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)

3H-Demethylphalloin (3H-DMP) a cyclopeptide very similar to phalloidin is taken up by isolated hepatocytes in vitro. Hepatocytes prepared from newborn animals are less sensitive to phalloidin. Their uptake of 3H-DMP is about one tenth of that of cells from adult animals. Ascites hepatoma cells, known to be insensitive to phalloidin took up negligible amounts of 3H-DMP. Cells prepared from regenerating livers took up insignificantly lower amounts of the toxin than in hepatocytes from adult animals. Treatment of hepatocytes with low concentrations of trypsin was found to switch off the phalloidin sensitivity in a reversible manner. This inhibition is due to a reduced uptake of 3H-DMP. Pretreatment of animals with CCl4, known to reduce the sensitivity to phalloidin, also decreases the uptake of 3H-DMP in isolated hepatocytes. Various agents, drugs and reagents were found to inhibit the response of isolated hepatocytes to phalloidin. All these compounds (bile acids, rifampicin, silybin, DIDS, glutardialdehyde, bromosulphophthalein, fusidic acid, antamanide, novobiocin) inhibit also the uptake of 3H-DMP in isolated hepatocytes. The results confirm our working hypothesis, presented in several previous papers, that decreased sensitivity to phalloidin is probably due to a reduced or blocked uptake of the toxin.
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PMID:Inhibition of 3H-demethylphalloin uptake in isolated rat hepatocytes under various experimental conditions. 55 48

A series of variant lines that utilize multiple pentoses for growth in place of glucose have been isolated from an 8-azaguanine resistant line of Novikoff hepatoma cells (N1S167). These variants utilize for growth ribose, xylose, arabinose, and/or deoxyribose. The variants growing on pentose containing medium (a) exhibit a density dependent cessation of growth, (b) have a morphology change to a more flattened cell type, (c) become binucleated in the presence of cyto chalasin B, and (d) show an altered sensitivity to trypsin treatment.
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PMID:Pentose utilizing variants of Novikoff hepatoma cells: modification of growth and morphological properties. 85 67

1. Biosynthesis of alpha 1-microglobulin and inter-alpha-trypsin inhibitor was investigated in a human hepatoma cell line HepG-2. 2. alpha 1-Microglobulin was translated as a precursor common with the light chain of inter-alpha-trypsin inhibitor. 3. alpha 1-Microglobulin was synthesized and secreted into the growth medium within 30 min. 4. Processing of inter-alpha-trypsin-inhibitor-related proteins appeared slow and incomplete. The light chain was connected via a chondroitinsulphate to a heavy chain to form a 125,000-Mr protein and secreted within 1-4 hr.
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PMID:Biosynthesis of inter-alpha-trypsin inhibitor and alpha 1-microglobulin in a human hepatoma cell line. 137 Aug 6

A pancreatic carcinoma and liver metastases associated with marked elevation of the serum alpha-fetoprotein (AFP) level were resected from a 57-year-old man. On microscopic examination, the tumor cells showed a predominantly acinar arrangement, with tubular and trabecular structures; in some foci it had features of a medullary pattern. Alpha-fetoprotein, lipase, trypsin, chymotrypsin, and alpha 1-antitrypsin were strongly demonstrated in tumor tissue by immunohistochemical techniques. A biochemical analysis of AFP on affinity sepharose columns revealed that the AFP derived from the tumor tissues was similar to that of hepatocellular carcinoma. Ultrastructural study showed that most of the tumor cells had abundant rough endoplastic reticulum and numerous zymogen granules. No squamoid corpuscles, neuroendocrine granules, bile production, or bile canaliculi were recognized. These findings suggest that this unique tumor originated from acinar cells.
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PMID:Alpha-fetoprotein-producing acinar cell carcinoma of the pancreas. 137 64

Amino acid sequence information was obtained for the NH2 terminus, and for endogenous peptides generated by trypsin digestion, of a purified, truncated form of rat hepatic squalene synthase (RSS, EC 2.5.1.21) (Shechter, I., Klinger, E., Rucker, M. L., Engstrom, R. G., Spirito, J. A., Islam, M. A., Boettcher, B. R., and Weinstein, D. B. (1992) J. Biol. Chem. 267, 8628-8635). Degenerate primers, based on the amino acid sequences, were synthesized and used for the amplification and sequencing of a 1708-base pair (bp) cDNA for RSS from the rat hepatoma cell line H35. An open reading frame of 1248 bp encoding 416 amino acids (M(r) = 48,103) was detected for RSS. We have constructed a pRSS1327 expression vector by molecular cloning of a 1327-bp cDNA, which includes sequences of the entire coding region for RSS, into pBluescript. Expression in Escherichia coli of a functional, full-length RSS was confirmed by immunoblot analysis and enzymatic activity. We present and evaluate a model for the secondary structure of RSS and its possible membrane orientation. The model predicts a 315-residue domain at the center of the protein that contains the catalytic site and is released in a soluble form by partial proteolysis. The 33-residue NH2-terminal and 98-residue COOH-terminal sections are not involved in catalysis. Sequence analysis of the catalytic domain of RSS indicate three regions with high homology to sequences in a number of functionally distinct proteins that utilize polyprenyl diphosphate substrates.
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PMID:Molecular cloning, expression, and characterization of the cDNA for the rat hepatic squalene synthase. 140 Apr 48

The effects of 11-deoxycorticosterone and aldosterone on liver delta 5 desaturase activity were examined. Both steroid hormones significantly depressed the conversion of [1-14C] eicosatrienoic acid to arachidonic acid. However, the mechanism of action of each of these hormones was different. The effect of 11-deoxycorticosterone was mediated by a soluble protein present in the liver cytosolic fraction. The biological activity of this protein, having a molecular weight lower than 25 kDa, was impaired by trypsin digestion. To determine whether the inhibitory protein was induced through glucocorticoid or mineralocorticoid receptor occupancy, cultured Morris minimal deviation hepatoma cells were pre-treated with the antiglucocorticoid cortexolone or the mineralocorticoid receptor antagonist spironolactone. The results obtained demonstrated that only glucocorticoid receptor structures were involved in the induction of this regulatory protein. The inhibitory response evoked by aldosterone was mediated by a different mechanism. In the case of aldosterone, the inhibitory action affected the microsomal membranes and was not mediated by a soluble protein messenger.
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PMID:Glucocorticoid and mineralocorticoid hormones depress liver delta 5 desaturase activity through different mechanisms. 140 70

To explore the process of lipoprotein assembly, plasmids encoding truncated forms of apolipoprotein B (apoB) were transfected into Chinese hamster ovary (CHO) fibroblasts. (One, encoding apoB53, the N-terminal 53% of apoB100, can direct the assembly and secretion of lipoproteins when expressed in hepatoma cells, while the other, encoding the shorter apoB15, does not direct lipoprotein assembly.) Expression of apoB15 in CHO cells resulted in the accumulation of apoB15 protein in both medium and cells. In contrast, apoB was not detectable in medium or within CHO cells transfected with the plasmid encoding apoB53, despite the expression of apoB53 mRNA. ApoB53 did accumulate within transfected cells incubated with the thiol protease inhibitor N-acetylleucylleucylnorleucinal (ALLN), suggesting that it is synthesized but completely degraded in the absence of the inhibitor. ApoB53 was not secreted despite its presence within ALLN-treated cells. Essentially all the apoB53 that accumulated in microsomes from ALLN-treated cells was associated with the membrane and was susceptible to degradation by exogenous trypsin, indicating exposure on the cytoplasmic face of the membrane. Thus, translocation of apoB53 across the endoplasmic reticulum membrane is blocked. However, the apoB53 bound to concanavalin A, suggesting that it is glycosylated and therefore partly exposed to the lumen as well. ApoB requires a unique process, not expressed in CHO fibroblasts, for its complete translocation and entrance into the secretory pathway. This process might account for the inability of abetalipoproteinemic patients to secrete apoB.
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PMID:Translocation of apolipoprotein B across the endoplasmic reticulum is blocked in a nonhepatic cell line. 140 18

H35 hepatoma cells were treated with trypsin to abolish insulin binding and insulin-stimulated receptor kinase activity. Insulin was, however, internalized by fluid-phase endocytosis in trypsin-treated cells. Furthermore, nuclear accumulation of insulin was similar in control and trypsin-treated hepatoma cells. Northern blot analysis revealed insulin increased g33 and c-fos mRNA concentrations identically in control and trypsin-treated cells but had no effect on beta 2-microglobulin mRNA. Actinomycin D treatment prior to or after insulin addition demonstrated that insulin increased gene transcription and had no effect on mRNA degradation. These studies suggest that the accumulation of intact insulin in cell nuclei may be directly involved in the increased transcription of immediate-early genes.
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PMID:Direct stimulation of immediate-early genes by intranuclear insulin in trypsin-treated H35 hepatoma cells. 140 84

We previously demonstrated that insulin accumulated in the nucleus in several cell types and partially characterized the uptake mechanisms and pathways in H35 rat hepatoma cells. Nuclear accumulation of insulin was energy independent, time, temperature, and insulin concentration dependent, but apparently nonsaturable. This study investigated further the initial endocytotic pathways that contribute to the nuclear accumulation of insulin using trypsin treatment of the cells to prevent insulin binding to its plasma membrane receptor. Total cell-associated, intracellular, and nuclear insulin were compared in control and trypsin-treated H35 hepatoma cells. Trypsin treatment markedly decreased total cell-associated and intracellular insulin as well as the nuclear accumulation of insulin when cells were incubated with 2.8 ng/ml insulin. When the cells were incubated with 100 ng/ml insulin, trypsin treatment totally inhibited insulin binding to the plasma membrane for at least 90 min. However, intracellular accumulation of insulin was reduced by only 50% at 60 min, and trypsin treatment failed to inhibit the nuclear accumulation of insulin. Chemical extraction and Sephadex G-50 chromatography revealed nuclear associated insulin in trypsin-treated cells was identical to that in control cells incubated with either 2.8 or 100 ng/ml insulin. These results suggest that a nonreceptor mediated uptake pathway, i.e., fluid-phase endocytosis, contributed significantly to the nuclear accumulation of insulin at high insulin concentrations, but at lower insulin concentrations the receptor-mediated pathway predominated. No matter which initial endocytotic route was used to internalize insulin, the insulin apparently associated with the same nuclear matrix proteins. This association of insulin with the nuclear matrix may be involved in regulation of nuclear events such as cell growth and differentiation or gene transcription.
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PMID:Nonreceptor mediated nuclear accumulation of insulin in H35 rat hepatoma cells. 144 21

We examined the properties of a new iron-binding protein purified previously from rat liver (T. Furukawa, S. Taketani, H. Kohno, and R. Tokunaga, 1991, Biochem. Biophys. Res. Commun. 181, 409-415). The protein was digested with trypsin and the peptides were analyzed by reverse-phase high-performance liquid chromatography. The partial amino acid sequences of the tryptic peptides coincided with that of rat ribosomal protein P2. Immunoblot analysis and iron-binding assay confirmed that the iron-binding protein and ribosomal protein P2 are identical. Then the iron binding ability of ribosomal protein P2 was examined in rat hepatoma H4IIEC3 cells incubated with radioactive iron. When immunoprecipitation with anti-iron-binding protein serum was performed using cells incubated with 59Fe-citrate, about 4% of the 59Fe radioactivity in cells was associated with the iron-binding protein through 30 to 90 min of incubation. About 1.5% of radioactive iron in cells incubated with 59Fe-transferrin was found in immunoprecipitates with anti-iron-binding protein serum during 1 to 5 h of incubation, and 4 to 7% of the radioactivity was found in immunoprecipitates with a monoclonal antibody against ribosomal P proteins in the same incubation. These results demonstrate that ribosomal proteins P2 binds iron taken up by the cells.
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PMID:Ribosomal protein P2, a novel iron-binding protein. 152 26


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