Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Stationary-phase, minimal deviation hepatoma H4-II-E-C3 cell cultures that are serum-deprived respond with a biphasic time course of phenylalanine hydroxylase induction when dialyzed fetal calf serum or insulin is added. These two agents induce phenylalanine hydroxylase additively, during both the initial 3-hour and the delayed 24-hour phases. The initial phase of induction by insulin is inhibited by cycloheximide but not by actinomycin D. The delayed induction by both dialyzed fetal calf serum and insulin is inhibited by 10(-6) M cycloheximide and 0.20 mug/ml actinomycin D. H4-II-E-C3 cells in culture do not synthesize the factor(s) in serum that induce phenylalanine hydroxylase.
 ...
PMID:Control of phenylalanine hydroxylase synthesis in tissue culture by serum and insulin. 0 1

1. A factor, which amplifies the inductions of several liver enzymes by glucocorticoid, was partially purified from Proteus mirabilis from rat intestine. The factor (amplifier) was completely inactivated by alpha-glucosidase, but not by other glycoside hydrolases, proteases, nucleases or phosphatases tested; it was also hydrolysed by HCl with liberation of reducing sugars. Thus the oligosaccharide in this factor seems to be essential for the amplification. 2. In adrenalectomized rats the amplifier increased the inductions of several liver enzymes, such as tyrosine aminotransferase and leucine aminotransferase, by glucocorticoid. But it did not amplify the induction of tyrosine aminotransferase by glucagon or insulin or the activities of enzymes that are not induced by glucocorticoid. The amplifier by itself did not have any glucocorticoid-like action in adrenalectomized rat. These results show that the amplifier specifically increases the inductions of liver enzymes by glucocorticoid. 3. Since similar amplification was also observed in isolated perfused liver and cultured hepatoma cells in vitro, the amplifier seems to act directly on the target organ or cells.
 ...
PMID:A new factor from enteric bacteria of rats amplifying induction of liver enzyme by glucocorticoid. 1. Purification, properties and biological action. 2 Oct 83

A new line of tissue culture cells derived from a slow-growing hepatoma 8999 was established and named 8999C. The isolation method, growth pattern, and morphology of the 8999C cells are described. Several hepatic enzyme activities in 8999C cells were compared to those in the original hepatoma 8999. The ornithine aminotransferase (EC 2.6.1.13), tyrosine aminotransferase (EC 2.6.1.5), and arginase (EC 3.5.3.1) activities in the 8999C cells were one-third, one-tenth, and one-hundredth of those of the respective activities in the original hepatoma 8999, and mitochondrial serine protease, which has much higher activity in hepatoma 8999 than in normal liver cells, was not detected in 8999C cells. Tyrosine aminotransferase in 8999C cells was induced by dexamethasone but not by N6,O2'-dibutyryladenosine 3',5'-cyclic monophosphate or insulin. Unlike in hepatoma 8999, glucocorticoid did not induce arginase in 8999C cells.
 ...
PMID:Establishment of a clonal strain of hepatoma cells derived from Morris hepatoma 8999. 2 74

Tyrosine adminotransferase (EC 2.6.1.5) has been found to be phosphorylated in intact rat hepatoma cells in culture. Incorporation of [32p]i into the enzyme is rapid and is exclusively found as phosphoserine. Cycloheximide treatment reduced phosphorylation of the aminotransferase only slightly and in the presence of three different inducers of this enzyme, dexamethasone, insulin, and dibutyryl cyclic AMP, [32P]I incorporation was increased. It is concluded that [32p]i incorporation into this enzyme probably reflects turnover of phosphate groups associated with pre-existing enzyme molecules catalyzed by a cyclic AMP-independent protein kinase.
 ...
PMID:Relationship between phosphorylation of tyrosine aminotransferase and regulation of its synthesis by cyclic AMP and hormones. 2 2

HTC cells, an established line of rat hepatoma cells in tissue culture, provide a useful experimental model system for studying the interaction of glucocorticoids and insulin in the regulation of protein metabolism. The actions of insulin and glucocorticoids on amino acid transport and protein degradation are antagonistic in this cell line. In contrast, the actions of these two hormones are additive with regard to the induction of tyrosine aminotransferase. The addition of insulin to HTC cells previously incubated with dexamethasone causes a rapid further doubling in the cellular concentration of this enzyme. The properties of the induction by insulin differ in several respects from the induction by glucocorticoids. The former occurs immediately, without the characteristic lag observed during induction by steroids. Insulin induction of transaminase does not require concomitant RNA synthesis, and does not cause the accumulation of specific mRNA for this enzyme as do glucocorticoids. Using specific immunoprecipitation techniques, we have demonstrated that insulin stimulates a nonselective increase in the rate of total protein synthesis in HTC cells, and a selective decrease in the rate of degradation of tyrosine aminotransferase relative to total protein. Thus the induction of transaminase by insulin involves two distinct actions of the hormone, affecting both synthesis and degradation of protein.
 ...
PMID:Syneristic and antagonistic effects of glucocorticoids on insulin action. 4 Jan 18

1. Cultured rat hepatoma cells accumulate 2-aminoisobutyrate to high concentrations by a transport mechanism probably of the A type mediation. 2. Transport is enhanced by the presence of serum. When cells are deprived of serum the rate of transport declines over a period of hours; conversely addition of serum leads over a period of hours to increase in transport activity. In the presence of serum the apparent Km for aminoisobutyrate uptake is about 8 mM. In cells deprived of serum the Km is much higher. 3. Addition of insulin produces both an immediate increase in the rate of aminoisobutyrate uptake and a time-dependent rise. 4. The presence of alanine diminished aminoisobutyrate uptake in a concentration-dependent fashion. Competition is seen both in the presence and absence of serum but not when cells are incubated at 4 degrees C. 5. Preincubation with alanine for 1 h also diminishes aminoisobutyrate uptake when the alanine is removed. Cells take a period of several hours to recover from the depression of transport induced by alanine. 6. Transport of aminoisobutyrate rapidly declines in the presence of cycloheximide. Actinomycin had no effect for at least 8 h.
 ...
PMID:Influence of serum and insulin on the accumulation of aminoisobutyrate by rat hepatoma cells. 6 Jan 38

Homogenate and plasma membrane fractions of Morris hepatoma 5123tc (h) and rat liver were studied with regard to their relative basal activties of adenylate cyclase and to the comparative responsiveness of this enzyme to glucagon, sodium fluoride, epinephrine, prostaglandin E1, and insulin. The basal adenylate cyclase activities of the hepatoma fractions were found to be similar to those of liver at an adenosine 5'triphosphate concentration of 3.2 mM; if the substrate affinity (Km adenosine 5'-triphosphate) of the tumor enzyme is comparable to that of liver, these findings suggest that the reduced basal cyclic adenosine 3':5'-monophosphate levels found to occur in hepatoma 5123tc (h) probably are not due to a decreased basal rate of formation of this cyclic nucleotide. Glucagon (5.6 muM) significantly stimulated adenylate cyclase in both fractions of hepatoma and livers; however, the responsiveness of the tumor enzyme to this hormone was substantially lower than the responsiveness of liver for both homogenate and plasma membrane preparations; i.e., activities were enhanced 18-fold (relative to the basal activity)for liver homogenate compared with only a 6-fold increase for tumor. With the plasma membrane preparations, glucagon increased the activities 5- and 3.5-fold in liver and hepatoma, respectively. Sodium fluoride (10mM), in contrast to glucagon, increased the adenylate cyclase activity to approximately the same extent (about 10-fold) in the liver and hepatoma preparations. Epinephrine (100 muM) enhanced the liver and hepatoma homogenate activites 3- to 4-fold and the hepatoma plasma membrane activities 2-fold; however, the liver plasma membrane activites were not increased. Prostaglandin E1 (56.6 MUM) significantly increased adenylate cyclase activites of liver and hepatoma homogenates (i.e., 1.5- and 3-fold, respectively) but not of the plasma membrane preparations. Insulin (0.7 muM) did not significantly alter adenylate cyclase activities in any of the preparations.
 ...
PMID:Comparative adenylate cyclase activities in homogenate and plasma membrane fractions of Morris hepatoma 5123tc (h). 16 85

The modes of action of insulin and of inhibitors of protein synthesis on the degradation of labeled cellular proteins have been studied in cultured hepatoma (HTC) cells. Protein breakdown is accelerated upon the deprivation of serum (normally present in the culture medium), and this enhancement is inhibited by either insulin or cycloheximide. An exception is a limited class of rapidly turning over cellular proteins, the degradation of which is not influenced by insulin or cycloheximide. Alternative hypotheses to explain the relationship of protein synthesis to the regulation of protein breakdown, viz., control by the levels of precursors of protein synthesis, regulation by the state of the ribosome cycle, or requirement for a product of protein synthesis, have been examined. Protein breakdown was not influenced by amino acid deprivation, and measurements of valyl-tRNA levels in HTC cells subjected to various experimental conditions showed no correlation between the levels of charged tRNAVal and the rates of protein degradation. Three different inhibitors of protein synthesis (puromycin, pactamycin, and cycloheximide) suppressed enhanced protein breakdown in a similar fashion. A direct relationship was found between the respective potencies of these drugs to inhibit protein synthesis and to block enhanced protein breakdown. When cycloheximide and insulin were added following a prior incubation of HTC cells in a serum-free medium, protein breakdown was maximally suppressed within 15-30 min. Actinomycin D inhibited protein breakdown only after a time lag of about 90 min. It is suggested that the regulation of protein breakdown in hepatoma cells requires the continuous formation of a product of protein synthesis, in a manner analogous to the mode of the control of this process in bacteria.
 ...
PMID:Requirement for protein synthesis in the regulation of protein breakdown in cultured hepatoma cells. 17 18

For the biochemical characterization of a new transplantable hepatoma derived from the MC-29 virus-induced liver tumor, the macromolecular content and the inducibility of glucose-6-phosphatase, glucose-6-phosphate dehydrogenase, and aryl hydrocarbon hydroxylase were compared in chicken liver and in this hepatoma. The alteration of the nucleocytoplasmic ratio was deduced from measurements of DNA, RNA, protein, and phospholipid contents of the whole cell homogenate and cell fractions. The increased nuclear and decreased cytoplasmic content of macromolecules suggests a dominancy of the nuclei in the tumor cells. Glucose-6-phosphatase and aryl hydrocarbon hydroxylase activities were lower by 60 and 80%, respectively, in the highly proliferating hepatoma than in the liver. In contrast, glucose-6-phosphate dehydrogenase activity increased in the hepatoma. However, enzyme inducers, such as methylcholanthrene, hydrocortisone, and insulin, were able to enhance the activity of these enzymes in the liver but had no stimulating effect on the hepatoma.
 ...
PMID:Biochemistry and enzyme induction in MC-29 virus-induced transplantable avian hepatoma. 17 98

1. Incubation of human and rat hepatoma cells with insulin (1 mU/10(6) cells) decreases their content of adenosine 3':5'-monophosphate by more than half after 1 h and by about a quarter after 4 h. 2. The activities of the ATP-metabolising enzymes, adenylate kinase and Mg2+-adenosine triphosphatase are significantly increased by insulin within 1 h and after 4 h. Activity of succinate dehydrogenase and lactic dehydrogenase showed no change at either time interval. 3. Insulin markedly stimulated glucose 6-phosphate dehydrogenase activity within 1 h but by 4 h the increase was less apparent. Glutamate dehydrogenase activity by contrast was not increased by 1 h but was elevated at 4 h.
 ...
PMID:The influence of insulin on various enzyme activities in human and rat hepatoma cells. 17 8


1 2 3 4 5 6 7 8 9 10 Next >>