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)

Scavenger receptor class B type I (SR-BI) and its human homologue CLA-1 plays an important role in reverse cholesterol transport (RCT). Using a previously established cell-based CLA-1 up-regulator screening assay, one of the positive strains, 04-9179, presented potent activity in elevating CLA-1 transcriptional level. We report here the identification of an active compound 9179A as a known compound trichostatin A (TSA), and its effects on CLA-1/SR-BI expression both in HepG2 human hepatoma cells and RAW 264.7 murine macrophage cells in vitro. The results showed that the mRNA and protein level of CLA-1/SR-BI were significantly up-regulated by 9179A both in HepG2 and RAW 264.7 cells. Corresponding to this, the uptake of DiI-HDL by both cells and the efflux of [(3)H]cholesterol by RAW 264.7 cells were increased by 9179A in dose-dependent manner. ABCA1 was also increased but SR-A decreased by 9179A in RAW 264.7 cells. Using a combination of reporter assays with various deletion in CLA-1 promoter and electrophoretic mobility shift assay, we demonstrated that -419/-232 bp fragment of the CLA-1 promoter mediated the effects of 9179A (i.e., TSA). Together, these studies identified TSA as a novel up-regulator of CLA-1/SR-BI both in HepG2 and RAW 264.7 cells.
Atherosclerosis 2009 May
PMID:Identification of trichostatin A as a novel transcriptional up-regulator of scavenger receptor BI both in HepG2 and RAW 264.7 cells. 1893 Apr 59

Excessive weight gain, hypertension, hyperlipidemia, and diabetes are frequently observed in patients having undergone liver transplantation (LTx). These alterations are probably multifactorial in origin, and cluster to generate a metabolic syndrome (MS), increasing the risk of cardiovascular events. We assessed the prevalence of MS (National Cholesterol Education Program-Adult Treatment Panel III criteria) in 296 LTx patients in the course of regular follow-up, at least 6 months after transplantation (median, 38 months). Several pre-LTx and post-LTx data were collected to identify the factors associated with the presence of MS. In a subset of 99 patients, insulin resistance was measured by the homeostasis model assessment. High blood pressure was present in 53% of cases, hyperlipidemia in 51%, high glucose in 37%, and enlarged waist circumference in 32%. Overall, MS (defined as 3 or more of the above features) was present in 44.5% of cases. Insulin resistance (homeostasis model assessment > 2.7) was observed in 41% of cases. Hypertension and hyperlipidemia were more frequent in subjects on cyclosporine than in tacrolimus-treated cases, whereas the type of immunosuppressive drug had no effect on the prevalence of diabetes, enlarged waist, and MS. In a logistic regression analysis, only pre-LTx body mass index (odds ratio, 1.20), body mass index increase (odds ratio, 1.18), and pre-LTx diabetes (odds ratio, 2.36) predicted MS; age, gender, etiology of liver disease, time from LTx, type of immunosuppressive drug, and previous hepatocellular carcinoma were removed from the model. Disorders related to MS are frequent in LTx patients, and are related to both pre-LTx conditions and to weight gain. Weight control is mandatory in LTx patients to prevent risk factors of premature atherosclerosis.
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PMID:Metabolic syndrome in liver transplantation: relation to etiology and immunosuppression. 1897 73

High-density lipoprotein (HDL) particles play a critical role in cholesterol metabolism. The hepatic scavenger receptor class B type I (SR-B1) binds HDL particles for mediating reverse cholesterol transport (RCT), thus lowering the risk of atherosclerosis. Thiazolidinediones (TZDs), known to have potent enhancing effects on insulin sensitivity, have been developed for the treatment of non-insulin-dependent diabetes mellitus. They are a high-affinity ligand for the peroxisome proliferator-activated receptor gamma (PPAR-gamma), which belongs to a nuclear receptor superfamily. In this study, we examined the effects of thiazolidinedione PPAR-gamma on hepatic SR-B1 gene expression in human hepatoma G2 cell-line (HepG2). Results showed that hepatic SR-B1 mRNA and protein were increased on exposure to thiazolidinediones. Transcriptional activity of human SR-B1 (hSR-B1) gene paralleled the endogenous expression of the gene and was dependent on the dose of thiazolidinediones. We investigated the influence on the promoter activity of vector expressing PPAR and retinoid X receptor (RXR), cotransfected into the HepG2 cells along with SR-B1 promoter-reporter gene constructs. PPAR-gamma and RXR sufficiently induced the SR-B1 promoter activity in the HepG2 cells. Chromatin immunoprecipitation (ChIP) assay confirmed the binding of the PPAR-gamma to the SR-B1 promoter region. The mutagenesis of this binding site abolished the ability of the thiazolidinediones or PPARs to stimulate promoter activity. Together, these results indicate that the stimulation of SR-B1 expression in the liver is mediated in part by activation of the PPAR-gamma and RXR, and raise the possibility that this stimulation using thiazolidinediones conditions provides a protective mechanism for accelerated atherosclerosis in diabetes mellitus.
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PMID:Human scavenger receptor class B type 1 is regulated by activators of peroxisome proliferators-activated receptor-gamma in hepatocytes. 1915 45

Identification and characterization of novel genes involved in derangement of metabolisms of glucose and triglycerides are important in understanding the development of metabolic syndrome (MS) and atherosclerosis. Model rats with certain phenotypes of MS were fed a high-carbohydrate diet. The rat hepatic subtracted cDNA libraries were constructed and screened. A novel cDNA of full length was identified by screening of a human hepatic cDNA library with a mixture of probes of the differentially expressed fragments from the rat hepatic subtracted cDNA libraries. The corresponding gene of the cDNA was temporarily named metabolic syndrome-associated gene (MSAG). The predicted protein encoded by MSAG contains 110 amino acids and has a theoretical molecular weight of 11667.04 and an isoelectric point of 4.91. Compared with the housekeeping gene of beta-actin, MSAG had low transcription activity. However, the mRNA level of MSAG in HepG2 cells, a human hepatoma cell line, was significantly increased by glucose and decreased by insulin concentrations higher than physiological levels. These results suggest that MSAG may be involved in the metabolism and/or its regulation of glucose, the functioning of insulin under non-physiological conditions, and further in the development of metabolic syndrome.
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PMID:Identification of a novel gene, MSAG, regulated by high levels of glucose and insulin. 1923 44

Sterol regulatory element-binding proteins 1 and 2 (SREBP-1 and SREBP-2) are important regulators of genes involved in cholesterol and fatty acid metabolism, but have also been implicated in the regulation of the cell cycle and have been associated with the pathogenesis of type 2 diabetes, atherosclerosis and obesity, among others. In this study, we aimed to characterize the binding sites of SREBP-1 and RNA polymerase II through chromatin immunoprecipitation and microarray analysis in 1% of the human genome, as defined by the Encyclopaedia of DNA Elements consortium, in a hepatocellular carcinoma cell line (HepG2). Our data identified novel binding sites for SREBP-1 in genes directly or indirectly involved in cholesterol metabolism, e.g. apolipoprotein C-III (APOC3). The most interesting biological findings were the binding sites for SREBP-1 in genes for host cell factor C1 (HCFC1), involved in cell cycle regulation, and for filamin A (FLNA). For RNA polymerase II, we found binding sites at classical promoters, but also in intergenic and intragenic regions. Furthermore, we found evidence of sterol-regulated binding of SREBP-1 and RNA polymerase II to HCFC1 and FLNA. From the results of this work, we infer that SREBP-1 may be involved in processes other than lipid metabolism.
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PMID:Novel genes in cell cycle control and lipid metabolism with dynamically regulated binding sites for sterol regulatory element-binding protein 1 and RNA polymerase II in HepG2 cells detected by chromatin immunoprecipitation with microarray detection. 1929 68

Octacosa-10,19-dien-1-ol is a newly synthesized long-chain alcohol, an unsaturated analogue of 1-octacosanol, the major component of policosanol, the purified natural mixture of different higher aliphatic alcohols obtained from sugarcane wax. Our efficient synthetic protocol (five steps with 50% overall yield) is well suited for gram scale preparations and a rapid generation of analogues with different degrees of unsaturation. Beneficial effects of policosanol in the prevention of atherosclerosis and thromboembolic disorders have been reported and related to the inhibition of sterol biosynthesis possibly by the regulation of the activity of HMGCoA reductase mediated by AMP-dependent kinase AMPK. We have compared the effect of octacosadienol and policosanol on the regulation of HMGCoA reductase in HUVEC and HepG2 human hepatoma cells. Octacosadienol was as effective as policosanol in inhibiting the upregulation of HMGCoA reductase, in inducing the phosphorylation of AMPK and in downregulating the HMGCoA reductase mRNA.
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PMID:Regulation of HMGCoA reductase activity by policosanol and octacosadienol, a new synthetic analogue of octacosanol. 1976 55

Since android overweight/obesity and insulin resistance are independent risk factors for cardiovascular disease, we investigated their impact on basal and postprandial scavenger receptor BI (SR-BI) and ATP binding cassette transporter A1 (ABCA1)-mediated serum cholesterol efflux. Twelve android overweight to obese and 9 normal weight controls women underwent body composition analysis by dual energy X-ray absorptiometry, a euglycemic hyperinsulinemic clamp, and an oral fat load with blood sampling at initial time (T0), 4h (T4) and 10h (T10) after the fat load. Serum lipids and HDL-parameters, capacities of serum to promote cholesterol efflux from SR-BI expressing Fu5AH hepatoma cells or from ABCA1-expressing J774 macrophages and to abilities of serum to induce a net removal of cholesterol from macrophage foam cells were measured at T0, T4 and T10. Sera from overweight/obese exhibited moderately decreased SR-BI-mediated cholesterol efflux capacities, in accordance with reduced HDL concentrations, but importantly increased ABCA1-mediated cholesterol efflux and increased cholesterol extraction capacities over the postprandial period, partly related to higher prebeta-HDL concentrations. In multiple regression analyses, android obesity-related parameters and HDL-PL or prebeta-HDL levels remained the only independent correlates for SR-BI or ABCA1-dependent fractional cholesterol efflux while only prebeta-HDL levels remained correlated to cholesterol extraction capacities. Our results suggest that android overweight/obesity may not result in an impaired cholesterol efflux capacity.
Atherosclerosis 2010 Apr
PMID:Impact of android overweight or obesity and insulin resistance on basal and postprandial SR-BI and ABCA1-mediated serum cholesterol efflux capacities. 1983 7

PON1 is a high density lipoprotein-associated enzyme that plays an important role in organophosphate detoxification and prevention of atherosclerosis. In vivo animal and human studies have indicated that estradiol (E2) supplementation enhances serum PON1 activity. In this study, we sought to determine if E2 directly up-regulates cell-associated PON1 activity in vitro and to characterize the mechanism of regulation. In vitro E2 treatment of both the human hepatoma cell line Huh7 and normal rat hepatocytes resulted in a 2- to 3-fold increase in cell-associated PON1 catalytic activity. E2 potently induced PON1 activity with average EC(50) values of 15nM for normal hepatocytes and 68nM for Huh7. The enhancement of PON1 activity by E2 was blocked by the estrogen receptor (ER) antagonist ICI 182,780 indicating that E2 was acting through the ER. The up-regulation of PON1 activity by E2 did not involve enhancement of PON1 mRNA or protein levels and did not promote secretion of PON1. Thus, E2 can enhance cell-associated PON1 activity in vitro without altering PON1 gene expression or protein level. Our data suggest that E2 may regulate the specific activity and/or stability of cell surface PON1.
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PMID:Estradiol enhances cell-associated paraoxonase 1 (PON1) activity in vitro without altering PON1 expression. 2051 Aug 79

A highly sensitive and rapid sandwich enzyme-linked immunosorbent assay (ELISA) procedure was developed for the detection of human fetuin A/AHSG (alpha2-HS-glycoprotein), a specific biomarker for hepatocellular carcinoma and atherosclerosis. Anti-human fetuin A antibody was immobilized on aminopropyltriethoxysilane-mediated amine-functionalized microtiter plates using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride and N-hydroxysulfosuccinimide-based heterobifunctional cross-linking. The analytical sensitivity of the developed assay was 39 pg/mL, compared to 625 pg/mL for the conventional assay. The generic nature of the developed procedure was demonstrated by performing human fetuin A assays on different polymeric matrixes, i.e., polystyrene, poly(methyl methacrylate), and polycyclo-olefin (Zeonex), in a modified microtiter plate format. Thus, the newly developed procedure has considerable advantages over the existing method.
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PMID:Development of a high sensitivity rapid sandwich ELISA procedure and its comparison with the conventional approach. 2070 94

The inferior phrenic artery (IPA) is the most common extrahepatic collateral vessel to hepatocellular carcinoma (HCC); however, there are many anatomical variations in its origin and branches. In addition, the IPA is frequently reconstructed through several pathways, mainly through the retroperitoneal network, because of the occlusion of its orifice due to atherosclerosis or previous catheter manipulation. Infrequently, selective catheterization into the IPA is impossible even using a microcatheter, particularly in the IPA that originates from the proximal or distal portion of the celiac trunk or from the aorta with an acute angle. In this article, we describe anatomical variations of the IPA and catheterization techniques, such as a catheter with a large side hole and a catheter with a cleft, to facilitate catheterization into the IPA that is difficult using a conventional coaxial technique. Radiologists should have sufficient knowledge of such variations and catheterization techniques to perform transcatheter arterial chemoembolization for HCCs through the IPA effectively and safely.
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PMID:Inferior phrenic arteries: angiographic anatomy, variations, and catheterization techniques for transcatheter arterial chemoembolization. 2079 15


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