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)

These studies indicate that autonomous cholesterol biosynthesis by hepatocellular carcinoma may result from absent or defective receptors for chylomicron remnants on the surface of the malignant hepatocytes. In vivo, DAB2 hepatoma or liver were perfused with chylomicron remnants labeled with tritiated palmitic acid. Normal liver had chylomicron remnant uptake/gm tissue that was ten times that of hepatoma. In vitro studies using isolated hepatocytes and cultured DAB2 hepatoma cells showed similar results. Uptake of chylomicron remnants labeled with 3H-palmitic acid by normal hepatocytes during a 4-hour period was ten times that of hepatoma cells. Both in vivo and in vitro differences were statistically highly significant (P less than 0.005). Since many surface receptors are related to the coated pits, the cellular membranes of both neoplastic and normal liver cells were examined by electron microscopy. Coated pits were present in both the hepatoma and normal liver cells and occupied 2.61% and 2.65% of the cell surface, respectively. The defective uptake of chylomicron remnants by DAB2 hepatoma appears to be related to the chylomicron remnant receptor and not to the coated pit-internalization mechanism.
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PMID:Autonomous cholesterol biosynthesis in murine hepatoma. A receptor defect with normal coated pits. 608 93

Our in vivo studies in mice have shown that LDL-receptor gene expression is regulated differently in both liver and intestine by dietary cholesterol and dietary saturated fat. While dietary cholesterol serves to regulate at transcriptional levels, dietary fatty acids do not. To study the mechanism of regulation of LDL-receptor by saturated fat and cholesterol at the cellular level, where any secondary effects of long-term feeding in vivo are minimized we used the cultured hepatoma and colon carcinoma cells, HepG2 and Caco2. LDL-receptor activity was determined by 125I-labeled LDL binding and uptake, LDL-receptor protein by Western blotting, LDL-receptor mRNA by RNase protection assay, and relative rates of LDL-receptor mRNA transcription by nuclear 'run-off' assay. Incubation of cells in lipoprotein-deficient serum (LPDS) for 48 h progressively induced LDL-receptor activity and LDL-receptor protein by 5- to 6-fold in HepG2 cells and 2- to 3-fold in Caco2 cells. Absolute levels of LDL-receptor mRNA and relative rates of LDL-receptor mRNA transcription also increased in parallel to the LDL-receptor activity and protein levels in both cell lines. These data suggest that LPDS induced the LDL-receptor gene by transcriptional mechanism. The suppressive effect of 25-hydroxycholesterol on LDL-receptor regulation was studied by incubating HepG2 and Caco2 cells grown either in 10% FCS or 10% LPDS for 24 h and then for 0-24 h with various doses of 25-hydroxycholesterol. In HepG2 cells, LDL-receptor activity and protein mass progressively decreased to 50% of zero time controls over 24 h. LDL-receptor mRNA levels and relative rates of transcription decreased in parallel. In Caco2 cells, 25-hydrocholesterol lowered LDL-receptor activity, mRNA, and transcription by approximately 35%. To examine the effects of palmitate on LDL-receptor regulation, palmitate was complexed with albumin. Palmitate decreased LDL-receptor activity by 25% in HepG2 cells without altering LDL-receptor mass, mRNA levels, or rates of mRNA transcription. Similarly, in Caco2 cells, palmitate decreased LDL-receptor activity and protein mass 30% of controls, but did not change LDL-receptor mRNA levels and/or rates of transcription. The combination of palmitate (0.8 mM) and 25-hydroxycholesterol (2.5-5 micrograms/ml) suppressed LDL-receptor activity by 65% in HepG2 cells and by 52% in Caco2 cells. However, LDL-receptor mRNA decreased by approximately 50% in HepG2 cells and 30-40% in Caco2 cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of low density lipoprotein receptor gene expression in HepG2 and Caco2 cells by palmitate, oleate, and 25-hydroxycholesterol. 759 67

cDNA encoding the precursor of rat very-long-chain acyl-CoA dehydrogenase (VLCAD) was cloned and sequenced. The longest cDNA insert had 2117 bases. This cDNA encodes the entire protein of 655 amino acids, including a 40-amino acid leader peptide and a 615-amino acid mature polypeptide. The identity of the VLCAD clone was confirmed by matching the amino acid sequence predicted from the cDNA to the NH2 terminus and seven internal proteolytic peptide sequences from purified rat liver VLCAD. The calculated molecular masses of the precursor protein, the mature protein, and the leader peptide are 70,961, 66,508, and 4,470 daltons, respectively. At the amino acid level, the significant homology to the other acyl-CoA dehydrogenases was found at the range from the 94th to the 473rd amino acid residue of the amino-terminal side. The catalytic residue and the residue lying near the dimethylbenzene side (si-side) of the flavin ring were speculated to be Glu-462 and Trp-249, respectively. The VLCAD cDNA was expressed in four kinds of hepatoma cells using a vaccinia virus expression system and was shown to encode the catalytically active enzyme. The cDNA expression in both rat hepatoma H4IIEC3 and McA-RH7777 enhanced about 3-fold mitochondrial beta-oxidation activity of long-chain fatty acids such as palmitic acid and stearic acid; hence, VLCAD is probably a rate-limiting enzyme in the long-chain fatty acid beta-oxidation system in these cell lines.
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PMID:Rat very-long-chain acyl-CoA dehydrogenase, a novel mitochondrial acyl-CoA dehydrogenase gene product, is a rate-limiting enzyme in long-chain fatty acid beta-oxidation system. cDNA and deduced amino acid sequence and distinct specificities of the cDNA-expressed protein. 803 67

We report here for the first time that ASGP-Rs expressed in the human hepatoma cell lines HuH-7 and HepG2 are fatty acylated. Cells were metabolically labeled with [3H]palmitate and active ASGP-Rs, which contain two subunits (HHL1 and HHL2), were purified by affinity chromatography and subjected to nonreducing SDS-PAGE and fluorography. [3H]Palmitate was covalently incorporated into both HHL1 and HHL2. When gel slices containing HHL1/HHL2 were treated at neutral pH with 1 M hydroxylamine, but not 1 M Tris, > 95% of the radioactivity was removed, indicating that the attachment of palmitate to ASGP-Rs is to cysteines. Furthermore, the same mild hydroxylamine treatment caused partial ASGP-R inactivation; 50-70% of receptors corresponding to the previously characterized State 2 ASGP-Rs were inactivated. We conclude that both HHL1 and HHL2 are covalently modified by fatty acylation, which may regulate the ligand-binding activity of human State 2 ASGP-Rs. We propose that fatty acylation/deacylation of cytoplasmic domains is a general mechanism by which extracellular ligand-binding activity of oligomeric transmembrane receptors can be regulated.
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PMID:The human asialoglycoprotein receptor is palmitoylated and fatty deacylation causes inactivation of state 2 receptors. 857 55

Dietary intake of fish oils, rich in the polyunsaturated fatty acids (PUFAs) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has given inconsistent results as to their influence on the plasma fibrinogen level (1, 2, 3, 4, 5, 6). In the present study we have examined the effects of various fatty acids, the PUFAs and the saturated fatty acid palmitic acid (PA), alone or combined with the antioxidant vitamin E (Vit.E), on the fibrinogen concentration in the growth medium of human hepatoma (HepG2) cells. Vit.E alone decreased the amount of fibrinogen in the medium in a dose dependent fashion, where fibrinogen was measured as Fibrinopeptide A (FPA) releasable by thrombin. EPA and Vit.E decreased the amount of fibrinogen additively. PUFAs alone increased the fibrinogen concentration in a dose dependent manner. PUFAs combined with a fixed dose of Vit.E decreased the fibrinogen concentration, also dose dependently. OA and PA had an inhibitory effect, both alone and combined with Vit.E. These results indicate that Vit.E may be necessary for PUFAs to have a fibrinogen lowering effect, whereas both OA and PA apparently may decrease the fibrinogen concentration in the cell medium of HepG2 cells, both alone and combined with Vit.E. Possibly, peroxidation of the PUFAs may increase the fibrinogen production, that may be counteracted and reversed by the simultaneous presence of Vit.E.
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PMID:Effects of various fatty acids alone or combined with vitamin E on cell growth and fibrinogen concentration in the medium of HepG2 cells. 857 40

The role of fatty acids in the expression of the gene for liver fatty acid-binding protein (L-FABP) was investigated in the well-differentiated FAO rat hepatoma cell line. Cells were maintained in serum-free medium containing 40 microM BSA/320 microM oleate. Western blot analysis showed that oleate triggered an approx. 4-fold increase in the cytosolic L-FABP level in 16 h. Oleate specifically stimulated L-FABP mRNA in time-dependent and dose-dependent manners with a maximum 7-fold increase at 16 h in FAO cells. Preincubation of FAO cells with cycloheximide prevented the oleate-mediated induction of L-FABP mRNA, showing that protein synthesis was required for the action of fatty acids. Run-on transcription assays demonstrated that the control of L-FABP gene expression by oleate was, at least in part, transcriptional. Palmitic acid, oleic acid, linoleic acid, linolenic acid and arachidonic acid were similarly potent whereas octanoic acid was inefficient. This regulation was also found in normal hepatocytes. Therefore long-chain fatty acids are strong inducers of L-FABP gene expression. FAO cells constitute a useful tool for studying the underlying mechanism of fatty acid action.
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PMID:Up-regulation of the expression of the gene for liver fatty acid-binding protein by long-chain fatty acids. 891 85

It is well-known that ethanol alters fatty acid and glycerolipid metabolism in liver, but most of the studies have been developed on rats, so little is known about the corresponding effects on human liver. We have chosen the Hep G2 human hepatoma cell line, which appears to be an excellent in vitro model system. Cells were incubated in ethanol containing medium (0-400 mM) for 48 h. Incorporation and metabolism of radioactive substrates (14C(U) glycerol,[1-14C] palmitic acid and [1-14C] eicosatrienoic acid (n-6) were analyzed in cellular and conditioned medium lipids. Cellular growth rate and lipid composition of control and ethanol-treated cells were also studied. The results showed that ethanol inhibited logarithmic cellular growth rate in a concentration dependent manner, without affecting viability. Ethanol (400 mM) did not modify cellular major lipid composition except for an increase of cholesteryl esters, but produced a decrease in the proportions of myristic, palmitic and palmitoleic acids. Ethanol enhanced the incorporation of radioactive fatty acids into cellular glycerolipids but did not alter the rate of incorporation of 14C(U) glycerol. This was attributed to an isotopic solution of the radioactive glycerol as a result of increased alpha-glycerophosphate biosynthesis. Incorporation of radioactive fatty acids and glycerol into conditioned medium glycerolipids were increased in cells incubated in presence of ethanol. The increased incorporation of 14C glycerol into conditioned medium together with a simultaneous diminution in labeling cellular glycerides suggest that there would be a stimulation of the export of these lipid classes to conditioned medium. Conversion of [1-14C] palmitic to oleic acid and eicosatrienoic to arachidonic acid were inhibited in 400 mM ethanol treated cells suggesting an inhibition of delta 9 and delta 5 desaturase activity.
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PMID:Effect of ethanol on glycerolipid and fatty acid metabolism in Hep G2 human-hepatoma cells. 899 70

The effect of oleic acid (OA), stearic acid (SA) and elaidic acid (EA) on cellular and secreted apolipoprotein (apo) B was examined in McArdle RH-7777 (McArdle) hepatoma cells and in primary rat hepatocytes. ApoB secretion by McArdle cells was significantly inhibited by 20% in 8 h incubations in medium containing EA and SA and by 50% in medium containing OA. In contrast, apo B secretion and cellular apo B of primary rat hepatocytes was relatively unaffected by incubations in medium containing fatty acids. Both B100 and B48 secretion in McArdle wild type and B48 in apo B mRNA editing enzyme catalytic polypeptide transfectants expressing B48 were inhibited to a similar extent indicating an effect of OA on both apo B species. The effect of OA occurred without changes in cellular apo B or in apo B mRNA abundance suggesting a post-transcriptional mechanism. Time course studies indicate that the suppressive effect of OA requires 4 h of incubation suggesting the depletion of a limiting factor important in apoB secretion. By increasing the proportion of palmitic acid to OA in the medium, apoB secretion by McArdle cells was progressively restored to control levels implicating an unique role for newly synthesized saturated fatty acid.
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PMID:Effects of fatty acids on apolipoprotein B secretion by McArdle RH-7777 rat hepatoma cells. 923 86

The aim of the present paper was to assess the utility of Levovist in defining the pathology of liver masses. Levovist is a new ultrasound contrast agent consisting of galactose microparticles, air bubbles and palmitic acid. Prospective studies were performed in patients referred for further evaluation of known liver masses. Levovist was peripherally injected and colour Doppler ultrasound studies were performed. Findings were correlated with clinicopathology and three other imaging modalities: biphasic spiral CT, CT arterial portography and contrast MRI. Twenty-five patients were studied (15 male and 10 female) in the age range 25-74 years. Liver masses ranged from 0.5 to 7 cm in maximum diameter. Thirteen lesions were benign and 12 were malignant (four hepatomas (HCC) and eight metastases). Levovist enhancement occurred in 18 lesions. Of these, six were benign (four focal nodular hyperplasias (FNH) and two haemangiomas). All 12 malignant lesions demonstrated enhancement. The HCC showed a mosaic pattern of central and peripheral enhancement, and the FNH demonstrated a spoke-wheel pattern. It was not possible to distinguish between haemangiomas and malignant lesions. Non-enhancing lesions may well be benign, with all malignancies showing some enhancement. Characteristic enhancement patterns were found for HCC (mosaic) and FNH (spoke-wheel). It was not possible to distinguish between metastases and benign lesions (haemangiomas) when the pattern of enhancement was peripheral.
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PMID:Early experience in the use of Levovist ultrasound contrast in the evaluation of liver masses. 1076 Dec 56

Retinoic acid (RA) induces apoptosis in Hep3B human hepatoma cells. 9-Cis-RA (c-RA) had a similar effect as all-trans-RA (t-RA) in inducing cell death in Hep3B cells. RA-induced Hep3B-cell death was associated with inhibited expression of the hepatocyte nuclear factor 4 (HNF-4) gene. Palmitoyl-CoA ((C16:0)-CoA), the reported HNF-4 ligand, prevented RA-induced apoptosis. The effect of (C16:0)-CoA was specific, since palmitic acid and co-enzyme A had no effect in preventing RA-induced apoptosis. Bovine serum albumin (BSA) also prevented RA-induced apoptosis. However, in contrast to BSA, which induced cell growth, (C16:0)-CoA alone had no effect on cell growth. Investigating the possible role of HNF-4 in apoptosis, the reported HNF-4 antagonist (C18:0)-CoA was employed, and it also prevented RA-induced apoptosis. By transient transfection, overexpression of HNF-4 did not prevent RA-induced apoptosis. The induction and prevention of apoptosis caused by RA and (C16:0)-CoA were associated, respectively with the induction and inhibition of the expression of transforming growth factor beta (TGFbeta), which is known to play a role in apoptosis. Furthermore, RA and (C16:0)-CoA can regulate AP-1, which is a key regulator of the TGFbeta gene. Our data indicate that fatty acyl-CoAs can prevent RA-induced apoptosis and that TGFbeta, rather than HNF-4, may play a role in these regulatory processes. Our data also suggest that (C16:0)-CoA and (C18:0)-CoA are not the agonist and antagonist for HNF4, respectively in the Hep3B cell system.
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PMID:Fatty acyl-CoAs inhibit retinoic acid-induced apoptosis in Hep3B cells. 1079 35


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