Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

At least 6 N-acetylglucosaminyltransferases (GlcNAc-T I, II, III, IV, V and VI) are involved in initiating the synthesis of the various branches found in complex asparagine-linked oligosaccharides (N-glycans), as indicated below: GlcNAc beta 1-6 GlcNAc-T V GlcNAc beta 1-4 GlcNAc-T VI GlcNAc beta 1-2Man alpha 1-6 GlcNAc-T II GlcNAc beta 1-4Man beta 1-4-R GlcNAc T III GlcNAc beta 1-4Man alpha 1-3 GlcNAc-T IV GlcNAc beta 1-2 GlcNAc-T I where R is GlcNAc beta 1-4(+/- Fuc alpha 1-6)GlcNAcAsn-X. HPLC was used to study the substrate specificities of these GlcNAc-T and the sequential pathways involved in the biosynthesis of highly branched N-glycans in hen oviduct (I. Brockhausen, J.P. Carver and H. Schachter (1988) Biochem. Cell Biol. 66, 1134-1151). The following sequential rules have been established: GlcNAc-T I must act before GlcNAc-T II, III and IV; GlcNAc-T II, IV and V cannot act after GlcNAc-T III, i.e., on bisected substrates; GlcNAc-T VI can act on both bisected and non-bisected substrates; both Glc-NAc-T I and II must act before GlcNAc-T V and VI; GlcNAc-T V cannot act after GlcNAc-T VI. GlcNAc-T V is the only enzyme among the 6 transferases cited above which can be essayed in the absence of Mn2+. In studies on the possible functional role of N-glycan branching, we have measured GlcNAc-T III in pre-neoplastic rat liver nodules (S. Narasimhan, H. Schachter and S. Rajalakshmi (1988) J. Biol. Chem. 263, 1273-1281). The nodules were initiated by administration of a single dose of carcinogen 1,2-dimethyl-hydrazine.2 HCl 18 h after partial hepatectomy and promoted by feeding a diet supplemented with 1% orotic acid for 32-40 weeks. The nodules had significant GlcNAc-T III activity (1.2-2.2 nmol/h/mg), whereas the surrounding liver, regenerating liver 24 h after partial hepatectomy and control liver from normal rats had negligible activity (0.02-0.03 nmol/h/mg). These results suggest that GlcNAc-T III is induced at the pre-neoplastic stage in liver carcinogenesis and are consistent with the reported presence of bisecting GlcNAc residues in N-glycans from rat and human hepatoma gamma-glutamyl transpeptidase and their absence in enzyme from normal liver of rats and humans (A. Kobata and K. Yamashita (1984) Pure Appl. Chem. 56, 821-832).
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PMID:The biosynthesis of highly branched N-glycans: studies on the sequential pathway and functional role of N-acetylglucosaminyltransferases I, II, III, IV, V and VI. 297 90

In order to study the effect of retinoic acid on the structure of N-glycans on the cell surface, the N-glycans of glycoproteins on the surface of 7721 human hepatocarcinoma cells were labelled with [3H] mannose, added to the culture medium. The 3H-labelled N-glycans were prepared from cell-surface glycoproteins, desialylated, and subjected to sequential chromatography on concanavalin A and Datura stranonium agglutinin affinity columns to separate the glycans into four fractions of different type and different antennary number. It was found that the percentage of C2C2 biantennary complex type N-glycans was increased, but the high-mannose type as well as the tri- and tetraantennary complex types, especially that with a C2.6 branched structure, were decreased after the cells had been treated with retinoic acid for 3-5 days. Using a Lens culinaris agglutinin affinity column, it was discovered that the core fucose in the biantennary glycan was also decreased. The enzymatic mechanisms of the above changes were revealed in further study to involve the decrease of N-acetylglucosaminyl-transferase V and core alpha-1,6-fucosyltransferase by retinoic acid.
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PMID:Effect of retinoic acid on the structure of N-glycans on the surface of human hepatocarcinoma cells and its enzymatic mechanism. 763 68

In order to investigate the changes of N-acetylglucosaminyl transferase (GlcNAc-T) III, IV and V in cell cycle, the synchronization of 7721 human hepatocellular carcinoma cells was performed using serum hunger method. The percentages of cells in different phases during cell cycle were measured by flow cytometry (FCM) and the cell cycle was checked by determining the activity of cellular p34cdc2 kinase. It was found that the activities of GlcNAc-T III increased in G0/G1 cell peak phase and had correlation with the cell percentage of G0/G1 phase (r = 0.760, P < 0.05), while GlcNAc-T V showed the highest activity when G2/M cells were most abundant and had an apparent correlation with the cell percentage of G2/M phase (r = 0.868, P < 0.001). The changes of GlcNAc-T IV activity seemed not related to the cell cycle. The changes in opposite directions of relative activities (percentage of total GlcNAc-T III, IV, V) of GlcNAc-T III and GlcNAc-T V were observed during cell cycle (r = -0.951, P < 0.001), suggesting that these two enzymes might be regulated differently and functioned oppositely in the cells: GlcNAc-T V may be related to the proliferation of 7721 cells, while GlcNAc-T III may be related to the non-mitotic silence phase of the cells, or, it may be a factor against proliferation. Immunohistochemical results showed that the protein content of GlcNAc-T V was not significantly changed during cell cycle, and had no correlation with the activity of GlcNAc-T V, suggesting that the changes of GlcNAc-T V activity in cell cycle might not be resulted from the alteration of enzyme protein synthesis. The correlation between the activities of GlcNAc-T V and p34cdc2 kinase (r = 0.752, P < 0.05) was observed in cell cycle, implicating that GlcNAc-T V might possibly be regulated by p34cdc2 kinase.
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PMID:[Changes with cell cycle of N-acetylglucosaminyl transferase III, IV and V in 7721 human hepatocarcinoma cells]. 1201 61