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)

cDNA complementary to mRNA coding for the beta subunit of dog renal (Na+ + K+)-ATPase has been cloned into lambda gt11 and the nucleotide sequence of the DNA has been determined. The amino acid sequence of the beta subunit polypeptide has also been deduced from the DNA. The mature form of the dog kidney beta subunit contains 302 amino acids with three potential asparagine-linked attachment sites for carbohydrate. The initiation methionine is removed during processing of the polypeptide to its mature form. Although the beta subunit is an integral membrane protein there is no signal sequence for the polypeptide, and hydropathy analysis predicts that the beta subunit polypeptide spans the cell membrane only once. Secondary structure predictions and a model for the structure of the beta subunit are proposed. DNA sequencing of the 5' non-coding region of the mRNA revealed a 200 bp inverted repeat from the coding region. Blot hybridization of a fragment of the beta subunit cDNA identified a single mRNA species of 2.7 kb in dog kidney and several rat tissues. RNA from rat liver was deficient in mRNA that hybridized to the dog kidney beta subunit cDNA, although mRNA that hybridized to an alpha subunit cDNA was detected. RNA from a human hepatoma cell line, HepG2, however, contained comparable levels of mRNA for both the alpha and the beta subunits.
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PMID:Molecular cloning and sequence analysis of the (Na+ + K+)-ATPase beta subunit from dog kidney. 303 Apr 34

The biosynthesis of C1 Inh (C1 inhibitor) was studied in a human hepatoma cell line (Hep G2) by metabolic labelling, immunoprecipitation with anti-(C1 Inh) serum, analysis on SDS/polyacrylamide gel slabs and fluorography. Two forms of C1 Inh are secreted by Hep G2: a minor form of Mr 90,000 and a major form of Mr approximately 100,000. The latter form is also found in small amounts intracellularly in co-existence with an 80,000-Mr form. Accumulation of the 80,000-Mr C1 Inh is favoured when the cells are labelled at 23 degrees C instead of 37 degrees C or when they are treated with monensin. In the presence of tunicamycin, a compound that blocks the formation of N-asparagine-linked oligosaccharide chains, a decrease in Mr of both secreted and intracellular major forms is observed, indicating that secreted and intracellular C1 Inh contain N-linked oligosaccharide units. The 100,000 Mr secreted C1 Inh is sensitive to endoglycosidase F but resistant to endoglycosidase H, and it incorporates [3H]galactose, [3H]glucosamine and [3H]galactosamine, indicating the presence of both N-linked oligosaccharides of the complex type and O-linked oligosaccharides. The intracellular C1 Inh contains N-linked oligosaccharide units of the high-mannose type as demonstrated by endoglycosidase H-sensitivity. The functional activity of C1 Inh during its biosynthesis was tested by studying its reactivity towards C1s. Both secreted and intracellular C1 Inh form covalent-like complexes with purified plasma C1s. The underglycosylated C1 Inh secreted in presence of tunicamycin is still reactive with purified C1s. These results clearly show that sugars are not essential for this inhibitory activity of C1 Inh.
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PMID:Biosynthesis of complement C1 inhibitor by Hep G2 cells. Reactivity of different glycosylated forms of the inhibitor with C1s. 309 50

A number of amino acids, most noticeably asparagine, were capable of inducing ornithine decarboxylase in H-35 rat hepatoma cells. The effective amino acids were all neutral and were substrates of the Na+-dependent transport systems A, ASC and N. Transport inhibitor studies indicated that there was an excellent correlation between the level of enzyme activity induced and the initial rate of asparagine transport into the cells by the A and the N systems. It is proposed that the activation of the Na+-dependent, pH-sensitive amino acid transport systems and the subsequent intracellular pH and ionic perturbation constitute part of the initiation signals for cell activation.
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PMID:Asparagine transport and the induction of ornithine decarboxylase in H-35 rat hepatoma cells. 345 89

Glucosidase II is regarded as a resident protein of the endoplasmatic reticulum. The enzyme removes alpha-1-3-linked glucose from high mannose oligosaccharides N-linked to asparagine residues of glycoproteins. Monospecific antibodies raised against the pig kidney enzyme are used to study the metabolism of the enzyme in a rat hepatoma cell line. These antiglucosidase II antibodies specifically immune precipitate glucosidase II as a 100,000-Da species from [35S]methionine-labeled cells. In addition, protein blotting and immune staining of cell extracts from both rat liver and human and rat hepatoma cell lines show identity in apparent Mr (100,000). Glucosidase II synthesized in the presence of tunicamycin is approximately 94,000 Da, indicating the presence of one or more N-linked oligosaccharide chains. Cell-free protein synthesis of rat hepatoma total RNA demonstrates that glucosidase II is synthesized as a slightly higher molecular weight species as compared to the polypeptide synthesized in whole cells in the presence of tunicamycin, indicating that the enzyme has a cleavable signal sequence. Using a pulse-chase protocol, the apparent molecular weight does not change upon longer chase periods. In addition, the 100,000-Da protein remains sensitive to endo-beta-N-acetylglucosaminidase H regardless of prolonged chase periods. The cells incorporate [3H]mannose into the enzyme; after release with endo-beta-N-acetylglucosaminidase H, most of the radioactivity comigrates with Glc1-Man9-GlcNAc on a gel filtration column. Phase separation in Triton X-114 shows a partition between the aqueous and the Triton phase, the major portion being separated in the aqueous phase. In rat hepatoma cells glucosidase II has a half-life of 50 min. This value is not altered if the cells are grown in the presence of monensin nor of methyl-deoxynoijirimycin. However, tunicamycin and low concentrations or primaquine (raising the pH of acidic compartments) causes a 100% increase in half-life of glucosidase II. We conclude that glucosidase II is a hydrophilic, probably not a transmembrane membrane, protein with a short half-life. It is the first example of an oligosaccharide-processing enzyme not being an integral membrane protein.
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PMID:Glucosidase II, a protein of the endoplasmic reticulum with high mannose oligosaccharide chains and a rapid turnover. 354 12

The core-specific lectin (CSL) synthesized and secreted by rat hepatocytes and the rat hepatoma H-4-II-E shows affinity for mannose and N-acetylglucosamine residues in the "core" region of asparagine-linked oligosaccharides. The CSL undergoes two stages of post-translational modification which result in an increase in its Mr from 24,000 to 26,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. We have determined that the lectin undergoes hydroxylation of proline and lysine and that the hydroxylysine is glycosylated to form glucosylgalactosylhydroxylysine (GlcGalHyLys). CSL metabolically labeled with [3H]lysine and [3H]proline contains hydroxylated forms of proline and lysine. The mature form of the lectin can also be metabolically labeled with [3H]galactose. alpha,alpha'-Dipyridyl, an inhibitor of collagen prolyl and lysyl hydroxylases, prevents the metabolic incorporation of [3H]galactose and the post-translational increases in the Mr of the CSL, indicating that both events are dependent upon hydroxylation of proline and lysine. Virtually all of the hydroxylysine present in the CSL is recovered as glucosylgalactosylhydroxylysine after alkaline hydrolysis. The post-translational modifications of the CSL place it in a select family of secreted proteins which contain collagen-like sequences, including the pulmonary surfactant proteins, complement component C1q, and the 18 S asymmetric form of acetylcholinesterase.
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PMID:Identification of the post-translational modifications of the core-specific lectin. The core-specific lectin contains hydroxyproline, hydroxylysine, and glucosylgalactosylhydroxylysine residues. 361 Oct 62

The polypeptide growth factors, nerve growth factor, epidermal growth factor, and platelet-derived growth factor, as well as insulin do not induce ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17) unless a minimal concentration of an ornithine decarboxylase-inducing amino acid, such as asparagine, is present in the medium. The effects of the growth factors were studied in appropriately responsive cell lines: pheochromocytoma (PC12) cells for nerve and epidermal growth factors, fibroblasts (NIH 3T3) for platelet-derived growth factor, and fibroblasts and hepatoma (KRC-7) cells for insulin. The nonmetabolizable amino acid analog alpha-aminoisobutyric acid can replace asparagine, indicating that the covalent modification of the inducing amino acid is not necessary for the induction of ornithine decarboxylase by these growth factors. For the same intracellular concentration of the inducing amino acid, the presence of the growth factors induces higher levels of ornithine decarboxylase. The evidence indicates that these growth factors do not induce ornithine decarboxylase by raising the intracellular concentration of amino acids but rather act synergistically with the inducing amino acid. Evidence is provided that the induction of polyamine-dependent growth by these growth factors is mediated by amino acids. The relationship of these results to the A and N amino acid transport systems and to the Na+ influxes in relation to growth is discussed.
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PMID:Induction of ornithine decarboxylase activity by insulin and growth factors is mediated by amino acids. 389 32

We have studied the processing of rat and human angiotensinogen precursors by microsomal membranes as a means of determining the number of asparagine-linked oligosaccharide units per angiotensinogen molecule, and thus the utilization of potential sites of N-glycosylation. Glycosylated, processed forms of angiotensinogen were isolated by chromatography on lentil lectin-Sepharose 4B. 35S-Methionine-labeled precursor and processed forms of angiotensinogen were compared with glycosylated and nonglycosylated 35S-methionine-labeled mature forms of angiotensinogen secreted by hepatoma cells, using immunoprecipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. N-Glycosylation of secreted angiotensinogen was inhibited using tunicamycin. For rat angiotensinogen, only 2 of 3 potential sites of N-glycosylation were utilized; in contrast, all 4 potential sites of N-glycosylation of human angiotensinogen were utilized. For neither rat or human angiotensinogen precursor was there any evidence for a prosequence.
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PMID:Processing of rat and human angiotensinogen precursors by microsomal membranes. 393 16

-A comparison of the elution profiles of 18 aminoacyl-tRNA's from Novikoff hepatoma with those from normal liver on a methylated albuminkieselguhr column revealed the occurrence of new species of tRNA for histidine, tyrosine, and asparagine in the hepatoma. In addition, the hepatoma tRNA's for arginine, isoleucine, lysine, methionine, serine, alanine, and tryptophan eluted at a higher salt concentration than the corresponding tRNA's of normal liver. The remaining eight amino acids did not show any significant differences in the elution profiles.
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PMID:Differences in the transfer RNA's of normal liver and Novikoff hepatoma. 430 99

1. The activity of l-asparaginase was very low in the liver of newborn rats and mice, and increased within a few days of birth. 2. In rats, but not in mice, the enzyme activity was higher in females than in males, was enhanced by administration of oestradiol, and was decreased by gonadectomy. 3. The enzyme activity decreased in mice starved or fed on a low-protein diet; in rats it was enhanced by starvation, by feeding them on a high-protein diet, or by administration of l-asparagine. 4. The asparaginase activity was decreased in regenerating liver, and was almost absent in the Morris hepatoma 5123.
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PMID:The regulation of L-asparaginase activity in rats and mice. Effects of normal and malignant growth, of sex and of dietary changes. 431 Oct 65

A comparative study using hydrazinolysis has revealed that the oligosaccharide pattern of gamma-glutamyltranspeptidase purified from rat AH-66 hepatoma cells is very different from that of the enzyme from rat liver. Studies of oligosaccharides in each fraction have clarified the structural basis of the difference found in the sugar chains of the two enzymes. The sugar chains of the liver enzyme were all acidic, while 28% of those of the hepatoma enzyme were neutral, the latter being composed of high-man-nose-type and complex-type sugar chains. Three prominent structural differences were found in the acidic sugar chains of the two enzymes: (a) the sugar chains of the liver enzyme have complete outer chains, Gal beta 1 leads to 4GlcNAc beta 1 leads to, while many of those of the hepatoma enzyme have incomplete outer chains without galactose (Gal); (b) the Gal beta 1 leads to 4GlcNAc beta 1 leads to Gal beta 1 leads to 4GlcNAc beta 1 leads to group is found in the sugar chains of the liver enzyme but not in those of the hepatoma enzyme; (c) more than 40% of the sugar chains of the hepatoma enzyme contain bisect N-acetylglucosamine (GlcNAc) residue which is not found in those of the liver enzyme. Furthermore, the total number of asparagine-linked sugar chains in one molecule of hepatoma enzyme was about 4 times that found in one molecule of liver enzyme.
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PMID:Comparative study of the sugar chains of gamma-glutamyltranspeptidases purified from rat liver and rat AH-66 hepatoma cells. 613 77


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