 5.5 years. Blood levels of steroid hormones and adrenocorticotropic hormone (ACTH) were measured during the catatonic state and in the intervals between catatonic states (non-catatonic states). Cortisol and dehydroepiandrosterone sulfate (DHEAS) were significantly higher during catatonia than in the non-catatonic state. Cortisol significantly correlated with the ACTH level, whereas blood DHEAS and progesterone correlated only during the non-catatonic state. In addition, the cortisol to DHEAS ratios did not differ between catatonic and non-catatonic states. Although the correlating elevations of ACTH and cortisol implied activation of the hypothalamic-pituitary-adrenal axis (HPA-axis) in the catatonic state, DHEAS levels did not seem to increase in a manner dependent on the HPA-axis or the production of progesterone. The results suggest that the catatonic state was a neuroendocrinological state of HPA-axis activation with comparable increases in DHEAS levels.
    Keywords:  DHEAS; HPA-axis; catatonia; cortisol; neuroactive steroids; stress
    DOI:  https://doi.org/10.1210/jcemcr/luad009
  3. J Neuroinflammation. 2023 Nov 01. 20(1): 251
    The novel HS-mimetic, Tet-29, regulates immune cell trafficking across barriers of the CNS during inflammation.
    Tessa Peck, Connor Davis, Georgia Lenihan-Geels, Maddie Griffiths, Sam Spijkers-Shaw, Olga V Zubkova, Anne Camille La Flamme.
       BACKGROUND: Disruption of the extracellular matrix at the blood-brain barrier (BBB) underpins neuroinflammation in multiple sclerosis (MS). The degradation of extracellular matrix components, such as heparan sulfate (HS) proteoglycans, can be prevented by treatment with HS-mimetics through their ability to inhibit the enzyme heparanase. The heparanase-inhibiting ability of our small dendrimer HS-mimetics has been investigated in various cancers but their efficacy in neuroinflammatory models has not been evaluated. This study investigates the use of a novel HS-mimetic, Tet-29, in an animal model of MS.
    METHODS: Neuroinflammation was induced in mice by experimental autoimmune encephalomyelitis, a murine model of MS. In addition, the BBB and choroid plexus were modelled in vitro using transmigration assays, and migration of immune cells in vivo and in vitro was quantified by flow cytometry.
    RESULTS: We found that Tet-29 significantly reduced lymphocyte accumulation in the central nervous system which, in turn, decreased disease severity in experimental autoimmune encephalomyelitis. The disease-modifying effect of Tet-29 was associated with a rescue of BBB integrity, as well as inhibition of activated lymphocyte migration across the BBB and choroid plexus in transwell models. In contrast, Tet-29 did not significantly impair in vivo or in vitro steady state-trafficking under homeostatic conditions.
    CONCLUSIONS: Together these results suggest that Tet-29 modulates, rather than abolishes, trafficking across central nervous system barriers.
    Keywords:  BBB; Choroid plexus; EAE; HS; HSPG; MS; Migration; Neuroinflammation; Tet-29
    DOI:  https://doi.org/10.1186/s12974-023-02925-4
  4. ACS Appl Mater Interfaces. 2023 Oct 30.
    Sulfated Polyglycerol-Modified Hydrogels for Binding HSV-1 and RSV.
    Jun Feng, Chuanxiong Nie, Enyu Xie, Boonya Thongrom, Valentin Reiter-Scherer, Stephan Block, Andreas Herrmann, Elisa Quaas, Christian Sieben, Rainer Haag.
      Heparan sulfate (HS) is a highly sulfated polysaccharide on the surface of mammalian cells and in the extracellular matrix and has been found to be important for virus binding and infection. In this work, we designed synthetic hydrogels with viral binding and deactivation activities through the postfunctionalization of an HS-mimicking polyelectrolyte and alkyl chains. Three polyglycerol-based hydrogels were prepared as substrates and postfunctionalized by sulfated linear polyglycerol (lPGS) via thiol-ene click reaction. The viral binding properties were studied using herpes simplex virus type 1 (HSV-1) and respiratory syncytial virus (RSV). The effect of hydrogel types and molecular weight (Mw) of conjugated lPGS on viral binding properties was also assessed, and promising binding activities were observed in all lPGS-functionalized samples. Further coupling of 11 carbons long alkyl chains to the hydrogel revealed virucidal properties caused by destruction of the viral envelope, as shown by atomic force microscopy (AFM) imaging.
    Keywords:  hydrogels; postfunctionalization; sulfated polyglycerol; viral binding; virucidal
    DOI:  https://doi.org/10.1021/acsami.3c09553
  5. Pain Ther. 2023 Nov 02.
    Glycosaminoglycan Replacement Therapy with Intravesical Instillations of Combined Hyaluronic Acid and Chondroitin Sulfate in Patients with Recurrent Cystitis, Post-radiation Cystitis and Bladder Pain Syndrome: A Narrative Review.
    Sławomir Poletajew, Magdalena M Brzózka, Wojciech Krajewski, Hubert Kamecki, Łukasz Nyk, Piotr Kryst.
      Defects in the glycosaminoglycan layer (GAG) of the bladder mucosa have been identified as a significant contributor to the pathogenesis and clinical progression of chronic inflammatory diseases of the bladder, such as post-radiation cystitis, bladder pain syndrome and recurrent urinary tract infections. This narrative review aims to explore the contemporary evidence on the role of GAG reconstitution with intravesical installations of hyaluronic acid and chondroitin sulfate in the management of those patients, with a goal to provide valuable insights for clinical practice. The reviewed studies consistently demonstrate that GAG reconstitution can result in varying degrees of clinical improvement in patients with post-radiation cystitis, bladder pain syndrome and recurrent urinary tract infections, and is associated with a very favorable safety profile. While the available evidence is growing, its level is still limited, mainly by relatively low number of randomized controlled trials, with small sample sizes. Further research with larger, well-designed trials is needed to solidify the findings and optimize the clinical application of GAG reconstitution.
    Keywords:  Bladder pain syndrome; Cystitis; Glycosaminoglycans; Interstitial cystitis; Intravesical instillation; Urinary tract infections
    DOI:  https://doi.org/10.1007/s40122-023-00559-1
  6. J Eur Acad Dermatol Venereol. 2023 Nov 01.
    High-resolution mass spectrometry imaging reveals skin lipid changes and the cholesterol sulfate cycle during keratinization.
    S Tokoro, T Ogawa, S Hayashi, K Igawa.
      
    Keywords:  MALDI; ceramide; cholesterol; imaging mass spectrometry; phospholipid; skin lipids
    DOI:  https://doi.org/10.1111/jdv.19621
  7. Int J Biol Macromol. 2023 Oct 31. pii: S0141-8130(23)04718-9. [Epub ahead of print] 127819
    α-Tocopherol-loaded multi-layer nanoemulsion using chitosan, and dextran sulfate: Cellular uptake, antioxidant activity, and in vitro bioaccessibility.
    Seong Eun Hong, Ji-Soo Lee, Hyeon Gyu Lee.
      The potential of multi-layer nanoemulsions (NEs) for improving the cellular uptake, antioxidant activity, and in vitro bioaccessibility of α-tocopherol (ToC) was examined. ToC-loaded multi-layer NEs were prepared using lecithin (primary-NE, P-NE), chitosan (secondary-NE, S-NE), and dextran sulfate (tertiary-NE, T-NE) as wall materials. The bioadhesion, cellular permeability, and uptake of the multi-layer NEs were significantly higher than that of the free coumarin 6 (C6). As a result of cellular uptake, the mean fluorescence intensity of T-NE was the highest among the three types of multi-layer NEs and was 9.8-fold higher than that of free C6. The cellular antioxidant abilities of P-NE, S-NE, and T-NE were 40, 45, and 50 %, respectively. Multi-layer nanoencapsulation sustains free fatty acid release after digestion. Moreover, the bioavailability of T-NE exhibited a two-fold increase compared with that of the free ToC. These findings indicate that by multi-layer NEs using a layer-by-layer method, the cellular uptake, in vitro bioaccessibility, and antioxidant activity of ToC can be improved. Furthermore, T-NEs using chitosan and dextran sulfate can potentially enhance the cellular uptake, in vitro bioaccessibility, and antioxidant activity of ToC. These findings would facilitate the application of multi-layer NEs for lipophilic bioactive compounds using biopolymers.
    Keywords:  Antioxidant activity; Cellular uptake; Chitosan; Dextran sulfate; In vitro bioaccessibility; Multi-layer nanoemulsions
    DOI:  https://doi.org/10.1016/j.ijbiomac.2023.127819
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