Hep G2 Cells: A human liver tumor cell line used to study a variety of liver-specific metabolic functions.Carcinoma, Hepatocellular: A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.Liver Neoplasms: Tumors or cancer of the LIVER.Hempa: A chemosterilant agent that is anticipated to be a carcinogen.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Propyl Gallate: Antioxidant for foods, fats, oils, ethers, emulsions, waxes, and transformer oils.Emetics: Agents that cause vomiting. They may act directly on the gastrointestinal tract, bringing about emesis through local irritant effects, or indirectly, through their effects on the chemoreceptor trigger zone in the postremal area near the medulla.Plasminogen Inactivators: Important modulators of the activity of plasminogen activators. The inhibitors belong to the serpin family of proteins and inhibit both the tissue-type and urokinase-type plasminogen activators.Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent: Specific hydroxymethylglutaryl CoA reductases that utilize the cofactor NAD. In liver enzymes of this class are involved in cholesterol biosynthesis.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Apolipoprotein A-I: The most abundant protein component of HIGH DENSITY LIPOPROTEINS or HDL. This protein serves as an acceptor for CHOLESTEROL released from cells thus promoting efflux of cholesterol to HDL then to the LIVER for excretion from the body (reverse cholesterol transport). It also acts as a cofactor for LECITHIN CHOLESTEROL ACYLTRANSFERASE that forms CHOLESTEROL ESTERS on the HDL particles. Mutations of this gene APOA1 cause HDL deficiency, such as in FAMILIAL ALPHA LIPOPROTEIN DEFICIENCY DISEASE and in some patients with TANGIER DISEASE.Artificial Organs: Devices intended to replace non-functioning organs. They may be temporary or permanent. Since they are intended always to function as the natural organs they are replacing, they should be differentiated from PROSTHESES AND IMPLANTS and specific types of prostheses which, though also replacements for body parts, are frequently cosmetic (EYE, ARTIFICIAL) as well as functional (ARTIFICIAL LIMBS).Asialoglycoprotein Receptor: A C-type lectin that is a cell surface receptor for ASIALOGLYCOPROTEINS. It is found primarily in the LIVER where it mediates the endocytosis of serum glycoproteins.Carboxypeptidase H: A ZINC-containing exopeptidase primarily found in SECRETORY VESICLES of endocrine and neuroendocrine cells. It catalyzes the cleavage of C-terminal ARGININE or LYSINE residues from polypeptides and is active in processing precursors of PEPTIDE HORMONES and other bioactive peptides.Receptors, LDL: Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.Hepatoblastoma: A malignant neoplasm occurring in young children, primarily in the liver, composed of tissue resembling embryonal or fetal hepatic epithelium, or mixed epithelial and mesenchymal tissues. (Stedman, 25th ed)Liver Neoplasms, Experimental: Experimentally induced tumors of the LIVER.Organosilicon Compounds: Organic compounds that contain silicon as an integral part of the molecule.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Oxaloacetic Acid: A dicarboxylic acid ketone that is an important metabolic intermediate of the CITRIC ACID CYCLE. It can be converted to ASPARTIC ACID by ASPARTATE TRANSAMINASE.Moraceae: The mulberry plant family of the order Urticales, subclass Hamamelidae, class Magnoliopsida. They have milky latex and small, petalless male or female flowers.Lipoproteins, LDL: A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues.Apolipoproteins A: Structural proteins of the alpha-lipoproteins (HIGH DENSITY LIPOPROTEINS), including APOLIPOPROTEIN A-I and APOLIPOPROTEIN A-II. They can modulate the activity of LECITHIN CHOLESTEROL ACYLTRANSFERASE. These apolipoproteins are low in atherosclerotic patients. They are either absent or present in extremely low plasma concentration in TANGIER DISEASE.Oleic Acid: An unsaturated fatty acid that is the most widely distributed and abundant fatty acid in nature. It is used commercially in the preparation of oleates and lotions, and as a pharmaceutical solvent. (Stedman, 26th ed)Apolipoproteins B: Major structural proteins of triacylglycerol-rich LIPOPROTEINS. There are two forms, apolipoprotein B-100 and apolipoprotein B-48, both derived from a single gene. ApoB-100 expressed in the liver is found in low-density lipoproteins (LIPOPROTEINS, LDL; LIPOPROTEINS, VLDL). ApoB-48 expressed in the intestine is found in CHYLOMICRONS. They are important in the biosynthesis, transport, and metabolism of triacylglycerol-rich lipoproteins. Plasma Apo-B levels are high in atherosclerotic patients but non-detectable in ABETALIPOPROTEINEMIA.Hydroxycholesterols: Cholesterol which is substituted by a hydroxy group in any position.Hydroxymethylglutaryl CoA Reductases: Enzymes that catalyze the reversible reduction of alpha-carboxyl group of 3-hydroxy-3-methylglutaryl-coenzyme A to yield MEVALONIC ACID.Mevalonic AcidCholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Kinetics: The rate dynamics in chemical or physical systems.Immunosorbent Techniques: Techniques for removal by adsorption and subsequent elution of a specific antibody or antigen using an immunosorbent containing the homologous antigen or antibody.Primaquine: An aminoquinoline that is given by mouth to produce a radical cure and prevent relapse of vivax and ovale malarias following treatment with a blood schizontocide. It has also been used to prevent transmission of falciparum malaria by those returning to areas where there is a potential for re-introduction of malaria. Adverse effects include anemias and GI disturbances. (From Martindale, The Extra Pharmacopeia, 30th ed, p404)Lipoproteins, HDL: A class of lipoproteins of small size (4-13 nm) and dense (greater than 1.063 g/ml) particles. HDL lipoproteins, synthesized in the liver without a lipid core, accumulate cholesterol esters from peripheral tissues and transport them to the liver for re-utilization or elimination from the body (the reverse cholesterol transport). Their major protein component is APOLIPOPROTEIN A-I. HDL also shuttle APOLIPOPROTEINS C and APOLIPOPROTEINS E to and from triglyceride-rich lipoproteins during their catabolism. HDL plasma level has been inversely correlated with the risk of cardiovascular diseases.PhenylenediaminesOleic Acids: A group of fatty acids that contain 18 carbon atoms and a double bond at the omega 9 carbon.Asialoglycoproteins: Endogenous glycoproteins from which SIALIC ACID has been removed by the action of sialidases. They bind tightly to the ASIALOGLYCOPROTEIN RECEPTOR which is located on hepatocyte plasma membranes. After internalization by adsorptive ENDOCYTOSIS they are delivered to LYSOSOMES for degradation. Therefore receptor-mediated clearance of asialoglycoproteins is an important aspect of the turnover of plasma glycoproteins. They are elevated in serum of patients with HEPATIC CIRRHOSIS or HEPATITIS.Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.Immunoelectrophoresis, Two-Dimensional: Immunoelectrophoresis in which a second electrophoretic transport is performed on the initially separated antigen fragments into an antibody-containing medium in a direction perpendicular to the first electrophoresis.Tunicamycin: An N-acetylglycosamine containing antiviral antibiotic obtained from Streptomyces lysosuperificus. It is also active against some bacteria and fungi, because it inhibits the glucosylation of proteins. Tunicamycin is used as tool in the study of microbial biosynthetic mechanisms.Apolipoprotein A-II: The second most abundant protein component of HIGH DENSITY LIPOPROTEINS or HDL. It has a high lipid affinity and is known to displace APOLIPOPROTEIN A-I from HDL particles and generates a stable HDL complex. ApoA-II can modulate the activation of LECITHIN CHOLESTEROL ACYLTRANSFERASE in the presence of APOLIPOPROTEIN A-I, thus affecting HDL metabolism.Blotting, Northern: Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Albumins: Water-soluble proteins found in egg whites, blood, lymph, and other tissues and fluids. They coagulate upon heating.Chenodeoxycholic Acid: A bile acid, usually conjugated with either glycine or taurine. It acts as a detergent to solubilize fats for intestinal absorption and is reabsorbed by the small intestine. It is used as cholagogue, a choleretic laxative, and to prevent or dissolve gallstones.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Vitamin K: A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.Cytochrome P-450 CYP2E1: An ethanol-inducible cytochrome P450 enzyme that metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Substrates include ETHANOL; INHALATION ANESTHETICS; BENZENE; ACETAMINOPHEN and other low molecular weight compounds. CYP2E1 has been used as an enzyme marker in the study of alcohol abuse.Apolipoprotein B-100: A 513-kDa protein synthesized in the LIVER. It serves as the major structural protein of low-density lipoproteins (LIPOPROTEINS, LDL; LIPOPROTEINS, VLDL). It is the ligand for the LDL receptor (RECEPTORS, LDL) that promotes cellular binding and internalization of LDL particles.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Sterol O-Acyltransferase: An enzyme that catalyzes the formation of cholesterol esters by the direct transfer of the fatty acid group from a fatty acyl CoA derivative. This enzyme has been found in the adrenal gland, gonads, liver, intestinal mucosa, and aorta of many mammalian species. EC Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Molecular Weight: The sum of the weight of all the atoms in a molecule.Anticholesteremic Agents: Substances used to lower plasma CHOLESTEROL levels.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Carboxypeptidases: Enzymes that act at a free C-terminus of a polypeptide to liberate a single amino acid residue.Lipoproteins: Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes.Prealbumin: A tetrameric protein, molecular weight between 50,000 and 70,000, consisting of 4 equal chains, and migrating on electrophoresis in 3 fractions more mobile than serum albumin. Its concentration ranges from 7 to 33 per cent in the serum, but levels decrease in liver disease.Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis.Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.FucoseChloramphenicol O-Acetyltransferase: An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.Carboxylic Ester Hydrolases: Enzymes which catalyze the hydrolysis of carboxylic acid esters with the formation of an alcohol and a carboxylic acid anion.Intracellular Fluid: The fluid inside CELLS.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Methionine: A sulfur-containing essential L-amino acid that is important in many body functions.Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.L-Lactate Dehydrogenase: A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist.Protein Synthesis Inhibitors: Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins.Cell Line, Tumor: A cell line derived from cultured tumor cells.Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.Apolipoproteins: Protein components on the surface of LIPOPROTEINS. They form a layer surrounding the hydrophobic lipid core. There are several classes of apolipoproteins with each playing a different role in lipid transport and LIPID METABOLISM. These proteins are synthesized mainly in the LIVER and the INTESTINES.Lipoproteins, VLDL: A class of lipoproteins of very light (0.93-1.006 g/ml) large size (30-80 nm) particles with a core composed mainly of TRIGLYCERIDES and a surface monolayer of PHOSPHOLIPIDS and CHOLESTEROL into which are imbedded the apolipoproteins B, E, and C. VLDL facilitates the transport of endogenously made triglycerides to extrahepatic tissues. As triglycerides and Apo C are removed, VLDL is converted to INTERMEDIATE-DENSITY LIPOPROTEINS, then to LOW-DENSITY LIPOPROTEINS from which cholesterol is delivered to the extrahepatic tissues.Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Glutathione: A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.RNA, Neoplasm: RNA present in neoplastic tissue.Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Cytochrome P-450 Enzyme System: A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Apolipoproteins E: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.Protein PrecursorsRecombinant Proteins: Proteins prepared by recombinant DNA technology.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor.Glucose: A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.TriglyceridesMitochondria: Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Gene Amplification: A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Reactive Oxygen Species: Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of signal transduction and gene expression, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.

Apoptosis of human hepatoma cell lines induced by transforming growth factor beta 1 (TGF-beta1) correlates with p53 and Smad4 activation. (1/2073)

OBJECTIVE: To determine the relationships between apoptosis induced by transforming growth factor beta 1(TGF-beta1) and Smad in human hepatoma cell lines. METHODS: Three human hepatic carcinoma cell lines, involving different status of the p53 gene respectively, were used in this study. TGF-beta1-induced apoptosis in hepatic carcinoma cell lines was quantitated using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. For identification of the mechanism of apoptosis induced by TGF-beta1, these cell lines were transfected with a TGF-beta1-inducible luciferase reporter plasmid containing Smad binding elements (SBE) and luciferase gene using LF2000, then were treated with TGF-beta1. Relative luciferase activity was assayed respectively. RESULTS: Among three cell lines studied with TUNEL assay, addition of TGF-beta1 induced apoptosis only in HepG2 cells (wild type p53). In contrast, Huh-7 (mutant p53) and Hep3B (deleted p53) cell lines lacked apoptosis. The detection of luciferase activity indicated that HepG2 cells dramatically increased the response to TGF-beta1 induction, Huh-7 and Hep3B cell lines significantly lowered luciferase expression. CONCLUSION: HepG2 cells were highly susceptible to TGF-beta1-induced apoptosis compared with Hep3B and Huh-7 cell lines. Smad4 may be a central mediator of the TGF-beta1 signaling transduction pathway.  (+info)

Effect of the venom of the spider Macrothele raveni on the expression of p21 gene in HepG2 cells. (2/2073)

This paper focuses on the effect of the venom of the spider Macrothele raveni on the proliferation of human hepatocelluar carcinoma cell line HepG2 and the related molecular mechanism. XTT test showed that the proliferation of HepG2 cells in vitro was inhibited by the spider venom (P<0.05) in a concentration-dependent manner. By using flow cytometry, it was found that the spider venom caused selective G(2)/M cell cycle arrest in HepG2 cells. RT-PCR and Western blot indicated the expressions of p21 mRNA and protein in HepG2 cells were obviously up-regulated by the spider venom. The venom of the spider Macrothele raveni inhibited the proliferation of HepG2 cells. These results suggest that the possible mechanism of the spider venom is to activate the expressions of p21 gene and protein and to cause selective cell cycle arrest at G(2)/M phase, leading to HepG2 cell apoptosis.  (+info)

Host gene expression profiling of dengue virus infection in cell lines and patients. (3/2073)

BACKGROUND: Despite the seriousness of dengue-related disease, with an estimated 50-100 million cases of dengue fever and 250,000-500,000 cases of dengue hemorrhagic fever/dengue shock syndrome each year, a clear understanding of dengue pathogenesis remains elusive. Because of the lack of a disease model in animals and the complex immune interaction in dengue infection, the study of host response and immunopathogenesis is difficult. The development of genomics technology, microarray and high throughput quantitative PCR have allowed researchers to study gene expression changes on a much broader scale. We therefore used this approach to investigate the host response in dengue virus-infected cell lines and in patients developing dengue fever. METHODOLOGY/PRINCIPAL FINDINGS: Using microarray and high throughput quantitative PCR method to monitor the host response to dengue viral replication in cell line infection models and in dengue patient blood samples, we identified differentially expressed genes along three major pathways; NF-kappaB initiated immune responses, type I interferon (IFN) and the ubiquitin proteasome pathway. Among the most highly upregulated genes were the chemokines IP-10 and I-TAC, both ligands of the CXCR3 receptor. Increased expression of IP-10 and I-TAC in the peripheral blood of ten patients at the early onset of fever was confirmed by ELISA. A highly upregulated gene in the IFN pathway, viperin, was overexpressed in A549 cells resulting in a significant reduction in viral replication. The upregulation of genes in the ubiquitin-proteasome pathway prompted the testing of proteasome inhibitors MG-132 and ALLN, both of which reduced viral replication. CONCLUSION/SIGNIFICANCE: Unbiased gene expression analysis has identified new host genes associated with dengue infection, which we have validated in functional studies. We showed that some parts of the host response can be used as potential biomarkers for the disease while others can be used to control dengue viral replication, thus representing viable targets for drug therapy.  (+info)

Structural antitumoral activity relationships of synthetic chalcones. (4/2073)


Malathion-induced oxidative stress, cytotoxicity, and genotoxicity in human liver carcinoma (HepG2) cells. (5/2073)


The antitumoral effect of Paris Saponin I associated with the induction of apoptosis through the mitochondrial pathway. (6/2073)


Activation of PXR induces hypercholesterolemia in wild-type and accelerates atherosclerosis in apoE deficient mice. (7/2073)


Vitamin K2 suppresses proliferation and motility of hepatocellular carcinoma cells by activating steroid and xenobiotic receptor. (8/2073)

Vitamin K2, known as a cofactor for gamma-carboxylase, also serves as a ligand of a nuclear receptor, Steroid and Xenobiotic Receptor (SXR). Several clinical trials revealed that vitamin K2 reduced de novo formation and recurrence of hepatocellular carcinoma (HCC). To examine the role of SXR in HCC as a receptor activated by vitamin K2, the cells stably overexpressing SXR were established using a HCC cell line, HuH7. Overexpression of SXR resulted in reduced proliferation and motility of the cells. Further suppression of proliferation and motility was observed when SXR overexpressing clones were treated with vitamin K2. These results suggest that the activation of SXR could contribute to tumor suppressive effects of vitamin K2 on HCC cells.  (+info)

  • METHODS: Cell survival curves and the half maximal inhibitory concentrations (IC(50)) were obtained after 24, 48 and 72 h of incubation in HepG2 cells with the IBD drugs azathioprine, 6-mercaptopurine, 6-thioguanine, methotrexate or infliximab by using the WST-1 cytotoxicity assay. (biomedsearch.com)
  • This effect was probably mediated by Ca 2+ , because incubation of cells with 20 mmol/L CaCl 2 abolished the E 2 response. (ahajournals.org)
  • Incubation of the cells with oleic acid had no significant effect on the rate of initiation of the apoB-100-containing lipoproteins, nor did it influence the amount of apoB-100 that was associated with the membrane or the turnover of apoB-100 in the membrane. (ahajournals.org)
  • Compared with normoxia (20% O2), EPO production by Hep G2 cells during a 72-h incubation was stimulated fivefold by exposure to low oxygen tension (1% O2) and nearly threefold by exposure to cobalt chloride (100 microM). (uni-regensburg.de)
  • During a 72-h incubation, EPO production by the cells was stimulated sevenfold by exposure to low oxygen tension (1%) and threefold by exposure to cobaltous chloride (100 μM). (ox.ac.uk)
  • Uptake to biotin by Hep G2 cells was appreciable and linear for up to 10 min of incubation. (elsevier.com)
  • A follow-up heat dehydration process was done to ensure the attachment of Hep G2 cells and the stability of cellular proteins. (genetex.com)
  • Microsomes from chrysin-treated cells probed with specific antibodies in Western analyses showed marked induction of the UGT1A family of proteins. (aspetjournals.org)
  • Toxicological biomarkers of 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) were investigated in proteins secreted by HepG2 cells and their expression levels were determined in the plasma of rats exposed to 2,3,7,8-TCDD and in the plasma of incineration workers exposed to dioxins. (elsevier.com)
  • MTT and Comet assays were performed to determine cytotoxicities and genotoxicities to select exposure concentrations for the proteomic analysis of proteins secreted by 2,3,7,8-TCDD-treated cells. (elsevier.com)
  • Expression of the LDL receptor and HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase genes was comparable in Hep G2 cells cultured in CDM and serum-containing medium. (biologists.org)
  • The LDL receptor binding activity, protein and mRNA, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase mRNA, cell cholesterol and cell lathosterol were measured. (biomedcentral.com)
  • The HMG-CoA reductase mRNA and the cell lathosterol concentration, indices of cholesterol synthesis, were also increased by 40% over control by treatment with 50 μM α-tocopherol. (biomedcentral.com)
  • However, at α-tocopherol concentrations higher than 50 μM, the LDL receptor binding activity, protein and mRNA, the HMG-CoA reductase mRNA and the cell lathosterol and cholesterol concentrations all returned to control levels. (biomedcentral.com)
  • Effects of several extracellular matrices (ECMs) on cytochrome P450-dependent monooxygenases (MFOs) induction and cytochrome P4501A1 (CYP1A1) gene expression were estimated in Hep G2 cells cultured in a serum-free medium. (springer.com)
  • These findings suggest that the gene expression in cultured cells is greatly influenced by ECMs. (springer.com)
  • Therefore, the aim of this study was to characterize the effect of low concentration of ethanol on gene expression profiling in HepG2 cells using cDNA microarrays with especial interest in genes with transcriptional and translational function. (medsci.org)
  • The gene expression pattern observed in the ethanol-treated HepG2 cells revealed a relatively similar pattern to that found in the untreated control cells. (medsci.org)
  • The cDNA microarray technique has been used to evaluate the global gene expression in HCC as well as HCC-derived cell lines [ 13 - 16 ]. (medsci.org)
  • Moreover, HepG2 cells can be used to analyze the effect of ethanol on gene expression in HCC, based on the fact that HepG2 cells retain the genomic expression of HCC [ 15 , 17 , 18 ]. (medsci.org)
  • Therefore, the aim of this study was to identify the effect of low concentration of ethanol (1 mM for 6 h) on gene expression, specifically from genes with transcriptional and translational function, in HepG2 cells compared to HepG2 cells not exposed to ethanol (control cells) using cDNA microarrays. (medsci.org)
  • Our data indicate that, as a result of Cu overload, Hep-G2 cells reduced their Fe content and their DMT1 protein levels. (physiology.org)
  • Fukai F, Iso T and Katayama T (1992) Stimulation of the protein synthesis by fibronectin is specific for untransformed fibroblastic cells. (springer.com)
  • Hep G2 cell slide is provided for immunocytochemical analysis of protein and protein-protein interaction. (genetex.com)
  • The results revealed that overexpression of CXCL5 regulated the expression of several genes, including N‑myc downregulated gene 3,w B‑cell lymphoma‑2 (Bcl‑2), Bcl‑2‑associated X protein, P53, vascular endothelial growth factor, interleukin (IL)‑18, IL‑1β and cystathionine‑γ‑lyase. (spandidos-publications.com)
  • Protein extracts of Lactobacillus sps (MTCC 4184, 9496 and 10093), Bacillus cereus (MTCC 7166, 9017 and 10202), Serratia marcence (MTCC 7641, 7298 and 7729), Shigella flexneri (MTCC 1457 and 9543) were evaluated for anticancer potential against human cancer cell lines MDA-MB-231 and Hep-G2. (omicsonline.org)
  • The results showed that protein extract of Lactobacillus sps (MTCC 4184), Bacillus cereus (MTCC 10202) and Shigella flexneri (MTCC 9543) inhibited both MDA-MB-231 and HepG2 cancer cell lines. (omicsonline.org)
  • Protein extract of Lactobacillus sps (MTCC 9496), Serratia marcence (MTCC 7298 and 7729) and Bacillus cereus (MTCC 7166) inhibited growth of MDA-MB-231, while no effect on HepG2 was observed. (omicsonline.org)
  • Protein extract of Lactobacillus sps (MTCC 10093), Bacillus cereus (MTCC 2763), Serratia marcence (MTCC 7641) and Shigella flexneri (MTCC1457) were none effective to any of the cell lines. (omicsonline.org)
  • UGT1A1 message as well as protein was detectable also in untreated Hep G2 cells. (aspetjournals.org)
  • The aim of this study was to determine the effects of vitamin E (α-tocopherol) on the low density lipoprotein (LDL) receptor, a cell surface protein which plays an important role in controlling blood cholesterol. (biomedcentral.com)
  • The biphasic effect on the LDL receptor was specific for α-tocopherol in that δ and γ-tocopherol suppressed LDL receptor binding activity, protein and mRNA at all concentrations tested despite the cells incorporating similar amounts of the three homologues. (biomedcentral.com)
  • Overexpression of microRNA-491_5p sensitized Hep G2 cells for TNF-alpha-induced apoptosis, and also caused an inhibition of alpha-fetoprotein, (AFP), heat shock protein-90 (hsp-90) and nuclear factor-kappaB (NF-kappaB). (escholarship.org)
  • These results suggest that PRELI is a crucial protein in the suppression of apoptosis in HepG2 cells in response to oxidative stress. (elsevier.com)
  • Cells exposed to 10 μM Cu exhibited a 22-fold increase in Cu content and a twofold decrease in Fe content compared with cells maintained in 0.4 μM Cu. 64 Cu uptake in Cu-deficient Hep-G2 cells showed a twofold decrease in K m compared with cells grown in 10 μM Cu. The decreased K m may represent an adaptive response to Cu deficiency. (physiology.org)
  • Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface.Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups.Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis. (nih.gov)
  • Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups. (nih.gov)
  • ECOD and methoxy- and ethoxyresorufin O-dealkylase activities in Hep G2 cells were enhanced by culturing the cells using a serum-free medium on fibronectin- or matrigel-coated dishes. (springer.com)
  • By using fibronectin-coated dishes to cell culture in a serum-free medium, reproducible and highly sensitive results can be obtained in experiments using cultured cells. (springer.com)
  • By flow cytometry assay, there was an increase in G2/M phase cells treated with ResN. (spie.org)
  • Cytotoxicity assay results indicated that Ccn-BNP-GA was significantly more cytotoxic to HepG2 cells and in a concentration-dependent manner. (nih.gov)
  • These cytotoxicity assay results were corroborated by analysis of cell apoptosis and the cell cycle. (nih.gov)
  • BLE and BSE improved cellular antioxidant status measured by FRAP assay and protected HepG2 cells against H 2 O 2 -induced cytotoxicity. (peerj.com)
  • This contrasted with the pattern of growth of cells cultured in the presence of serum on type I collagen gels and cells cultured on tissue-culture plastic in either CDM or medium containing serum which formed foci of multilayered cells. (biologists.org)
  • These findings are similar to those seen with native liver tissue preparations and demonstrate the suitability of Hep G2 cells for in‐depth investigations of the cellular and molecular regulation of biotin uptake by the liver. (elsevier.com)
  • Because studies in humans were limited, other investigators examined disposition, metabolism, and induction potential of chrysin in clinical studies or immortalized human cell lines. (aspetjournals.org)
  • Further studies demonstrated a 20-fold induction of the glucuronidation of bilirubin by the chrysin-treated cells and a 7.9-fold induction of the glucuronidation of the oral contraceptive drug ethinylestradiol, two of the best known and specific UGT1A1 substrates, demonstrating the potential importance of this induction. (aspetjournals.org)
  • The induction resulted in as much as a 14-fold increase in the glucuronidation of chrysin by the cell homogenate. (aspetjournals.org)
  • miRNA-491_5p was overexpressed in Hep G2 cells, followed by the addition of tumour necrosis factor (TNF)-alpha, and induction of apoptosis as well as genes involved in apoptosis pathways were evaluated. (escholarship.org)
  • Expression of these genes protects cells from oxidative damage and can prevent mutagenesis and cancer. (thermofisher.com)
  • In this study, the ability of the water extracts of the leaf (BLE) and stem (BSE) from the shoots to protect HepG2 cells against oxidative damage was studied. (peerj.com)
  • Antioxidant analyses of B. racemosa using cellular model has never been conducted and information obtained from such study can provide useful data particularly with regards to their ability to protect cells against oxidative damage. (peerj.com)
  • In this study, HepG2 cells were used as a cellular model to further investigate the effects of the water extracts of B. racemosa on the antioxidant defense systems as well as their ability to protect the cells against oxidative damage. (peerj.com)
  • In conclusion, α-tocopherol, exhibits a specific, concentration-dependent and biphasic "up then down" effect on the LDL receptor of HepG2 cells which appears to be at the level of gene transcription. (biomedcentral.com)
  • In order to explore the mechanism of HBV cccDNA formation, researchers used HepG2 to express the HBV receptor, the sodium ion-taurocholic acid co-transporter (NTCP). (ubigene.us)
  • The Hep G2 cells were fixed in 4% paraformaldehyde and arrayed on a 12-well (5 mm) adhesive coated slide, with each wellis surface specifically treated to enhance cellular attachment and to minimize background staining. (genetex.com)
  • abstract = "Little is known about the cellular and molecular regulation of the uptake process of the water‐soluble vitamin biotin into liver cells, the major site of biotin utilization and metabolism. (elsevier.com)
  • These findings demonstrate that biotin uptake by these cultured liver cells is mediated through a specialized carrier system that is dependent on Na+‐gradient, temperature, and energy and transports the vitamin by an electroneutral process. (elsevier.com)
  • Doostdar H, Burke MD, Melvin WT and Grant MH (1991) The effects of dimethyl-sulphoxide and 5-aminolaevulinic acid on the activities of cytochrome P450-dependent mixed function oxidase and UDP-glucuronosyltransferase activities in human Hep G2 hepatoma cells. (springer.com)
  • Oleic acid induced a 2.7-fold increase in the rate of the biosynthesis of triacylglycerol but not of phosphatidylcholine in Hep G2 cells. (ahajournals.org)
  • Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface. (nih.gov)
  • A competitive binding experiment was also conducted, and the results revealed that the apoptotic cells was gradually reduced by 35.12% when compared with Ccn-BNP-GA. These observations infer that Ccn-BNP-GA preferentially targeted GA receptors on the HepG2 cells. (nih.gov)
  • This study strongly indicated that POLK is a key cell molecule for HBV cccDNA formation in the HBV-infected HepG2-NTCP cell model, which provides new ideas for research in the molecular mechanism of cccDNA formation and new treatments for chronic hepatitis B. (ubigene.us)

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