Glycoconjugate Journal最新文献

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Analysis of site-dependent mucins in rat intestinal mucosa using anti-glycan monoclonal antibodies. 用抗多糖单克隆抗体分析大鼠肠黏膜中位点依赖性粘蛋白。
IF 3.1 4区 生物学
Glycoconjugate Journal Pub Date : 2025-08-01 Epub Date: 2025-06-28 DOI: 10.1007/s10719-025-10187-w
Makoto Kurihara, Yukinobu Goso, Rei Kawashima, Takafumi Ichikawa, Kazuhiko Ishihara
{"title":"Analysis of site-dependent mucins in rat intestinal mucosa using anti-glycan monoclonal antibodies.","authors":"Makoto Kurihara, Yukinobu Goso, Rei Kawashima, Takafumi Ichikawa, Kazuhiko Ishihara","doi":"10.1007/s10719-025-10187-w","DOIUrl":"10.1007/s10719-025-10187-w","url":null,"abstract":"<p><p>Intestinal gel-forming mucins are high-molecular weight glycoproteins, and their glycan moieties vary depending on the intestinal site. Although the means of analyzing mucin glycans are limited, monoclonal antibodies are expected to be a powerful analysis tool. In this study, 12 monoclonal antibodies were generated using rat intestinal mucin as the immunogen, and the epitopes of the antibodies were studied. The analyses using resins with the glycans of blood group-associated antigens and neoglycolipids synthesized from mucin glycans revealed that most antibodies recognize glycans. Furthermore, some recognize blood group-related antigens on glycans, whereas others recognize immaturely synthesized mucin-type glycans. Immunostaining of the rat jejunum, ileum, proximal colon, and distal colon with antibodies produced a site-dependent staining intestinal image. Affinity chromatography using an antibody-conjugated column was utilized to fractionate rat small intestinal mucins. Mucins with various glycan compositions were produced, suggesting the possibility of obtaining site-specific mucins. The site-specific mucins with various glycan compositions result in site-specific glycan functions, and the antibodies developed in this study could be useful tools for their analysis.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"187-198"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of GM1 ganglioside and its derivatives on ETI-rescued F508del-CFTR maturation and host-pathogen interactions in cystic fibrosis bronchial cells. GM1神经节苷脂及其衍生物对囊性纤维化支气管细胞中eti拯救的F508del-CFTR成熟和宿主-病原体相互作用的影响
IF 3.1 4区 生物学
Glycoconjugate Journal Pub Date : 2025-08-01 Epub Date: 2025-07-15 DOI: 10.1007/s10719-025-10191-0
Dorina Dobi, Alessandro Rimessi, Nicoletta Loberto, Laura Mauri, Rosaria Bassi, Elena Chiricozzi, Debora Olioso, Giulia Pellielo, Paolo Pinton, Valentino Bezzerri, Giulio Cabrini, Giuseppe Lippi, Anna Tamanini, Giulia Lunghi, Massimo Aureli
{"title":"Effects of GM1 ganglioside and its derivatives on ETI-rescued F508del-CFTR maturation and host-pathogen interactions in cystic fibrosis bronchial cells.","authors":"Dorina Dobi, Alessandro Rimessi, Nicoletta Loberto, Laura Mauri, Rosaria Bassi, Elena Chiricozzi, Debora Olioso, Giulia Pellielo, Paolo Pinton, Valentino Bezzerri, Giulio Cabrini, Giuseppe Lippi, Anna Tamanini, Giulia Lunghi, Massimo Aureli","doi":"10.1007/s10719-025-10191-0","DOIUrl":"10.1007/s10719-025-10191-0","url":null,"abstract":"<p><p>Cystic Fibrosis (CF), a life-threatening hereditary disease, arises from mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, which encodes a chloride-conducting channel widely expressed in epithelial cells. The most common mutation, F508del, causes CFTR misfolding, premature degradation, and impaired mucociliary clearance, leading to recurrent respiratory infections and inflammation. The triple combination therapy with Elexacaftor, Tezacaftor, and Ivacaftor (ETI) has revolutionized CF management by partially restoring mutated CFTR function. However, enhancing CFTR rescue and stabilizing host immune responses remain critical challenges. In airway epithelial cells, CFTR interacts with proteins and lipids in macromolecular complexes that influence its stability. Among these, the ganglioside GM1 plays a key role in modulating plasma membrane protein dynamics, including CFTR. This study investigates the effects of exogenous GM1 supplementation as an adjuvant to ETI treatment. Our results demonstrate that GM1 enhances F508del-CFTR maturation and stability, even under Pseudomonas aeruginosa infection, which typically suppresses CFTR expression and function. Furthermore, GM1 restores xenophagic activity in bronchial epithelial cells, improving host defence mechanisms against the bacteria. These findings underscore the therapeutic potential of GM1 and its analogues in optimizing the plasma membrane environment for CFTR correction, suggesting that by enhancing the efficacy of CFTR modulators, GM1 could pave the way for innovative approaches to improve CF management.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"173-186"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Progress in research on DDOST dysregulation in related diseases. DDOST在相关疾病中的失调研究进展。
IF 3.1 4区 生物学
Glycoconjugate Journal Pub Date : 2025-08-01 Epub Date: 2025-07-02 DOI: 10.1007/s10719-025-10188-9
Haoan Sun, Chunbao Xie
{"title":"Progress in research on DDOST dysregulation in related diseases.","authors":"Haoan Sun, Chunbao Xie","doi":"10.1007/s10719-025-10188-9","DOIUrl":"10.1007/s10719-025-10188-9","url":null,"abstract":"<p><p>DDOST is an important subunit of N-glycosylated oligosaccharyltransferase and is closely related to protein N-glycosylation. Some studies have reported that abnormal expression of DDOST is associated with congenital disorders of glycosylation, solid tumours and other diseases. To better understand the progress of research on DDOST in diseases, we herein provide a comprehensive review of the basic functions of DDOST, interactions molecules, DDOST-congenital disorders of glycosylation (DDOST-CDG) and solid tumours. Our review findings will lay a foundation for researchers to better understand the functions of DDOST and to investigate its specific mechanisms of action.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"125-135"},"PeriodicalIF":3.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the impact of advanced glycation end products on diabetic salivary gland dysfunctions. 探讨晚期糖基化终产物对糖尿病唾液腺功能障碍的影响。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2025-04-01 Epub Date: 2025-03-25 DOI: 10.1007/s10719-025-10182-1
Heba A Hassan
{"title":"Exploring the impact of advanced glycation end products on diabetic salivary gland dysfunctions.","authors":"Heba A Hassan","doi":"10.1007/s10719-025-10182-1","DOIUrl":"10.1007/s10719-025-10182-1","url":null,"abstract":"<p><p>The role of Advanced Glycation End Products (AGEs) in the pathophysiology of salivary gland dysfunction in diabetes has not been fully addressed. In this work, we discuss the pathophysiological mechanisms of salivary gland dysfunctions in diabetes, focusing on the role of AGEs. Hyperglycemia induces the generation and accumulation of AGEs, induces oxidative stress, and activates the receptor for AGEs (RAGE), with detrimental effects on the salivary glands and the submandibular autonomic innervation. Structural and ultrastructural alterations have been described in the three major salivary glands, and hypo-salivation development has been linked to early autonomic neuropathy. Poor metabolic control aggravates the salivary flow rate via injury to the autonomic nerve fiber bundles or direct damage to the secretory acinar cells of the glands. Chronic hyperglycemia, the most crucial feature of diabetes, leads to the generation and accumulation of advanced glycation end products (AGEs). The interest in the role of AGEs in the pathogenesis of diabetic complications has grown exponentially, and AGEs have been implicated as a primary culprit in the pathophysiology of diabetes and its various complications, including neuropathy, nephropathy, retinopathy, vasculopathy, and cardiomyopathy.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"97-106"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Computational insights into DC-SIGN's enhanced recognition of mannotriose CPS units via Ca2+ ion cross-talk. DC-SIGN通过Ca2+离子串扰增强对甘露糖CPS单位的识别的计算见解。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2025-04-01 Epub Date: 2025-02-19 DOI: 10.1007/s10719-025-10179-w
Hemchandra Deka, Arabinda Ghosh, Debabrat Baishya
{"title":"Computational insights into DC-SIGN's enhanced recognition of mannotriose CPS units via Ca<sup>2+</sup> ion cross-talk.","authors":"Hemchandra Deka, Arabinda Ghosh, Debabrat Baishya","doi":"10.1007/s10719-025-10179-w","DOIUrl":"10.1007/s10719-025-10179-w","url":null,"abstract":"<p><p>The Carbohydrate Recognition Domain (CRD) of immune system's c-type lectin receptors (CLRs) preferentially interacts with the Capsular Polysaccharides (CPS) units. Implicit Ca<sup>2+</sup> ions are crucial to CRD function. Increment of the ionic concentration explicitly affects the CPS recognition by CRD many-fold. DC-SIGN is one such CLR that acts for the differential recognition of the microbial CPS. The CPS mannotriose had the lowest binding energy (ΔG -4.7 kcal/mol) and the maximum affinity for DC-SIGN with implicit Ca<sup>2+</sup> ion. In the present investigation the ligand affinity increases with the rise of Ca<sup>2+</sup> concentration up to 1.5 M. Again, within the CRD the residues viz; Glutamate (347), Proline (348), and Asparagine (349) (EPN) were reported previously as essential for CPS unit coordination. Our analysis demonstrated that besides the EPN residues, CPS unit interacts with the neighboring Asparagine (350), Glutamate (354) and Asparagine (355) residues. Thus, these residues were replaced one at a time with Alanine (a charge neutral residue) to test their effect on the contact event. The CRD loses its affinity for recognition on the N350A, E354A, and D355A substitutions. Thus, this heterogeneity of CRD recognition towards Carbohydrate provides fresh information about the immune system's theragnostic function. This new understanding of Ca<sup>2+</sup>-induced recognition may help design new theragnostic applications that boost our immune defenses against pathogenic evasion.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"61-76"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Plant glycosides and glycosidases: classification, sources, and therapeutic insights in current medicine. 植物糖苷和糖苷酶:分类、来源和当前医学中的治疗见解。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2025-04-01 Epub Date: 2025-02-24 DOI: 10.1007/s10719-025-10180-3
Kumaresan Kowsalya, Nandakumar Vidya, Jayachandran Halka, Jaganathan Sakthi Yazhini Preetha, Muthukrishnan Saradhadevi, Jesudass Joseph Sahayarayan, Packiaraj Gurusaravanan, Muthukrishnan Arun
{"title":"Plant glycosides and glycosidases: classification, sources, and therapeutic insights in current medicine.","authors":"Kumaresan Kowsalya, Nandakumar Vidya, Jayachandran Halka, Jaganathan Sakthi Yazhini Preetha, Muthukrishnan Saradhadevi, Jesudass Joseph Sahayarayan, Packiaraj Gurusaravanan, Muthukrishnan Arun","doi":"10.1007/s10719-025-10180-3","DOIUrl":"10.1007/s10719-025-10180-3","url":null,"abstract":"<p><p>Plant glycosides have a broad spectrum of pharmaceutical activities primarily due to the glycosidic residues present in their structure. Especially, the therapeutic glycosides can be classified into many compounds based on the sugar moiety, chains/ saccharide units, glycosidic linkages, and aglycones. Among many classes, the widely used pharmacological classification is based on the aglycones linked to the glycoside molecule. Based on these non-sugar moiety (aglycones), plant glycosides are further classified into twelve different types of glycosides along with the recent discovery of novel (cannabinoid) glycosides. They are called alcoholic, anthraquinone, coumarin, chromone, cyanogenic, flavonoid, phenolic, cardiac, saponin, thio, steviol, iridoid, and cannabinoid glycosides. Each of the plant glycosides has been discussed in this paper with, origin, structure, and abundant presence in a specific family of plants. Besides, the therapeutic roles of these plant glycosides are further described in detail to validate their efficacies in the human health care system. On the other hand, glycosides are inactive until enzymatic hydrolysis releases their active aglycone, enabling targeted drug delivery. This process enhances aglycone solubility and stability, improving bioavailability and therapeutic efficacy. They target specific receptors or enzymes, minimizing off-target effects and enhancing pharmacological outcomes. Derived from plants, glycosides offer diverse chemical structures for drug development. They are integral to traditional medicine and modern pharmaceuticals, utilized in therapies ranging from cardiology to antimicrobial treatments.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"107-124"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Substrate flexibility of Mycoplasma fermentans mf1 phosphorylcholine transferase. 发酵支原体mf1磷酸胆碱转移酶的底物柔韧性。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2025-04-01 Epub Date: 2025-03-22 DOI: 10.1007/s10719-025-10181-2
Lena Nuschy, Biswajit Sarkar, Alla Zamyatina, Iain B H Wilson
{"title":"Substrate flexibility of Mycoplasma fermentans mf1 phosphorylcholine transferase.","authors":"Lena Nuschy, Biswajit Sarkar, Alla Zamyatina, Iain B H Wilson","doi":"10.1007/s10719-025-10181-2","DOIUrl":"10.1007/s10719-025-10181-2","url":null,"abstract":"<p><p>Zwitterionic modifications of glycans such as phosphorylcholine or phosphoethanolamine occur in a wide range of prokaryotic and eukaryotic organisms and are known for interaction with the mammalian immune system. Unlike the biosynthesis of membrane phospholipids which is well elucidated, very little is known about the transfer of zwitterionic phosphodiester moieties onto glycoconjugates. The presence and function of relevant enzymes has been suggested by gene knockout or mutation and corresponding aberrant phosphorylcholine metabolism. In the current study, the Mycoplasma fermentans phosphorylcholine transferase mf1, with previously confirmed in-vitro activity synthesizing phosphorylcholine-α-glucosyl-1,2-dipalmitoyl glycerol, is demonstrated to not only transfer phosphorylcholine but also phosphoethanolamine from CDP-ethanolamine. Moreover, mf1 is capable of using the β-configuration of the presumed natural substrate but transfers neither to simpler substrates with glucose moieties such as β-D-octyl-glucopyranoside nor to an extended lipid substrate with an additional galactose residue. These findings suggest a certain, but limited, substrate flexibility for bacterial PC-transferases. Mf1 activity is inhibited by β-glycerophosphate, an isomer of part of CDP-glycerol which is known to compete with CDP-ribitol in enzymatic reactions catalyzed by fukutin, a human protein sharing structural homology with mf1. For the first time, a phosphorylcholine transferase, mf1, could be biochemically characterized in vitro and its lipid products with zwitterionic phosphodiesters attached could be detected specifically with the pentraxin serum amyloid P.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"87-96"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11982090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cartilaginous fishes-derived chondroitin sulfates potentially suppress lipid droplet accumulation in the differentiated 3T3-L1 adipocytes. 软骨鱼来源的硫酸软骨素可能抑制分化的3T3-L1脂肪细胞中的脂滴积累。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2025-04-01 Epub Date: 2025-03-10 DOI: 10.1007/s10719-025-10183-0
Danang Dwi Cahyadi, Katsuhiko Warita, Naoko Takeda-Okuda, Jun-Ichi Tamura, Yoshinao Z Hosaka
{"title":"Cartilaginous fishes-derived chondroitin sulfates potentially suppress lipid droplet accumulation in the differentiated 3T3-L1 adipocytes.","authors":"Danang Dwi Cahyadi, Katsuhiko Warita, Naoko Takeda-Okuda, Jun-Ichi Tamura, Yoshinao Z Hosaka","doi":"10.1007/s10719-025-10183-0","DOIUrl":"10.1007/s10719-025-10183-0","url":null,"abstract":"<p><p>In this study, we investigated for cell proliferative and adipogenic differentiation inhibitory activities of chondroitin sulfate (CS) from cartilaginous fish: mako shark (Isurus oxyrinchus, spine part, Ms-CS), blue shark (Prionace glauca, spine part, Bs-CS), sharpspine skate (Okamejei acutispina, head and tail parts, Sp-CS) and stingray (Dasyatis akajei, head part, St-CS) on 3T3-L1 cells. Most of the CSs from cartilaginous fish showed concentration-dependent cell proliferative activity of 3T3-L1 cells within the retrieved concentration range (0-1,000 μg/mL), while under induction of adipocyte differentiation, they inhibited lipid accumulation. In particular, Ms-CS and Sp-CS were highly active in inhibiting lipid accumulation in the cells. The present study revealed that cartilaginous fish-derived CS has inhibitory activity on 3T3-L1 adipocyte differentiation by suppressing lipid droplet accumulation, although the degree of suppression varied depending on the composition of the CS and its origin. In addition, a significant increase in chondroitin sulfate N-acetylgalactosaminyltransferase 2 (Csgalnact2) expression of the Sp-CS group at the concentration of 500 µg/mL was observed. Csgalnact2 expression is associated with chondroitin N-acetylgalactosaminyltransferase-2 (ChGn-2), one of the glycosyltransferases that catalyzes the chain initiation and elongation of the CS backbone in its biosynthesis. Exogenous CS from cartilaginous fishes increased Csgalnact2 expression, although further studies are needed to confirm changes in CS biosynthesis. We observed reduced lipid accumulation in differentiated 3T3-L1 cells. Our findings highlight the role of CS polysaccharides, in inhibiting adipogenesis, even though further investigation is required to understand the underlying mechanism.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"77-86"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of CFTR modulators Elexacaftor/Tezacaftor/Ivacaftor on lipid metabolism in human bronchial epithelial cells. CFTR调节剂Elexacaftor/Tezacaftor/Ivacaftor对人支气管上皮细胞脂质代谢的影响。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2025-02-01 Epub Date: 2025-01-11 DOI: 10.1007/s10719-024-10174-7
Dorina Dobi, Nicoletta Loberto, Laura Mauri, Rosaria Bassi, Elena Chiricozzi, Giulia Lunghi, Massimo Aureli
{"title":"Effect of CFTR modulators Elexacaftor/Tezacaftor/Ivacaftor on lipid metabolism in human bronchial epithelial cells.","authors":"Dorina Dobi, Nicoletta Loberto, Laura Mauri, Rosaria Bassi, Elena Chiricozzi, Giulia Lunghi, Massimo Aureli","doi":"10.1007/s10719-024-10174-7","DOIUrl":"10.1007/s10719-024-10174-7","url":null,"abstract":"<p><p>Cystic Fibrosis (CF) is a life-threatening hereditary disease resulting from mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene that encodes a chloride channel essential for ion transport in epithelial cells. Mutations in CFTR, notably the prevalent F508del mutation, impair chloride transport, severely affecting the respiratory system and leading to recurrent infections. Recent therapeutic advancements include CFTR modulators such as ETI, a combination of two correctors (Elexacaftor and Tezacaftor) and a potentiator (Ivacaftor), that can improve CFTR function in patients with the F508del mutation. This study investigated ETI's impact on the maturation of the mutated CFTR, the expression levels of its scaffolding proteins, and lipid composition of cells using bronchial epithelial cell lines expressing both wild-type and F508del CFTR. Our findings revealed that ETI treatment enhances CFTR and its scaffolding proteins expression and aids in rescuing mature F508del CFTR, causing also significant alterations in the lipid profile including reduced levels of lactosylceramide and increased content of gangliosides GM1 and GD1a. These changes were linked to ETI's influence on enzymes involved in the sphingolipid metabolism, in particular GM3 synthase and sialidase. Through this work, we aim to deepen understanding CFTR interactions with lipids, and to elucidate the mechanisms of action of CFTR modulators. Our findings may support the development of potential therapeutic strategies contributing to the ongoing efforts to design effective correctors and potentiators for CF treatment.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"1-14"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of chondroitin sulphate-degrading enzyme Chondroitinase ABC by dextran sulphate. 硫酸葡聚糖对硫酸软骨素降解酶ABC的抑制作用。
IF 2.7 4区 生物学
Glycoconjugate Journal Pub Date : 2025-02-01 Epub Date: 2025-01-16 DOI: 10.1007/s10719-024-10175-6
Sagar Dalal, Rachana Pathak, Edward X S Moh, Nicolle H Packer
{"title":"Inhibition of chondroitin sulphate-degrading enzyme Chondroitinase ABC by dextran sulphate.","authors":"Sagar Dalal, Rachana Pathak, Edward X S Moh, Nicolle H Packer","doi":"10.1007/s10719-024-10175-6","DOIUrl":"10.1007/s10719-024-10175-6","url":null,"abstract":"<p><p>Chondroitin sulphate (CS) is a sulphated glycosaminoglycan (GAG) polysaccharide found on proteoglycans (CSPGs) in extracellular and pericellular matrices. Chondroitinase ABC (CSase ABC) derived from Proteus vulgaris is an enzyme that has gained attention for the capacity to cleave chondroitin sulphate (CS) glycosaminoglycans (GAG) from various proteoglycans such as Aggrecan, Neurocan, Decorin etc. The substrate specificity of CSase ABC is well-known for targeting various structural motifs of CS chains and has gained popularity in the field of neuro-regeneration by selective degradation of CS GAG chains. Within this context, our investigation into the biochemistry of CSase ABC led us to a previously unreported inhibition of CSase ABC activity by Dextran Sulphate (DexS). To understand the inhibitory effects of DexS, we compared its inhibition of CSase ABC to that of other polysaccharides such as Heparan Sulphate, Heparin, Colominic Acid, Fucoidan, and Dextran. This analysis identified key structural factors such as monosaccharide composition and linkage, sulphation degree and overall charge as influencing CSase ABC inhibition. Remarkably, DexS emerged as a unique inhibitor of CSase ABC, with distinctive inhibitory effects that correlate with its chain length. DexS has been used to reliably induce ulcerative colitis in mice, effectively mimicking inflammatory bowel diseases in humans, and has been previously shown to inhibit both RNA polymerase and reverse transcriptase. Our investigation emphasizes the interplay between the properties of DexS and CSase ABC, providing significant insights into the utilization of polysaccharide-based inhibitors for modulating enzyme activity.</p>","PeriodicalId":12762,"journal":{"name":"Glycoconjugate Journal","volume":" ","pages":"53-59"},"PeriodicalIF":2.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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