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 previous study in rats showed that even though probucol substantially lowers high density lipoprotein (HDL) levels, near-normal mass transport of HDL cholesterol esters (CE) to the liver is maintained by the induction of "selective" (direct) uptake of HDL CE. The present study describes a parallel result in cultured Hep G2 human hepatoma cells. Cells were preincubated in the presence or absence of probucol before measuring the uptake of doubly labeled HDL3 in the absence of probucol. Preincubation with probucol decreased the uptake of HDL3 particles (iodine-125-labeled N-methyltyramine cellobiose-apolipoprotein [125I-NMTC-apo] A-I uptake) but increased the uptake of [3H]cholesteryl oleyl ether in excess of 125I-NMTC-apo A-I (i.e., selective uptake) in a dose-dependent fashion. The reversibly cell-associated pool of CE tracer, a precursor for selective uptake, enlarged on probucol treatment, but the increase was not in proportion to the increase in selective uptake. HDL3 particle uptake decreased on probucol treatment. The decrease was evident after less than 20 minutes of probucol exposure and was maximal after 6 hours; in contrast, HDL3 CE selective uptake increased only after greater than 13 hours and had not reached a plateau after 20 hours. Thus, effects on particle uptake and selective uptake were dissociated in time.
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PMID:Probucol increases the selective uptake of HDL cholesterol esters by Hep G2 human hepatoma cells. 131 37

To address the hypothesis that phospholipid efflux from cells contributes to lipoprotein structure, we have examined the efflux of biosynthetically labeled [32P]phospholipid from cells to lipoproteins. With normal human skin fibroblasts in monolayer culture, high density lipoprotein (HDL3) promoted the efflux of phospholipid in a concentration-dependent manner. As analyzed by TLC, the major phospholipids released from fibroblasts were phosphatidylcholine, sphingomyelin, lysophosphatidylcholine and phosphatidylethanolamine. At identical concentrations, HDL3 and dimethylsuberimidate treated-HDL3 promoted similar efflux, suggesting that efflux did not depend on specific binding of HDL3 to the cell surface. When the content of cholesterol in fibroblasts was doubled by pre-incubation with LDL and cholesterol-rich liposomes, the fractional efflux of phospholipid to HDL3 and other acceptors was stimulated about 2-fold. Most of this stimulation was due to enhanced release of phosphatidylcholine. Similar effects of enrichment were found with Fu5AH rat hepatoma cells, but not with J774 mouse macrophages. The results support the hypothesis that the efflux of phospholipid from cells contributes to the phospholipid content of HDL. This may enhance the ability of HDL to remove cholesterol from cells, the initial step in reverse cholesterol transport.
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PMID:Efflux of phospholipid from fibroblasts with normal and elevated levels of cholesterol. 189 80

HDL-subfraction was studied in blood serum of drinkers after alcohol intake and control group of men-nondrinkers. Blood serum incubation with fibroblasts culture did not indicate principal differences between drinkers and nondrinkers both with normolipemia and hyperalphacholesterolemia. Increase of HDL2 and decrease of HDL3-subfraction were observed. Incubation of the same species with hepatoma cells culture (Hep G-2) demonstrated significant differences between normolipemia and hyperalphacholesterolemia. The reduction of HDL2 subfraction level and increase of HDL3 have been found in nondrinkers with normolipemia. The raise of HDL2 was demonstrated in hyperalphacholesterolemia (due to HDL2b and HDL2a in drinkers and HDL2a in nondrinkers). Besides, in several samples of normolipidemic blood serum taken after alcohol abuse the changes of HDL-subfractions were identical to those receiving in hyperalphacholesterolemia. It is postulated that one of the mechanisms of the alcoholic hyperalphacholesterolemia development is the decline of the transfer rate of cholesterol ethers to the liver and accumulation of HDL2 particles in total HDL pool.
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PMID:[Effects of recent alcohol intake on high density lipoprotein accepting properties and their interactions with liver cells]. 196 13

The effects of the calcium channel blocker of the arylalkylamine series verapamil have been investigated on high-density lipoprotein (HDL3) catabolism in the human hepatoma cell line Hep G2. It was found that verapamil markedly enhanced HDL3 binding, uptake and degradation in Hep G2 cells preloaded with nonlipoprotein cholesterol. This effect was dose-dependent, and a 1.5-2-fold increase of the three studied parameters was observed in cells pretreated 24 h with 100 microM verapamil. No significant effect of the drug was found in cells not preincubated with cholesterol. Verapamil induced an increase in the cellular cholesterol content in preloaded cells. Other calcium antagonists such as diltiazem, nifedipine, nitrendipine or amphiphilic drugs such as phenothiazines and propranolol also enhanced HDL3 uptake by Hep G2 cells. These effects of verapamil on HDL3 metabolism could be related to its amphiphilic characteristics, and to its calcium antagonist properties.
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PMID:Verapamil enhances high-density lipoprotein processing in Hep G2 cells preloaded with cholesterol. 215 47

Subfractional alterations of high density lipoproteins (HDL) were studied after incubation of blood serum from patients with normal lipid spectrum and with four types of dyslipidemia (hypercholesterolemia, hypertriglyceridemia, hypo- and hyper-alpha-cholesterolemia) in mixtures containing human skin fibroblasts and G-2 hepatoma cells used as typical populations of peripheric and liver cells. Incubation of normolipidemic blood sera with fibroblasts overloaded with cholesterol led to conversion of small HDL3 particles into large HDL2 subfractions arising due to the lipoprotein acception of cholesterol. At the same time, incubation of these blood sera with the hepatoma cells resulted in a decrease of the large particles ratio in total pool of HDL because of their absorption by the cells. No distinct differences were detected in formation of large particles from small subfractions when cholesterol was accepted from fibroblasts under conditions of hypercholesterolemia, hypertriglyceridemia and hyper-alpha-cholesterolemia, while formation of the largest particles HDL2b was impaired in hypo-alpha-cholesterolemia. These HDL2b particles interacted less effectively with hepatoma cells, thus suggesting the decreased cholesterol transport function of HDL in hypo-alpha-cholesterolemia. Content of HDL2b in total pool of HDL was unaltered if blood serum from patients with hyper-alpha-cholesterolemia was incubated together with the hepatoma cells. Antiatherogenic effect of hyper-alpha-cholesterolemia was caused mainly by active transfer of cholesterol from low density lipoproteins to HDL and a decrease in the LDL concentration but not by increased absorption of HDL particles by liver cells.
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PMID:[Changes in high density lipoprotein subfractions during interaction with fibroblasts and hepatoma G-2 in various dyslipidemias]. 217 87

To gain insight into the transport of sterol from lysosomes to the plasma membrane, we studied the efflux of lysosomal free cholesterol from intact Fu5AH rat hepatoma cells to high density lipoprotein (HDL) and other extracellular acceptors that promote sterol desorption from the plasma membrane. The procedures involved pulsing cells at 15 degrees C with low density lipoprotein that had been reconstituted with [3H]cholesteryl oleate and then incubating the cells at 37 degrees C in the presence of a sterol acceptor, while monitoring both the hydrolysis of [3H]cholesteryl oleate in lysosomes and the efflux of the resulting [3H]free cholesterol to the acceptor. After warming cells to 37 degrees C, rapid hydrolysis of [3H]cholesteryl oleate began after 10-20 min, and the lysosomally generated [3H]free cholesterol became available for efflux after an additional delay of 40-50 min. The kinetics of hydrolysis and the delay between hydrolysis and efflux were unchanged over a wide range of HDL3 concentrations (10-1000 micrograms of protein/ml), and with acceptors that do not interact with HDL-specific cell surface binding sites (phospholipid vesicles, dimethyl suberimidate cross-linked HDL). In addition, the delivery of lysosomal cholesterol to the plasma membrane was unaffected when cellular cholesterol content was elevated 2.6-fold above the normal control level, or when the activity of cellular acyl-coenzyme A/cholesterol acyltransferase (ACAT) was stimulated with exogenous oleic acid. We conclude that in the Fu5AH cell, a maximum of 40-50 min is required for the transport of cholesterol from lysosomes to the plasma membrane and that this transport is not regulated in response to either specific extracellular acceptors or the content of sterol in cells. The lack of effect of increased ACAT activity implies that the pathway for this transport does not involve passage of sterol through the rough endoplasmic reticulum, the subcellular location of ACAT.
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PMID:The efflux of lysosomal cholesterol from cells. 231 24

Using gradient gel electrophoresis, the dynamics of subfractional spectrum of high density lipoproteins (HDL) according to the particle size was studied during HDL interaction with hepatoma Hep-G2 cells and human skin fibroblasts. It was found that incubation of sera obtained from normolipidemic donors with cholesterol-loaded fibroblasts results in a decrease of the proportion of all small-sized particles of the HDL3 subclass, i.e., HDL3a, HDL3b and HDL3c as well as in an increase in the proportion of large-sized particles of the HDL2 subclass (HDL2a and HDL2b) due to cholesterol acceptance by HDL. In contrast, incubation of the same sera with hepatoma Hep-G2 cells causes a decrease in the proportion of HDL2b and a release of smaller cholesterol-deficient HDL3a particles. The dynamics of subfractional spectrum of HDL in hypoalphacholesterolemic sera is somewhat different, i.e., incubation with fibroblasts results in a decrease of the proportion of HDL3b and HDL3c; that of HDL2a is increased. The HDL2b fraction is unchanged. After incubation of the same sera with hepatoma Hep-G2 cells, the proportion of HDL2b does not fall as in the case of normolipidemic sera, but shows a marked increase. It is concluded that hypoalphacholesterolemia is characterized not only by a low HDL level in the plasma, but also by the formation of HDL2b-deficient particles which less effectively interact with liver cells.
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PMID:[Hypoalphacholesterolemia: dynamics of the subfractional spectrum of high density lipoproteins during their interaction with fibroblasts and hepatoma Hep-G2 cell line]. 275 63

Apolipoprotein B-containing high-density lipoprotein was detected in the high-density lipoprotein fraction of the concentrated conditioned medium of human hepatoma HuH-7 cells (Apo-B-containing HDLHuH-7). Electrophoretically, the Apo-B-containing HDLHuH-7 migrated more slowly and broadly than beta-lipoprotein on agarose gel. The Apo-B-containing HDLHuH-7 was not precipitated by heparin-Mn2+ treatment. High-performance gel filtration chromatography indicated that the peak of Apo-B-containing HDLHuH-7 was eluted faster than that of plasma LDL and electron microscopic analysis demonstrated that the particles of Apo-B-containing HDLHuH-7 ranged from 140 A to about 450 A, indicating the heterogeneity of Apo-B-containing HDLHuH-7. The protein/lipid ratio of HDLHuH-7 (1.35) is higher than that of plasma HDL3 (1.2). The lipids of HDLHuH-7 are composed of phospholipids (170 micrograms/mg protein), free cholesterol (410 micrograms/mg protein), cholesterol ester (20 micrograms/mg protein) and triacylglycerols (140 micrograms/mg protein). The results described above indicated that Apo-B-containing HDLHuH-7 was a novel lipoprotein discovered for the first time.
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PMID:A newly discovered apolipoprotein B-containing high-density lipoprotein produced by human hepatoma cells. 282 4

Characterization of the membrane receptor for the low density lipoproteins (LDL) has led to insights into cellular receptor physiology as well as mammalian lipid transport. Result with LDL have stimulated the search for specific receptors for other plasma lipoproteins. Receptors for high density lipoproteins (HDL) have been identified in human fibroblasts and smooth muscle cells. Specificity for this receptor has been difficult to define since normal HDL contains several apolipoproteins, and particles containing apolipoproteins B and E have been shown to compete for HDL binding. In the present study, we demonstrate that HDL isolated from a patient devoid of apolipoprotein E was bound specifically by human hepatic membranes. This binding reached saturation within 2 hours and was EDTA-resistant. Assuming a single receptor model, we found that 2.9 x 10(15) receptors/mg membrane protein bound with an affinity KD = 3.5 x 10(-7) M at 0 to 4 degrees C and KD = 1.9 x 10(-7) M at 37 degrees C. The binding was effectively competed with intact HDL3, with HDL3 that had undergone selective arginine and lysine residue modification, and with antibodies to apolipoproteins A-I and A-II. However, LDL, asialofetuin, and HDL3 which had undergone tyrosine modification by nitration, and anti-apolipoprotein B did not compete with apo A-I HDL binding. In contrast to LDL binding, the human hepatoma cell line, HEPG2, increased HDL binding with cholesterol loading that was specific for HDL3. Thus, hepatic tissue can modulate its recognition of HDL. Finally, hepatic membranes from a patient lacking normal hepatic LDL receptors bound apo A-I HDL normally. These data indicate that a saturable, specific regulatable receptor for apo E-free HDL is present in human liver.
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PMID:Characterization of a human hepatic receptor for high density lipoproteins. 298 87

Hepatic lipase can enhance the delivery of high-density lipoprotein (HDL) cholesterol to cells by a process which does not involve apoprotein catabolism. The incorporation of HDL-free (unesterified) cholesterol, phospholipid, and cholesteryl ester by cells has been compared to establish the mechanism of this delivery process. Human HDL was reconstituted with 3H-free cholesterol and [14C]sphingomyelin, treated with hepatic lipase in the presence of albumin to remove the products of lipolysis, reisolated, and then incubated with cultured rat hepatoma cells. Relative to control HDL, modification of HDL with hepatic lipase stimulated both the amount of HDL-free cholesterol taken up by the cell and the esterification of HDL-free cholesterol but did not affect the delivery of sphingomyelin. Experiments utilizing HDL reconstituted with 14C-free cholesterol and [3H]cholesteryl oleoyl ether suggest that hepatic lipase enhances the incorporation of HDL-esterified cholesterol. However, the amount of free cholesterol delivered as a result of treatment with hepatic lipase was 4-fold that of esterified cholesterol. On the basis of HDL composition, the cellular incorporation of free cholesterol was about 10 times that which would occur by the uptake and degradation of intact particles. The preferential incorporation of HDL-free cholesterol did not require the presence of lysophosphatidylcholine. To correlate the events observed at the cellular level with alterations in lipoprotein structure, high-resolution, proton-decoupled 13C nuclear magnetic resonance spectroscopy (90.55 MHz) was performed on HDL3 in which the cholesterol molecules were replaced with [4-13C]cholesterol by particle reconstitution.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of the hepatic lipase induced accumulation of high-density lipoprotein cholesterol by cells in culture. 389 72


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