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At least 19 recordsLinked to original sources
PubMed1978

Induction and 'superinduction' of sialylation of membrane-bound gamma-glutamyltransferase during liver regeneration.

The present paper shows that in the regenerating rat liver the membrane-bound-gamma-glutamyltransferase exists in two molecular forms. Depending on the state of proliferation, a sialic-acid-rich enzyme (in the fetal or regenerating liver) or a sialic-acid-poor enzyme (in the adult or quiescent liver) could be detected. In regeneration liver (24 h after 2/3 resection) only the sialic-acid-rich or fetal enzyme could be found. Since total enzyme activity (adult + fetal type) remained unchanged, it is assumed that the adult type of gamma-glutamyltransferase was modified by sialylation during the initial phase of liver regeneration. This process of sialylation was prevented by inhibitors of RNA or protein synthesis such as D-galactosamine, actinomycin D or cycloheximide, provided that the inhibitor (D-galactosamine) was given within the first 8 h after partial hepatectomy. Sialylation was not impaired by inhibitors of DNA synthesis, e.g. hydroxyurea or cytosine arabinoside. Administration of actinomycin D during a defined phase of proliferation (24 to 48 h after partial hepatectomy) stimulated the transfer of sialic acid to gamma-glutamyltransferase, a finding which describes for the first time the so-called 'superinduction' of a sialylation process.

Animals↗
PubMed1979

The sialoglycoproteins of murine erythrocyte ghosts. A modified periodic acid-Schiff stain procedure staining nonsubstituted and O-acetylated sialyl residues on glycopeptides.

Murine erythrocyte ghosts (from DBA/2, CD-1, and B6D2 strains) contain significant amounts of O-acetylated sialyl residues, which are slowly oxidized by periodate. Sialic acids have been purified from murine erythrocyte ghosts and the existence of O-acetylated sialic acids has been confirmed: 1) by assaying with the Warren procedure before and after de-O-acetylation with 0.1 N NaOH for 45 min at 4 degrees C; 2) by thin layer chromatography on cellulose; and 3) by gas-liquid chromatography. Because these sialyl residues are unevenly distributed on the sialoglycoproteins of murine erythrocyte ghosts, the periodic acid-Schiff staining detects only one major sialoglycoprotein. A modification of the periodic acid-Schiff stain method removes these O-acetyl groups after electrophoresis and reveals two additional sialoglycoproteins which bear the majority of the O-acetylated sialyl residues. Rat erythrocyte ghosts have similar residues on one of their two sialoglycoproteins. Ghosts of human, rabbit, and guinea pig erythrocytes do not contain detectable amounts of O-acetylated sialyl residues.

Acetylation↗
PubMed2025

Prognostic and immunological implications of sialylation-associated gene signatures in hepatocellular carcinoma.

OBJECTIVE: The absence of effective biomarkers continues to limit early diagnostic accuracy and prognostic evaluation in patients with hepatocellular carcinoma (HCC). Aberrant sialylation (SI) has been demonstrated to contribute to therapeutic resistance and tumor progression. The aim of this investigation was to identify a sialylation-related gene (SRG) signature, evaluate its prognostic significance, and investigate associated immunological characteristics in HCC. METHODS: Transcriptomic profiles and corresponding clinical data for patients with HCC were obtained from UCSC Xena, the International Cancer Genome Consortium (ICGC), and the Molecular Signatures Database (MsigDB). Differential expression analysis, Cox regression analysis modeling, and least absolute shrinkage and selection operator (LASSO) regression analysis were applied to identify independent prognostic markers and develop predictive models. The tumor immune microenvironment and its relationship with the identified SRGs were assessed by evaluating immune infiltration patterns. A gene co-expression network for the prognostic SRGs was constructed using GeneMANIA to identify potentially targetable signaling pathways. RESULTS: Four SRGs (ST6GALNAC4, B4GALT5, B4GALNT1, and NEU1) were significantly associated with the prognosis of patients with HCC. Prognostic models constructed using these genes demonstrated strong predictive performance. Notable differences were observed in immune cell populations and immune checkpoint expression between the high-risk and low-risk groups. Additionally, the half-maximal inhibitory concentration values for 101 therapeutic compounds varied between these groups. Lipopolysaccharide and sphingolipid metabolism were identified as key biological processes linked to tumor progression and modulation of the immune microenvironment. CONCLUSION: The four identified SRGs were significantly associated with clinical outcomes and immunological features in HCC. These findings provide a foundation for advancing early diagnostic strategies, refining prognostic assessments, and guiding personalized therapeutic approaches for patients with HCC.

Humans↗
PubMed2026

Characterization of a series of patients with GNE-related thrombocytopenia: insights into pathogenesis, diagnosis, and treatment.

BACKGROUND: GNE-related thrombocytopenia (GNE-RT) is a very rare disorder caused by biallelic variants in GNE, which encodes a key enzyme in sialic acid biosynthesis. Patients usually present with severe thrombocytopenia and excessive bleeding. Knowledge of this condition remains limited. There are no recognized diagnostic tests for the diagnosis of GNE-RT. A previous study showed reduced platelet half-life as a mechanism of thrombocytopenia; however, it remains unclear whether the sialylation defect also impairs platelet biogenesis. OBJECTIVES: To gain insights into the clinical aspects and platelet biogenesis of GNE-RT. METHODS: We investigated 4 new GNE-RT patients (3 families). A recently standardized flow cytometry assay was used to characterize platelet sialylation. Patients' megakaryocytes were cultured to study megakaryopoiesis and proplatelet formation. A validated 3-dimensional bone marrow model was used to investigate platelet production. RESULTS: We characterized 3 novel GNE variants and demonstrated the pathogenicity of 2 variants of uncertain significance. In all individuals, platelet flow cytometry showed increased RCA-1 and ECL lectin binding and decreased MAL-II binding. Sialylation of serum transferrin showed no clear alterations. Despite the sialylation defect, patients' megakaryocytes showed preserved differentiation, maturation, and proplatelet formation. Ex vivo, megakaryocytes produced a normal number of normal-sized platelets. Two patients received eltrombopag and achieved a durable clinical response (38- and 72-month follow-up). CONCLUSION: The profound megakaryocyte sialylation defect induced by GNE variants does not affect platelet biogenesis. Platelet flow cytometry assessing RCA-1 and MAL-II binding is a reliable, simple assay for diagnosing GNE-RT. Based on a literature review, 55% of GNE-RT patients respond to thrombopoietin mimetics.

GNE gene↗
PubMed1977

Purification and properties of rabbit spermatozoal acrosomal neuraminidase.

Treatment of rabbit spermatozoa with 50mM-MgCl2 removes the plasma and the outer acrosomal membranes. Subsequent treatment with the detergents Hyamine 2389 and Triton X-100 solubilizes spermatozoal neuraminidase bound to the inner acrosomal membrane. The enzyme was further purified by DEAE-cellulose, Sephadex G-150 and Bio-Gel P-300 column chromato. The enzyme showed a single major band, with the possibility of some minor contaminants, on disc-gel electrophoresis. It had a specific activity of 0.37 micronmal of sialic acid released/min per mg with purified boar Cowper's-gland mucin as the substrate. The enzyme had marked specificity for 2 leads to 6'-linked sialic acid in glycoproteins. The Km of spermatozoal neuraminidase was 1.72 X 10(-6)M with Cowper's-gland mucin, 1.17 X 10(-5)M with fetuin and 8.8 X 10(-4)M with sialyl-lactose as a substrates. The Vmax. was 0.112 micronmol/min per mg with the Cowper's-gland mucin, 0.071 micronmol/min per mg with fetuin and 0.033 micronmol/min per mg with sialyl-lactose as substrate. The enzyme hydrolysed sheep submaxillary-gland mucin as readily as the Cowper's-gland mucin. The optimum of enzyme activity was at pH 5.0 on the Cowper's-gland mucin and at pH4.3 on sialyl-lactose. The enzyme activity was unaffected by 20mM-Na+ and-K+, but was inhibited by 20mM-Ca2+,-Mn2+,-Co2+ and -Cu2+. The enzyme was unstable in dilute solutions, but could be stored indefinitely freeze-dried at --20 degrees C.

Acrosome↗
PubMed1977

Species-specific aggregation factor in sponges. Sialyltransferase associated with aggregation factor.

The sialyltransferase (= glycoprotein-sialic acid transferase) was studied in the sponge Geodia cydonium, a mesozoan organism. The experiments were performed both in intact cellular and in isolated enzyme systems. It is shown, that desialylated cells show a lower aggregation potency than the controls. During aggregation enzymic sialylation of desialylated sponge cells occurs in the presence of an aggregation factor, which is associated with a high molecular weight particle. The sialylation process is temperature-dependent and can be inhibited by N-ethylmaleimide. Sialylation occurs predominantly at a distinct cell surface component, the aggregation receptor. The sialyltransferase was isolated and purified by the following steps: Sepharose 4B, CM-cellulose, Nonidet treatment, and Sephadex G-100. By this procedure the enzyme was purified 680-fold with a 31% yield. The sialyltransferase is originally associated with the high molecular weight particle also carrying the aggregation factor. In the last step the aggregation factor was separated from the sialyltransferase. The enzyme catalyzes the transfer of sialic acid from CMP-sialic acid to the desialylated aggregation receptor. The molecular weight of the sialyltransferase has been determined to be 52,000. Kinetic studies revealed no lag phase and a dependence on enzyme concentration. The purified transferase has a pH optimum of 7.75 and requires 200 mM NaCl for activity. No requirement for Mg2+ or Ca2+ could be observed. The reaction is inhibited by 10 micronM N-ethylmaleimide.

Animals↗
PubMed2024

GRable Version 1.0: A Software Tool for Site-Specific Glycoform Analysis With Improved MS1-Based Glycopeptide Detection With Parallel Clustering and Confidence Evaluation With MS2 Information.

High-throughput intact glycopeptide analysis is crucial for elucidating the physiological and pathological status of the glycans attached to each glycoprotein. Mass spectrometry-based glycoproteomic methods are challenging because of the diversity and heterogeneity of glycan structures. Therefore, we developed an MS1-based site-specific glycoform analysis method named "Glycan heterogeneity-based Relational IDentification of Glycopeptide signals on Elution profile (Glyco-RIDGE)" for a more comprehensive analysis. This method detects glycopeptide signals as a cluster based on the mass and chromatographic properties of glycopeptides and then searches for each combination of core peptides and glycan compositions by matching their mass and retention time differences. Here, we developed a novel browser-based software named GRable for semi-automated Glyco-RIDGE analysis with significant improvements in glycopeptide detection algorithms, including "parallel clustering." This unique function improved the comprehensiveness of glycopeptide detection and allowed the analysis to focus on specific glycan structures, such as pauci-mannose. The other notable improvement is evaluating the "confidence level" of the GRable results, especially using MS2 information. This function facilitated reduced misassignment of the core peptide and glycan composition and improved the interpretation of the results. Additional improved points of the algorithms are "correction function" for accurate monoisotopic peak picking; one-to-one correspondence of clusters and core peptides even for multiply sialylated glycopeptides; and "inter-cluster analysis" function for understanding the reason for detected but unmatched clusters. The significance of these improvements was demonstrated using purified and crude glycoprotein samples, showing that GRable allowed site-specific glycoform analysis of intact sialylated glycoproteins on a large-scale and in-depth. Therefore, this software will help us analyze the status and changes in glycans to obtain biological and clinical insights into protein glycosylation by complementing the comprehensiveness of MS2-based glycoproteomics. GRable can be freely run online using a web browser via the GlyCosmos Portal (https://glycosmos.org/grable).

Glycopeptides↗
PubMed2026

Dysregulation of the serum and IgG N-glycome in decompensated cirrhosis and its association with Model for End-Stage Liver Disease-Sodium (MELD-Na).

BACKGROUND AND AIMS: N-glycans modulate glycoprotein structure and function and are altered during chronic inflammation. We sought to define the extent of serum and IgG N-glycan disruption in patients with decompensated liver cirrhosis from alcohol-related liver disease (ALD), primary sclerosing cholangitis (PSC), and ALD-related hepatocellular carcinoma (HCC). Finally, we aimed to examine whether serum and IgG glycosylation is associated with changes in Model for End-stage Liver Disease-Sodium (MELD-Na) scores, a clinical marker used to prioritise liver transplantation. METHODS: Serum samples were obtained from patients with ALD (n = 17), PSC (n = 7), ALD-related HCC (n = 4), and healthy controls (n = 10). N-glycans were released, fluorescently labelled, and profiled by hydrophilic interaction ultra performance liquid chromatography (HILIC-UPLC). Chromatograms were integrated into 46 and 23 glycan peaks for serum and IgG respectively. These peaks and their associated glycosylation traits were statistically compared with healthy controls using age- and sex-adjusted linear regression models. RESULTS: In serum, decompensated cirrhosis shows statistically significant shifts toward less complex, agalactosylated and asialylated biantennary glycans, accompanied by significant losses of highly branched, galactosylated and sialylated structures. IgG mirrored this pattern, which is characteristic of a pro-inflammatory signature, with increased agalactosylation and bisected glycan levels, along with reduced levels of digalactosylated and sialylated species. N-glycan profiles showed significant associations with MELD-Na scores, indicating that inflammatory processes in decompensated liver cirrhosis continue to reshape serum glycoproteins. CONCLUSION: Decompensated liver cirrhosis shows profound remodelling of serum and IgG N-glycans. These data establish a reference framework for terminal glycomic disruption in liver disease and highlight the potential value of incorporating glycosylation analysis into broader assessments of liver disease progression.

Humans↗
PubMed2026

From glycosylation to inflammation: insights from NMR-Derived GlycA and GlycB.

Post-translational modifications (PTMs) play a crucial role in increasing proteomic diversity. N-linked glycosylation acts as a key regulatory layer that influences protein stability, trafficking, circulation, and immune responses. Unlike conventional inflammatory biomarkers that measure individual proteins, nuclear magnetic resonance (NMR) spectroscopy identifies the combined signals GlycA and GlycB from glycoproteins, offering an overall view of systemic glycoprotein changes. These signals represent the N-glycosylation patterns of several abundant acute-phase proteins (APPs), giving detailed molecular insights. This review offers a detailed assessment of GlycA and GlycB as mechanistically grounded indicators of liver glycoprotein remodeling and systemic inflammation. GlycA mainly indicates the levels and structural complexity of N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc) residues linked to acute-phase glycoproteins and glycan branching. In contrast, GlycB reflects changes in terminal sialylation, which influences glycoprotein half-life, immune recognition via lectins, and inflammatory signaling. Collectively, these biomarkers combine measurements of hepatic APP production with variations in glycan structure, offering mechanistically anchored reporters of hepatic glycoprotein remodeling. We explore the enzymatic pathways responsible for N-glycan branching, fucosylation, and sialylation, as well as the roles of major APP scaffolds in the GlycA and GlycB resonances. We also highlight the emerging clinical significance of these signals across infectious, autoimmune, cardiovascular, metabolic, neurodegenerative, and cancer-related diseases. Rather than serving simply as markers of inflammation, GlycA and GlycB provide mechanistically interpretable readouts of cytokine-driven hepatic glycoprotein remodeling and systemic immune activation, supporting their application in disease risk stratification, longitudinal monitoring, therapeutic response assessment, and precision medicine.

GlycA↗
PubMed1976

Microheterogeneity of arylsulfatase A from human tissues.

Human arylsulfatase A (cerebroside-3-sulfate 3-sulfohydrolase, EC 3.1.6.8) exhibited microheterogeneity on isoelectric focusing in polyacrylamide gels. Pure urinary enzyme gave 3 bands of activity with pI values of 4.7, 4.8 and 4.9, whereas purified liver enzyme yielded six equally spaced bands from pI 4.4 to 4.9. Detection of enzyme in the gel was made by either methylumbelliferyl sulfate or nitrocatechol sulfate. Crude enzyme preparations from human liver, kindey, placenta, brain and testis showed the six-banded pattern with varying amounts of activity in the different bands. The banding pattern of cultured human fibroblast extracts was distinctive: in addition to activity in the area of Bands 1-6 a sharp band at pI 5.1 was observed with both enzyme stains. This latter band was also present in metachromatic leukodystrophy fibroblast extracts. However, in this case the band did not appear when the specific aryl-sulfatase A stain was used. Enzyme Bands 1, 2 and 3 from urine were isolated by extraction of the gel. The three bands refocused in their initial positions; showed nearly identical enzymatic activities toward methylumbelliferyl sulfate, mitrocatechol sulfate, cerebroside sulfate and ascorbic acid 2-sulfate; and demonstrated equivalent immunological competence by antibody titration. The banding pattern of urinary arylsulfatase A was unchanged with neuraminidase treatment, whereas Bands 4-6 of the liver enzyme were converted to Bands 1-3 by this treatment. It appears that Bands 4-6 are due to sialylation of aryl-sulfatase A but that Bands 1-3 are probably due to some other type of post-ribosomal protein modification.

Brain↗
PubMed1977

Studies on human alpha-fetoprotein. Isolation and characterization of monomeric and polymeric forms and amino-terminal sequence analysis.

Human alpha-fetoprotein has been isolated from the serum and ascitic fluid of a patient with hepatoma by a combination of immunoadsorbent column chromatography and Sephadex G-150 gel filtration. Human alpha-fetoprotein is a sialylated glycoprotein with an estimated molecular weight of 67 500, composed of a single-chain polypeptide of approximately 580 amino acid residues and 3.6% carbohydrate. It is a negatively charged protein with an acid isoelectric point (pH 4.57). In addition to the monomeric form of alpha-fetoprotein, we have identified human alpha-fetoprotein polymers, including dimeric and trimeric forms, which dissociate to the monomer only upon exposure to disulfide-reducing reagents, implying that their formation is dependent upon intermolecular disulfide bonds. These polymers are found in human alpha-fetoprotein isolated by isoelectric focusing in both the major (pI 4.57) and minor (pI 5.2) alpha-fetoprotein fractions. The first 17 residues of the NH2-terminal amino acid sequence of the hepatoma-derived human alpha-fetoprotein have been identified. Fetal alpha-fetoprotein is indistinguishable from hepatoma alpha-fetoprotein by several criteria, including immunoelectrophoresis, acryalmide gel electrophoresis, and proclivity for dimerization.

Amino Acid Sequence↗
PubMed1977

Effects of denervation on the neuraminidase activity of slow and fast muscles of rabbits.

The presence in skeletal muscles of rabbits of neuraminidase activity on sialyl lactose was demonstrated. By comparing the specific activity of this enzyme in different control muscles, it was shown that it was 2.3 times higher in the slow than in the fast muscles. Seven days after denervation, we observed a significant increase of activity in fast muscle and a significant decrease of activity in slow muscle. These results, together with previous data, are in favour of the hypothesis that turnover of muscle glycoconjugates is under a type-specific neural control.

Animals↗
PubMed1976

Properties of mouse alpha-galactosidase.

alpha-Galactosidase has been examined in various murine tissues using the substrate 4-methylumbelliferyl-alpha-galactoside. Mouse liver appears to contain a single major form of the enzyme, as judged by chromatography and electrophoresis. The enzmye was purified 467-fold with a yield of about 40% by a method involving chromatography on Concanavalin A-Sepharose. It has maximal activity at pH 4.2, a Km value of 1.4 mM, and energy of activation of 16 400 cal/mol, and a molecular weight of 150 000 at pH 5.2. It is inhibited at high concentrations of myoinositol and appears to contain N-acetylneuraminic acid. In these characteristics it resembles human alpha-galactosidase A. The enzyme from various tissues differs in electrophoretic mobility. After treatment with neuraminidase, however, the enzyme from all tissues comigrates as a single band of activity. By this criterion the alpha-galactosidase of liver is most heavily sialylated and that from kidney the least. As estimated by gel filtration, the enzyme from liver and kidney exists as species of molecular weight 320 000, 150 000 and 70 000, depending upon pH and ionic strength. This appears to be the result of aggregation of the enzyme, since the forms are interconvertible and under some conditions a single molecular weight species is observed. The liver enzyme is primarily lysosomal, while the kidney enzyme is distributed approximately equally between lysosomal and microsomal fractions.

Animals↗
PubMed1979

Glycoprotein biosynthesis in calf kidney. Glycoprotein sialyltransferase activities towards serum glycoproteins and calf Tamm-Horsfall glycoprotein.

CMP-AcNeu:glycoprotein sialyltransltransltransltransltransferase of calf kidney cortex was characterized using serum glycoproteins and Tamm-Horsfall glycoprotein, obtained from calf urine, as acceptors. Native calf Tamm-Horsfall glycoprotein showed the best acceptor properties, followed by desialylated calf fetuin and desialylated human alpha 1-acid glycoprotein exhibiting V values of, respectively, 114, 63 and 41 nmol/h per g wet wt. of kidney cortex and Km values of 0.12, 0.16 and 0.26 mM glycoprotein acceptor. Desialylated ovine submaxillary mucine appeared to be a very poor acceptor. Tamm-Horsfall glycoprotein sialyltransferase could be distinguished from serum glycoprotein sialyltransferase by competition studies. In addition the two glycoprotein sialyltransferase activities showed different distributions over the three regions of the calf kidney: the ratios of the Tamm-Horsfall to serum glycoprotein sialyltransferase activities decreased from 3.3 in the cortex to 0.8 and 0.4 in the medulla and the papilla, respectively. It was concluded that in calf kidney at least two different sialyltransferases exist. The high cortical Tamm-Horsfall glycoprotein sialyltransferases activity corresponds markedly to the origin of the urinary Tamm-Horsfall glycoprotein, namely the distal part of the kidney tubule. Inactivation of glycoprotein sialyltransferase activity by preincubation at various temperatures and during storage at 0 degree C, could be reduced by the addition of CMP-AcNeu. The possible relevance towards the in vivo sialylation of this finding is discussed.

Animals↗
PubMed2026

Crown ethers as artificial decoys: A supramolecular strategy to block SARS-CoV-2 entry via host-guest interactions.

Coronavirus disease (COVID-19) remains a major global health challenge, highlighting the need for antiviral strategies that act at the earliest stages of infection. Given that viral entry and spike-receptor interaction are critical steps in the coronavirus life cycle, targeting these processes represents a powerful strategy to block infection at its earliest stage. Inspired by the glycan-recognition and extracellular viral-trapping functions of pulmonary surfactant collectins (SP-A and SP-D), this work integrates supramolecular chemistry, pulmonary surfactant biology, and antiviral research to establish a biomimetic supramolecular molecular-decoy framework based on crown ethers, cyclodextrins, and related macrocyclic architectures. Through host-guest molecular recognition, these macrocyclic scaffolds can be engineered to mimic sialylated host receptors and multivalent glycan motifs, enabling competitive binding to viral spike proteins, virion capture, and sequestration away from epithelial surfaces. By redirecting viruses toward artificial host-mimetic structures, supramolecular decoys could intercept SARS-CoV-2 and other enveloped respiratory viruses before host-cell attachment, membrane fusion, or genome release. Acting upstream of intracellular replication, this strategy may prevent initiation of the viral replication cycle and subsequent hijacking of the host protein synthesis machinery, while potentially minimizing interference with host metabolic pathways and reducing the likelihood of resistance development. Furthermore, it can be translated into inhalation nanoformulations for pulmonary delivery and localized formulations targeting the upper respiratory tract. Overall, by integrating the biological principles of pulmonary surfactant immunity with supramolecular host-guest chemistry, this work provides a conceptual foundation for biomimetic molecular-decoy antivirals and highlights a promising direction for next-generation broad-spectrum antiviral design against emerging respiratory viruses.

Antiviral Agents↗