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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Comparative study by using hydrazinolysis has revealed that the carbohydrate moieties of gamma-glutamyl transpeptidases purified from rat liver and rat AH-66 hepatoma are quite different. The sugar chains of the liver enzyme were all acidic, while 29% of those of hepatoma enzyme was neutral. Three prominent structural differences were found in the acidic sugar chains of the two enzymes: 1) The liver enzyme has asparagine-linked sugar chains with complete outer chain, NeuAc alpha----Gal beta 1----4GlcNAc, while hepatoma enzyme has sugar chains incomplete in their outer chain moieties; 2) Gal beta 1----4GlcNAc beta 1----4GlcNAc group is found in the sugar chains of liver enzyme but not in those of hepatoma enzyme; 3) More than 40% of the sugar chains of hepatoma enzyme contain bisecting N-acetylglucosamine which is not found in those of liver enzyme.
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PMID:[Structural change of sugar chains of glycoproteins by cell transformation and its application to the diagnosis of cancer]. 614 30

In contrast to the changes seen in membrane transport systems for other neutral, anionic, and cationic amino acids, System N for glutamine, histidine, and asparagine in the rat hepatocytes shows nearly constant properties at the fetal, differentiated, and cultured hepatoma stages. These properties were tested by measuring the Na+-dependent transport of glutamine. This approximate constancy applies not only to the transport selectivity of the system among neutral amino acids, but also to its tolerance of Li+ as a substitute for Na+, its characteristic sensitivity to pH lowering, its relative sensitivity to N-ethylmaleimide, its stimulation by amino acid deprivation, and its failure to respond to insulin or glucagon. The properties of histidine as a substrate for System N were also examined. Inhibition studies with different cell types suggest that the Na+-dependent glutamine and histidine uptake is more restricted to System N in the hepatoma line H35 (H4-11-EC,3) and in the fetal hepatocyte than in hepatoma line HTC and the Ehrlich cells. The Na+-independent component of glutamine and histidine uptake was greater in the hepatoma cells in continuous culture than in fetal and adult hepatocytes in primary culture. Trans-stimulation of glutamine and histidine influx into H35 cells occurs predominantly by the Na+-independent route.
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PMID:Comparison of system N in fetal hepatocytes and in related cell lines. 630 40

The induction and decay of ornithine decarboxylase (ODC) by insulin and asparagine in cultures of H4-II-EC3 (H35) hepatoma cells was studied in a modified Waymouth medium in the presence of fetal bovine serum (FBS) and in serum-free media. The insulin response was enhanced by the presence of asparagine although the effect of asparagine was not so much on the initial increase as it was on a slowing of the decline after the maximum was reached at 6 to 8 h after the supplements were added together with fresh medium. In all cases the initial ODC activity was zero at zero time for addition of media and supplements, and, after reaching the maximum, activity declined to near zero by 24 h. Fetal bovine serum gave induction that followed a similar time course but was inferior to the combination of insulin plus asparagine and, in fact, FBS inhibited the latter response. Putrescine (the product formed from ornithine by ODC), at 10(-5) M, markedly inhibited the induction of ODC by insulin or FBS, but the inhibition was less when asparagine was present.
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PMID:Cultured hepatoma cells for the study of enzyme regulation: induction of ornithine decarboxylase by insulin and asparagine. 638 19

Tumor nucleic acids have frequently been found to be deficient in methylated and other modified nucleotides. In particular, cytoplasmic transfer RNAs (tRNAs) from various neoplasms partially lack the hypermodified nucleoside queuosine, a modification specific for anticodons of histidine-, tyrosine-, asparagine-, and aspartic acid-accepting tRNAs. Using aspartate tRNA as an example, we show here that liver mitochondria contain tRNA fully modified with respect to queuosine, while the corresponding tRNA from mitochondria of Morris hepatoma 5123D completely lacks this constituent. The sequences of these tRNAs, which were determined by a highly sensitive 32P-postlabeling procedure entailing the direct identification of each position of the polynucleotide chains, were found to be (sequence in text) Lack of queuosine in the hepatoma mitochondrial tRNA may be due to the inavailability of queuine in the hepatoma mitochondria for incorporation into tRNA or to inhibition of the modifying enzyme, tRNA (guanine)-transglycosylase, in the tumor. Taking into account results of others indicating a possible involvement of the queuosine modification in differentiation of eukaryotic cells, we hypothesize that the queuosine defect may develop at an early stage of carcinogenesis (i.e., during the promotion phase) and be directly involved in abnormalities of mitochondria which have been observed frequently in transformed cells and tumors.
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PMID:Specific lack of the hypermodified nucleoside, queuosine, in hepatoma mitochondrial aspartate transfer RNA and its possible biological significance. 642 54

Isolated plasma membranes from rat liver and ascites hepatoma cells were shown by SDS-polyacrylamide gel electrophoresis and concanavalin A reactivity to contain a variety of glycoproteins having asparagine-linked oligosaccharides. Membrane oligosaccharides were released by almond glycopeptidase digestion, and the pyridylamino derivatives were analyzed by high-performance liquid chromatography. Forty-four percent of the total carbohydrates in the original membranes were released and suggested to be of the complex type. Hepatoma membranes showed different oligosaccharide patterns from normal.
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PMID:Analysis of asparagine-linked oligosaccharides from plasma membranes of rat normal liver and ascites hepatoma cells. 647 25

Angiotensinogen precursors synthesized by rabbit reticulocyte lysate primed with rat liver RNA were compared with angiotensinogen secreted by rat hepatoma cells and rat hepatocytes using immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Inhibition of glycosylation with tunicamycin permitted identification of the nonglycosylated form of secreted angiotensinogen. Whereas angiotensinogen secreted by hepatoma cells and hepatocytes showed electrophoretic heterogeneity (mol wt, 52-62 X 10(3], tunicamycin-treated cells secreted only a single angiotensinogen species [mol wt, 48.3 +/- 0.7 X 10(3) (mean +/- SD)], which could be cleaved by renin. Two putative angiotensinogen precursors were synthesized in the reticulocyte lysate: a major protein of 52.5 +/- 1.0 X 10(3) mol wt and a minor protein of 55.7 +/- 1.3 X 10(3) mol wt. Evidence that these proteins represent separate angiotensinogen precursors includes the following. 1) Both proteins were recognized by five different polyclonal antibodies and two monoclonal antibodies. 2) Both proteins increased in parallel in reticulocyte lysates primed with liver RNA from rats nephrectomized and given hormones that increase liver angiotensinogen production. 3) Both proteins were cleaved by renin to produce a single protein of 47.6 +/- 0.8 X 10(3) mol wt. 4) The des-angiotensin I-angiotensinogen generated by renin treatment of the lysate had an electrophoretic mobility identical to that of des-AI-angiotensinogen produced by renin treatment of nonglycosylated angiotensinogen secreted by tunicamycin-treated hepatoma cells and hepatocytes. These studies suggest that rat liver synthesizes two separate angiotensinogen precursors which may differ only in the size of their prepro sequence. The heterogeneity of secreted angiotensinogen can be fully accounted for by differences in N-glycosylation of asparagine residues of the molecule. Glycosylation of angiotensinogen is not essential for its synthesis, processing, and secretion or its hydrolysis by renin.
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PMID:Characterization of precursor and secreted forms of rat angiotensinogen. 669 62

A lectin, previously designated the Man/GlcNAc-specific lectin or mannan-binding protein, is found in rat liver and plasma. Analysis of the structural requirements for oligosaccharide binding indicated that the specificity of this lectin is directed primarily at the "core" and peptide region of glycopeptides (Maynard, Y., and Baenziger, J. U. (1982) J. Biol. Chem. 257, 3788-3794). We have examined synthesis and secretion of the core-specific lectin by primary rat hepatocytes and a rat hepatoma, H-4-II-E, utilizing pulse labeling with [35S]methionine, immunoprecipitation with a monospecific rabbit antibody raised against the purified lectin, and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. A post-translational modification occurs between 10 and 40 min of chase which results in an increase in the Mr from 24,000 to 26,000. This modification is not due to asparagine-linked glycosylation or oligosaccharide processing. The kinetics of secretion are unusual. Secretion begins at 1 h of chase and proceeds linearly for approximately 8 h until a maximum of 70% of the lectin has been secreted. Secretion, but not the post-translational modification is inhibited by monensin. The pattern of synthesis and secretion in conjunction with the presence of the lectin in plasma indicate that it is a plasma protein of hepatocyte origin. The slow kinetics of secretion compared to other secretory proteins indicate an unusual mechanism for the segregation of the lectin from other secretory proteins and/or a different intracellular pathway for secretion.
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PMID:Synthesis, processing, and secretion of the core-specific lectin by rat hepatocytes and hepatoma cells. 670 87

Stimulation of System N transport of glutamine by amino acid starvation of the rat hepatocyte can be repressed by one of its substrates, histidine, but not by two others, glutamine or asparagine. Furthermore, 2-(methylamino)isobutyric acid is also repressive, although it is not perceptibly a substrate or inhibitor of that system. The repression of System A by glutamine proves in contrast not to be dissociated from transport: relatively slow System A uptake of glutamine has now been shown in this cell. System A transport of glutamine is conspicuous in the hepatoma cell HTC and is increased after amino acid starvation of both hepatocytes and the hepatoma cells. Differential repression of the systems could be shown, although lowering the pH prevented the derepression of one system as much as the other on amino acid starvation.
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PMID:Incomplete correspondence between repressive and substrate action by amino acids on transport systems A and N in monolayered rat hepatocytes. 705 75

It has been shown that supraphysiological concentrations of asparagine and hypoosmotic shock stimulate ornithine decarboxylase activity in cultured cancer cells by increasing the synthesis and the half-life of the enzyme protein. Since extracellular Ca2+ is essential for the action of asparagine and is also important for cell volume regulation in certain cell types, aspects of Ca2+ physiology in asparagine-treated H-35 rat hepatoma cells were investigated. The initial rate of influx of 45Ca increased from 0.25 to 1.04 nmol/min/mg protein immediately after exposure to 10 mM asparagine. With a one-minute lag the efflux rate also increased 2.2-fold over a five minute period. Asparagine did not cause a net-gain in cellular Ca2+ as measured by 45Ca equilibration, nor did it have any effect on the cytosolic free Ca2+ as measured by Fura-2 fluorescence spectroscopy and Fluo-3 fluorescence confocal microscopy.
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PMID:Membrane Ca2+ fluxes in rat hepatoma cells exposed to a supraphysiological concentration of asparagine. 749 52

A full-length cDNA clone for rat asparagine synthetase (AS) was isolated from a cDNA library enriched for amino acid-regulated sequences. The AS cDNA was used to investigate the amino acid-dependent repression of AS mRNA content in rat Fao hepatoma cells. In response to complete amino acid starvation, there was an approximately 10-fold increase in the level of AS mRNA. Three species of mRNA, of approx. sizes 2.0, 2.5 and 4.0 kb, were detected and each was simultaneously regulated to the same degree. The expression of AS mRNA increased by 6 h after removal of amino acids, reached a plateau after 9 h, and was blocked by either actinomycin D or cycloheximide. Partial repression of the AS mRNA content was maintained by the presence of a single amino acid in the culture medium, but the degree of effectiveness for each one varied widely. Glutamine showed the greatest ability to repress the AS mRNA content, even at an extracellular concentration 10 times below its plasma level. Other effective repressors included the amino acids asparagine, histidine and leucine, as well as ammonia. Depletion of selected single amino acids from an otherwise complete culture medium also caused up-regulation. In particular, removal of histidine, threonine or tryptophan from the medium, or the addition of histidinol to inhibit histidinyl-tRNA synthetase, resulted in a significant increase in AS mRNA content. The data indicate that nutrient regulation of AS mRNA occurs by a general control mechanism that is responsive to a spectrum of amino acids.
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PMID:Cloning of rat asparagine synthetase and specificity of the amino acid-dependent control of its mRNA content. 781 76


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