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)

A protein preparation that specifically binds insulin-like growth factors (IGFs) I and II was purified from medium conditioned by rat liver BRL-3A cells using molecular sieve chromatography in 1 M acetic acid followed by affinity chromatography on IGF-II-agarose. The affinity-purified IGF-binding protein exhibits a single major band with apparent Mr = 36,300 under reducing conditions on sodium dodecyl sulfate-polyacrylamide gels. The IGF-binding protein is efficiently and specifically cross-linked to either 125I-IGF-I (human) or 125I-IGF-II (rat) using disuccinimidyl suberate. An IGF-binding protein of similar apparent molecular weight was also affinity purified from rat hepatoma H-35 cell conditioned medium and found to differ from the BRL-3A protein such that potent polyclonal antisera prepared in rabbits against the purified BRL-3A IGF-binding protein exhibited a much lower titer for the H-35 protein in an enzyme-linked immunosorbent assay and upon immunoblotting. In order to determine whether a single BRL-3A IGF-binding protein is present in the affinity-purified preparation, the protein was prepared for sequencing on a Sephacryl S-300 column in 6 M guanidine HCl after reduction and alkylation. The amino acid composition (expressed in percentages) of this IGF-binding protein was determined to be: Cys = 5.5, Lys = 4.8, His = 2.8, Arg = 7.8, Asx = 10.2, Thr = 5.1, Ser = 3.9, Glx = 15.7, Gly = 17.4, Ala = 7.3, Val = 4.6, Met = 1.4, Ile = 2.4, Leu = 8.3, Tyr = 1.0, Phe = 1.9. Sequencing of the NH2-terminal portion of this protein led to the identification of 31 amino acids in the following order: Phe-Arg-Cys-Pro-Pro-Cys-Thr-Pro-Glu-Arg-Leu-Ala-Ala-Cys-Gly-Pro-Pro-Pro- Asp-Ala-Pro-Cys-Ala-Glu-Leu-Val-Arg-Glu-Pro-Gly-Cys. We conclude that rat liver BRL-3A cells secrete a single major IGF-binding protein capable of binding both IGF-I and IGF-II.
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PMID:Purification and amino-terminal sequence of an insulin-like growth factor-binding protein secreted by rat liver BRL-3A cells. 242 67

Sulfation of human alpha 2-antiplasmin, the major plasma inhibitor of fibrinolysis, was examined using both protein isolated from human plasma and protein synthesized and biosynthetically labeled with [35S]sulfate by a human hepatoma-derived cell line. Linkage of sulfate to tyrosine was demonstrated by recovery of labeled tyrosine sulfate after base hydrolysis of sulfate-labeled alpha 2-antiplasmin. Analysis by reverse-phase high performance liquid chromatography of peptides released from alpha 2-antiplasmin by cleavage with trypsin or cyanogen bromide indicated that sulfate is linked to a single segment of the protein. A cyanogen bromide peptide corresponding to the sulfate-labeled peptide was prepared from alpha 2-antiplasmin isolated from human plasma. Consistent with the presence of tyrosine sulfate in this peptide, its chromatographic elution was altered by treatment with acid under conditions which release sulfate from a tyrosine residue. No peptide in the total digest of alpha 2-antiplasmin by cyanogen bromide eluted at the position of the peptide following desulfation, suggesting that all of the protein is in a sulfated form. The sequence of the sulfate-containing cyanogen bromide peptide as determined by sequential Edman degradation, amino acid composition, and fast atom-bombardment-mass spectrometry was: Glu-Glu-Asp-Tyr(SO4)-Pro-Gln-Phe-Gly-Ser-Pro-Lys-COOH. This peptide is a segment of the previously identified plasmin-binding domain of alpha 2-antiplasmin.
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PMID:Sulfation of a tyrosine residue in the plasmin-binding domain of alpha 2-antiplasmin. 243 96

Our previous studies indicated that amino acid residues 240-250 in the cysteine-rich region of the human insulin receptor alpha-subunit constitute a site in which insulin binds (Yip, C. C., Hsu, H., Patel, R. G., Hawley, D. M., Maddux, B. A., and Goldfine, I. D. (1988) Biochem. Biophys. Res. Commun. 157, 321-329). We have now constructed a human insulin receptor mutant in which 3 residues in this sequence were altered (Thr-Cys-Pro-Pro-Pro-Tyr-Tyr-His-Phe-Gln-Asp to Thr-Cys-Pro-Arg-Arg-Tyr-Tyr-Asp-Phe-Gln-Asp) and have expressed this mutant in rat hepatoma (HTC) cells. When compared with cells transfected with normal insulin receptors, cells transfected with mutant receptors had an increase in insulin-binding affinity and a decrease in the dissociation of bound 125I-insulin. Studies using solubilized receptors also demonstrated that mutant receptors had a higher binding affinity than normal receptors. In contrast, cells transfected with either mutant or normal receptors bound monoclonal antibodies against the receptor alpha-subunit with equal affinity. When receptor tyrosine kinase activity and alpha-aminoisobutyric acid uptake were measured, cells transfected with mutant insulin receptors were more sensitive to insulin than cells transfected with normal receptors. These findings lend further support therefore to the hypothesis that amino acid sequence 240-250 of the human insulin receptor alpha-subunit constitutes one site that interacts with insulin, and they indicate that mutations in this site can influence insulin receptor binding and transmembrane signaling.
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PMID:Mutation of the high cysteine region of the human insulin receptor alpha-subunit increases insulin receptor binding affinity and transmembrane signaling. 255 Apr 26

A cDNA encoding human nucleophosmin (protein B23) was obtained by screening a human placental cDNA library in lambda gtll first with monoclonal antibody to rat nucleophosmin and then with confirmed partial cDNA of human nucleophosmin as probes. The cDNA had 1311 bp with a coding sequence encoding a protein of 294 amino acids. The identity of the cDNA was confirmed by the presence of encoded amino acid sequences identical with those determined by sequencing pure rat nucleophosmin (a total of 138 amino acids). The most striking feature of the sequence is an acidic cluster located in the middle of the molecule. The cluster consists of 26 Asp/Glu and 1 Phe and Ala. Comparison of human nucleophosmin and Xenopus nucleolar protein NO38 shows 64.3% sequence identity. The N-terminal 130 amino acids of human nucleophosmin also bear 50% identity with that of Xenopus nucleoplasmin. Northern blot analysis of rat liver total RNA with a partial nucleophosmin cDNA as probe demonstrated a homogeneous mRNA band of about 1.6 kb. Similar observations were made in hypertrophic rat liver and Novikoff hepatoma. However, the quantity of nucleophosmin mRNA is 50- and 5-fold higher in Novikoff hepatoma and hypertrophic rat liver, respectively, when compared with normal rat liver. Dot blot analysis also showed a nucleophosmin mRNA ratio of 64:5:1 in the three types of rat liver. When the protein levels were compared with Western blot immunoassays, Novikoff hepatoma showed 20 times more nucleophosmin, while only about 5 times more nucleophosmin was observed in hypertrophic rat liver than in unstimulated normal liver.
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PMID:Characterization of the cDNA encoding human nucleophosmin and studies of its role in normal and abnormal growth. 271 55

Incubation of H4-II-E-C3 rat hepatoma cells with either hydrocortisone or dexamethasone resulted in 3- to 5-fold increases in the levels of both phenylalanine hydroxylase and its essential cofactor, tetrahydrobiopterin. Maximum elevation of phenylalanine hydroxylase was noted after 24 h of incubation, whereas significant increases in tetrahydrobiopterin were found only after 48 h exposure of the cells to glucocorticoids. Removal of hormone from the culture medium resulted in rapid loss of cell tetrahydrobiopterin, but a much slower decline in the level of phenylalanine hydroxylase. Thus, although the levels of both phenylalanine hydroxylase and tetrahydrobiopterin in rat hepatoma cells are regulated by glucocorticoids, this regulation is apparently not strictly coordinated. Nevertheless, control of cellular tetrahydrobiopterin levels may be an important regulator of hepatic phenylalanine catabolism since significant increases in the ability of intact rat liver cells to hydroxylate phenylalanine were observed only after 48 h exposure to glucocorticoids, in correlation with increases in cell tetrahydrobiopterin content.
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PMID:Glucocorticoid stimulation of tetrahydrobiopterin levels and phenylalanine hydroxylase activity in rat hepatoma cells. 277 31

Cyclo(-Phe(p-NH[1-14C]Ac)-Thr-Lys-(CO(p-N3)C6H4)-Trp-Phe-DPro++ +), in the following named azidobenzamido-008, was synthesized in order to identify binding sites for c(Phe-Thr-Lys-Trp-Phe-DPro), named 008, (a cyclosomatostatin with retro sequence) in liver cell plasma membranes. In the dark the above photolabel was taken up into isolated hepatocytes, inhibiting the sodium dependent uptake of cholate and taurocholate in a competitive manner (Ki for cholate uptake inhibition = 1 microM; Ki for taurocholate uptake inhibition = 5 microM). When activated by flashed light the inhibition became irreversible (IC50 for cholate uptake inhibition = 2 microM; IC50 for taurocholate uptake inhibition = 9 microM) and the activated cyclopeptide bound chiefly to hepatocellular membrane proteins of 67, 54, 50, 37 kDa. Excess of the initial 008, or of cholate or phalloidin partially protected the above membrane components against labeling with 14C-labeled azidobenzamido-008. In contrast AS 30 D ascites hepatoma cells, known to be deficient in bile acid and cyclosomatostatin transport, could not be specifically labeled by azidobenzamido-008. The membrane proteins preferentially labeled in hepatocytes (50 and 54 kDa) are integral glycoproteins. The 67 kDa protein is a hydrophilic nonglycosylated membrane component. Independent of labeling with 14C-labeled azidobenzamido-008 or with 14C-labeled azidobenzamido-taurocholate, the main radioactive peaks in the pH region of 7, 5.5, 5.25 were identical after solubilization with Nonidet P-40 and subsequent isoelectric focusing. Proteins of 67, 54, 50 and 37 kDa could be enriched by use of 008-containing gels in affinity electrophoresis. Binding sites for 008 were not destroyed by SDS or Nonidet P-40 treatment of plasma membranes.
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PMID:Azidobenzamido-008, a new photosensitive substrate for the 'multispecific bile acid transporter' of hepatocytes: evidence for a common transport system for bile acids and cyclosomatostatins in basolateral membranes. 290 68

Ochratoxin B (OTB), the dechloro-analogue of ochratoxin A (OTA), was studied separately and in combination with OTA on the aminoacylation of phenylalanine tRNA (tRNAPhe) catalysed by mice liver phenylalanyl-tRNA synthetase. OTB was neither a significant inhibitor of the reaction nor an antagonist of OTA. OTB was also assayed for its possible antagonistic effect on the in vivo protein synthesis inhibition caused by OTA in hepatoma tissue culture cells. No prevention of OTA inhibition could be found for OTB. It rather showed a slight additional inhibitory activity when mixed (100-180 microM) with low concentrations of OTA (40-60 microM). In conclusion, these results are not in favor of an antagonistic effect of OTB with respect to OTA action, at least on the level of cellular protein synthesis.
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PMID:Influence of ochratoxin B on the ochratoxin A inhibition of phenylalanyl-tRNA formation in vitro and protein synthesis in hepatoma tissue culture cells. 291 8

Deprivation of cultured H4 rat hepatoma cells for an essential amino acid (leucine, methionine, tryptophan or phenylalanine) under conditions in which the cells remain highly viable leads to a decrease in cytoplasmic albumin mRNA. The magnitude of this decrease is greatest in tryptophan-deprived and phenylalanine-deprived cells. In the tryptophan-deprived cells there is approximately a 15-17-fold decrease in albumin mRNA relative to total cytoplasmic RNA, and a 7-8-fold specific decrease in albumin mRNA relative to alpha-tubulin mRNA. Deprivation of the H4 cells for leucine or tryptophan causes approximately a 40-45% decrease in albumin gene transcription; however, this effect does not account for the 15-17-fold decrease in albumin mRNA abundancy caused by tryptophan limitation, or the greater effect of tryptophan limitation as compared to leucine limitation on albumin mRNA. Therefore, the decrease in albumin mRNA caused by tryptophan limitation is caused primarily by a post-transcriptional regulatory mechanism.
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PMID:Regulation of albumin mRNA in H4 rat hepatoma cells by the availability of essential amino acids. 317 36

1. The occurrence and characterization of acidic amino acid transport in the plasma membrane of a variety of cells and tissues of a number of organisms is reviewed. 2. Several cell types, especially in brain, possess both high- and low-affinity transport systems for acidic amino acids. 3. High-affinity systems in brain may function to remove neurotransmitter amino acid from the extracellular environment. 4. Many cell systems for acidic amino acid transport are energized by an inwardly directed Na+ gradient. Moreover, certain cell types, such as rat brain neurons, human placental trophoblast and rabbit and rat kidney cortex epithelium, respond to an outwardly directed K+ gradient as an additional source of energization. This simultaneous action may account for the high accumulation ratios seen with acidic amino acids. 5. Rabbit kidney has been found to have a glutamate-H+ co-transport system which is subject to stimulation by protons in the medium. 6. Acidic amino acid transport in rat brain neurons occurs with a stoichiometric coupling of 1 mol of amino acid to 2 mol of Na+. For rabbit intestine, one Na+ is predicted to migrate for each mol of amino acid. 7. Uptake in rat kidney cortex and in high-K+ dog erythrocytes is electrogenic. However, uptake in rabbit and newt kidney and in rat and rabbit intestine is electroneutral. 8. Na+-independent acidic amino acid transport systems have been described in the mouse lymphocyte, the human fibroblast, the mouse Ehrlich cell and in rat hepatoma cells. 9. In a number of cell systems, D-acidic amino acids have substantial affinity for transport; D-glutamate, in a number of systems, however, appears to have little reactivity. 10. Acidic amino acid transport in some cell systems appears to occur via the "classical" routes (Christensen, Adv. Enzymol. Relat. Areas Mol. Biol. 49, 41-101, 1979). For example, uptake in the Ehrlich cell is partitioned between the Na+-dependent A system (which transports a wide spectrum of neutral amino acids), the Na+-dependent ASC system (which transports alanine, serine, threonine, homoserine, etc.), and the Na+-independent L system (which shows reactivity centering around neutral amino acids such as leucine and phenylalanine). Also, a minor component of uptake in mouse lymphocytes occurs by a route resembling the A system. 11. Human fibroblasts possess a Na+-independent adaptive transport system for cystine and glutamate that is enhanced in activity by cystine starvation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acidic amino acid transport in animal cells and tissues. 330 25

The effects of a combined dietary restriction of tyrosine and phenylalanine on metastasis were investigated with the use of 3 rodent tumor cell lines: B16-bladder 6 (BL6) melanoma inoculated into (C57BL/6 X DBA/2)F1 mice, Lewis lung (3LL) carcinoma inoculated into C57BL/6 mice, and RT7-4bs hepatocarcinoma inoculated into BD-IV rats. When examined for effects on spontaneous metastasis, dietary restriction of tyrosine and phenylalanine had no effect on metastasis to draining lymph nodes in either BL6 or 3LL tumors. However, the restriction did reduce metastasis of RT7-4bs cells to draining lymph nodes by 60%. In all tumor systems, the dietary restriction effectively inhibited the subsequent growth of lymph node tumors. The most marked effect of the dietary restriction was on spontaneous hematogenous metastasis, which was almost totally blocked for BL6 cells and was reduced by 85% for RT7-4bs cells. Tumor-associated splenomegaly also was completely inhibited in 3LL tumor-bearing mice. The selective dietary amino acid restriction failed to reduce initial lung colonization in the experimental metastasis assay but clearly inhibited subsequent tumor outgrowth in the lungs. These findings demonstrate that modification of host nutritional status by restriction of the dietary intake of tyrosine and phenylalanine exerts a dramatic antimetastatic effect directed particularly on spontaneous hematogenous metastasis. Although the preliminary data suggest a primary modulating effect on tumor cell populations growing in diet-restricted animals to reduce inherent metastatic ability, the actual mechanisms remain to be defined.
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PMID:Dietary restriction of tyrosine and phenylalanine: inhibition of metastasis of three rodent tumors. 347 May 51


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