bims-supasi 2024-05-05 papers

bims-supasi

Biomed News

on Sulfation pathways and signalling

Issue of 2024–05–05
twelve papers selected by
Jonathan Wolf Mueller, University of Birmingham

Cytosolic sulfotransferases in endocrine disruption.
Analytical methods for quantitating sulfate in plasma and serum.
Intermediate molecular weight-fucosylated chondroitin sulfate from sea cucumber Cucumaria frondosa is a promising anticoagulant targeting intrinsic factor IXa.
Heparan Sulfate Chain-Conjugated Laminin-E8 Fragments Advance Paraxial Mesodermal Differentiation Followed by High Myogenic Induction from hiPSCs.
Substrate binding plasticity revealed by Cryo-EM structures of SLC26A2.
Microwave-assisted synthesis of highly sulfated mannuronate glycans as potential inhibitors against SARS-CoV-2.
Syndecans and diabetic complications: a narrative review.
Alleviative effects of sulfated polysaccharide from Ishige Okamurae against DSS-induced ulcerative colitis via inhibiting inflammation and modulating gut microbiota.
Type II Heparin-Induced Thrombocytopenia Manifesting As Cardiac Arrest Following Intravenous Heparin Bolus During an Elective Procedure: A Case Report and Literature Review.
Metabolism of Endogenous and Exogenous Estrogens in Women.
Sweet, bloody consumption - what we eat and how it affects vascular ageing, the BBB and kidney health in CKD.
DHEA-S, Androstenedione, 17-β-estradiol signature as novel biomarkers for early prediction of risk of malignant pleural mesothelioma linked to asbestos-exposure: A preliminary investigation.

Essays Biochem. 2024 May 03. pii: EBC20230101. [Epub ahead of print]

Cytosolic sulfotransferases in endocrine disruption.

Michael W Duffel.

  The mammalian cytosolic sulfotransferases (SULTs) catalyze the sulfation of endocrine hormones as well as a broad array of drugs, environmental chemicals, and other xenobiotics. Many endocrine-disrupting chemicals (EDCs) interact with these SULTs as substrates and inhibitors, and thereby alter sulfation reactions responsible for metabolism and regulation of endocrine hormones such as estrogens and thyroid hormones. EDCs or their metabolites may also regulate expression of SULTs through direct interaction with nuclear receptors and other transcription factors. Moreover, some sulfate esters derived from EDCs (EDC-sulfates) may serve as ligands for endocrine hormone receptors. While the sulfation of an EDC can lead to its excretion in the urine or bile, it may also result in retention of the EDC-sulfate through its reversible binding to serum proteins and thereby enable transport to other tissues for intracellular hydrolysis and subsequent endocrine disruption. This mini-review outlines the potential roles of SULTs and sulfation in the effects of EDCs and our evolving understanding of these processes.

Keywords:  endocrine disruption; estradiol; steroid sulfatase; sulfation; sulfotransferase; thyroxine

DOI:  https://doi.org/10.1042/EBC20230101
Essays Biochem. 2024 May 03. pii: EBC20230092. [Epub ahead of print]

Analytical methods for quantitating sulfate in plasma and serum.

Prasidhee Vijayakumar, Paul A Dawson.

  Circulating sulfate needs to be maintained at sufficiently high levels for healthy growth and development. Animal studies have shown the adverse physiological consequences of low circulating sulfate level on the skeletal, neurological and reproductive systems. However, sulfate is not routinely measured in clinical investigations, despite the importance of sulfate being documented over the past several decades. Several methods have been developed for measuring serum and plasma sulfate level in animals and humans, including a range of barium sulfate precipitation techniques that have been a major focus of sulfate analytics since the 1960s. Evaluation of an ion chromatography method demonstrated its utility for investigation of sulfate levels in human health. More recently, liquid chromatography-tandem mass spectrometry has been used to show hyposulfatemia in a human case of mild skeletal dysplasia. This article provides an overview of analytical methods for measuring sulfate in serum and plasma, highlighting the strengths and limitations of each method.

Keywords:  Assay; Biochemical pathology; Method; Sulfataemia; Sulfate

DOI:  https://doi.org/10.1042/EBC20230092
Int J Biol Macromol. 2024 Apr 29. pii: S0141-8130(24)02757-0. [Epub ahead of print] 131952

Intermediate molecular weight-fucosylated chondroitin sulfate from sea cucumber Cucumaria frondosa is a promising anticoagulant targeting intrinsic factor IXa.

Yuanjie Liu, Rongfeng Li, Lin Song, Kecheng Li, Huahua Yu, Ronge Xing, Song Liu, Pengcheng Li.

  Thromboembolic diseases pose a serious risk to human health worldwide. Fucosylated chondroitin sulfate (FCS) is reported to have good anticoagulant activity with a low bleeding risk. Molecular weight plays a significant role in the anticoagulant activity of FCS, and FCS smaller than octasaccharide in size has no anticoagulant activity. Therefore, identifying the best candidate for developing novel anticoagulant FCS drugs is crucial. Herein, native FCS was isolated from sea cucumber Cucumaria frondosa (FCScf) and depolymerized into a series of lower molecular weights (FCScfs). A comprehensive assessment of the in vitro anticoagulant activity and in vivo bleeding risk of FCScfs with different molecule weights demonstrated that 10 kDa FCScf (FCScf-10 K) had a greater intrinsic anticoagulant activity than low molecular weight heparin (LMWH) without any bleeding risk. Using molecular modeling combined with experimental validation, we revealed that FCScf-10 K can specifically inhibit the formation of the Xase complex by binding the negatively charged sulfate group of FCScf-10 K to the positively charged side chain of arginine residues on the specific surface of factor IXa. Thus, these data demonstrate that the intermediate molecular weight FCScf-10 K is a promising candidate for the development of novel anticoagulant drugs.

Keywords:  Anticoagulant; Bleeding risk; Coagulation factor; Cucumaria frondosa; Fucosylated chondroitin sulfate; Sea cucumber

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.131952
Adv Sci (Weinh). 2024 Apr 29. e2308306

Heparan Sulfate Chain-Conjugated Laminin-E8 Fragments Advance Paraxial Mesodermal Differentiation Followed by High Myogenic Induction from hiPSCs.

Mingming Zhao, Yukimasa Taniguchi, Chisei Shimono, Tatsuya Jonouchi, Yushen Cheng, Yasuhiro Shimizu, Minas Nalbandian, Takuya Yamamoto, Masato Nakagawa, Kiyotoshi Sekiguchi, Hidetoshi Sakurai.

  Human-induced pluripotent stem cells (hiPSCs) have great therapeutic potential. The cell source differentiated from hiPSCs requires xeno-free and robust methods for lineage-specific differentiation. Here, a system is described for differentiating hiPSCs on new generation laminin fragments (NGLFs), a recombinant form of a laminin E8 fragment conjugated to the heparan sulfate chains (HS) attachment domain of perlecan. Using NGLFs, hiPSCs are highly promoted to direct differentiation into a paraxial mesoderm state with high-efficiency muscle lineage generation. HS conjugation to the C-terminus of Laminin E8 fragments brings fibroblast growth factors (FGFs) bound to the HS close to the cell surface of hiPSCs, thereby facilitating stronger FGF signaling pathways stimulation and initiating HOX gene expression, which triggers the paraxial mesoderm differentiation of hiPSCs. This highly efficient differentiation system can provide a roadmap for paraxial mesoderm development and an infinite source of myocytes and muscle stem cells for disease modeling and regenerative medicine.

Keywords:  fibroblast growth factor signaling; heparan sulfate; human pluripotent stem cells; new generation laminin fragments; paraxial mesoderm

DOI:  https://doi.org/10.1002/advs.202308306
Nat Commun. 2024 Apr 29. 15(1): 3616

Substrate binding plasticity revealed by Cryo-EM structures of SLC26A2.

Wenxin Hu, Alex Song, Hongjin Zheng.

SLC26A2 is a vital solute carrier responsible for transporting essential nutritional ions, including sulfate, within the human body. Pathogenic mutations within SLC26A2 give rise to a spectrum of human diseases, ranging from lethal to mild symptoms. The molecular details regarding the versatile substrate-transporter interactions and the impact of pathogenic mutations on SLC26A2 transporter function remain unclear. Here, using cryo-electron microscopy, we determine three high-resolution structures of SLC26A2 in complexes with different substrates. These structures unveil valuable insights, including the distinct features of the homodimer assembly, the dynamic nature of substrate binding, and the potential ramifications of pathogenic mutations. This structural-functional information regarding SLC26A2 will advance our understanding of cellular sulfate transport mechanisms and provide foundations for future therapeutic development against various human diseases.

DOI: https://doi.org/10.1038/s41467-024-48028-3
Org Biomol Chem. 2024 May 02.

Microwave-assisted synthesis of highly sulfated mannuronate glycans as potential inhibitors against SARS-CoV-2.

Yirong Zhu, Xiaotong Wang, Siqian Lu, Jibin Zheng, Youling Liang, Liangliang Zhang, Pengfei Fang, Peng Xu, Biao Yu, You Yang.

Algae-based marine carbohydrate drugs are typically decorated with negative ion groups such as carboxylate and sulfate groups. However, the precise synthesis of highly sulfated alginates is challenging, thus impeding their structure-activity relationship studies. Herein we achieve a microwave-assisted synthesis of a range of highly sulfated mannuronate glycans with up to 17 sulfation sites by overcoming the incomplete sulfation due to the electrostatic repulsion of crowded polyanionic groups. Although the partially sulfated tetrasaccharide had the highest affinity for the receptor binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, the fully sulfated octasaccharide showed the most potent interference with the binding of the RBD to angiotensin-converting enzyme 2 (ACE2) and Vero E6 cells, indicating that the sulfated oligosaccharides might inhibit the RBD binding to ACE2 in a length-dependent manner.

DOI: https://doi.org/10.1039/d4ob00466c
Am J Med Sci. 2024 Apr 30. pii: S0002-9629(24)01210-2. [Epub ahead of print]

Syndecans and diabetic complications: a narrative review.

Yasamin Rajabloo, Maryam Saberi-Karimian, Sara Saffar Soflaei, Gordon A Ferns, Majid Ghayour-Mobarhan.

  Syndecan (SDC) is a member of the heparan sulfate proteoglycan (HSPG) family. It appears to play a role in the aetiology of diabetic complications, with decreased levels of SDCs being reported in the kidney, retina, and cardiac muscle in models of diabetes mellitus (DM). The reduced levels of SDCs may play an important role in the development of albuminuria in DM. Some studies have provided the evidence supporting the mechanisms underlying the role of SDCs in DM. However, SDCs and the molecular mechanisms involved are complex and need to be further elucidated. This review focuses on the underlying molecular mechanisms of SDCs that are involved in the development and progression of the complications of DM, which may help in developing new strategies to prevent and treat these complications.

Keywords:  Diabetes mellitus; Diabetic complication; Review; Syndecan

DOI:  https://doi.org/10.1016/j.amjms.2024.04.017
Int J Biol Macromol. 2024 Apr 26. pii: S0141-8130(24)02720-X. [Epub ahead of print]268(Pt 2): 131915

Alleviative effects of sulfated polysaccharide from Ishige Okamurae against DSS-induced ulcerative colitis via inhibiting inflammation and modulating gut microbiota.

Ling Qin, Hui Xu, Junhan Cao, Kai Wang, Liping Zhang, Mengke Yao, Huan Lin, Changfeng Qu, Jinlai Miao.

  A water-soluble polysaccharide from the brown alga Ishige Okamurae, designated IOP-0, was obtained by preparative anion-exchange and size-exclusion chromatography. Chemical and spectroscopic investigations revealed that IOP-0 was a sulfated fucoidan with a backbone primarily composed of 3-linked and 4-linked-L-fucose with sulfate groups at C-2/C-4 of the 3-linked-L-fucose. The protective effect of IOP-0 on ulcerative colitis was evaluated in this work. The results showed that IOP-0 could significantly alleviate the symptoms of ulcerative colitis by preventing weight loss, preserving the structure of intestinal tissues, and ameliorating the dysregulation of inflammatory cytokines (TNF-α, IL-6, and IL-10). Meanwhile, IOP-0 protected the colonic mucosal barrier by promoting the tight junction protein ZO-1 and occludin expression. In addition, IOP-0 was able to maintain intestinal homeostasis and improve intestinal function by regulating the gut microbiota and their metabolites, such as short-chain fatty acids (SCFAs). These results suggest that IOP-0 might be a potential dietary supplement for the prevention and treatment of ulcerative colitis.

Keywords:  Gut microbiota; Short-chain fatty acids; Sulfated polysaccharide; Ulcerative colitis

DOI:  https://doi.org/10.1016/j.ijbiomac.2024.131915
Cureus. 2024 Mar;16(3): e57072

Type II Heparin-Induced Thrombocytopenia Manifesting As Cardiac Arrest Following Intravenous Heparin Bolus During an Elective Procedure: A Case Report and Literature Review.

Nisha Nepal, Dhiraj Patel, Opeyemi Omosebi, Yong Shin.

  Heparin-induced thrombocytopenia (HIT) is a rare and life-threatening autoimmune-mediated adverse drug reaction seen in patients who are exposed to various forms of pharmacological heparin, including unfractionated heparin (UFH) and low molecular weight heparin (LMWH). Despite the presence of thrombocytopenia, these patients face the risk of clot formation and bleeding simultaneously. Prompt cessation of heparin and the initiation of non-heparin anticoagulants are important for the patient's survival. Typically, clinical diagnosis of HIT is necessary, and waiting for lab test results, which can take days, may not be always feasible. Here, we present a case of an unusual presentation of type II HIT, complicated by significant thrombocytopenia, pulmonary hemorrhage, and cardiac arrest after receiving intravenous (IV) heparin bolus during an elective cardiac ablation procedure for paroxysmal atrial fibrillation.

Keywords:  anaphylactoid reaction; anti-pf4 antibody; cardiac arrest; direct anticoagulants; pulmonary hemorrhage; serotonin release assay; thromboembolism; type ii hit; unfractionated heparin

DOI:  https://doi.org/10.7759/cureus.57072
J Steroid Biochem Mol Biol. 2024 Apr 29. pii: S0960-0760(24)00087-6. [Epub ahead of print] 106539

Metabolism of Endogenous and Exogenous Estrogens in Women.

Frank Z Stanczyk.

  Estrogens regulate important processes in reproductive, skeletal, cardiovascular, and central nervous systems that impact women's overall health. Understanding endogenous and exogenously administered estrogen metabolism is vital to determining therapeutic estrogen levels. The present review provides an overview of estrogen metabolites formed in non-pregnant and pregnant women, and those resulting from exogenous estrogen administration. There are four principal endogenous estrogens: estrone (E1), estradiol (E2), estriol (E3), and estetrol (E4). E4, which is produced only in pregnancy, has emerged recently as an estrogen with significant therapeutic potential. E1, E2, and E3 undergo extensive metabolism primarily through phase I (hydroxylation, oxidation, reduction) and phase II (primarily conjugation) reactions, whereas E4 undergoes only phase II reactions. Exogenous estrogens commonly used for menopausal treatment and/or contraception, including micronized E2, conjugated equine estrogens, and ethinyl estradiol, also undergo phase I and phase II reactions, but differ widely in the types of metabolites formed. The mechanisms by which estrogen metabolites are formed and their excretion in urine, bile, and feces, are still poorly understood. We highlight areas that require further research to foster a better understanding of how estrogen metabolism impacts dosing of estrogens for therapeutic use, as well as the physiological regulation of endogenous estrogens.

Keywords:  conjugated equine estrogens; estetrol; estradiol; estrogens; metabolism

DOI:  https://doi.org/10.1016/j.jsbmb.2024.106539
Gut Microbes. 2024 Jan-Dec;16(1):16(1): 2341449

Sweet, bloody consumption - what we eat and how it affects vascular ageing, the BBB and kidney health in CKD.

Angelina Schwarz, Leah Hernandez, Samsul Arefin, Elisa Sartirana, Anna Witasp, Annika Wernerson, Peter Stenvinkel, Karolina Kublickiene.

  In today's industrialized society food consumption has changed immensely toward heightened red meat intake and use of artificial sweeteners instead of grains and vegetables or sugar, respectively. These dietary changes affect public health in general through an increased incidence of metabolic diseases like diabetes and obesity, with a further elevated risk for cardiorenal complications. Research shows that high red meat intake and artificial sweeteners ingestion can alter the microbial composition and further intestinal wall barrier permeability allowing increased transmission of uremic toxins like p-cresyl sulfate, indoxyl sulfate, trimethylamine n-oxide and phenylacetylglutamine into the blood stream causing an array of pathophysiological effects especially as a strain on the kidneys, since they are responsible for clearing out the toxins. In this review, we address how the burden of the Western diet affects the gut microbiome in altering the microbial composition and increasing the gut permeability for uremic toxins and the detrimental effects thereof on early vascular aging, the kidney per se and the blood-brain barrier, in addition to the potential implications for dietary changes/interventions to preserve the health issues related to chronic diseases in future.

Keywords:  artificial sweeteners; blood brain barrier; chronic kidney disease; cognitive decline; dysbiosis; early vascular aging; gut microbiome; red meat; uremic toxins

DOI:  https://doi.org/10.1080/19490976.2024.2341449
Biomed Pharmacother. 2024 Apr 30. pii: S0753-3322(24)00546-8. [Epub ahead of print]175 116662

DHEA-S, Androstenedione, 17-β-estradiol signature as novel biomarkers for early prediction of risk of malignant pleural mesothelioma linked to asbestos-exposure: A preliminary investigation.

Barbara Nuvoli, Andrea Sacconi, Grazia Bottillo, Francesca Sciarra, Roberta Libener, Antonio Maconi, Mariantonia Carosi, Giorgio Piperno, Eliuccia Mastropasqua, Maria Papale, Emanuela Camera, Rossella Galati.

  17-β-estradiol, involved in mesothelioma pathogenesis, and its precursors were explored as potential biomarkers for the early diagnosis of mesothelioma. Using enzyme-linked immunosorbent assay(ELISA) for 17-β-estradiol and ultra-high performance liquid chromatography/tandem mass spectrometry(UHPLC-MS/MS) for 19 17-β-estradiol precursors, a comprehensive analysis of 20steroid hormones was conducted in the serum of mesothelioma patients(n=67), asbestos-exposed healthy subjects(n=39), and non-asbestos-exposed healthy subjects(n=35). Bioinformatics analysis explored three potential serum biomarkers: 17-β-estradiol, DHEA-S, and androstenedione. The results revealed significant differences in 17-β-estradiol levels between mesothelioma patients and both non-asbestos-exposed and asbestos-exposed healthy subjects. No significant variations in serum 17-β-estradiol levels were observed among mesothelioma patients at different stages, suggesting its potential as an early diagnostic marker. 17-β-estradiol levels were similar in mesothelioma patients with environmental and occupational asbestos exposure, while males with occupational asbestos exposure exhibited significantly higher levels of 17-β-estradiol compared to females. Significant reduction in androstenedione and an increase in DHEA-S were observed in asbestos-exposed individuals compared to non-asbestos-exposed individuals. The analysis of DHEA-S-androstenedione-17-β-estradiol signature score showed an increase in asbestos-exposed individuals and mesothelioma patients compared to non-asbestos-exposed individuals, and this score effectively distinguished between the groups. The Cancer Genome Atlas data was utilized to analyze the expression of 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 genes. The findings indicated that mesothelioma patients with elevated gene values for 5-α-reductase1 and hydroxysteroid-17β-dehydrogenase2 have a worse or better prognosis on overall survival, respectively. In conclusion, this study suggests 17-β-estradiol, DHEA-S, and androstenedione as biomarkers for mesothelioma risk and early diagnosis of mesothelioma in asbestos-exposed individuals, aiding timely intervention and improved care.

Keywords:  17-β-estradiol; Androstenedione; Asbestos; DHEA-S; Malignant pleural mesothelioma; UHPLC-MS/MS, Biomarker

DOI:  https://doi.org/10.1016/j.biopha.2024.116662