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Proceedings of the Japan Academy.... 2019Glycosylation is an important posttranslational modification in mammals. The glycans of glycoproteins are classified into two groups, namely, N-glycans and O-glycans,...
Glycosylation is an important posttranslational modification in mammals. The glycans of glycoproteins are classified into two groups, namely, N-glycans and O-glycans, according to their glycan-peptide linkage regions. Recently, O-mannosyl glycan, an O-glycan, has been shown to be important in muscle and brain development. A clear relationship between O-mannosyl glycans and the pathomechanisms of some congenital muscular dystrophies has been established in humans. Ribitol-5-phosphate is a newly identified glycan component in mammals, and its biosynthetic pathway has been elucidated. The discovery of new glycan structures and the identification of highly regulated mechanisms of glycan processing will help researchers to understand glycan functions and develop therapeutic strategies.
Topics: Animals; Disease; Glycosylation; Humans; Mammals; Mannose; Polysaccharides
PubMed: 30643095
DOI: 10.2183/pjab.95.004 -
Methods in Molecular Biology (Clifton,... 2020The Galanthus nivalis lectin, abbreviated as GNA, is the model protein for a large group of mannose-binding lectins. Here, we describe the purification of GNA starting...
The Galanthus nivalis lectin, abbreviated as GNA, is the model protein for a large group of mannose-binding lectins. Here, we describe the purification of GNA starting from dry bulbs. Using a combination of ion exchange chromatography and affinity chromatography on mannose-Sepharose, a highly pure preparation of GNA can be obtained.
Topics: Chromatography, Affinity; Chromatography, Ion Exchange; Galanthus; Mannose; Mannose-Binding Lectins; Plant Lectins; Plant Roots; Sepharose
PubMed: 32306348
DOI: 10.1007/978-1-0716-0430-4_40 -
Microbial Pathogenesis Dec 2023Pseudomonas aeruginosa is a Gram-negative bacteria and it has been demonstrated that immunization with the outer membrane proteins of the microbe produces most of the... (Review)
Review
Pseudomonas aeruginosa is a Gram-negative bacteria and it has been demonstrated that immunization with the outer membrane proteins of the microbe produces most of the relevant human antibodies. The peritrichous P. aeruginosa strain with MSHA fimbriae (PA-MSHA strain) has been found to be effective in the inhibition of growth and proliferation of different types of cancer cells. Furthermore, it has been revealed that PA-MSHA exhibits cytotoxicity because of the presence of MSHA and therefore it possesses anti-carcinogenic ability against different types of human cancer cell lines including, gastric, breast, hepatocarcinoma and nasopharyngeal cells. Studies have revealed that PA-MSHA exhibits therapeutic potential against cancer growth by induction of apoptosis, arrest of cell cycle, activating NF-κB/TLR5 pathway, etc. In China, PA-MSHA injections have been approved for the treatment of malignant tumor patients from very long back. The present review article demonstrates the therapeutic potential of PA-MSHA against various types of human cancers and explains the underlying mechanism.
Topics: Humans; Signal Transduction; Pseudomonas aeruginosa; Hemagglutinins; Mannose; Cell Proliferation; Liver Neoplasms
PubMed: 37871855
DOI: 10.1016/j.micpath.2023.106422 -
Neurochemical Research Aug 2017Glucose is the main peripheral substrate for energy production in the brain. However, as other hexoses are present in blood and cerebrospinal fluid, we have investigated...
Glucose is the main peripheral substrate for energy production in the brain. However, as other hexoses are present in blood and cerebrospinal fluid, we have investigated whether neurons have the potential to metabolize, in addition to glucose, also the hexoses mannose, fructose or galactose. Incubation of primary cerebellar granule neurons in the absence of glucose caused severe cell toxicity within 24 h, which could not be prevented by application of galactose or fructose, while the cells remained viable during incubation in the presence of either mannose or glucose. In addition, cultured neurons produced substantial and almost identical amounts of lactate after exposure to either glucose or mannose, while lactate production was low in the presence of fructose and hardly detectable during incubations without hexoses or with galactose as carbon source. Determination of the K values of hexokinase in lysates of cultured neurons for the hexoses revealed values in the micromolar range for mannose (32 ± 2 µM) and glucose (59 ± 10 µM) and in the millimolar range for fructose (4.4 ± 2.3 mM), demonstrating that mannose is efficiently phosphorylated by neuronal hexokinase. Finally, cultured neurons contained reasonable specific activity of the enzyme phosphomannose isomerase, which is required for isomerization of the hexokinase product mannose-6-phosphate into the glycolysis intermediate fructose-6-phosphate. These data demonstrate that cultured cerebellar granule neurons have the potential and express the required enzymes to efficiently metabolize mannose, while galactose and fructose serve at best poorly as extracellular carbon sources for neurons.
Topics: Animals; Animals, Newborn; Cell Survival; Cells, Cultured; Cerebellum; Mannose; Neurons; Rats; Rats, Wistar
PubMed: 28345119
DOI: 10.1007/s11064-017-2241-9 -
Journal of the American Chemical Society Jan 2024() is one of history's most successful human pathogens. By subverting typical immune responses, can persist within a host until conditions become favorable for growth...
() is one of history's most successful human pathogens. By subverting typical immune responses, can persist within a host until conditions become favorable for growth and proliferation. Virulence factors that enable mycobacteria to modulate host immune systems include a suite of mannose-containing glycolipids: phosphatidylinositol mannosides, lipomannan, and lipoarabinomannan (LAM). Despite their importance, tools for their covalent capture, modification, and imaging are limited. Here, we describe a chemical biology strategy to detect and visualize these glycans. Our approach, biosynthetic incorporation, is to synthesize a lipid-glycan precursor that can be incorporated at a late-stage step in glycolipid biosynthesis. We previously demonstrated selective mycobacterial arabinan modification by biosynthetic incorporation using an exogenous donor. This report reveals that biosynthetic labeling is general and selective: it allows for cell surface mannose-containing glycolipid modification without nonspecific labeling of mannosylated glycoproteins. Specifically, we employed azido-()-farnesyl phosphoryl-β-d-mannose probes and took advantage of the strain-promoted azide-alkyne cycloaddition to label and directly visualize the localization and dynamics of mycobacterial mannose-containing glycolipids. Our studies highlight the generality and utility of biosynthetic incorporation as the probe structure directs the selective labeling of distinct glycans. The disclosed agents allowed for direct tracking of the target immunomodulatory glycolipid dynamics in cellulo. We anticipate that these probes will facilitate investigating the diverse biological roles of these glycans.
Topics: Humans; Glycolipids; Mannose; Lipopolysaccharides; Polysaccharides; Mycobacterium tuberculosis
PubMed: 38112296
DOI: 10.1021/jacs.3c09495 -
Biochimica Et Biophysica Acta. General... Mar 2021C-mannosylation is a type of protein glycosylation. Human Isthmin-1 (ISM1) is a 52-kDa secreted protein with a thrombospondin type 1 repeat (TSR) domain, containing two...
BACKGROUND
C-mannosylation is a type of protein glycosylation. Human Isthmin-1 (ISM1) is a 52-kDa secreted protein with a thrombospondin type 1 repeat (TSR) domain, containing two consensus C-mannosylation sequences at Trp and Trp. In this study, we sought to examine the role of C-mannosylation in the secretion of ISM1.
METHODS
We established and cultured an ISM1-overexpressing HT1080 cell line and purified recombinant ISM1 for analysis from the conditioned medium by LC-MS/MS. Subcellular localization of ISM1 was observed by confocal fluorescence microscopy.
RESULTS
We found that ISM1 is C-mannosylated at Trp and Trp in the TSR domain. To determine the functions of the C-mannosylation of ISM1, we established a C-mannosylation-defective mutant ISM1-overexpressing HT1080 cell line and measured its secretion of ISM1. The secretion of ISM1 decreased significantly in this mutant ISM1-overexpressing line compared with wild-type cells. Furthermore, ISM1 was N-glycosylated only in these C-mannosylation-defective cells.
CONCLUSIONS
ISM1 is C-mannosylated in its TSR domain, and the status of the C-mannosylation of ISM1 affects its N-glycosylation.
GENERAL SIGNIFICANCE
The C-mannosylation of ISM1 regulates its N-glycosylation status.
Topics: Amino Acid Motifs; Amino Acid Substitution; Cell Line, Tumor; Culture Media, Conditioned; Fibroblasts; Gene Expression; Genetic Vectors; Glycosylation; Humans; Mannose; Mutation; Protein Processing, Post-Translational; Recombinant Proteins; Thrombospondins
PubMed: 33412225
DOI: 10.1016/j.bbagen.2020.129840 -
Multivalent mannose-conjugated siRNA causes robust gene silencing in pancreatic macrophages in vivo.European Journal of Pharmaceutics and... Feb 2023Nucleic acid therapeutics have been utilized for gene regulation, and their recent advancement has led to approval of novel drugs for liver-related disorders. However,...
Nucleic acid therapeutics have been utilized for gene regulation, and their recent advancement has led to approval of novel drugs for liver-related disorders. However, systemic extrahepatic delivery remains challenging. Here, we report newly designed mannose-conjugated oligonucleotides for delivering oligonucleotides to macrophages by leveraging the mannose receptor, C-type 1 (MRC1, CD206), which is abundantly expressed in macrophages. We investigated the relationship between cellular uptake and multivalency (mono to tetra) of mannose ligands or linker length and selected a trivalent-mannose ligand. Trivalent-mannose (Man3)-conjugated siRNA induced concentration-dependent gene silencing in both human CD206-overexpressing cells and human macrophages in vitro. After subcutaneous injection into mice, we observed a high distribution of Man3-conjugated oligonucleotides in the liver and pancreata as well as cellular uptake into Kupffer cells and pancreatic macrophages. A single subcutaneous injection of Man3-conjugated siRNA (10 mg/kg) targeting β-microglobulin (B2M) silenced B2m mRNA expression by ∼50% and decreased its protein levels in mouse pancreatic macrophages compared to those in saline-treated mice. Of note, multiple subcutaneous injections decreased B2m gene expression and B2M protein levels by ∼80% and ∼85%, respectively. These results show that mannose-conjugation with oligonucleotides is expected to help deliver oligonucleotides to macrophages and regulate gene expression in vivo, particularly in the pancreas.
Topics: Humans; Animals; Mice; RNA, Small Interfering; Mannose; Macrophages; Gene Silencing; Ligands; Pancreas; Oligonucleotides
PubMed: 36603692
DOI: 10.1016/j.ejpb.2022.12.017 -
Current Drug Delivery 2021To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit Seed Starch Nanoparticles (JFSSNPs) for site-specific delivery.
AIM
To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit Seed Starch Nanoparticles (JFSSNPs) for site-specific delivery.
BACKGROUND
Liver cancer is the third leading cause of death in the world and the fifth most often diagnosed cancer. It is a major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target-specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of the drug in normal tissues.
OBJECTIVE
To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5- FU) loaded Jackfruit Seed Starch Nanoparticles (JFSSNPs) for effective treatment of liver cancer.
MATERIALS AND METHODS
5-FU loaded JFSSNPs were prepared and optimized formulations having higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. The potential of NPs was studied using in vitro cytotoxicity assay, in vivo kinetic studies, and bio-distribution studies.
RESULT AND DISCUSSION
5-Fluorouracil loaded NPs had a particle size between 336 to 802 nm with drug entrapment efficiency between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of the drug in amorphous form. DSC study suggests there was no physical interaction between 5-FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assisted in the selective accumulation of 5-FU in the liver (vs. other organs spleen, kidney, lungs, and heart) compared to unconjugated one and plain drug.
CONCLUSION
In vivo, bio-distribution, and plasma profile studies resulted in a significantly higher concentration of 5-Fluorouracil liver, suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.
Topics: Drug Carriers; Drug Delivery Systems; Fluorouracil; Humans; Kinetics; Liver Neoplasms; Mannose; Nanoparticles; Particle Size; Starch
PubMed: 32885751
DOI: 10.2174/1567201817666200903171124 -
Carbohydrate Research Jul 2019A series of 3-carbamoyl- and 2,3-dicarbamoyl-mannose derivatives were synthesized, conjugated to a fluorescent dye (Cy5, AF 647 or NBD) and their cellular uptake in A549...
A series of 3-carbamoyl- and 2,3-dicarbamoyl-mannose derivatives were synthesized, conjugated to a fluorescent dye (Cy5, AF 647 or NBD) and their cellular uptake in A549 and THP-1 cell lines was studied by FACS. In contrast to earlier studies on carbamoyl mannosides, the observed uptake was not related to carbamoyl group on the mannose residue but rather to the cyanine dye attached, a trend previously observed for Cy5-fructose conjugates. The NBD-conjugates however, showed a temperature and concentration dependent uptake in case of mannose conjugates. These results suggest a profound impact of the dye which should be taken into consideration when studying the uptake of small molecules by dye conjugation.
Topics: A549 Cells; Biological Transport; Chemistry Techniques, Synthetic; Flow Cytometry; Humans; Mannose; Temperature
PubMed: 31252337
DOI: 10.1016/j.carres.2019.06.008 -
Cellular Signalling Jan 2024The rewiring of cellular metabolism is a defining characteristic of cancer, as tumor cells adapt to acquire essential nutrients from a nutrient-poor environment to... (Review)
Review
The rewiring of cellular metabolism is a defining characteristic of cancer, as tumor cells adapt to acquire essential nutrients from a nutrient-poor environment to sustain their viability and biomass. While hypoxia has been identified as a major factor depriving cancer cells of nutrients, recent studies have revealed that cancer cells distant from supporting blood vessels also face nutrient limitations. To overcome this challenge, hypoxic cancer cells, which heavily rely on glucose as an energy source, employ alternative pathways such as glycogen metabolism and reductive carboxylation of glutamine to meet their energy requirements for survival. Our preliminary studies, alongside others in the field, have shown that under glucose-deficient conditions, hypoxic cells can utilize mannose and maltose as alternative energy sources. This review aims to comprehensively examine the hypoxic cancer microenvironment, its association with drug resistance, and potential therapeutic strategies for targeting this unique niche. Furthermore, we will critically evaluate the current literature on hypoxic cancer microenvironments and explore state-of-the-art techniques used to analyze alternate carbohydrates, specifically mannose and maltose, in complex biological fluids. We will also propose the most effective analytical methods for quantifying mannose and maltose in such biological samples. By gaining a deeper understanding of the hypoxic cancer cell microenvironment and its role in drug resistance, novel therapeutic approaches can be developed to exploit this knowledge.
Topics: Humans; Cell Hypoxia; Maltose; Mannose; Neoplasms; Hypoxia; Glucose; Tumor Microenvironment; Drug Resistance
PubMed: 37805102
DOI: 10.1016/j.cellsig.2023.110911