bims-supasi 2024-04-07 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2024–04–07
eleven papers selected by
Jonathan Wolf Mueller, University of Birmingham

Editorial: Heparan sulfate-binding proteins in health and disease.
The role of genetic polymorphisms in the sulfation of pregnenolone by human cytosolic sulfotransferase SULT2B1a.
Cardiac arrhythmia in individuals with steroid sulfatase deficiency (X-linked ichthyosis): candidate anatomical and biochemical pathways.
Hair dehydroepiandrosterone sulfate as biomarker of employees' well-being? A longitudinal investigation of support, resilience, and work engagement during COVID-19 pandemic.
Collagen short nanofiber-embedded chondroitin sulfate-hyaluronic acid nanocomposite: A cartilage-mimicking in situ-forming hydrogel with fine-tuned properties.
Indoxyl sulfate contributes to colorectal cancer cell proliferation and increased EGFR expression by activating AhR and Akt.
Molecular recognition and proteoglycan mimic arrangement: modulating cisplatin toxicity.
Phagocyte-expressed glycosaminoglycans promote capture of alphaviruses from the blood circulation in a host species-specific manner.
Identification and characterization of a PL35 GAGs lyase with 4-O-sulfated N-acetylgalactosamine (A-type)-rich structures producing property.
Determination of indoxyl sulfate by spectrofluorimetric method in human plasma through extraction with deep eutectic solvent.
Chiral resolution of cationic piperazine derivatives by capillary electrophoresis using sulfated β-cyclodextrin.

Front Mol Biosci. 2024 ;11 1386623

Editorial: Heparan sulfate-binding proteins in health and disease.

Lauren A Gandy, Fuming Zhang, Ding Xu, Lars C Pedersen, Kay Grobe, Chunyu Wang.



Keywords:  fucoidan (FPS); glycosaminoglycan (GAG); hedgehog autoprocessing; heparan sulfate (HS); heparin; heparin-binding proteins; sepsis; tauopathies

DOI:  https://doi.org/10.3389/fmolb.2024.1386623
Sci Rep. 2024 Apr 05. 14(1): 8050

The role of genetic polymorphisms in the sulfation of pregnenolone by human cytosolic sulfotransferase SULT2B1a.

Eid Alatwi, Ahsan F Bairam.

  Pregnenolone is a key intermediate in the biosynthesis of many steroid hormones and neuroprotective steroids. Sulfotransferase family cytosolic 2B member 1 (SULT2B1a) has been reported to be highly selective to sulfate pregnenolone. This study aimed to clarify the effect of missense single nucleotide polymorphisms (SNPs) of the human SULT2B1 gene on the sulfating activity of coded SULT2B1a allozymes toward Pregnenolone. To investigate the effects of single nucleotide polymorphisms of the SULT2B1 gene on the sulfation of pregnenolone by SULT2B1a allozymes, 13 recombinant SULT2B1a allozymes were generated, expressed, and purified using established procedures. Human SULT2B1a SNPs were identified by a comprehensive database search. 13 SULT2B1a nonsynonymous missense coding SNPs (cSNPs) were selected, and site-directed mutagenesis was used to generate the corresponding cDNAs, packaged in pGEX-2TK expression vector, encoding these 13 SULT2B1a allozymes, which were bacterially expressed in BL21 E. coli cells and purified by glutathione-Sepharose affinity chromatography. Purified SULT2B1a allozymes were analyzed for sulfating activities towards pregnenolone. In comparison with the wild-type SULT2B1a, of the 13 allozymes, 11 showed reduced activity toward pregnenolone at 0.1 µM. Specifically, P134L and R259Q allozymes, reported to be involved in autosomal-recessive congenital ichthyosis, displayed low activity (1-10%) toward pregnenolone. The findings of this study may demonstrate the impact of genetic polymorphism on the sulfation of pregnenolone in individuals with different SULT2B1 genotypes.

Keywords:  Pregnenolone; SNPs; SULT2B1a; Sulfation

DOI:  https://doi.org/10.1038/s41598-024-56303-y
Essays Biochem. 2024 Apr 04. pii: EBC20230098. [Epub ahead of print]

Cardiac arrhythmia in individuals with steroid sulfatase deficiency (X-linked ichthyosis): candidate anatomical and biochemical pathways.

Georgina H Wren, William Davies.

  Circulating steroids, including sex hormones, can affect cardiac development and function. In mammals, steroid sulfatase (STS) is the enzyme solely responsible for cleaving sulfate groups from various steroid molecules, thereby altering their activity and water solubility. Recent studies have indicated that Xp22.31 genetic deletions encompassing STS (associated with the rare dermatological condition X-linked ichthyosis), and common variants within the STS gene, are associated with a markedly elevated risk of cardiac arrhythmias, notably atrial fibrillation/flutter. Here, we consider emerging basic science and clinical findings which implicate structural heart abnormalities (notably septal defects) as a mediator of this heightened risk, and propose candidate cellular and biochemical mechanisms. Finally, we consider how the biological link between STS activity and heart structure/function might be investigated further and the clinical implications of work in this area.

Keywords:  Cellular communication network (CCN) factor; dehydroepiandrosterone sulfate (DHEAS); laminin; sex hormones; ventricular

DOI:  https://doi.org/10.1042/EBC20230098
Front Psychol. 2024 ;15 1337839

Hair dehydroepiandrosterone sulfate as biomarker of employees' well-being? A longitudinal investigation of support, resilience, and work engagement during COVID-19 pandemic.

Damiano Girardi, Laura Dal Corso, Elvira Arcucci, Murat Yıldırım, Isabella Pividori, Alberto Prandi, Alessandra Falco.

   Introduction: Building on the motivational process of the job demands-resources (JD-R) theory, in the current research we investigated the longitudinal association between supervisor support/resilience as job/personal resources, work engagement (WE) and hair dehydroepiandrosterone sulfate, or DHEA(S), as a possible biomarker of employees' well-being.
Methods: In the context of the COVID-19 pandemic, 122 workers completed two self-report questionnaires (i.e., psychological data): the former at Time 1 (T1) and the latter three months afterwards, at Time 2 (T2). Participants also collected a strand of hair (i.e., biological data) at T2.
Results: Results from path analysis showed that both SS and resilience at T1 were positively related to WE at T2, which, in its turn, was positively related to hair DHEA(S) at T2. Both SS and resilience at T1 had a positive indirect effect on hair DHEA(S) at T2 through WE at T2, which fully mediated the association between job/personal resources and hair DHEA(S).
Discussion: Overall, results are consistent with the motivational process of the JD-R. Furthermore, this study provides preliminary evidence for the role of hair DHEA(S) as a biomarker of WE, a type of work-related subjective well-being that plays a central role in the motivational process of the JD-R, leading to favorable personal and organizational outcomes. Finally, the article outlines practical implications for organizations and professionals to foster WE within the workplace.

Keywords:  COVID-19; biomarker; hair dehydroepiandrosterone sulfate; organizational well-being; resilience; supervisor support; work engagement

DOI:  https://doi.org/10.3389/fpsyg.2024.1337839
Int J Biol Macromol. 2024 Mar 29. pii: S0141-8130(24)01856-7. [Epub ahead of print]266(Pt 2): 131051

Collagen short nanofiber-embedded chondroitin sulfate-hyaluronic acid nanocomposite: A cartilage-mimicking in situ-forming hydrogel with fine-tuned properties.

Ayoob Karimizade, Elham Hasanzadeh, Mozhgan Abasi, Seyed Ehsan Enderami, Esmaeil Mirzaei, Nasim Annabi, Amir Mellati.

  In situ-forming hydrogels that possess the ability to be injected in a less invasive manner and mimic the biochemical composition and microarchitecture of the native cartilage extracellular matrix are desired for cartilage tissue engineering. Besides, gelation time and stiffness of the hydrogel are two interdependent factors that affect cells' distribution and fate and hence need to be optimized. This study presented a bioinspired in situ-forming hydrogel composite of hyaluronic acid (HA), chondroitin sulfate (CS), and collagen short nanofiber (CSNF). HA and CS were functionalized with aldehyde and amine groups to form a gel through a Schiff-base reaction. CSNF was fabricated via electrospinning, followed by fragmentation by ultrasonics. Gelation time (11-360 s) and compressive modulus (1.4-16.2 kPa) were obtained by varying the concentrations of CS, HA, CSNFs, and CSNFs length. The biodegradability and biocompatibility of the hydrogels with varying gelation and stiffness were also assessed in vitro and in vivo. At three weeks, the assessment of hydrogels' chondrogenic differentiation also yields varying levels of chondrogenic differentiation. The subcutaneous implantation of the hydrogels in a mouse model indicated no severe inflammation. Results demonstrated that the injectable CS/HA@CSNF hydrogel was a promising hydrogel for tissue engineering and cartilage regeneration.

Keywords:  Cartilage; Collagen short nanofiber; In situ-forming hydrogel

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.131051
Biomed Res. 2024 ;45(2): 57-66

Indoxyl sulfate contributes to colorectal cancer cell proliferation and increased EGFR expression by activating AhR and Akt.

Yu Ichisaka, Shozo Yano, Kohji Nishimura, Toshimitsu Niwa, Hidehisa Shimizu.

Although patients with chronic kidney disease (CKD) have a higher risk of colorectal cancer (CRC) aggravation, the connection between these two diseases is not well understood. Recent studies have shown that both CKD and CRC aggravation are closely related to an increased abundance of indole-producing Fusobacterium nucleatum in the gut. The indole absorbed from the gut is eventually metabolized to indoxyl sulfate in the liver. Since indoxyl sulfate is involved not only in accelerating CKD progression but also in the initiation and development of its associated complications, the present study aimed to clarify whether indoxyl sulfate induces the proliferation of CRC cells. This study found that indoxyl sulfate induced the proliferation of CRC-derived HCT-116 cells by activating the aryl hydrocarbon receptor (AhR) and the proto-oncogene Akt. The AhR antagonist CH223191 and Akt inhibitor MK2206 suppressed indoxyl sulfate-induced proliferation of HCT-116 cells. We also found that indoxyl sulfate upregulated epidermal growth factor receptor (EGFR) expression, which is associated with poor prognosis of CRC, whereas CH223191 and MK2206 repressed EGFR expression. Furthermore, indoxyl sulfate increased the sensitivity of CRC cells to EGF by upregulating EGFR expression. These findings suggest that indoxyl sulfate may be an important link between CKD and CRC aggravation.

DOI: https://doi.org/10.2220/biomedres.45.57
Chem Commun (Camb). 2024 Apr 03.

Molecular recognition and proteoglycan mimic arrangement: modulating cisplatin toxicity.

Saurabh Anand, Sandhya Mardhekar, Preeti Ravindra Bhoge, Sandeep Kumar Mishra, Raghavendra Kikkeri.

We have demonstrated that cisplatin (CP), an anticancer drug, showed a preference for binding the sulfated-L-iduronic acid (S-L-IdoA) unit over the sulfated-D-glucuronic acid unit of heparan sulfate. The multivalency of S-L-IdoA, such as in the proteoglycan mimic, resulted in distinct modes of cell-surface engineering in normal and cancer cells, with these disparities having a significant impact on CP-mediated toxicity.

DOI: https://doi.org/10.1039/d4cc00464g
PNAS Nexus. 2024 Apr;3(4): pgae119

Phagocyte-expressed glycosaminoglycans promote capture of alphaviruses from the blood circulation in a host species-specific manner.

Stephanie E Ander, M Guston Parks, Bennett J Davenport, Frances S Li, Angela Bosco-Lauth, Kathryn S Carpentier, Chengqun Sun, Cormac J Lucas, William B Klimstra, Gregory D Ebel, Thomas E Morrison.

  The magnitude and duration of vertebrate viremia are critical determinants of arbovirus transmission, geographic spread, and disease severity-yet, mechanisms determining arbovirus viremia levels are poorly defined. Previous studies have drawn associations between in vitro virion-glycosaminoglycan (GAG) interactions and in vivo clearance kinetics of virions from blood circulation. From these observations, it is commonly hypothesized that GAG-binding virions are rapidly removed from circulation due to ubiquitous expression of GAGs by vascular endothelial cells, thereby limiting viremia. Using an in vivo model for viremia, we compared the vascular clearance of low and enhanced GAG-binding viral variants of chikungunya, eastern- (EEEV), and Venezuelan- (VEEV) equine encephalitis viruses. We find GAG-binding virions are more quickly removed from circulation than their non-GAG-binding variant; however individual clearance kinetics vary between GAG-binding viruses, from swift (VEEV) to slow removal from circulation (EEEV). Remarkably, we find phagocytes are required for efficient vascular clearance of some enhanced GAG-binding virions. Moreover, transient depletion of vascular heparan sulfate impedes vascular clearance of only some GAG-binding viral variants and in a phagocyte-dependent manner, implying phagocytes can mediate vascular GAG-virion interactions. Finally, in direct contrast to mice, we find enhanced GAG-binding EEEV is resistant to vascular clearance in avian hosts, suggesting the existence of species-specificity in virion-GAG interactions. In summary, these data support a role for GAG-mediated clearance of some viral particles from the blood circulation, illuminate the potential of blood-contacting phagocytes as a site for GAG-virion binding, and suggest a role for species-specific GAG structures in arbovirus ecology.

Keywords:  alphavirus; arbovirus; glycosaminoglycan; heparan sulfate; viremia

DOI:  https://doi.org/10.1093/pnasnexus/pgae119
Int J Biol Macromol. 2024 Mar 30. pii: S0141-8130(24)02088-9. [Epub ahead of print]266(Pt 2): 131283

Identification and characterization of a PL35 GAGs lyase with 4-O-sulfated N-acetylgalactosamine (A-type)-rich structures producing property.

Danrong Lu, Wenwen Wang, Xiaoyun Li, Luping Wang, Yankai Guo, Changjian Zhu, Xiaohui Wang, Bo Lian, Jingkun Bai, Qingdong Zhang.

  Glycosaminoglycan (GAG) lyases are important tools for investigating the structure of GAGs and preparing low-molecular-weight GAGs. The PL35 family, a recently established polysaccharide lyase family, should be further investigated. In this study, we discovered a new GAG lyase, CHa1, which belongs to the PL35 family. When expressed heterologously in Escherichia coli (BL21), CHa1 exhibited high expression levels and solubility. The optimal activity was observed in Tris-HCl buffer (pH 7.0) or sodium phosphate buffer (pH 8.0) at 30 °C. The specific activities towards HA, CSA, CSC, CSD, CSE, and HS were 3.81, 13.03, 36.47, 18.46, 6.46, and 0.50 U/mg protein, respectively. CHa1 digests substrate chains randomly that acting as an endolytic lyase and shows a significant preference for GlcA-containing structures, prefers larger oligosaccharides (≥UDP8) and can generate a series of oligosaccharides composed mainly of the A unit when digesting CSA. These oligosaccharides include ΔC-A, ΔC-A-A, ΔC-A-A-A, ΔC-A-A-A-A, and ΔC-A-A-A-A-A. The residues Tyr257 and His421 play crucial roles in the catalytic process, and Ser211, Asn212, Asn213, Trp214, Gln216, Lys360, Arg460 and Gln462 may participate in the binding process of CHa1. This study on CHa1 contributes to our understanding of the PL35 family and provides valuable tools for investigating the structure of GAGs.

Keywords:  Chondroitinase; Glycosaminoglycans; PL35 family

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.131283
BMC Chem. 2024 Mar 30. 18(1): 61

Determination of indoxyl sulfate by spectrofluorimetric method in human plasma through extraction with deep eutectic solvent.

Samira Shafiee, Siavoush Dastmalchi, Afshin Gharekhani, Ali Shayanfar.

  A rapid and efficient analytical method was established to quantify indoxyl sulfate (IS) in plasma through extraction technique with a deep eutectic solvent (DES) and spectrofluorimetric method. DES (choline chloride: urea) was mixed with plasma samples for the extraction of IS, followed by the addition of dipotassium hydrogen phosphate (K2HPO4) solution to form an aqueous two-phase system. The fluorescence intensity of IS which was first extracted to the DES-rich-phase and then back-extracted into the salt-rich-phase, was measured by spectrofluorimetric method. Some key factors such as pH, centrifugation speed and time, the volume ratio of DES/salt, and salt concentration were optimized. Under the optimized conditions, the suggested method had a dynamic range between 20 and 160 µg/mL with a coefficient of determination (R2) of 0.99. Precision (relative standard deviation) was less than 15% and accuracy (% relative recovery) was ± 15% at the nominal concentration level. In addition, results showed that IS levels in real samples were higher than 40 µg/mL which was compatible with reported IS levels in end-stage renal disease (ESRD) patients. Overall, all the results reflect the fact that the presented analytical method can potentially be used for the determination of IS in real plasma samples.

Keywords:  Deep eutectic solvent (DES); Extraction; Indoxyl sulfate (IS); Spectrofluorimetry

DOI:  https://doi.org/10.1186/s13065-024-01172-9
Electrophoresis. 2024 Apr 04.

Chiral resolution of cationic piperazine derivatives by capillary electrophoresis using sulfated β-cyclodextrin.

Navid Niaei, Soodabeh Hassanpour, Jan Petr.

  This research focuses on the development and validation of a capillary electrophoresis (CE) method for the chiral separation of three H1-antihistamine drugs chlorcyclizine, norchlorcyclizine, and neobenodine using sulfated β-cyclodextrin (S-β-CD) as the chiral selector. The study explores various factors influencing the separation efficiency, including CD concentration, organic modifier content, voltage application, and buffer pH. Optimal conditions were identified as a 100 mM phosphate buffer (pH 6.0) with 34 mg mL-1 S-β-CD and 40% (v/v) methanol. The method demonstrated excellent linearity in calibration curves, with coefficients of determination exceeding 0.99 for each enantiomer. Precision studies revealed good intra- and inter-day precision for migration times and peak areas. The limits of detection and quantification for the analytes were within the ranges of 5.9-11.4 and 18-34.6 µmol L-1, respectively. Overall, the developed CE method offers a robust and precise approach for the chiral separation of H1-antihistamine drugs, holding promise for pharmaceutical applications.

Keywords:  capillary electrophoresis; chiral separation; methanol; piperazine derivatives; sulfated β‐cyclodextrin

DOI:  https://doi.org/10.1002/elps.202300271