bims-supasi Biomed News
on Sulfation pathways and signalling
Issue of 2022–08–07
sixteen papers selected by
Jonathan Wolf Mueller, University of Birmingham
  1. Design and Synthesis of 1-O- and 6'-C-Modified Heparan Sulfate Trisaccharides as Human Endo-6-O-Sulfatase 1 Inhibitors.
  2. Enzymatic Production of Chondroitin Oligosaccharides and Its Sulfate Derivatives.
  3. Sulfated glycosaminoglycans inhibit transglutaminase 2 by stabilizing its closed conformation.
  4. Phosphorylation and sulfation share a common biosynthetic pathway, but extend biochemical and evolutionary diversity of biological macromolecules in distinct ways.
  5. Spike-heparan sulfate interactions in SARS-CoV-2 infection.
  6. Dehydroepiandrosterone sulfate levels at 7 years old are positively associated with more advanced pubertal development between 10 and 13 years old in girls: Conclusion.
  7. Overexpression of NDST1 attenuates fibrotic response in murine adipose-derived stem cells.
  8. Curcumin enhances p-cresyl sulfate-induced cytotoxic effects on renal tubular cells.
  9. Indoxyl sulfate, homocysteine, and antioxidant capacities in patients at different stages of chronic kidney disease.
  10. Short-time intensive insulin therapy upregulates 3 beta- and 17 beta-hydroxysteroid dehydrogenase levels in men with newly diagnosed T2DM.
  11. Cholesterol sulfate alleviates ulcerative colitis by promoting cholesterol biosynthesis in colonic epithelial cells.
  12. HS3ST1 Promotes Non-Small-Cell Lung Cancer Progression by Targeting the SPOP/FADD/NF-κB Pathway.
  13. Novel silkworm (Bombyx mori) sulfotransferase swSULT ST3 is involved in metabolism of polyphenols from mulberry leaves.
  14. Sulfated Fucogalactan From Laminaria Japonica Ameliorates β-Cell Failure by Attenuating Mitochondrial Dysfunction via SIRT1-PGC1-α Signaling Pathway Activation.
  15. Sulfated Polysaccharides Derived from Hypnea valentiae and Their Potential of Antioxidant, Antimicrobial, and Anticoagulant Activities with In Silico Docking.
  16. Aha1 Is an Autonomous Chaperone for SULT1A1.
  1. Front Chem. 2022 ;10 947475
    Design and Synthesis of 1-O- and 6'-C-Modified Heparan Sulfate Trisaccharides as Human Endo-6-O-Sulfatase 1 Inhibitors.
    Kuei-Yao Tseng, Zheng-Hao Tzeng, Ting-Jen Rachel Cheng, Pi-Hui Liang, Shang-Cheng Hung.
      The extracellular human endo-6-O-sulfatases (Sulf-1 and Sulf-2) are responsible for the endolytic cleavage of the 6-sulfate groups from the internal D-glucosamine residues in the highly sulfated subdomains of heparan sulfate proteoglycans. A trisaccharide sulfate, IdoA2OS-GlcNS6S-IdoA2OS, was identified as the minimal size of substrate for Sulf-1. In order to study the complex structure with Sulf-1 for developing potential drugs, two trisaccharide analogs, IdoA2OS-GlcNS6OSO2NH2-IdoA2OS-OMe and IdoA2OS-GlcNS6NS-IdoA2OS-OMe, were rationally designed and synthesized as the Sulf-1 inhibitors with IC50 values at 0.27 and 4.6 μM, respectively.
    Keywords:  carbohydrate chemistry; endo-6-O-sulfatases; glycosaminoglycans; heparan sulfate; inhibitors
    DOI:  https://doi.org/10.3389/fchem.2022.947475
  2. Front Bioeng Biotechnol. 2022 ;10 951740
    Enzymatic Production of Chondroitin Oligosaccharides and Its Sulfate Derivatives.
    Weijiao Zhang, Ruirui Xu, Xuerong Jin, Yang Wang, Litao Hu, Tianmeng Zhang, Guocheng Du, Zhen Kang.
      Chondroitin sulfate (CS) has a wide range of physiological functions and clinical applications. However, the biosynthesis of chondroitin oligosaccharides (o-CHs) and sulfate derivatives with specific length is always challenging. Herein, we report enzymatic strategies for producing homogeneous o-CHs and its sulfate derivatives from microbial sourced chondroitin. Chondroitin disaccharides, tetrasaccharides, hexasaccharides, octasaccharides, and decasaccharides with defined structure were produced by controllably depolymerizing microbial sourced chondroitin with an engineered chondroitinase ABC I. The highest conversion rates of the above corresponding o-CHs were 65.5%, 32.1%, 12.7%, 7.2%, and 16.3%, respectively. A new efficient enzymatic sulfation system that directly initiates from adenosine 5'-triphosphate (ATP) and sulfate was developed and improved the sulfation of chondroitin from 8.3% to 85.8% by optimizing the temperature, sulfate and ATP concentration. o-CHs decasaccharide, octasaccharide, hexasaccharide, tetrasaccharide and disaccharide were modified and the corresponding sulfate derivatives with one sulfate group were prepared. The enzymatic approaches constructed here for preparing o-CHs and its sulfate derivatives pave the way for the study of structure-activity relationship and applications.
    Keywords:  chondroitin; chondroitin sulfate; chondroitinase ABC I; oligosaccharides; sulfation system
    DOI:  https://doi.org/10.3389/fbioe.2022.951740
  3. Sci Rep. 2022 Aug 03. 12(1): 13326
    Sulfated glycosaminoglycans inhibit transglutaminase 2 by stabilizing its closed conformation.
    Claudia Damaris Müller, Gloria Ruiz-Gómez, Sophie Cazzonelli, Stephanie Möller, Robert Wodtke, Reik Löser, Joanna Freyse, Jan-Niklas Dürig, Jörg Rademann, Ute Hempel, M Teresa Pisabarro, Sarah Vogel.
      Transglutaminases (TGs) catalyze the covalent crosslinking of proteins via isopeptide bonds. The most prominent isoform, TG2, is associated with physiological processes such as extracellular matrix (ECM) stabilization and plays a crucial role in the pathogenesis of e.g. fibrotic diseases, cancer and celiac disease. Therefore, TG2 represents a pharmacological target of increasing relevance. The glycosaminoglycans (GAG) heparin (HE) and heparan sulfate (HS) constitute high-affinity interaction partners of TG2 in the ECM. Chemically modified GAG are promising molecules for pharmacological applications as their composition and chemical functionalization may be used to tackle the function of ECM molecular systems, which has been recently described for hyaluronan (HA) and chondroitin sulfate (CS). Herein, we investigate the recognition of GAG derivatives by TG2 using an enzyme-crosslinking activity assay in combination with in silico molecular modeling and docking techniques. The study reveals that GAG represent potent inhibitors of TG2 crosslinking activity and offers atom-detailed mechanistic insights.
    DOI:  https://doi.org/10.1038/s41598-022-17113-2
  4. J R Soc Interface. 2022 Aug;19(193): 20220391
    Phosphorylation and sulfation share a common biosynthetic pathway, but extend biochemical and evolutionary diversity of biological macromolecules in distinct ways.
    M A Lima, T R Rudd, D G Fernig, E A Yates.
      Phosphate and sulfate groups are integral to energy metabolism and introduce negative charges into biological macromolecules. One purpose of such modifications is to elicit precise binding/activation of protein partners. The physico-chemical properties of the two groups, while superficially similar, differ in one important respect-the valency of the central (phosphorus or sulfur) atom. This dictates the distinct properties of their respective esters, di-esters and hence their charges, interactions with metal ions and their solubility. These, in turn, determine the contrasting roles for which each group has evolved in biological systems. Biosynthetic links exist between the two modifications; the sulfate donor 3'-phosphoadenosine-5'-phosphosulfate being formed from adenosine triphosphate (ATP) and adenosine phosphosulfate, while the latter is generated from sulfate anions and ATP. Furthermore, phosphorylation, by a xylosyl kinase (Fam20B, glycosaminoglycan xylosylkinase) of the xylose residue of the tetrasaccharide linker region that connects nascent glycosaminoglycan (GAG) chains to their parent proteoglycans, substantially accelerates their biosynthesis. Following observations that GAG chains can enter the cell nucleus, it is hypothesized that sulfated GAGs could influence events in the nucleus, which would complete a feedback loop uniting the complementary anionic modifications of phosphorylation and sulfation through complex, inter-connected signalling networks and warrants further exploration.
    Keywords:  macromolecules; phosphorylation; sulfation
    DOI:  https://doi.org/10.1098/rsif.2022.0391
  5. Curr Opin Struct Biol. 2022 Jul 06. pii: S0959-440X(22)00118-X. [Epub ahead of print]76 102439
    Spike-heparan sulfate interactions in SARS-CoV-2 infection.
    Fiona L Kearns, Daniel R Sandoval, Lorenzo Casalino, Thomas M Clausen, Mia A Rosenfeld, Charlotte B Spliid, Rommie E Amaro, Jeffrey D Esko.
      Recent biochemical, biophysical, and genetic studies have shown that heparan sulfate, a major component of the cellular glycocalyx, participates in infection of SARS-CoV-2 by facilitating the so-called open conformation of the spike protein, which is required for binding to ACE2. This review highlights the involvement of heparan sulfate in the SARS-CoV-2 infection cycle and argues that there is a high degree of coordination between host cell heparan sulfate and asparagine-linked glycans on the spike in enabling ACE2 binding and subsequent infection. The discovery that spike protein binding and infection depends on both viral and host glycans provides insights into the evolution, spread and potential therapies for SARS-CoV-2 and its variants.
    DOI:  https://doi.org/10.1016/j.sbi.2022.102439
  6. Clin Endocrinol (Oxf). 2022 Aug 02.
    Dehydroepiandrosterone sulfate levels at 7 years old are positively associated with more advanced pubertal development between 10 and 13 years old in girls: Conclusion.
    Rita Santos-Silva, Manuel Fontoura, Milton Severo, Ana Cristina Santos.
       OBJECTIVE: We aimed to explore the association between dehydroepiandrosterone sulfate (DHEAS) levels at age 7, pubertal development between ages 10 and 13, and age at menarche.
    METHODS: Longitudinal study of 603 individuals (301 girls, 302 boys) from the Generation XXI cohort. Evaluation of the participants at ages 7, 10 and 13 included anthropometry and Tanner staging. Pubertal development between ages 10-13 was categorized using Latent Class Analysis, based on Tanner stages. The association between DHEAS at age 7 and pubertal development between ages 10-13 was conducted with binomial logistic regression, adjusted for BMI z-score. The variation of age at menarche in relation to DHEAS levels at age 7, controlling for maternal age at menarche, birth weight z-score and BMI z-score, was estimated fitting a linear regression model.
    RESULTS: Pubertal development at ages 10-13 was categorized in two classes - class 1 had higher probability for lower Tanner stage (less advanced sexual maturation) and class 2 had higher probability for higher Tanner stage (more advanced sexual maturation). In girls, taking class 1 as a reference, class 2 was positively associated with BMI z-score and DHEAS. In boys, class 2 was positively associated with BMI, but not with DHEAS. DHEAS levels at age 7 were negatively associated with age at menarche, after adjustment for maternal age at menarche, birth weight and BMI. This article is protected by copyright. All rights reserved.
    Keywords:  Generation XXI; Tanner stages, puberty; adrenarche; dehydroepiandrosterone sulfate
    DOI:  https://doi.org/10.1111/cen.14805
  7. Stem Cells Dev. 2022 Aug 03.
    Overexpression of NDST1 attenuates fibrotic response in murine adipose-derived stem cells.
    Takayoshi Otsuka, Ho-Man Kan, Timothy D Mason, Lakshmi S Nair, Cato T Laurencin.
      Adipose-derived stem cells (ADSCs) hold tremendous potential for treating diseases and repairing damaged tissues. Heparan sulfate (HS) plays various roles in cellular signaling mechanisms. The importance of HS in stem cell function has been reported and well documented. However, there has been little progress in using HS for therapeutic purposes. We focused on one of the sulfotransferases, NDST1, which influences overall HS chain extent and sulfation pattern, with the expectation to enhance stem cell function by increasing the N-sulfation level. We herein performed transfections of a GFP-vector control and NDST1-vector into mouse ADSCs to evaluate stem cell functions. Overexpression of NDST1 suppressed the osteogenic differentiation of ADSCs. There was no pronounced effect observed on the stemness, inflammatory gene expression, nor any noticeable effect in adipogenic and chondrogenic differentiation. Under the tumor necrosis factor-alpha (TNF-α) stimulation, NDST1 overexpression induced several chemokine productions that attract neutrophils and macrophages. Finally, we identified an anti-fibrotic response in ADSCs overexpressing NDST1. This study provides a foundation for the evaluation of HS-related effects in ADSCs undergoing ex vivo gene manipulation.
    DOI:  https://doi.org/10.1089/scd.2022.0053
  8. Int J Med Sci. 2022 ;19(7): 1138-1146
    Curcumin enhances p-cresyl sulfate-induced cytotoxic effects on renal tubular cells.
    Chyou-Wei Wei, Tsai-Kun Wu, Shu-Cing Wu, Yi-Lin Chen, Ying-Ru Pan, Yi-Chung Chien, Jia-Yan Wu, Yung-Lung Yu, Giou-Teng Yiang.
      Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), protein-bound uremic toxins, can induce oxidative stress and cause renal disease progression. However, the different cytotoxic effects on renal cells between IS and PCS are not stated. Due to uremic toxins are generally found in CKD patients, the mechanisms of uremic toxins-induced renal injury are required to study. Curcumin has anti-oxidant, anti-inflammatory and anti-apoptotic effects which may be potential used to protect against renal damage. In contrast, curcumin also exert cytotoxic effects on various cells. In addition, curcumin may reduce or enhance cytotoxicity combined with different chemicals treatments. However, whether curcumin may influence uremic toxins-induced renal injury is unclear. The goal of this study is to compare the different cytotoxic effects on renal cells between IS and PCS treatment, as well as the synergistic or antagonistic effects by combination treatments with curcumin and PCS. Our experimental result shows the PCS exerts a stronger antiproliferative effect on renal tubular cells than IS treatment. In addition, our study firstly demonstrates that curcumin enhances PCS-induced cell cytotoxicity through caspase-dependent apoptotic pathway and cell cycle alteration.
    Keywords:  Curcumin; Indoxyl sulfate; p-cresyl sulfate
    DOI:  https://doi.org/10.7150/ijms.72646
  9. Nutr Res Pract. 2022 Aug;16(4): 464-475
    Indoxyl sulfate, homocysteine, and antioxidant capacities in patients at different stages of chronic kidney disease.
    Cheng-Hsu Chen, Shih-Chien Huang, En-Ling Yeh, Pei-Chih Lin, Shang-Feng Tsai, Yi-Chia Huang.
       BACKGROUND/OBJECTIVES: Increased levels of uremic toxins and decreased antioxidant capacity have a significant impact on the progression of chronic kidney disease (CKD). However, it remains unclear whether they interact with each other to mediate the damage of kidney function. The purpose of this study was to investigate whether uremic toxins (i.e., homocysteine and indoxyl sulfate [IS]), as well as glutathione-dependent antioxidant enzyme activities are dependently or independently associated with kidney function during different stages of CKD patients.
    SUBJECTS/METHODS: One hundred thirty-two patients diagnosed with CKD at stages 1 to 5 participated in this cross-sectional study.
    RESULTS: Patients who had reached an advanced CKD stage experienced an increase in plasma uremic toxin levels, along with decreased glutathione peroxidase (GSH-Px) activity. Plasma homocysteine, cysteine, and IS concentrations were all positively associated with each other, but negatively correlated to GSH-Px activity levels after adjusting for potential confounders in all CKD patients. Although plasma homocysteine, cysteine, IS, and GSH-Px levels were significantly associated with kidney function, only plasma IS levels still had a significant association with kidney function after these parameters were simultaneously adjusted. In addition, plasma IS could interact with GSH-Px activity to be associated with kidney function.
    CONCLUSIONS: IS plays a more dominant role than homocysteine and GSH-Px activity in relation to kidney function.
    Keywords:  Uremic toxins; chronic kidney disease; glutathione peroxidase; homocysteine; indoxyl sulfate
    DOI:  https://doi.org/10.4162/nrp.2022.16.4.464
  10. Front Endocrinol (Lausanne). 2022 ;13 894743
    Short-time intensive insulin therapy upregulates 3 beta- and 17 beta-hydroxysteroid dehydrogenase levels in men with newly diagnosed T2DM.
    Yun Hu, Ying Wang, Ting-Ting Cai, Lu Liu, Dong-Mei Li, Jian-Hua Ma, Bo Ding.
       Objective: Our previous study has found that short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes mellitus (T2DM) increased serum testosterone levels, but the underlying mechanisms remain unclear.
    Design and methods: In this self-controlled study, 43 men with newly diagnosed drug naïve T2DM, aged 18-60 years, with HbA1c >9.0% were treated with continuous subcutaneous insulin infusion (CSII) to normalize blood glucose within one week. Venous blood specimens were collected for measuring of serum total testosterone, dehydroepiandrosterone sulfate (DHEA-S), 3β- and 17β-hydroxysteroid dehydrogenase (3β- and 17β-HSD) concentrations before and after insulin therapy.
    Results: Testosterone increased from 13.0 (11.3, 14.6) nmol/L to 15.7 (13.9, 17.5) nmol/L after intensive insulin therapy (p<0.001), while the levels of DHEA-S decreased significantly after treatment (from 6.5 (5.7, 7.3) μmol/L to 6.0 (5.3, 6.7) μmol/L, p=0.001). The ratio of testosterone/DHEA-S increased significantly (2.4 (2.0, 2.8) vs. 3.1 (2.6, 3.7) nmol/μmol, p<0.001). After blood glucose normalization with the short-term CSII therapy, 3β-HSD increased from 11.0 (9.5, 12.5) pg/mL to 14.6 (13.5, 15.7) pg/mL, p=0.001, and 17β-HSD increased from 20.7 (16.3, 25.2) pg/mL to 28.2 (23.8, 32.5) pg/mL, p=0.009.
    Conclusions: Blood glucose normalization via short-term intensive insulin therapy increases plasma total testosterone levels in men with newly diagnosed type 2 diabetes, associated with a decreased level of DHEA-S, probably because of the enhanced conversion from DHEA to testosterone catalyzed by 3β-HSD and 17β-HSD.
    Keywords:  beta-hydroxysteroid dehydrogenase; dehydroepiandrosterone sulfate; diabetes mellitus; insulin; testosterone
    DOI:  https://doi.org/10.3389/fendo.2022.894743
  11. Nat Commun. 2022 Jul 30. 13(1): 4428
    Cholesterol sulfate alleviates ulcerative colitis by promoting cholesterol biosynthesis in colonic epithelial cells.
    Dongke Xu, Ruijun Ma, Yi Ju, Xiaowei Song, Baolin Niu, Wenting Hong, Rong Wang, Qin Yang, Zhi Zhao, Yuchen Zhang, Yufan Zheng, Qianming Bai, Mingfang Lv, Ning Sun, Xiaobo Li.
      Cholesterol sulfate, produced by hydroxysteroid sulfotransferase 2B1 (SULT2B1), is highly abundant in the intestine. Herein, we study the functional role and underlying intestinal epithelial repair mechanisms of cholesterol sulfate in ulcerative colitis. The levels of cholesterol and cholesterol sulfate, as well as the expression of Sult2b1 and genes involved in cholesterol biosynthesis, are significantly higher in inflamed tissues from patients with ulcerative colitis than in intestinal mucosa from healthy controls. Cholesterol sulfate in the gut and circulation is mainly catalyzed by intestinal epithelial SULT2B1. Specific deletion of the Sult2b1 gene in the intestinal epithelial cells aggravates dextran sulfate sodium-induced colitis; however, dietary supplementation with cholesterol sulfate ameliorates this effect in acute and chronic ulcerative colitis in mice. Cholesterol sulfate promotes cholesterol biosynthesis by binding to Niemann-Pick type C2 protein and activating sterol regulatory element binding protein 2 in colonic epithelial cells, thereby alleviates ulcerative colitis. In conclusion, cholesterol sulfate contributes to the healing of the mucosal barrier and exhibits therapeutic efficacy against ulcerative colitis in mice.
    DOI:  https://doi.org/10.1038/s41467-022-32158-7
  12. Biomed Res Int. 2022 ;2022 5509346
    HS3ST1 Promotes Non-Small-Cell Lung Cancer Progression by Targeting the SPOP/FADD/NF-κB Pathway.
    Xianxiu Ji, Kebin Cheng, Caixia Gao, Huikang Xie, Ren Zhu, Jie Luo.
      Heparan sulfate proteoglycan is a key component of cell microenvironment and plays an important role in cell-cell interaction, adhesion, migration, and signal transduction. Heparan sulfate 3-O-sulfotransferase 1 (HS3ST1) is a metabolic-related gene of HS. The present study was aimed at exploring the role of HS3ST1 in the progress of non-small-cell lung cancer (NSCLC). Our results illustrated that HS3ST1 promoted the malignant behaviors of NSCLC cells both in vitro and in vivo. HS3ST1 was found to inhibit spot-type zinc finger protein (SPOP) expression, which might inhibit the NF-κB pathway activation through mediating the degradation of Fas-associated death domain protein (FADD). By analyzing NSCLC patient samples, we also found increased HS3ST1 expression and decreased SPOP expression in tumor tissues in contrast with those in adjoining normal tissues. In conclusion, HS3ST1 promotes NSCLC tumorigenesis by regulating SPOP/FADD/NF-κB pathway.
    DOI:  https://doi.org/10.1155/2022/5509346
  13. PLoS One. 2022 ;17(8): e0270804
    Novel silkworm (Bombyx mori) sulfotransferase swSULT ST3 is involved in metabolism of polyphenols from mulberry leaves.
    Kohji Yamamoto, Naotaka Yamada, Satoshi Endo, Katsuhisa Kurogi, Yoichi Sakakibara, Masahito Suiko.
      Polyphenols in plants are important for defense responses against microorganisms, insect herbivory, and control of feeding. Owing to their antioxidant, anti-cancer, and anti-inflammatory activities, their importance in human nutrition has been acknowledged. However, metabolism of polyphenols derived from mulberry leaves in silkworms (Bombyx mori) remains unclear. Sulfotransferases (SULT) are involved in the metabolism of xenobiotics and endogenous compounds. The purpose of this study is to investigate the metabolic mechanism of polyphenols mediated by B. mori SULT. Here, we identified a novel SULT in silkworms (herein, swSULT ST3). Recombinant swSULT ST3 overexpressed in Escherichia coli effectively sulfated polyphenols present in mulberry leaves. swSULT ST3 showed high specific activity toward genistein among the polyphenols. Genistein-7-sulfate was produced by the activity of swSULT ST3. Higher expression of swSULT ST3 mRNA was observed in the midgut and fat body than in the hemocytes, testis, ovary, and silk gland. Polyphenols inhibited the aldo-keto reductase detoxification of reactive aldehydes from mulberry leaves, and the most noticeable inhibition was observed with genistein. Our results suggest that swSULT ST3 plays a role in the detoxification of polyphenols, including genistein, and contributes to the effects of aldo-keto reductase in the midgut of silkworms. This study provides new insight into the functions of SULTs and the molecular mechanism responsible for host plant selection in lepidopteran insects.
    DOI:  https://doi.org/10.1371/journal.pone.0270804
  14. Front Endocrinol (Lausanne). 2022 ;13 881256
    Sulfated Fucogalactan From Laminaria Japonica Ameliorates β-Cell Failure by Attenuating Mitochondrial Dysfunction via SIRT1-PGC1-α Signaling Pathway Activation.
    Nan Wu, Weihua Jin, Yuchen Zhao, Hong Wang, Sunyue He, Wenjing Zhang, Jiaqiang Zhou.
      As mitochondrial metabolism is a major determinant of β-cell insulin secretion, mitochondrial dysfunction underlies β-cell failure and type 2 diabetes mellitus progression. An algal polysaccharide of Laminaria japonica, sulfated fucogalactan (SFG) displays various pharmacological effects in a variety of conditions, including metabolic disease. We investigated the protective effects of SFG against hydrogen peroxide (H2O2)-induced β-cell failure in MIN6 cells and islets. SFG significantly promoted the H2O2-inhibited proliferation in the cells and ameliorated their senescence, and potentiated β-cell function by regulating β-cell identity and the insulin exocytosis-related genes and proteins in H2O2-induced β-cells. SFG also attenuated mitochondrial dysfunction, including alterations in ATP content, mitochondrial respiratory chain genes and proteins expression, and reactive oxygen species and superoxide dismutase levels. Furthermore, SFG resulted in SIRT1-PGC1-α pathway activation and upregulated the downstream Nrf2 and Tfam. Taken together, the results show that SFG attenuates H2O2-induced β-cell failure by improving mitochondrial function via SIRT1-PGC1-α signaling pathway activation. Therefore, SFG is implicated as a potential agent for treating pancreatic β-cell failure.
    Keywords:  SIRT1–PGC1-α; insulin exocytosis; mitochondrial dysfunction; pancreatic β-cell failure; senescence
    DOI:  https://doi.org/10.3389/fendo.2022.881256
  15. Evid Based Complement Alternat Med. 2022 ;2022 3715806
    Sulfated Polysaccharides Derived from Hypnea valentiae and Their Potential of Antioxidant, Antimicrobial, and Anticoagulant Activities with In Silico Docking.
    Kokila Palani, Balamuralikrishnan Balasubramanian, Arunkumar Malaisamy, Viji Maluventhen, Vijaya Anand Arumugam, Naif Abdullah Al-Dhabi, Mariadhas Valan Arasu, Karthika Pushparaj, Wen-Chao Liu, Maruthupandian Arumugam.
      Carrageenan, a sulfated polysaccharide, was produced by certain species of marine red seaweeds, which have been used as a significant source of food, feed, and antibiotic agent throughout history due to their alleged human health benefits. The present study aimed to derive the polysaccharides from Hypnea valentiae and describe the biological applications. Carrageenan was characterized by FT-IR, C-NMR, AFM, and their antimicrobial, antioxidant, and anticoagulant capabilities; furthermore, the larvicidal effect of methanol extract was generated from the seaweed against Aedes aegypti larvae at various concentrations. The molecular docking experiments were carried out computationally for finding the molecular insight of the macromolecules and small molecules' interaction using GLIDE docking by using Schrodinger software. Antibacterial zones of inhibition in different concentrations are compared with the 40 mg/mL higher activity against bacterial pathogens. Carrageenan is strong in all antioxidant activities, with the overall antioxidant (70.1 ± 0.61%) of radical at 250 μg/mL concentration being exhibited. The DPPH scavenging is effective in the inhibition of (65.74 ± 0.58%) radical at a concentration of 160 μg/mL and the hydroxyl scavenging (65.72 ± 0.60%) of activity at a concentration of 125 μg/mL being exhibited. Anticoagulant activities (APPT and PT) of carrageenan fraction were tested. H. valentiae and heparin sulphate shows higher activity of APTT (106.50 IU at 25 μg/mL) in comparison with the PT test (57.86 IU at 25 μg/mL) and the methanol extraction of higher larvicidal activity on A. aegypti (LC50 = 99.675 μg/mL). In this study, the carrageenan was exploited through in vitro and in silico molecular docking studies against antimicrobial, antioxidant, and anticoagulant properties. The results were establishing the potentiality of the carrageenan which is an alternative source to control the mosquitocidal property in the future. Moreover, molecular docking of carrageenan against multiple targets results in -7 to -6 Kcal/mol binding score. Findings of carrageen from in vitro to in silico studies are needed for further validation of clinical pieces of evidence.
    DOI:  https://doi.org/10.1155/2022/3715806
  16. Chem Res Toxicol. 2022 Aug 04.
    Aha1 Is an Autonomous Chaperone for SULT1A1.
    Xiaochuan Liu, Yinsheng Wang.
      The cochaperone Aha1 activates HSP90 ATPase to promote the folding of its client proteins; however, very few client proteins of Aha1 are known. With the use of an ascorbate peroxidase (APEX)-based proximity labeling method, we identified SULT1A1 as a proximity protein of HSP90 that is modulated by genetic depletion of Aha1. Immunoprecipitation followed by Western blot analysis showed the interaction of SULT1A1 with Aha1, but not HSP90. We also observed a reduced level of SULT1A1 protein upon genetic depletion of Aha1 but not upon pharmacological inhibition of HSP90, suggesting that the SULT1A1 protein level is regulated by Aha1 alone. Maturation-dependent interaction assay results showed that Aha1, but not HSP90, binds preferentially to newly synthesized SULT1A1. Reconstitution of Aha1-depleted cells with wild-type Aha1 and its E67K mutant, which is deficient in interacting with HSP90, restored SULT1A1 protein to the same level. Nonetheless, complementation of Aha1-depleted cells with an Aha1 mutant lacking the first 20 amino acids, which disrupts its autonomous chaperone function, was unable to rescue the SULT1A1 protein level. Together, our study revealed, for the first time, Aha1 as an autonomous chaperone in regulating SULT1A1. SULT1A1 is a phase-II metabolic enzyme, where it adds sulfate groups to hydroxyl functionalities in endogenous hormones and xenobiotic chemicals to improve their solubilities and promote their excretion. Thus, our work suggests the role of Aha1 cochaperone in modulating the detoxification of endogenous and environmental chemicals.
    DOI:  https://doi.org/10.1021/acs.chemrestox.2c00167
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