Disease relevance of Gne

• These results show that the Gne((-/-)) hGNEV572L-Tg mouse mimics the clinical, histopathological and biochemical features of DMRV/h-IBM, making it useful for understanding the pathomechanism of this myopathy and for employing different strategies for therapy [1].
• We conclude that susceptibility of cells to HSV-1 entry depends on (1) presence of heparan sulfate chains to which virus can bind and (2) 3-O-sulfation of specific glucosamine residues in heparan sulfate to generate gD-binding sites or the expression of other previously identified gD-binding receptors [2].
• In vivo chemotherapy of mice bearing TA3 ascites tumors was most effective with respect to tumor growth inhibition and animal survival when GlcN and FUrd were combined [3].
• Hepatoma (HepG2) cells and endothelial cells cultured in high glucose also showed decreased sulfate and glucosamine incorporation into HSPG [4].
• Certain Escherichia coli mutants altered in phosphatidylglycerol metabolism accumulate fatty acyl derivatives of glucosamine 1-phosphate [5].

High impact information on Gne

• However, protein-polysaccharide fractions with nearly 40% of the incorporated glucosamine and only 5% mannose and 1% leucine were insensitive to inhibition by tunicamycin [6].
• Both the glycolipid precursor and the aqueous products were monitored by labeling with radioactive inositol and glucosamine [7].
• The toxin is a complex polysaccharide composed of glucose, glucosamine or galactosamine, and a heptose, is heat-stable, devoid of protein and lipid, and has a molecular weight of 73,000 [8].
• Here we have studied the involvement of endothelial heparan sulfate in inflammation by inactivating the enzyme N-acetyl glucosamine N-deacetylase-N-sulfotransferase-1 in endothelial cells and leukocytes, which is required for the addition of sulfate to the heparin sulfate chains [9].
• Antibody binding also was blocked by the presence of fucose linked to the penultimate glucosamine residue of N-acetyllactosamine glycosphingolipids [10].

Chemical compound and disease context of Gne

• Exposure to glucosamine (1 mg/ml) or tunicamycin (0.2 to 0.4 micrograms/ml) induces a marked pigment loss within melanoma cells in vitro with a decrease in their grown curves [11].
• LBP was found to bind to a variety of LPS types from both rough and smooth strains of Gram-negative bacteria, to lipid A, and to the tetraacyl glucosamine disaccharide diphosphate precursor IVA, but bound very poorly to the diacyl glucosamine phosphate, lipid X [12].
• Anoxia, glucose starvation, calcium ionophore A23187, EDTA, glucosamine, and several other conditions that adversely affect the function of the endoplasmic reticulum (ER) induce the synthesis of the glucose-regulated class of stress proteins (GRPs) [13].
• Mucin from xenografts of LS174T human colon cancer cells was treated with anhydrous HF for 1 h at 0 degree C to give a product (HFA) with over 80% of the glucosamine and hexose removed, but retaining some galactosamine, and for 3 h at room temperature to give a product (HFB) devoid of carbohydrate [14].
• The novel chemical structure of Porphyromonas (Bacteroides) gingivalis strain 381 lipid A was determined to be a glucosamine beta-(1-6) disaccharide 1-monophosphate acylated by 3-hydroxy-15-methylhexadecanoic acid and 3-hexadecanoyloxy-15-methylhexadecanoic acid at the 2- and 2'-positions, respectively [15].

Biological context of Gne

• Addition of equimolar amounts of glucose or mannose, but not of fructose, galactose, fucose, or glucosamine, to medium containing 50 mM 2-dG results in substantial reversal of the inhibitory effect of 2-dG on Fc and C3 receptor mediated phagocytosis [16].
• We conclude that (a) heparin's anti-inflammatory effects are mainly mediated by blocking P- and L-selectin-initiated cell adhesion; (b) the sulfate groups at C6 on the glucosamine residues play a critical role in selectin inhibition; and (c) some non-anticoagulant forms of heparin retain anti-inflammatory activity [17].
• Insulin resistance induced through the HSP by glucosamine and chronic insulin treatment correlated with increased O-GlcNAc levels on nucleocytoplasmic proteins [18].
• Both the secreted and the intracellular forms incorporate glucosamine label, indicating that at least a portion of the modification observed here is in the form of glycosylation [19].
• This protein was present in membrane enriched fractions and could be metabolically labeled with [3H )glucosamine, confirming that the transfected mdr1 gene encodes a membrane glycoprotein [20].

Anatomical context of Gne

• A Gne knockout mouse expressing human V572L mutation develops features similar to distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy [1].
• By the use of an M6 monoclonal antibody, which crossreacts with 20 different M protein types, and antibodies to the N-acetyl glucosamine determinant of the cell wall, we have been able to identify the M protein molecules released from the streptococcal cell wall with muralytic enzymes, particularly group C phage-associated lysin [21].
• Plasma membrane glycoproteins labeled with radioactive glucosamine showed significantly different patterns on both polyacrylamide gel electrophoresis and electrofocusing [22].
• Isolated Kupffer cells have mannose and/or N-acetyl glucosamine receptor activity but do not internalize CEA by that mechanism [23].
• Assay of tyrosinase of glucosamine- or tunicamycin-induced unpigmented melanoma cells has revealed a selective and marked decrease in the melanosome-rich large-granule fraction, but no substantial decrease in the total activity of remaining subcellular fractions [11].

Associations of Gne with chemical compounds

• Among other natural sugars examined, only mannose competed effectively with 2-DG and reversed the inhibition of cytolysis, whereas sodium pyruvate, fructose, galactose, fucose, and glucosamine were without effect [24].
• Effects of D-glucosamine and 6-azauridine on nucleotide contents, 5-fluorouridine uptake, and cytotoxicity in TA3 mammary tumor cells [3].
• The amino acid composition of gp 160 is compatible with the linkage of carbohydrates (galactose, glucosamine, and sialic acid) to the protein portion [25].
• In TA3 mammary carcinoma cells in suspension culture, D-glucosamine X HCl (GlcN) induced a diversion of uridylate from UTP into UDP-N-acetylhexosamines, reducing the intracellular pool of UTP and eliciting an increased rate of de novo uridylate synthesis [3].
• Treatment of TA3 cells with FUrd after a pretreatment with 6-AzaUrd and GlcN resulted in a 2.5-fold increase in [14C]FUrd uptake and a duplication of 5-fluorouridylate incorporation into the RNA [3].

Physical interactions of Gne

• Glucosamine did not alter basal glucose transport and insulin stimulation of GLUT-1 translocation and mitogen-activated protein kinase [26].
• Structural gene products of the murine Ah complex. Differences in ontogenesis and glucosamine incorporation between liver microsomal cytochromes P1-450 and P-448 induced by polycyclic aromatic compounds [27].
• A high proportion of antithrombin-binding sequence was also indicated by the finding that 3-O-sulfated glucosamine residues accounted for about 10% of the total O-sulfate groups [28].

Enzymatic interactions of Gne

• HS 3-O-sulfotransferases (3-OST) catalyze the transfer of sulfate groups to the 3-O position of glucosamine residues of HS, a rare, but essential HS chain modification required for HS fine structure [29].

Regulatory relationships of Gne

• In conclusion, our data suggest that the mechanism by which glucosamine inhibits insulin-stimulated GLUT4 translocation involves modification of Munc18c [30].
• In these cells, glucosamine also inhibited insulin stimulation of p70 S6 kinase [26].
• Glucosamine (6 h) did not affect insulin-stimulated tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 and -2 and weakly, if at all, impaired insulin stimulation of phosphatidylinositol 3-kinase [26].
• It has been recently reported that in vitro treatment of fat and muscle cells with hexosamines and acute glucosamine infusion in intact rats stimulate leptin secretion [31].
• The esterase was found to increase markedly the mEGF-induced incorporation of glucosamine into extracellular hyaluronic acid, while the addition of ascorbic acid did not significantly alter glucosamine incorporation [32].

Other interactions of Gne

• All these modifications are believed to depend on initial glucosamine N-sulfation carried out by the enzyme glucosaminyl N-deacetylase/N-sulfotransferase (NDST) [33].
• Role of glucosamine synthesis in the stimulation of TGF-alpha gene transcription by glucose and EGF [34].
• Glutamine:fructose-6-phosphate amidotransferase (GFAT) is the enzyme that is rate limiting in the synthesis of glucosamine and hexosamines [35].
• Defective Akt activation is associated with glucose- but not glucosamine-induced insulin resistance [36].
• Glucosamine-induced insulin resistance is coupled to O-linked glycosylation of Munc18c [30].

Analytical, diagnostic and therapeutic context of Gne

• More importantly, glucosamine administration prolonged allogeneic cardiac allograft survival in vivo [37].
• We thus investigated the therapeutic effect of glucosamine on experimental autoimmune encephalomyelitis (EAE), an animal model of MS [38].
• As glucosamine is able to effectively suppress acute EAE, has low or absent toxicity, and has been safely used in humans orally, our study suggests a potential use for this drug alone or in combination with other disease-modifying immunotherapies to enhance their efficacy and reduce their doses in MS and possibly other autoimmune disorders [38].
• Characterization of a sustained-release delivery system for combined cytokine/peptide vaccination using a poly-N-acetyl glucosamine-based polymer matrix [39].
• The D-1-14C galactose and D-1-14C glucosamine-labelled neutral GSL and gangliosides of these tumor cells, and additionally ConA-stimulated spleen T cells from normal mice, were analysed by thin-layer chromatography [40].

References