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)

Experiments were performed to evaluate the utility of a perfluorochemical emulsion as an artificial blood substitute for studies of lipoprotein metabolism in rats. Perfusing the liver of fed rats with perfluorochemical emulsion FC-34 at the same rate as a 20% red blood cell (RBC) perfusate, there was comparable oxygen uptake; however, there was a greater release of glucose and production of lactate than in RBC perfused livers. Under the stimulation of a low level of free fatty acid, there was less free fatty acid uptake and less triglyceride secretion in emulsion perfused livers. The lipoprotein secreted contained similar apoprotein, but there was a lower triglyceride to cholesterol ratio in the emulsion perfused liver. In addition to these moderate metabolic alterations, the uptake of radiolabeled chylomicron remnants by the perfused liver was almost completely suppressed when the perfluorochemical emulsion was used as an oxygen carrier. In vivo the presence of the perfluorochemical emulsion (5% of blood volume) decreased the rate of clearance of chylomicron remnants, beta-very-low-density lipoprotein (beta-VLDL) and cholesterol-rich high-density lipoprotein (HDLc), but not of low-density lipoprotein (LDL). In the presence of the emulsion, the degradation of 125I remnants, but not of [125I]LDL, by rat hepatoma cells was inhibited. The perfluorochemical emulsion did not inactivate lipoprotein lipase. The perfluorochemical emulsion did not change the triglyceride concentration or apoprotein composition of chylomicron remnants when they were incubated with the perfluorochemical emulsion at 37 degrees C for 1 hour and reisolated. The detergent used to solubilize the fluorocarbon FC-43, Pluronic F-68, did not affect the removal of chylomicron remnants in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of perfluorochemical artificial blood on lipoprotein metabolism in rats. 236 60

A newly developed human hepatoma cell line, designated Hep G-2, expresses high-affinity insulin receptors meeting all the expected criteria for classic insulin receptors. 125I-insulin binding is time-dependent and temperature-dependent and unlabeled insulin competes for the labeled hormone with a half-maximal displacement of 1-3 ng/ml. This indicates a Kd of about 10(-10) M. Since Scatchard analysis of the binding data results in a curvilinear plot and unlabeled insulin accelerates the dissociation of bound hormone, these receptors exhibit the negative cooperative interactions characteristic of insulin receptors in many other cell and tissue types. Proinsulin and des(Ala, Asp)-insulin compete for 125I-insulin binding with 4% and 2%, respectively, of the potency of insulin. Anti-(insulin receptor) antibody competes fully for insulin binding. The two insulin-like growth factors, multiplication-stimulating activity and IGF-I are 2% as potent as insulin against the Hep G-2 insulin receptor. Furthermore, Hep G-2 cells respond to insulin in several bioassays. Glucose uptake, glycogen synthase, uridine incorporation into RNA and acetate incorporation into lipid are all stimulated to varying degrees by physiological concentrations of insulin. In addition, these cells 'down-regulate' their insulin receptor, internalize 125I-insulin and degrade insulin in a manner similar to freshly isolated rodent hepatocytes. This is the first available human liver cell line in permanent culture in which both insulin receptors and biological responses have been carefully examined.
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PMID:Insulin receptors and bioresponses in a human liver cell line (Hep G-2). 241 Feb 71

To investigate our earlier hypothesis that carbohydrates play a regulatory role in the intracellular transport of secretory glycoproteins, we used 1-deoxynojirimycin (DNJ), and inhibitor of glucosidase I and II of the rough endoplasmic reticulum (RER), to modify the structure of N-linked glycan moieties of secretory glycoproteins of human hepatoma (Hep G2) cells in culture. Using a pulse-chase protocol, we found that treatment of Hep G2 cultures with 1.25 mM DNJ markedly reduced the rate of secretion of alpha 1-protease inhibitor, ceruloplasmin, and alpha 2-macroglobulin, but had no effect on the export of fibronectin, alpha-fetoprotein and transferrin, nor on albumin which lacks carbohydrate. For example, 50% of newly synthesized alpha 1-protease inhibitor, the glycoprotein most dramatically affected, was secreted by 27 min in control cultures versus 110 min in DNJ-treated cultures. Percoll gradient cell fractionation analyses revealed that DNJ inhibited transport of the affected secretory glycoproteins in the RER segment of the ER/Golgi pathway. For example, 50% of newly synthesized alpha 1-protease inhibitor was lost from the RER fraction by 10 min in untreated cells, but 70 min was required for the transport of a similar amount of protein in DNJ-treated cells. DNJ treatment also inhibited the rate at which the N-linked glycan moieties of the affected glycoproteins became resistant to endo H in the Golgi. Since the glycan moiety of secreted forms of the affected glycoproteins were fully processed to the complex structure, suggesting escape from DNJ inhibition, we concluded that removal of terminal glucose residues from the glycan chain of secretory glycoproteins is required for their transport from the RER to the Golgi. We suggest that the oligosaccharide moieties on alpha 1-protease inhibitor, ceruloplasmin and alpha 2-macroglobulin form part of the binding site for a receptor which regulates transport of these glycoproteins.
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PMID:Differential effects of 1-deoxynojirimycin on the intracellular transport of secretory glycoproteins of human hepatoma cells in culture. 243 31

Metabolism of arabinose 5-P, ribose 5-P and glucose 6-P in permeabilized and resealed Morris hepatoma 5123TC cells was investigated by measuring the contribution of these compounds to nucleic acid biosynthesis. The level of [14C]-arabinose (non-phosphorylated) incorporation into nucleic acids was slight, presumably due to the low activity of the transport system or the absence or low activity of a specific 'kinase' enzyme. The permeabilizing procedure involved the brief treatment of Morris hepatoma 5123TC cells with lysolecithin and resulted in a cell population which was permeable to charged compounds i.e. sugar phosphates and nucleotides, that otherwise could not cross the plasma membrane. The permeabilized (and resealed cells) retained normal cellular morphology and intactness of specific organelles as judged by the maintenance of functional properties. Following permeabilization, these cells resealed when transferred back to normal growth medium, and continued to divide and increase at the same rates as control non-permeabilized cell cultures. The permeabilized cells incorporated deoxyribonucleotides ([methyl -3H]-TTP) into DNA at a linear rate of 0.047 nmol per 10(7) cells min-1, representing 90-100 per cent of the DNA synthesis rate in vivo. The permeabilization technique, when coupled with procedures to establish cell synchrony, permitted the comparative estimate of the contributions of [14C]-labelled arabinose 5-P, ribose 5-P and glucose 6-P to RNA, DNA, amino acids, CO2, lactate and sugar mono- and bisphosphates. The percentage of [14C]-isotope incorporated into total nucleic acids by these three labelled sugar phosphates were 2.3, 4.9 and 6.3 respectively. Possible reasons for the lower incorporation of 14C from arabinose 5-P are given. The results are consistent with the proposal that arabinose 5-P, an intermediate of the L-type pentose pathway activity of 5123TC cells, was incorporated into nucleic acids by its interconversion with ribulose 5-P and ribose 5-P and thus into PRPP. This study represents the first report of sugar phosphate as opposed to free sugar metabolism by tumour cells in culture.
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PMID:Introduction and metabolism of pentose and hexose phosphates in permeabilized Morris hepatoma 5123TC cells. 244

The immunoglobulin G (IgG) fraction obtained from the serum of a patient (B-10) with type B insulin resistance and acanthosis nigricans stimulated both glucose oxidation in rat adipocytes and autophosphorylation of tyrosine residues in the beta-subunit of insulin receptors in H-35 hepatoma cells. Partially purified insulin receptor from H-35 cells, when incubated with B-10 IgG, had increased tyrosine kinase activity for a synthetic peptide sequentially similar to the site of tyrosine phosphorylation in pp60v-arc (the gene product responsible for cellular transformation by the Rous sarcoma virus). In H-35 cells, both B-10 IgG and insulin stimulated tyrosine phosphorylation in an endogenous 185,000 mol wt protein. This phosphoprotein may be similar to the cellular substrate for insulin in hepatoma and other cultured cell lines demonstrated by others. These results suggest that antiinsulin receptor antibodies (B-10) may initiate their insulin-like effects via tyrosine phosphorylation of the insulin receptor, activation of its tyrosine kinase activity, and phosphorylation of a cellular protein substrate of 185,000 mol wt.
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PMID:Autoantibodies to the insulin receptor (B-10) can stimulate tyrosine phosphorylation of the beta-subunit of the insulin receptor and a 185,000 molecular weight protein in rat hepatoma cells. 246 44

Insulin elicits the autophosphorylation of the beta-subunit of its receptor on tyrosine residues: this effect appears to be the earliest post-binding event involved in insulin action. In the present study we have raised highly specific antibodies to phosphotyrosine residues, and we have taken advantage of these antibodies to further evaluate the role of the insulin receptor tyrosine kinase in the generation of insulin's biological responses. Using a cell-free phosphorylation assay, we show here that these antibodies increase the tyrosine kinase activity of the receptor, and its phosphorylation on tyrosine residues. In contrast, the antibodies do not interfere with dephosphorylation of the insulin receptor. Introduction of the same antibodies in living Fao hepatoma cells enhances the effect of insulin on both glucose transport and aminoacid uptake. As a whole our data indicate that the insulin receptor kinase is involved in the generation of an early (glucose transport) and late (aminoacid uptake) response to insulin. Further, conformational changes in phosphotyrosine containing domains of the insulin receptor appear to modulate insulin's biological effects. Finally, the injection of antibodies in intact cells provides us with a novel and promising tool to search for cellular substrates for the insulin receptor tyrosine kinase.
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PMID:Antiphosphotyrosine antibodies modulate insulin receptor kinase activity and insulin action. 248 34

Starvation of a mouse hepatoma cell line, Hepa, for any essential amino acid results in the mono-ADP-ribosylation of an 80-kDa protein, P80. The ADP-ribose acceptor and its putative precursor were identified in two-dimensional gel patterns and isolated by electroelution. Amino-terminal sequence analysis showed they were the 78-kDa glucose-regulated protein, GRP78. Starvation of Hepa cells for tryptophan or glucose stimulated the relative rate of synthesis, and the ADP-ribosylation of GRP78. Inhibition of N-linked glycosylation by treatment with tunicamycin, 2-deoxy-D-glucose or glucosamine stimulated the synthesis of non-ADP-ribosylated GRP78 up to sixfold with relatively little effect on its ADP-ribosylation. Both forms were identified in mouse liver, lung, heart, kidney, spleen and brain.
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PMID:ADP-ribosylation of the 78-kDa glucose-regulated protein during nutritional stress. 251 84

Glucose is known to affect mRNA levels of several genes. In order to investigate possible effects of glucose on insulin receptor mRNA levels, we cultured human hepatoma cells (HepG2) in two different culture media: DMEM containing 100 mg/dl glucose and DMEM containing 450 mg/dl glucose. Insulin receptor mRNA levels and insulin binding activity were reduced in HepG2 cultured at lower glucose concentrations. These data suggest that glucose affects insulin receptor gene expression.
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PMID:Effect of two different glucose concentrations on insulin receptor mRNA levels in human hepatoma HepG2 cells. 254 99

Paradoxical growth hormone (GH) responses in 50 g or 75 g oral glucose tolerance tests (OGTT) have been demonstrated in 24 patients with hepatocellular carcinoma, whereas no significant changes in serum GH levels after OGTT were shown in 10 normal controls, 6 patients with cirrhosis of liver, and with chronic active hepatitis. There were no significant difference in the GH responses in OGTT as well as in the incidence of paradoxical GH responses between diabetic and non-diabetic patients with HCC. Informatively, the basal somatomedin C level was very low in all cases examined.
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PMID:[Clinical studies on the relation of abnormal growth hormone secretions to hepatic diabetes mellitus in patients with hepatocellular carcinoma]. 254 47

Insulin and insulin-like growth factor (IGF)-I inhibit intracellular protein degradation in a variety of different cell types. In the present studies, the IGF-I-induced inhibition of protein metabolism in Chinese hamster ovary (CHO) cells was found to be blocked by polyclonal antibodies to the IGF-II/mannose-6-phosphate phosphate (Man-6-P) receptor, but not by control immunoglobulin. In contrast, these antibodies had no effect on the ability of IGF-I to stimulate glucose uptake in the same cells. The antibodies to the IGF-II/Man-6-P receptor also inhibited the effect of IGF-I and insulin on protein catabolism in human foreskin fibroblasts and human hepatoma cells, respectively. Moreover, CHO cells overexpressing a cDNA coding for the IGF-II/Man-6-P receptor were found to exhibit an increased effect of insulin on protein catabolism. In contrast, the insulin stimulation of glucose uptake is the same in these transfected cells as in the parental CHO cells. These results implicate the IGF-II/Man-6-P receptor in the insulin- and IGF-I-induced inhibition of protein catabolism.
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PMID:A role for the insulin-like growth factor II/mannose-6-phosphate receptor in the insulin-induced inhibition of protein catabolism. 254 2


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