bims-supasi Biomed News
on Sulfation pathways and signalling
Issue of 2022‒02‒20
five papers selected by
Jonathan Wolf Mueller
University of Birmingham

  1. J Vet Med Sci. 2022 Feb 16.
      Myogenesis, the formation of muscle fibers, is affected by certain glycoproteins, including chondroitin sulfate (CS), which are involved in various cellular processes. We aimed to investigate the mechanism underlying CS-E-induced suppression of myotube formation using the myoblast cell line C2C12. Differentiated cells treated with 0.1 mg/ml CS-E for nine days showed multinucleated and rounded myotubes with myosin heavy chain positivity. No difference was found between the CS-E-treated group with rounded myotubes and CS (-) controls with elongated myotubes in the levels of phospho-cofilin, a protein involved in the dynamics of actin cytoskeleton. Interestingly, N-cadherin, which is involved in the gene expression of myoblast fusion factors (myomaker and myomixer), was significantly downregulated at both the mRNA and protein levels following CS-E treatment. These results suggest that N-cadherin downregulation is one of the mechanisms underlying the CS-E-induced suppression of myotube formation.
    Keywords:  N-cadherin; chondroitin sulfate E; myoblast; myotube
  2. Molecules. 2022 Jan 20. pii: 654. [Epub ahead of print]27(3):
      During liver fibrogenesis, there is an imbalance between regeneration and wound healing. The current treatment is the withdrawal of the causing agent; thus, investigation of new and effective treatments is important. Studies have highlighted the action of chondroitin sulfate (CS) in different cells; thus, our aim was to analyze its effect on an experimental model of bile duct ligation (BDL). Adult Wistar rats were subjected to BDL and treated with CS for 7, 14, 21, or 28 days intraperitoneally. We performed histomorphometric analyses on Picrosirius-stained liver sections. Cell death was analyzed according to caspase-3 and cathepsin B activity and using a TUNEL assay. Regeneration was evaluated using PCNA immunohistochemistry. BDL led to increased collagen content with corresponding decreased liver parenchyma. CS treatment reduced total collagen and increased parenchyma content after 21 and 28 days. The treatment also promoted changes in the hepatic collagen type III/I ratio. Furthermore, it was observed that CS treatment reduced caspase-3 activity and the percentage of TUNEL-positive cells after 14 days and cathepsin B activity only after 28 days. The regeneration increased after 14, 21, and 28 days of CS treatment. In conclusion, our study showed a promising hepatoprotective action of CS in fibrogenesis induced by BDL.
    Keywords:  apoptosis; chondroitin; fibrosis; inflammation; liver; regeneration
  3. Carbohydr Polym. 2022 May 01. pii: S0144-8617(21)01441-7. [Epub ahead of print]283 119054
      Sulfated glycosaminoglycan (GAG) analogues derived from plant, algae or microbial sourced polysaccharides are highly interesting in order to gain bioactivities similar to sulfated GAGs but without risks and concerns derived from their typical animal sources. Since the exopolysaccharide (EPS) produced by the bacterium Vibrio diabolicus HE800 strain from deep-sea hydrothermal vents is known to have a GAG-like structure with a linear backbone composed of unsulfated aminosugar and uronic acid monomers, its structural modification through four different semi-synthetic sulfation strategies has been performed. A detailed structural characterization of the six obtained polysaccharides revealed that three different sulfation patterns (per-O-sulfation, a single N-sulfation and a selective primary hydroxyls sulfation) were achieved, with molecular weights ranging from 5 to 40 kDa. A Surface Plasmonic Resonance (SPR) investigation of the affinity between such polysaccharides and a set of growth factors revealed that binding strength is primarily depending on polysaccharide sulfation degree.
    Keywords:  Exopolysaccharides; Glycosaminoglycans; Growth factors; Semi-synthesis; Sulfation
  4. J Oleo Sci. 2022 Feb 11.
      Liposomes are widely used as carrier system for bioactive ingredients and usually need to be stabilized by cholesterol. However, the relationship between cholesterol intake and human health has been controversial. The objective of this study was to develop novel multifunctional nanoliposomes stabilized by sea cucumber sulfated sterols via the thin-film hydration method. The liposomes obtained from this study were obviously stable for more than 27 days at 4°C. Astaxanthin was successfully encapsulated by a novel uniform liposome prepared with a mass ratio of egg yolk lecithin to sea cucumber sulfated sterols at 3:1. The mean particle size was 109.53±0.30 nm with 0.241±0.005 polydispersity index and zeta potential value of -21.13±1.01 mV. Astaxanthin-loaded liposome stabilized by sea cucumber sulfated sterols exhibited significantly higher antioxidant activities in terms of DPPH radical-scavenging activity and reducing power than the mixture of astaxanthin and blank sea cucumber sulfated sterols liposome during storage of 6 and 12 days, respectively. The in vivo digestion and absorption results showed that the bioavailability of dietary astaxanthin encapsulated in liposomes could significantly be improved. Being an efficient carrier with multi-functions, the novel liposome stabilized by sea cucumber sulfated sterols had great potential in functional food development and biomedical applications.
    Keywords:  astaxanthin; bioavailability; cholesterol; liposome; sea cucumber sulfated sterols
  5. Clin Drug Investig. 2022 Feb 18.
      BACKGROUND AND OBJECTIVES: Mycophenolic acid (MPA) is a commonly prescribed life-long immunosuppressant for kidney transplant recipients. The frequently observed large variations in MPA plasma exposure may lead to severe adverse outcomes; therefore, characterizations of contributing factors can potentially improve the precision dosing of MPA. Our group recently reported the potent inhibitory effects of p-cresol (a protein-bound uremic toxin that can be accumulated in kidney transplant patients) on the hepatic metabolism of MPA in human in vitro models. Based on these data, the hypothesis for this clinical investigation was that a direct correlation between p-cresol and MPA plasma exposure should be evident in adult kidney transplant recipients.METHODS: Using a prospective and observational approach, adult kidney transplant recipients within the first year after transplant on oral mycophenolate mofetil (with tacrolimus ± prednisone) were screened for recruitment. The exclusion criteria were cold ischemia time > 30 h, malignancy, pregnancy, severe renal dysfunction (i.e., estimated glomerular filtration rate, eGFR, < 10 mL/min/1.73 m2), active graft rejection, or MPA intolerance. Patients' demographic and biochemistry data were collected. Total and free plasma concentrations of MPA, MPA glucuronide (MPAG), and total p-cresol sulfate (the predominant, quantifiable form of p-cresol in the plasma) were quantified using validated assays. Correlational and categorical analyses were performed using GraphPad Prism.
    RESULTS: Forty patients (11 females) were included: donor type (living/deceased: 20/20), induction regimen (basiliximab/thymoglobulin/basiliximab followed by thymoglobulin: 35/3/2), post-transplant time (74 ± 60 days, mean ± standard deviation), age (53.7 ± 12.4 years), bodyweight (79.8 ± 18.5 kg), eGFR (51.9 ± 18.0 mL/min/1.73 m2), serum albumin (3.6 ± 0.5 g/dL), prednisone dose (18.5 ± 13.2 mg, n = 33), and tacrolimus trough concentration (9.4 ± 2.4 µg/L). Based on Spearman analysis, significant control correlations supporting the validity of our dataset were observed between total MPA trough concentration (C0) and total MPAG C0 (correlation coefficient [R] = 0.39), ratio of total MPAG C0-to-total MPA C0 and post-transplant time (R = - 0.56), total MPAG C0 and eGFR (R = - 0.35), and p-cresol sulfate concentration and eGFR (R = - 0.70). Our primary analysis indicated the novel observation that total MPA C0 (R = 0.39), daily dose-normalized total MPA C0 (R = 0.32), and bodyweight-normalized total MPA C0 (R = 0.32) were significantly correlated with plasma p-cresol sulfate concentrations. Consistently, patients categorized with elevated p-cresol sulfate concentrations (i.e., ≥ median of 3.2 µg/mL) also exhibited increased total MPA C0 (by 57 % vs those below median), daily dose-normalized total MPA C0 (by 89 %), and bodyweight-normalized total MPA C0 (by 62 %). Our secondary analyses with MPA metabolites, unbound concentrations, free fractions, and MPA metabolite ratios supported additional potential interacting mechanisms.
    CONCLUSION: We have identified a novel, positive association between p-cresol sulfate exposure and total MPA C0 in adult kidney transplant recipients, which is supported by published mechanistic in vitro data. Our findings confirm a potential role of p-cresol as a significant clinical variable affecting the pharmacokinetics of MPA. These data also provide the justifications for conducting subsequent full-scale pharmacokinetic-pharmacodynamic studies to further characterize the cause-effect relationships of this interaction, which could also rule out potential confounding variables not adequately controlled in this correlational study.