ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.ATP Binding Cassette Transporter 1: A superfamily of large integral ATP-binding cassette membrane proteins whose expression pattern is consistent with a role in lipid (cholesterol) efflux. It is implicated in TANGIER DISEASE characterized by accumulation of cholesteryl ester in various tissues.Biological 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.Multidrug Resistance-Associated Proteins: A sequence-related subfamily of ATP-BINDING CASSETTE TRANSPORTERS that actively transport organic substrates. Although considered organic anion transporters, a subset of proteins in this family have also been shown to convey drug resistance to neutral organic drugs. Their cellular function may have clinical significance for CHEMOTHERAPY in that they transport a variety of ANTINEOPLASTIC AGENTS. Overexpression of proteins in this class by NEOPLASMS is considered a possible mechanism in the development of multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although similar in function to P-GLYCOPROTEINS, the proteins in this class share little sequence homology to the p-glycoprotein family of proteins.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.Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.Orphan Nuclear Receptors: A broad category of receptor-like proteins that may play a role in transcriptional-regulation in the CELL NUCLEUS. Many of these proteins are similar in structure to known NUCLEAR RECEPTORS but appear to lack a functional ligand-binding domain, while in other cases the specific ligands have yet to be identified.P-Glycoprotein: A 170-kDa transmembrane glycoprotein from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many ANTINEOPLASTIC AGENTS. Overexpression of this glycoprotein is associated with multidrug resistance (see DRUG RESISTANCE, MULTIPLE).Tangier Disease: An autosomal recessively inherited disorder caused by mutation of ATP-BINDING CASSETTE TRANSPORTERS involved in cellular cholesterol removal (reverse-cholesterol transport). It is characterized by near absence of ALPHA-LIPOPROTEINS (high-density lipoproteins) in blood. The massive tissue deposition of cholesterol esters results in HEPATOMEGALY; SPLENOMEGALY; RETINITIS PIGMENTOSA; large orange tonsils; and often sensory POLYNEUROPATHY. The disorder was first found among inhabitants of Tangier Island in the Chesapeake Bay, MD.P-Glycoproteins: A subfamily of transmembrane proteins from the superfamily of ATP-BINDING CASSETTE TRANSPORTERS that are closely related in sequence to P-GLYCOPROTEIN. When overexpressed, they function as ATP-dependent efflux pumps able to extrude lipophilic drugs, especially ANTINEOPLASTIC AGENTS, from cells causing multidrug resistance (DRUG RESISTANCE, MULTIPLE). Although P-Glycoproteins share functional similarities to MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS they are two distinct subclasses of ATP-BINDING CASSETTE TRANSPORTERS, and have little sequence homology.Drug Resistance, Multiple: Simultaneous resistance to several structurally and functionally distinct drugs.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.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.Membrane Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.Hydrocarbons, FluorinatedAmino 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.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.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.Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells.Bacterial Proteins: Proteins found in any species of bacterium.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Maltose: A dextrodisaccharide from malt and starch. It is used as a sweetening agent and fermentable intermediate in brewing. (Grant & Hackh's Chemical Dictionary, 5th ed)Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Maltose-Binding Proteins: Periplasmic proteins that bind MALTOSE and maltodextrin. They take part in the maltose transport system of BACTERIA.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Adenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.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.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Periplasmic Binding Proteins: Periplasmic proteins that scavenge or sense diverse nutrients. In the bacterial environment they usually couple to transporters or chemotaxis receptors on the inner bacterial membrane.Scavenger Receptors, Class B: A family of scavenger receptors that are predominately localized to CAVEOLAE of the PLASMA MEMBRANE and bind HIGH DENSITY LIPOPROTEINS.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Monosaccharide Transport Proteins: A large group of membrane transport proteins that shuttle MONOSACCHARIDES across CELL MEMBRANES.Drug Resistance, Multiple, Fungal: The ability of fungi to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance phenotype may be attributed to multiple gene mutations.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Cholates: Salts and esters of CHOLIC ACID.Biological Transport, Active: The movement of materials across cell membranes and epithelial layers against an electrochemical gradient, requiring the expenditure of metabolic energy.Organic Anion Transporters: Proteins involved in the transport of organic anions. They play an important role in the elimination of a variety of endogenous substances, xenobiotics and their metabolites from the body.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.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.Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Vanadates: Oxyvanadium ions in various states of oxidation. They act primarily as ion transport inhibitors due to their inhibition of Na(+)-, K(+)-, and Ca(+)-ATPase transport systems. They also have insulin-like action, positive inotropic action on cardiac ventricular muscle, and other metabolic effects.Receptors, Cytoplasmic and Nuclear: Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.Leukotriene C4: The conjugation product of LEUKOTRIENE A4 and glutathione. It is the major arachidonic acid metabolite in macrophages and human mast cells as well as in antigen-sensitized lung tissue. It stimulates mucus secretion in the lung, and produces contractions of nonvascular and some VASCULAR SMOOTH MUSCLE. (From Dictionary of Prostaglandins and Related Compounds, 1990)Drug Resistance, Neoplasm: Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Mitoxantrone: An anthracenedione-derived antineoplastic agent.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.Atherosclerosis: A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Glyburide: An antidiabetic sulfonylurea derivative with actions similar to those of chlorpropamide.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.Anion Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of negatively charged molecules (anions) across a biological membrane.Hydroxycholesterols: Cholesterol which is substituted by a hydroxy group in any position.Acrocallosal Syndrome: Autosomal recessive syndrome characterized by hypogenesis or agenesis of CORPUS CALLOSUM. Clinical features include MENTAL RETARDATION; CRANIOFACIAL ABNORMALITIES; digital malformations, and growth retardation.Mice, Inbred C57BLProtein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).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.Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Cholesterol, HDL: Cholesterol which is contained in or bound to high-density lipoproteins (HDL), including CHOLESTEROL ESTERS and free cholesterol.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.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.Hep G2 Cells: A human liver tumor cell line used to study a variety of liver-specific metabolic functions.Kinetics: The rate dynamics in chemical or physical systems.Phytosterols: A class of organic compounds known as STEROLS or STEROIDS derived from plants.Rhodamines: A family of 3,6-di(substituted-amino)-9-benzoate derivatives of xanthene that are used as dyes and as indicators for various metals; also used as fluorescent tracers in histochemistry.Lipoproteins, HDL3: Intermediate-density subclass of the high-density lipoproteins, with particle sizes between 7 to 8 nm. As the larger lighter HDL2 lipoprotein, HDL3 lipoprotein is lipid-rich.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.Antigens, CD36: Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS.Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Hypoalphalipoproteinemias: Conditions with abnormally low levels of ALPHA-LIPOPROTEINS (high-density lipoproteins) in the blood. Hypoalphalipoproteinemia can be associated with mutations in genes encoding APOLIPOPROTEIN A-I; LECITHIN CHOLESTEROL ACYLTRANSFERASE; and ATP-BINDING CASSETTE TRANSPORTERS.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Lactococcus lactis: A non-pathogenic species of LACTOCOCCUS found in DAIRY PRODUCTS and responsible for the souring of MILK and the production of LACTIC ACID.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Fungal Proteins: Proteins found in any species of fungus.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Proteolipids: Protein-lipid combinations abundant in brain tissue, but also present in a wide variety of animal and plant tissues. In contrast to lipoproteins, they are insoluble in water, but soluble in a chloroform-methanol mixture. The protein moiety has a high content of hydrophobic amino acids. The associated lipids consist of a mixture of GLYCEROPHOSPHATES; CEREBROSIDES; and SULFOGLYCOSPHINGOLIPIDS; while lipoproteins contain PHOSPHOLIPIDS; CHOLESTEROL; and TRIGLYCERIDES.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Cell Line, Tumor: A cell line derived from cultured tumor cells.Multigene Family: A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)Genes, MDR: Genes for MEMBRANE TRANSPORT PROTEINS that confer resistance to toxic compounds. Several superfamilies of these multidrug export proteins are known and found in both prokaryotes and eukaryotes.Sterols: Steroids with a hydroxyl group at C-3 and most of the skeleton of cholestane. Additional carbon atoms may be present in the side chain. (IUPAC Steroid Nomenclature, 1987)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.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Benzimidazoles: Compounds with a BENZENE fused to IMIDAZOLES.Sulfonamides: A group of compounds that contain the structure SO2NH2.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Genetic Complementation Test: A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.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.Caco-2 Cells: Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells, such as ENTEROCYTES. These cells are valuable in vitro tools for studies related to intestinal cell function and differentiation.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.AcridinesCrystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Nucleotides: The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)Glucose Transporter Type 1: A ubiquitously expressed glucose transporter that is important for constitutive, basal GLUCOSE transport. It is predominately expressed in ENDOTHELIAL CELLS and ERYTHROCYTES at the BLOOD-BRAIN BARRIER and is responsible for GLUCOSE entry into the BRAIN.Arabidopsis: A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.Macrophages, Peritoneal: Mononuclear phagocytes derived from bone marrow precursors but resident in the peritoneum.GlucosidesCricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Genes, Bacterial: The functional hereditary units of BACTERIA.Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable.HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Lipids: A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)Symporters: Membrane transporters that co-transport two or more dissimilar molecules in the same direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is "powered" by the movement of another ion or molecule with its electrochemical gradient.Retinaldehyde: A carotenoid constituent of visual pigments. It is the oxidized form of retinol which functions as the active component of the visual cycle. It is bound to the protein opsin forming the complex rhodopsin. When stimulated by visible light, the retinal component of the rhodopsin complex undergoes isomerization at the 11-position of the double bond to the cis-form; this is reversed in "dark" reactions to return to the native trans-configuration.Amino Acid Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.Serotonin Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of serotonergic neurons. They are different than SEROTONIN RECEPTORS, which signal cellular responses to SEROTONIN. They remove SEROTONIN from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. Regulates signal amplitude and duration at serotonergic synapses and is the site of action of the SEROTONIN UPTAKE INHIBITORS.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Monocarboxylic Acid Transporters: A family of proteins involved in the transport of monocarboxylic acids such as LACTIC ACID and PYRUVIC ACID across cellular membranes.Arabidopsis Proteins: Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Mutagenesis, Insertional: Mutagenesis where the mutation is caused by the introduction of foreign DNA sequences into a gene or extragenic sequence. This may occur spontaneously in vivo or be experimentally induced in vivo or in vitro. Proviral DNA insertions into or adjacent to a cellular proto-oncogene can interrupt GENETIC TRANSLATION of the coding sequences or interfere with recognition of regulatory elements and cause unregulated expression of the proto-oncogene resulting in tumor formation.Anticholesteremic Agents: Substances used to lower plasma CHOLESTEROL levels.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Dopamine Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of dopaminergic neurons. They remove DOPAMINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS and are the target of DOPAMINE UPTAKE INHIBITORS.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Blood-Brain Barrier: Specialized non-fenestrated tightly-joined ENDOTHELIAL CELLS with TIGHT JUNCTIONS that form a transport barrier for certain substances between the cerebral capillaries and the BRAIN tissue.Rhodamine 123: A fluorescent probe with low toxicity which is a potent substrate for P-glycoprotein and the bacterial multidrug efflux transporter. It is used to assess mitochondrial bioenergetics in living cells and to measure the efflux activity of P-glycoprotein in both normal and malignant cells. (Leukemia 1997;11(7):1124-30)Phospholipid Transfer Proteins: A ubiquitous family of proteins that transport PHOSPHOLIPIDS such as PHOSPHATIDYLINOSITOL and PHOSPHATIDYLCHOLINE between membranes. They play an important role in phospholipid metabolism during vesicular transport and SIGNAL TRANSDUCTION.O Antigens: The lipopolysaccharide-protein somatic antigens, usually from gram-negative bacteria, important in the serological classification of enteric bacilli. The O-specific chains determine the specificity of the O antigens of a given serotype. O antigens are the immunodominant part of the lipopolysaccharide molecule in the intact bacterial cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.Green Fluorescent Proteins: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.Estrone: An aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone, a major mammalian estrogen. It is converted from ANDROSTENEDIONE directly, or from TESTOSTERONE via ESTRADIOL. In humans, it is produced primarily by the cyclic ovaries, PLACENTA, and the ADIPOSE TISSUE of men and postmenopausal women.Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.Excitatory Amino Acid Transporter 2: A glutamate plasma membrane transporter protein found in ASTROCYTES and in the LIVER.Plant Roots: The usually underground portions of a plant that serve as support, store food, and through which water and mineral nutrients enter the plant. (From American Heritage Dictionary, 1982; Concise Dictionary of Biology, 1990)Open Reading Frames: A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Genes, Reporter: Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.Operon: In bacteria, a group of metabolically related genes, with a common promoter, whose transcription into a single polycistronic MESSENGER RNA is under the control of an OPERATOR REGION.Azides: Organic or inorganic compounds that contain the -N3 group.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.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Excitatory Amino Acid Transporter 3: A neuronal and epithelial type glutamate plasma membrane transporter protein.Intestines: The section of the alimentary canal from the STOMACH to the ANAL CANAL. It includes the LARGE INTESTINE and SMALL INTESTINE.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Detergents: Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties.Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Sulfonylurea Receptors: ATP-BINDING CASSETTE PROTEINS that are highly conserved and widely expressed in nature. They form an integral part of the ATP-sensitive potassium channel complex which has two intracellular nucleotide folds that bind to sulfonylureas and their analogs.Amino Acid Transport System X-AG: A family of POTASSIUM and SODIUM-dependent acidic amino acid transporters that demonstrate a high affinity for GLUTAMIC ACID and ASPARTIC ACID. Several variants of this system are found in neuronal tissue.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.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.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.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Receptors, Scavenger: A large group of structurally diverse cell surface receptors that mediate endocytic uptake of modified LIPOPROTEINS. Scavenger receptors are expressed by MYELOID CELLS and some ENDOTHELIAL CELLS, and were originally characterized based on their ability to bind acetylated LOW-DENSITY LIPOPROTEINS. They can also bind a variety of other polyanionic ligand. Certain scavenger receptors can internalize micro-organisms as well as apoptotic cells.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Antifungal Agents: Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.Organic Cation Transporter 1: An organic cation transporter found in kidney. It is localized to the basal lateral membrane and is likely to be involved in the renal secretion of organic cations.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.Excitatory Amino Acid Transporter 1: A glial type glutamate plasma membrane transporter protein found predominately in ASTROCYTES. It is also expressed in HEART and SKELETAL MUSCLE and in the PLACENTA.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.Gene Expression Regulation, Fungal: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Retinoids: A group of tetraterpenes, with four terpene units joined head-to-tail. Biologically active members of this class are used clinically in the treatment of severe cystic ACNE; PSORIASIS; and other disorders of keratinization.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Norepinephrine Plasma Membrane Transport Proteins: Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of noradrenergic neurons. They remove NOREPINEPHRINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS. It regulates signal amplitude and duration at noradrenergic synapses and is the target of ADRENERGIC UPTAKE INHIBITORS.Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.Organ Specificity: Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.Sitosterols: A family of sterols commonly found in plants and plant oils. Alpha-, beta-, and gamma-isomers have been characterized.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Endoplasmic Reticulum: A system of cisternae in the CYTOPLASM of many cells. In places the endoplasmic reticulum is continuous with the plasma membrane (CELL MEMBRANE) or outer membrane of the nuclear envelope. If the outer surfaces of the endoplasmic reticulum membranes are coated with ribosomes, the endoplasmic reticulum is said to be rough-surfaced (ENDOPLASMIC RETICULUM, ROUGH); otherwise it is said to be smooth-surfaced (ENDOPLASMIC RETICULUM, SMOOTH). (King & Stansfield, A Dictionary of Genetics, 4th ed)Polymorphism, Single Nucleotide: A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.Integrons: DNA elements that include the component genes and insertion site for a site-specific recombination system that enables them to capture mobile gene cassettes.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Cation Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of positively charged molecules (cations) across a biological membrane.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Retinoid X Receptors: A subtype of RETINOIC ACID RECEPTORS that are specific for 9-cis-retinoic acid which function as nuclear TRANSCRIPTION FACTORS that regulate multiple signaling pathways.
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