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)

Distribution of transglutaminase activity was determined in normal rat liver, a 3'-methyl-4-dimethylaminoazobenzene-induced primary hepatoma, and the Novikoff hepatoma. Over 90% of the total enzyme activity was found in the 105,000 X g supernatant of normal liver, whereas only 30% was found in this fraction of the hepatomas, the remainder being found in the particulate fraction. The is distribution pattern did not correlate with protein distribution nor did it change during cellular proliferation, since regenerating liver and embryonic tissue had the same pattern as normal liver. Cell protein was a suitable acceptor substrate for the enzyme. Kinetic analyses showed that liver and hepatoma enzymes had a similar Km and Vmax for putrescine incorporation into cell protein. Hepatoma particulate enzyme was more stable than either liver or hepatoma supernatant enzyme. The enzyme may also act as the acceptor molecule.
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PMID:Differential transglutaminase distribution in normal rat liver and rat hepatoma. 0 47

The transglutaminase-mediated incorporation of [14C]methylamine into tissue slices obtained from normal rat liver and diethylnitrosamine-induced hepatocellular carcinomas was used as a means of characterising the endogenous substrates of the transglutaminase enzymes present in these tissues. The amount of radiolabel incorporated was found to be similar in both tissues with the major radiolabelled protein identified as a high molecular weight polymer unable to traverse a 3.0% (w/v) acrylamide gel and with a molecular weight of at least 5 x 10(6) Da. Measurement of the crosslink, epsilon-(gamma-glutamyl)lysine, in the hepatocellular carcinoma and in normal liver indicated a 3-fold reduction in the levels found in tumour tissue when compared to normal liver. In contrast, the levels of covalently bound polyamines present in the hepatocellular carcinoma were found to be comparable or greater than those found in normal liver. Considering that there is a selective reduction (approx. 5-fold) in the activity of the cytosolic transglutaminase present in hepatocellular carcinomas with no change in the activity of the particulate enzyme (Hand et al. (1988) Biochim. Biophys. Acta 970, 137-145) these results suggests that the two enzymes may be differentially activated and that they may act on different substrates within the cell.
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PMID:Characterisation of the cellular substrates for transglutaminase in normal liver and hepatocellular carcinoma. 196 51

A significant increase in the molecular weights of lamin A and more so of lamin C was observed when isolated Novikoff hepatoma chromatin was incubated in the presence of Ca2+. This increase did not occur to any significant degree in similar preparations of normal rat liver nuclei. Although detectable in Coomassie Brilliant Blue stained gels, this increase to a higher molecular weight (by approximately 2000 Mr) was much more visible when the electrophoretically separated lamins were transferred to nitrocellulose sheets and stained (using peroxidase-antiperoxidase) with polyclonal antiserum to the three major lamin proteins. This modification could also be induced when whole Novikoff hepatoma cell lysates were incubated in the presence of calcium. Again, this change did not occur in normal rat liver cells treated in the same manner. Further analysis has provided evidence that this modification is most likely mediated by the transaminating activity of an intrinsic nuclear transglutaminase forming a cross-link between the affected lamins and an unknown low molecular weight (approximately equal to 2000 Mr) moiety.
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PMID:Enzymatic modification of Novikoff hepatoma lamins A and C. 257 66

Transglutaminase activity and subcellular distribution have been examined in both normal and tumour tissue. Subcellular fractionation of rat liver demonstrated a bimodial distribution for transglutaminase between the particulate (approximately 40%) and cytosol (approximately 60%) fractions. Isolation of enriched plasma membrane fractions indicated the presence of membrane associated transglutaminase activity which co-distributed with that of 5'-nucleotidase and Na+/K+-ATPase. Induction of hepatocellular carcinomas in rats by treatment with either diethylnitrosamine or 6-p-dimethylaminophenylazobenzothiazole resulted in a reduction in transglutaminase activity which was accompanied by redistribution of the enzyme to the particulate fraction of the cell. The tumour bearing liver appeared to represent an intermediate stage between the hepatocellular carcinoma and control liver when assayed for content and distribution of transglutaminase activity. The transglutaminase activity of four transplantable rat sarcomas (P7, P8, MC3 and CC5) was found to be greatly reduced when compared with the normal tissues of rat liver, lung and spleen. A further reduction in this activity occurred in the primary growths of the sarcomas P7 and P8 following detection of metastases. Our data suggest that such changes in the distribution and content of transglutaminase may be a feature of tumour tissue and may be of value in both monitoring and investigating the carcinogenic process.
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PMID:Alterations in the distribution and activity of transglutaminase during tumour growth and metastasis. 285 74

Transglutaminase (EC 2.3.2.13) activity in chemically induced rat hepatocellular carcinomas was reduced by some 65% when compared to normal rat livers. The majority of the remaining activity (approx. 85%) was found in the particulate fraction. The use of non-ionic detergent to extract the transglutaminase activity present in both normal and tumour tissue followed by its separation on a Mono-Q column revealed two distinct peaks of activity. These peaks of activity were equivalent to those previously identified as a membrane-bound transglutaminase and the more characteristic cytosolic or tissue transglutaminase. The ratio of the activity of the cytosolic enzyme to that of the membrane-bound enzyme in normal liver was calculated as 5:1. In hepatocellular carcinomas, this ratio was reduced to 0.4:1. No significant change in the activity of the membrane-bound enzyme was detectable in tumour tissue. Comparison of the cytosolic enzyme found in hepatocellular carcinomas with that found in normal liver indicated no change in its molecular weight, Km,app for putrescine incorporation into N,N'-dimethylcasein and sensitivity to activation by Ca2+. These observations suggest that the reduction in transglutaminase activity observed in the hepatocellular carcinoma is due to a selective reduction in the expression of the cytosolic transglutaminase.
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PMID:Expression of the cytosolic and particulate forms of transglutaminase during chemically induced rat liver carcinogenesis. 289 62

The plasma transglutaminase, factor XIIIa (FXIIIa), circulates as a zymogen containing two proteins, A and B, arranged in a noncovalent tetrameric complex, A2B2. Biosynthesis of plasma FXIII has not previously been demonstrated. In the present study, direct evidence has been obtained that two human hepatoma cell lines, Hep G2 and PLC/PRF/5, synthesize and secrete FXIII B protein. Secretion of the B subunit of FXIII by Hep G2 was demonstrated by immunoblotting. De novo synthesis by Hep G2 was confirmed in 35S-methionine-labeled cultures. Radiolabeled conditioned medium was concentrated, mixed (1:1) with purified B protein, and examined by crossed immunoelectrophoresis with antiserum to the B subunit. The single protein precipitin arc of purified B protein comigrated with the radiolabeled FXIII from Hep G2 visualized by autoradiography, indicating both electrophoretic and antigenic identity. The data presented here represent the first demonstrations of biosynthesis of FXIII B protein by any cell type and suggest that the liver is the site of synthesis of FXIII B protein. Further analysis of concentrated Hep G2 serum-free conditioned medium (SFCM) and cell lysate by immunoblotting following nondenaturing agarose gel electrophoresis demonstrated the FXIII A protein as well as the B protein and also revealed synthesis and secretion of the A and B proteins by PLC/PRF/5. Crossed immunoelectrophoresis studies of Hep G2 SFCM and cell lysate suggest that Hep G2 cells also synthesize and secrete the plasma FXIII zymogen. With a specific radioimmunoassay for B protein, FXIII was found in Hep G2 SFCM at approximately 4 ng/mL; with an amplified rocket immunoelectrophoresis technique the level was approximately 5 ng/mL.
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PMID:Biosynthesis of factor XIII B subunit by human hepatoma cell lines. 302 46

Transglutaminase activity was reduced in malignant hepatoma, virus-transformed human and hamster cells, and chemically transformed mouse cells when compared to normal counterparts. The reduction in enzyme activity reflected the presence of fewer transglutaminase molecules in transformed cells. Greater amounts of the enzyme activity were particulate-associated in confluent and arrested normal human cells. Indirect immunofluorescence studies with antibody to cellular transglutaminase demonstrated the presence of transglutaminase in Triton X-100-insoluble material. A parallel between pericellular fibronectin and transglutaminase (TGase) was demonstrated. Normal human and mouse cells that elicited contact inhibition of growth and had the high TGase activity also had more epsilon-(gamma-glutamyl) lysine isopeptide bonds than transformed counterparts. Similarly nonproliferating human cells had higher transglutaminase activity and isopeptide levels than did proliferating populations. These results suggest that isopeptide bond formation stabilizes the cell membrane and contributes to a nonproliferating state. Inhibition of isopeptide formation should therefore lead to a mitogenic response. Preliminary results support such a relationship. A model depicting control of isopeptide formation at either enzyme or substrate level is presented.
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PMID:Transglutaminase and epsilon-(gamma-glutamyl) lysine isopeptide bonds in eukaryotic cells. 610 9

We investigated transglutaminase-induced cross-linking of cytokeratin polypeptides in liver and hepatoma cells. To overcome the difficulties in the biochemical analysis of highly cross-linked polymers and aggregates of cytokeratins, cross-linked cytokeratin dimers were analyzed by immunoblotting to evaluate the degree of cross-linking of cytokeratins. Covalently cross-linked cytokeratin dimers were not detectable in normal rat liver cells. However, cytokeratin dimers and high-molecular-weight cytokeratin polymers were detected in liver tissue with histological evidence of coagulative necrosis induced by ischemia or carbon tetrachloride. Treatment of cultured hepatoma cells with the Ca2+ ionophore A23187 showed a dose-dependent, time-dependent decrease of cell viability. The appearance of cytokeratin dimers was shown to be correlated with cell death. These results suggest that the transglutaminase-induced cross-linking of cytokeratin polypeptides in liver and hepatoma cells is closely associated with the process of cell degeneration and death.
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PMID:Cross-linked cytokeratin polypeptides in liver and hepatoma cells: possible association with the process of cell degeneration and death. 767 72

We report here that transforming growth factor-beta 1 induces cell death in the Morris hepatoma cell line McA-RH7777. We assessed the type of cell death induced by transforming growth factor-beta 1 in this hepatoma cell line on the basis of morphological and biochemical characteristics. Dying cells, which detached from the cell monolayer, showed morphological characteristics of apoptosis (programmed cell death) such as chromatin condensation, nuclear disintegration and cellular fragmentation into clusters of eosinophilic globules. DNA isolated from these cells showed a ladder pattern consisting of multimers of 180 to 190 bp, indicating extensive DNA cleavage into oligonucleosomal units by an endogenous endonuclease. Treatment of the dead cells with detergents and chaotropic agents resulted in formation of insoluble shells, so-called apoptotic bodies, suggesting extensive cross-linking of cell proteins by tissue transglutaminase. Furthermore, increased amounts of cytosolic tissue transglutaminase, which has been recognized as a possible marker of apoptosis, and extensive cross-linking of cytokeratin polypeptides was demonstrated in TGF-beta 1-treated hepatoma cells on immunoblot analysis. These results provide strong evidence that the cell death induced by TGF-beta 1 in McA-RH7777 hepatoma cells is mainly apoptotic. It also suggests that a specific induction of the cytosolic tissue transglutaminase may be involved in the TGF-beta 1-induced pathways of apoptotic cell death in McA-RH7777 hepatoma cells.
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PMID:Induction of apoptosis by transforming growth factor-beta 1 in the rat hepatoma cell line McA-RH7777: a possible association with tissue transglutaminase expression. 769 7

Close correlation between tissue transglutaminase (tTG) induction and growth regulation and/or cell death processes has been suggested in many cell lineages. In this study, the regulation of the tTG levels by various growth and differentiation factors and its relation to growth rate and cell death processes were investigated in two rat hepatoma cell lines, McA-RH7777 and McA-RH8994, using a monoclonal antibody against liver tTG. Transforming growth factor-beta 1 (TGF-beta 1) and retinoic acid (RA) each increased tTG to the level of 8- to 32-fold above that of control cultures in both cell lines after 72-h treatment. Dexamethasone (DEX) induced a 16- to 32-fold of tTG in McA-RH8994 cells while it did not change the enzyme level in McA-RH7777 cells. Simultaneous addition of DEX and RA increased the tTG level to more than 50-fold in McA-RH7777 cells as well as McA-RH8994 cells. Other factors, such as TGF-alpha, hepatocyte growth factor, dimethyl sulfoxide, and protein kinase C activator, did not show significant increases of the tTG levels. Although tTG induction by TGF-beta 1 or DEX appeared to be correlated with their growth suppressive effects, RA increased the tTG level without suppressing the growth rate of hepatoma cells. TGF-beta 1 was also shown to induce cell death in both cell lines. Our results demonstrate that RA and DEX are capable of modulating the TGF-beta 1-induced cell death processes independent of the tTG levels. We present evidence here that tTG induction by itself is not the direct cause of growth suppression and cell death in these hepatoma cells.
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PMID:Differential regulation of tissue transglutaminase in rat hepatoma cell lines McA-RH7777 and McA-RH8994: relation to growth rate and cell death. 790 35


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