bims-supasi 2025-04-27 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2025–04–27
thirteen papers selected by
Jonathan Wolf Mueller, University of Birmingham

Untangling Heparan Sulfate 3-O-Sulfation Using a Novel Offline Cationic-Peptide Affinity Enrichment, Followed by HILIC-cIM-MS.
Myostatin Exacerbates Endothelial Dysfunction Induced by Uremic Toxin Indoxyl Sulfate and Is Associated with Hemodialysis Arteriovenous Access Complications.
Herpes simplex virus 1 glycoprotein C promotes virus penetration from endosomes during entry, independent of interaction with heparan sulfate.
Ultrasound-assisted extraction, purification, sulfation of Perilla leaves polysaccharide and hypoglycemic and hypolipidemic activities.
Aggrecan immobilizes to perineuronal nets through hyaluronan-dependent and independent binding activities.
Sulfated modification of polysaccharides from Sophora flavescens: Impact on antioxidant, antitumor, and immunomodulatory activities.
Amphiphilic Glycoprobes for Cell Surface Engineering and Drug Delivery.
Early warning value of multiple serum indicators combined with ultrasound detection in girls with central precocious puberty.
Age and BMI-related changes in hormonal profile in women with polycystic ovary syndrome (PCOS): Association with infertility.
Long-term safety of '4-hour' hemoadsorption combined with hemodialysis (HAHD) in maintenance hemodialysis patients: A multicenter prospective cohort study.
Steroids Static Postural Balance Changes After Exercise Intervention Correlate with Steroidome in Elderly Female.
Overexpression of Syndecan-4 inhibits myogenesis by regulating the expression of myogenic regulatory factors.
Rational Design and Engineering of 3-O-Sulfotransferase 1 Based on Enzyme Affinity for Improved Enzymatic Heparin Preparation.

Anal Chem. 2025 Apr 20.

Untangling Heparan Sulfate 3-O-Sulfation Using a Novel Offline Cationic-Peptide Affinity Enrichment, Followed by HILIC-cIM-MS.

Elias Mernie, Gustavo J Cavallero, Chaoshuang Xia, Cheng Lin, Joseph Zaia.

Heparan sulfate (HS) is a linear polysaccharide that modifies proteoglycans. HS biosynthesis is regulated in a spatiotemporal manner, leading to structural diversity, including variable de-N-acetylation, N-sulfation, hexuronic acid C5 epimerization, and 2-O-, 6-O-, and 3-O-sulfation. Specific structural motifs within HS chains offer multiple specific binding sites for protein partners. The occurrence of HS 3-O-sulfation is relatively rare; however, there is accumulating evidence identifying the importance of this low-abundance modification in many different biological scenarios. Initially described as a key determinant for binding and activation of antithrombin, and more recently, as a coreceptor for viral infection, 3-O-sulfation has been associated with the progression of several neurological disorders. The analytical ability to study the biological roles of HS 3-O-sulfation is hindered by its low abundance within HS chains and the complex isomeric nature of highly sulfated HS, which places a burden on the tandem mass spectrometry step for assigning saccharide structures. In this context, we developed a specific cationic peptide-affinity method for 3-O-sulfation enrichment, followed by hydrophilic interaction liquid chromatography-cyclic ion mobility mass spectrometry analysis (HILIC-cIM-MS). We first demonstrated the high specificity of this approach to capture 3-O-sulfated HS oligosaccharides within complex mixtures. We next showed the influence of specific sulfate and epimerization patterns on HS binding selectivity. Finally, we used the enrichment strategy to analyze 3-O-sulfated HS oligosaccharides from heparin lyase III-digested HS from porcine intestinal mucosa (HSPIM). We concluded that this enrichment method was useful to guide new studies to reveal the biological roles of 3-O-sulfation and to elucidate new HS structural motifs.

DOI: https://doi.org/10.1021/acs.analchem.4c05019
Toxins (Basel). 2025 Mar 22. pii: 159. [Epub ahead of print]17(4):

Myostatin Exacerbates Endothelial Dysfunction Induced by Uremic Toxin Indoxyl Sulfate and Is Associated with Hemodialysis Arteriovenous Access Complications.

Justine Solignac, Laetitia Dou, Rania Chermiti, Nathalie McKay, Philippe Giaime, Nathalie Pedinielli, Hamza Benjelloun, Guillaume Lano, Julien Mancini, Stéphane Burtey, Stanislas Bataille.

  Hemodialysis patients exhibit endothelial dysfunction, contributing to elevated cardiovascular risk and complications of the arteriovenous access. These patients have elevated serum levels of myostatin, a member of the transforming growth factor-β (TGFβ) superfamily, and of the uremic toxin indoxyl sulfate, both of which are pro-inflammatory towards endothelial cells. We hypothesized that myostatin and indoxyl sulfate may synergistically induce endothelial dysfunction by impairing endothelial proliferation and promoting a pro-inflammatory phenotype. We first investigated the effect of myostatin on cultured endothelial cells in the presence of indoxyl sulfate. We then examined the association between serum myostatin concentrations and the occurrence of cardiovascular and arteriovenous access complications in hemodialysis patients. In vitro, myostatin exhibited endotheliotoxic effects in the presence of a uremic concentration of indoxyl sulfate, enhanced its antiproliferative effect, and amplified MCP-1 and IL-8 chemokine upregulation. In patients, high myostatin concentrations correlated with indoxyl sulfate concentrations and were associated with an increased risk of arteriovenous access complications. These findings suggest that myostatin amplifies endothelial injury mediated by indolic uremic toxins and might contribute to AV access complications.

Keywords:  arteriovenous access complications; endothelial dysfunction; hemodialysis; indoxyl sulfate; myostatin

DOI:  https://doi.org/10.3390/toxins17040159
Front Microbiol. 2025 ;16 1549349

Herpes simplex virus 1 glycoprotein C promotes virus penetration from endosomes during entry, independent of interaction with heparan sulfate.

Seth M Schneider, Giulia Tebaldi, Katrina A Gianopulos, Darin J Weed, Suzanne M Pritchard, Chloe Leach, Anthony V Nicola.

  Herpes simplex virus 1 (HSV-1) gC is a multi-functional glycoprotein present in the viral envelope and on the surface of infected cells. Virion gC, and to a lesser extent the fusion protein gB, interacts with host heparan sulfate to mediate HSV-1 attachment to the cell surface. Virion gC selectively facilitates HSV-1 entry into cells that support entry by a low pH-dependent endocytic pathway. gC regulates fusion-associated conformational changes in gB. Here we investigated the mechanism by which gC plays a post-attachment role in HSV-1 entry into cells. HSV-1 entered HS-deficient cells by a low pH-dependent route. Similarly, HSV-1 deleted for HS-binding domains entered HS-bearing cells by a low pH pathway. Thus, the presence of HS on cells and the ability of HSV-1 to engage HS do not direct HSV-1 to a pH-dependent entry pathway. HSV-1 lacking gC accumulated in endosomes during viral entry, supporting the notion that gC influences viral penetration from endosomes. Interestingly, the pH-neutral cell-cell fusion mediated by HSV-1 glycoproteins gB, gD, and gH/gL was not altered by gC. Soluble heparin inhibited cell-cell fusion regardless of the presence of gC or heparan sulfate. The kinetics of endocytic uptake of gC-null HSV-1 was rapid and very similar to wild type virus. Thus, the role of gC in regulating low pH entry of HSV-1 occurs downstream of internalization of enveloped particles from the plasma membrane. Together, the results presented here and elsewhere support a post-attachment, post-internalization function for gC in HSV-1 entry that is independent of HS.

Keywords:  fusion; glycoprotein C; heparan sulfate; herpes simplex virus; virus entry; virus penetration

DOI:  https://doi.org/10.3389/fmicb.2025.1549349
Ultrason Sonochem. 2025 Feb 20. pii: S1350-4177(25)00048-3. [Epub ahead of print]117 107269

Ultrasound-assisted extraction, purification, sulfation of Perilla leaves polysaccharide and hypoglycemic and hypolipidemic activities.

Jing Guan, Peng Guo, Meng Chen, Wenzhao Wang, Xinyu Chen, Qiuyun Li, Yiyang He, Jiayue Liang, Ningxin Yu, Pengna Gao, Yanli Wu.

  Perilla leaves are a common traditional medicinal and edible crop, in order to further explore its medicinal value, after determining the optimal ultrasound-assisted extraction conditions a neutral polysaccharide was extracted. Its structure was analyzed, and sulfation modification was carried out. After purification by different column chromatography, the optimal process for sulfation modification of PLP-2-1 was established, and sulfated modified PLP-2-1 (S-PLP-2-1) was successfully prepared. The potential structural framework and molecular weight of PLP-2-1 were determined by high performance liquid chromatography (HPLC), methylation analysis, and nuclear magnetic resonance (NMR) techniques, while sulfated modified S-PLP-2-1 maintained a high degree of structural similarity to PLP-2-1. Particle size analysis, Zeta potential measurement, infrared spectroscopy, and NMR analysis confirmed the presence of sulfate groups in S-PLP-2-1, while thermogravimetric and rheological analyses provided support for the development and utilization of these two polysaccharides. After determined the safe concentration range in vitro, the antioxidant and hypoglycemic activities of PLP-2-1 and S-PLP-2-1 were measured. Besides, the effects on the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in oleic acid (OA) induced high-fat HepG2 cells of both polysaccharides were determined. The results indicated that the various biological activities of S-PLP-2-1 were significantly enhanced after sulfation modification. Therefore, PLP-2-1 and S-PLP-2-1 have the potential to be developed as drugs for anti-glycolipid metabolism disorders.

Keywords:  Hypoglycemic activity; Hypolipidemic activity; Perilla leaves polysaccharide; Purification; Sulfation modification

DOI:  https://doi.org/10.1016/j.ultsonch.2025.107269
J Biol Chem. 2025 Apr 22. pii: S0021-9258(25)00374-6. [Epub ahead of print] 108525

Aggrecan immobilizes to perineuronal nets through hyaluronan-dependent and independent binding activities.

Matthew Y Otsuka, Leslie B Essel, Ashis Sinha, Gabrielle Nickerson, Seth M Mejia, Ashley Edge, Russell T Matthews, Samuel Bouyain.

  Aggrecan (ACAN) is a large, secreted chondroitin sulfate proteoglycan that includes three globular regions named G1, G2, G3, and is decorated with multiple glycosaminoglycan attachments between its G2 and G3 domains. The N-terminal G1 region interacts with the glycosaminoglycan hyaluronan (HA), which is an essential component of the vertebrate extracellular matrix. In the central nervous system, ACAN is found in perineuronal nets (PNNs), honeycomb-like structures that localize to the surface of parvalbumin-positive neurons in specific neural circuits. PNNs regulate the plasticity of the central nervous system, and it is believed that association between ACAN and HA is a foundational event in the assembly of these reticular structures. Here, we report the co-crystal structure of the G1 region of ACAN in the absence and presence of a HA decasaccharide and analyze the importance of the HA-binding activity of ACAN for its integration into PNNs. We demonstrate that the single immunoglobulin domain and the two Link modules that comprise the G1 region form a single structural unit, and that HA is clamped inside a groove that spans the length of the tandem Link domains. Introducing point mutations in the glycosaminoglycan-binding site eliminates HA-binding activity in ACAN, but, surprisingly, only decreases the integration of ACAN into PNNs. Thus, these results suggest that ACAN can be recruited into PNNs independently of its HA-binding activity.

Keywords:  X‐ray crystallography; aggrecan; cartilage; extracellular matrix; glycosaminoglycan; hyaluronan; perineuronal net; plasticity; protein‐carbohydrate interaction; proteoglycan

DOI:  https://doi.org/10.1016/j.jbc.2025.108525
Fitoterapia. 2025 Apr 19. pii: S0367-326X(25)00185-6. [Epub ahead of print]183 106560

Sulfated modification of polysaccharides from Sophora flavescens: Impact on antioxidant, antitumor, and immunomodulatory activities.

Xiaoliang Zhao, Qingsong Zhou, He Mou, Li Ma, Yanmei Liu, Kaili Qi, Cunjin Wang, Jing Zhang, Ji Zhang, Weijie Zhang.

  Three polysaccharides, namely SHC, SFH, and SFA, were extracted from Sophora sophora under various conditions. A single-factor experimental design was employed to investigate the influence of reaction solvent, sulfating reagent ratio, reaction time, and temperature on the yield of sulfated products, the degree of sulfate group substitution, and their inhibitory effects on HepG2 cell proliferation. Three sulfated derivatives, SHCS, SFHS, and SFAS, were synthesized and confirmed through Fourier Transform Infrared Spectroscopy, Ultraviolet Spectroscopy, and Nuclear Magnetic Resonance Spectroscopy. Among these, SFHS exhibited the highest degree of substitution (DS) at 1.22, followed by SFAS at 0.97 and SFCS at 0.56. In vitro analyses revealed that sulfated modification significantly enhanced free radical scavenging activity, tumor cell growth inhibition, and immune response enhancement. Specifically, SFHS exhibited scavenging activities against DPPH, hydroxyl, and superoxide anion free radicals with rates of 69.8 % ± 6.1 %, 50.4 % ± 4.2 %, and 58.5 % ± 5.1 %, respectively, at 5 mg/mL. Furthermore, it inhibited the proliferation of HepG2 cells by 51.9 % ± 5.6 % at 400 μg/mL and HeLa cells by 43.7 % ± 1.8 % at 800 μg/mL. At 800 μg/mL, SFHS treatment resulted in a phagocytosis rate of neutral red by RAW264.7 macrophages, which was 246.6 % ± 13.9 % relative to the control group, while nitric oxide production was measured at 237.6 % ± 6.2 %. These results suggest that sulfation can enhance the biological functions of polysaccharides derived from S. flavescens, indicating potential applications in functional foods and pharmaceuticals.

Keywords:  Antioxidant activity; Antitumor activity; Immune enhancing activity; Polysaccharides; Sophora flavescens; Sulfated modification

DOI:  https://doi.org/10.1016/j.fitote.2025.106560
Methods Mol Biol. 2025 ;2926 157-173

Amphiphilic Glycoprobes for Cell Surface Engineering and Drug Delivery.

Saurabh Anand, Preeti Ravindra Bhoge, Raghavendra Kikkeri.

  Amphiphilic glycopeptides and glycopolymers have been characterized as potential glycocalyx engineering probes to regulate growth factors mediated stem cell differentiation and neural plasticity. Here, we describe a rational and facile method to synthesize fluorescent tagged amphiphilic multivalent glycoprobes using solid-phase peptide synthesizer and copper-free click chemistry. As a prototype, we report the synthesis of fluorescently tagged penta-valent sulfated L-iduronic acid glycopeptide for cell surface engineering and imaging.

Keywords:  Cell surface engineering; Fluorescent; Heparan sulfate; Multivalent; Proteoglycan

DOI:  https://doi.org/10.1007/978-1-0716-4542-0_12
Front Endocrinol (Lausanne). 2025 ;16 1518764

Early warning value of multiple serum indicators combined with ultrasound detection in girls with central precocious puberty.

Xiaolong Song, Jianping Zhou, Tiantian Han, Zhifeng Lin, Xu Chen, Yufang Li.

   Aim: The aim of this study was to evaluate the early diagnostic potential of various serum biomarkers and ultrasound characteristics in girls diagnosed with early central precocious puberty (CPP).
Methods: A cohort of 125 girls presenting breast development was assessed between May 2020 and January 2023. Following a six-month follow-up and GnRH agonist stimulation test, 78 girls were classified into the CPP group and 47 into the premature thelarche (PT) group. Serum biomarkers, including insulin-like growth factor-binding protein 3 (IGFBP-3), insulin-like growth factor 1 (IGF-1), and dehydroepiandrosterone sulfate (DHEAs), as well as bone age index (BAI) and ultrasound features, were compared between the groups.
Results: Chronological age did not significantly differ between the groups, but bone age and BAI were notably higher in the CPP group. Most serum levels, except for peak FSH, were significantly elevated in the CPP group. Ultrasound metrics such as uterine volume, cervical ratio, ovarian volume, and milk bud characteristics also showed significant differences. Correlation analyses revealed positive associations between both physical and serum indices and peak LH levels. Receiver operating characteristic (ROC) curve analysis identified basal LH as having the highest area under the curve (AUC) of 0.927, followed by DHEAs (AUC = 0.924). Logistic regression identified LH and DHEAs as independent risk factors for CPP, with optimal diagnostic efficacy achieved when both markers were combined (AUC = 0.973).
Conclusion: Basal LH, IGF-1, IGFBP-3, DHEAs, and associated ultrasound features are valuable early indicators for CPP in girls. The combination of LH and DHEAs enhances diagnostic accuracy, establishing them as significant independent risk factors for CPP.

Keywords:  DHEAS; IGF-1; IGFBP-3; basal LH; precocious puberty; premature thelarche

DOI:  https://doi.org/10.3389/fendo.2025.1518764
Int J Gynaecol Obstet. 2025 Apr 21.

Age and BMI-related changes in hormonal profile in women with polycystic ovary syndrome (PCOS): Association with infertility.

Ewa Zabiegło, Robert Jach, Magdalena Piróg.

   OBJECTIVE: The aim of the study was to evaluate age- and body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters)-related changes in hormonal profile in women with PCOS and to compare hormonal changes among women with polycystic ovary syndrome (PCOS) with and without infertility.
METHODS: In this case-control study, conducted from March 2018 to January 2024, we enrolled women with PCOS with infertility (n = 265) and controls (n = 265) matched for age and BMI at the Department of Endocrinological Gynecology in University Hospital, Krakow, Poland. The assessment of anti-Müllerian hormone (AMH) along with hormonal profile including follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), androgens (testosterone, 17-hydroxyprogesterone [17-OHP], dehydroepiandrosterone sulfate [DHEA-S]) as well as sex-hormone binding globulin was performed among these women, after assignment to different age BMI groups.
RESULTS: Women with POCS and infertility showed higher AMH (+42.9%), E2 (+15.9%) and LH (+41.9%) along with increased androgen levels reflected by increased testosterone (+20%), DHEA-S (+28.7%) and lower FSH (-10.3%) in contrary to women without infertility. Younger women (≤25 years) showed higher AMH, LH and androgens levels (total testosterone and DHEA-S) with lower FSH concentration. Women with higher BMI (≥30) had lower AMH together with increased free androgen index (FAI) and decreased sex hormone binding globulin (SHBG).
CONCLUSION: Infertile women with PCOS represent higher AMH together with elevated total testosterone, DHEA-S and FAI levels in contrary to fertile ones. Higher BMI together with older age have a negative impact on AMH in women with PCOS.

Keywords:  anti‐Műllerian hormone; body mass index; infertility; polycystic ovary syndrome

DOI:  https://doi.org/10.1002/ijgo.70160
Blood Purif. 2025 Apr 21. 1-16

Long-term safety of '4-hour' hemoadsorption combined with hemodialysis (HAHD) in maintenance hemodialysis patients: A multicenter prospective cohort study.

Dongliang Zhang, Cuiping Liu, Tao Yang, Jingxin Zhao, Xiaofei Wang, Liping Zhang, Yuanyuan Li, Yangyang Shen, Yanjun Gao, Hongjuan Zhang.

INTRODUCTION: Current guidelines recommend limiting hemoadsorption (HA) duration to 2 hours during hemodialysis (HD) sessions due to theoretical concerns about adsorbent saturation and clotting risks. This multicenter prospective cohort study evaluated the long-term safety and efficacy of a novel "4Hs" protocol (4-hour HA-HD with blood flow >250 mL/min).
METHODS: Seventy-eight maintenance HD patients from four centers underwent 26 weeks of 4Hs therapy. Key outcomes included dialysis adequacy (spKt/V, urea reduction ratio [URR]), uremic toxin (UT) clearance (indoxyl sulfate [IS], p-cresyl sulfate [pCS], β2-microglobulin [B2MG]), clotting rates, and adverse events (AEs). Statistical comparisons were made against pre-study conventional HA+HD (2-hour HA) data using paired t-tests and repeated-measures ANOVA.
RESULTS: The 4Hs protocol demonstrated non-inferior safety to conventional HA+HD, with comparable clotting rates (1.79% vs. 1.62%, p=0.665) and no significant differences in anemia markers or hypoalbuminemia. Dialysis efficacy improved significantly: spKt/V increased by 0.28 (p=0.012), URR by 1.18% (p=0.003), and UT reduction rates (IS: 56.17% vs. 40.14%, p<0.001; p-CS: 47.39% vs. 35.91%, p<0.001; B2MG: 55.82% vs. 48.41%, p<0.001). Albumin loss remained comparable between protocols (Δ0.5 g/L, p>0.05).
CONCLUSION: Extending HA duration to 4 hours with high-flow hemodynamics (Qb >250 mL/min) is safe and enhances toxin clearance without increasing clotting risks. These findings challenge current SOP limitations on HA duration and support protocol optimization in maintenance HD patients.

DOI: https://doi.org/10.1159/000545988
Metabolites. 2025 Apr 01. pii: 239. [Epub ahead of print]15(4):

Steroids Static Postural Balance Changes After Exercise Intervention Correlate with Steroidome in Elderly Female.

Zuzanna Kornatovská, Martin Hill, Dobroslava Jandová, Milada Krejčí, Anna Zwierzchowska.

   BACKGROUND: Aging is associated with the development of various disorders, including postural imbalance, which increases the risk of falls and related health complications. This study examines changes in static postural balance after a 4-week intervention involving appropriate exercise and an optimized daily regimen. Additionally, it explores the relationship between these changes and the steroidome.
METHODS: The study was conducted on a clinically homogeneous group of 41 females around their sixth decade, diagnosed with anxiety-depressive syndrome and treated with selective serotonin reuptake inhibitors (SSRIs). Postural balance was assessed using the dual-scales method (DLLL-DSM), which estimates postural imbalance by evaluating differences in the lower limb load in the standing position. Correlations between initial DLLL-DSM values, age, BMI, and the baseline levels of nine serum steroids, as well as post-intervention changes in five steroids, were analyzed using multivariate regression (OPLS model).
RESULTS: A significant reduction in lower limb load differences (-ΔDLLL-DSM), indicating improved postural balance, was observed. The -ΔDLLL-DSM strongly correlated with initial DLLL-DSM values, age, BMI, initial levels of nine serum steroids, and post-intervention changes in five steroids (R = 0.892, p < 0.001). Furthermore, initial DLLL-DSM values negatively correlated with adrenal androgen androstenediol sulfate and various sulfated 5α/β-reduced androgen metabolites (R = 0.323, p < 0.05), suggesting that the activity of steroid sulfotransferase (SULT2A1) and C17-hydroxylase-C17,20-lyase (CYP17A1) at the lyase step is negatively associated with postural imbalance in elderly females.
CONCLUSIONS: The findings suggest that even severe postural imbalance can be effectively and relatively rapidly improved through an appropriate exercise-based intervention and an optimized daily regimen, provided that initial adrenal activity is not significantly impaired. Additionally, the identified associations between steroid levels and postural balance provide new insights into the hormonal mechanisms regulating balance control in older individuals.

Keywords:  aging; exercise intervention; gas chromatography-tandem mass spectrometry; multivariate statistics; static postural balance; steroidome

DOI:  https://doi.org/10.3390/metabo15040239
J Anim Sci Technol. 2025 Mar;67(2): 410-420

Overexpression of Syndecan-4 inhibits myogenesis by regulating the expression of myogenic regulatory factors.

Sarang Choi, Jeong-Woong Park, Sang In Lee, Sangsu Shin.

  Syndecan-4, a type of heparan sulfate proteoglycan, plays an important role in muscle development, regeneration, and maintenance. Although the important effects of Syndecan-4 on the regulation of myogenesis in mice, turkeys, and bovines have been consistently reported, the molecular mechanisms of Syndecan-4 in myogenesis are not well understood. In this study, the role of Syndecan-4 in regulating myogenesis was investigated in quail myoblast (QM7) cells, which constituting a quail myogenic cell line. Overexpression of Syndecan-4 inhibited myogenesis, resulting in reduced myoblast fusion and shorter myotubes than in the control group. Therefore, the cells overexpressing Syndecan-4 showed a smaller total myotube area than did the control cells. Furthermore, these cells had lesser myosin heavy chain proteins, suggesting that muscle differentiation is inhibited by Syndecan-4. To investigate the inhibitory effect of Syndecan-4 on myogenic differentiation, the mRNA expression levels in several genes known to regulate myoblast proliferation and differentiation were compared. Myogenic regulatory factors, including myogenic factor 5, myogenic differentiation 1, and myogenin, showed significantly different expressions between the groups during myogenesis. Myostatin, a negative regulator of muscle growth, showed significantly higher expression on day 4 in cells overexpressing Syndecan-4. In conclusion, Syndecan-4 could delay and inhibit muscle differentiation by regulating the expression levels of myogenic factors and muscle growth regulator in quail myocytes. This study provides valuable information regarding the role of Syndecan-4 in myogenesis, which may aid in improving the production of poultry meat.

Keywords:  Muscle differentiation; Myogenesis; Myogenic regulatory factors; QM7 cell line; syndecan-4

DOI:  https://doi.org/10.5187/jast.2024.e8
J Agric Food Chem. 2025 Apr 23.

Rational Design and Engineering of 3-O-Sulfotransferase 1 Based on Enzyme Affinity for Improved Enzymatic Heparin Preparation.

Tiansu Tan, Jing Yu, Jianyu Long, Xiaojing Li, Zheng-Jun Li, Yang Zhang, Mingjia Yu, Tianwei Tan.

  Heparin, a naturally occurring glycosaminoglycan, is renowned for its potent anticoagulant properties, which are critical for various medical applications. A significant determinant of its anticoagulant activity is the degree of 3-O-sulfation. Gaining insight into the substrate binding characteristics of 3-O-sulfotransferase-1 (3-OST-1) could enhance our understanding of the sulfotransferase family and facilitate the enzymatic preparation of heparin. This study aimed to identify mutants of 3-OST-1 with improved catalytic activities through a rational design. The enzyme activities of the mutants W72R and H144R were recorded at 26.40 and 17.21 U/L, respectively, representing increases of 1.7 and 1.1 times compared to the wild-type (WT) 3-OST-1. Notably, the enzyme activity of the double mutant W72R/H144R reached 34.41 U/L, which is 2.2 times greater than that of the WT. The heparin modified by the 3-OST-1 mutants exhibited superior anticoagulant properties compared with those modified by the WT, with W72R/H144R demonstrating the highest anticoagulant potency. Furthermore, enzyme kinetic assays and molecular dynamics simulations illustrated that the enhanced catalytic activity of the mutant enzyme resulted from an increased affinity for the substrate.

Keywords:  3-O-sulfotransferase; affinity; heparin; modification; rational design

DOI:  https://doi.org/10.1021/acs.jafc.4c07514