PPAR alpha: A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR GAMMA is important to metabolism of LIPIDS. It is the target of FIBRATES to control HYPERLIPIDEMIAS.PPAR gamma: A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR ALPHA is important in regulation of GLUCOSE metabolism and CELL GROWTH PROCESSES. It is a target of THIAZOLIDINEDIONES for control of DIABETES MELLITUS.PPAR delta: A nuclear transcription factor. It is activated by PROSTACYCLIN.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.Fenofibrate: An antilipemic agent which reduces both CHOLESTEROL and TRIGLYCERIDES in the blood.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Peroxisome Proliferators: A class of nongenotoxic CARCINOGENS that induce the production of hepatic PEROXISOMES and induce hepatic neoplasms after long-term administration.Peroxisome Proliferator-Activated Receptors: TRANSCRIPTION FACTORS that are activated by ligands and heterodimerize with RETINOID X RECEPTORS and bind to peroxisome proliferator response elements in the promoter regions of target genes.Chromosomes, Artificial, Human: DNA constructs that are composed of, at least, all elements, such as a REPLICATION ORIGIN; TELOMERE; and CENTROMERE, required for successful replication, propagation to and maintainance in progeny human cells. In addition, they are constructed to carry other sequences for analysis or gene transfer.Thiazolidinediones: THIAZOLES with two keto oxygens. Members are insulin-sensitizing agents which overcome INSULIN RESISTANCE by activation of the peroxisome proliferator activated receptor gamma (PPAR-gamma).Clofibrate: A fibric acid derivative used in the treatment of HYPERLIPOPROTEINEMIA TYPE III and severe HYPERTRIGLYCERIDEMIA. (From Martindale, The Extra Pharmacopoeia, 30th ed, p986)Enoyl-CoA Hydratase: An enzyme that catalyzes reversibly the hydration of unsaturated fatty acyl-CoA to yield beta-hydroxyacyl-CoA. It plays a role in the oxidation of fatty acids and in mitochondrial fatty acid synthesis, has broad specificity, and is most active with crotonyl-CoA. EC 4.2.1.17.Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.alpha 1-Antitrypsin: Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.Peroxisomes: Microbodies which occur in animal and plant cells and in certain fungi and protozoa. They contain peroxidase, catalase, and allied enzymes. (From Singleton and Sainsbury, Dictionary of Microbiology and Molecular Biology, 2nd ed)Microbodies: Electron-dense cytoplasmic particles bounded by a single membrane, such as PEROXISOMES; GLYOXYSOMES; and glycosomes.Alkane 1-Monooxygenase: A P450 oxidoreductase that catalyzes the hydroxylation of the terminal carbon of linear hydrocarbons such as octane and FATTY ACIDS in the omega position. The enzyme may also play a role in the oxidation of a variety of structurally unrelated compounds such as XENOBIOTICS, and STEROIDS.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.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.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.Acetyl-CoA C-Acyltransferase: Enzyme that catalyzes the final step of fatty acid oxidation in which ACETYL COA is released and the CoA ester of a fatty acid two carbons shorter is formed.Receptors, Adrenergic, alpha: One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.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.PhenylpropionatesTranscription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Hypoxia-Inducible Factor 1, alpha Subunit: Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.Hypolipidemic Agents: Substances that lower the levels of certain LIPIDS in the BLOOD. They are used to treat HYPERLIPIDEMIAS.Peroxisomal Bifunctional Enzyme: A monomeric protein found in liver peroxisomes that contains two enzymatically active domains; an enoyl-CoA hydratase/3,2-trans-enoyl-CoA isomerase domain, and an (S)-3-hydroxyacyl-CoA dehydrogenase domain. The enzyme is stereospecific with regards to how cis and trans double bonds are metabolized. It is complemented by PEROXISOMAL MULTIFUNCTIONAL PROTEIN-2, which has the opposite stereospecificity.Receptors, Retinoic Acid: Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized.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.Mediator Complex Subunit 1: A mediator complex subunit that is believed to play a key role in the coactivation of nuclear receptor-activated transcription by the mediator complex. It interacts with a variety of nuclear receptors including RETINOIC ACID RECEPTORS; THYROID HORMONE RECEPTORS; VITAMIN D RECEPTORS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; ESTROGEN RECEPTORS; and GLUCOCORTICOID RECEPTORS.Oxazoles: Five-membered heterocyclic ring structures containing an oxygen in the 1-position and a nitrogen in the 3-position, in distinction from ISOXAZOLES where they are at the 1,2 positions.Gamma Rays: Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source.Mice, Inbred C57BLCells, 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.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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.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.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)3-Hydroxyacyl CoA Dehydrogenases: Enzymes that reversibly catalyze the oxidation of a 3-hydroxyacyl CoA to 3-ketoacyl CoA in the presence of NAD. They are key enzymes in the oxidation of fatty acids and in mitochondrial fatty acid synthesis.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.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.alpha7 Nicotinic Acetylcholine Receptor: A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric a7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.Antimetabolites: Drugs that are chemically similar to naturally occurring metabolites, but differ enough to interfere with normal metabolic pathways. (From AMA Drug Evaluations Annual, 1994, p2033)Cell Line: Established cell cultures that have the potential to propagate indefinitely.Hepatocytes: The main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Fatty Acids: Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)Integrin alpha3beta1: Cell surface receptor for LAMININ, epiligrin, FIBRONECTINS, entactin, and COLLAGEN. Integrin alpha3beta1 is the major integrin present in EPITHELIAL CELLS, where it plays a role in the assembly of BASEMENT MEMBRANE as well as in cell migration, and may regulate the functions of other integrins. Two alternatively spliced isoforms of the alpha subunit (INTEGRIN ALPHA3), are differentially expressed in different cell types.Integrin alpha4: An integrin alpha subunit that is unique in that it does not contain an I domain, and its proteolytic cleavage site is near the middle of the extracellular portion of the polypeptide rather than close to the membrane as in other integrin alpha subunits.Integrin alpha6: An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.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.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.Integrin alpha5beta1: An integrin found in FIBROBLASTS; PLATELETS; MONOCYTES, and LYMPHOCYTES. Integrin alpha5beta1 is the classical receptor for FIBRONECTIN, but it also functions as a receptor for LAMININ and several other EXTRACELLULAR MATRIX PROTEINS.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).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.Oleic Acids: A group of fatty acids that contain 18 carbon atoms and a double bond at the omega 9 carbon.ThiazolesIntegrin alpha4beta1: Integrin alpha4beta1 is a FIBRONECTIN and VCAM-1 receptor present on LYMPHOCYTES; MONOCYTES; EOSINOPHILS; NK CELLS and thymocytes. It is involved in both cell-cell and cell- EXTRACELLULAR MATRIX adhesion and plays a role in INFLAMMATION, hematopoietic cell homing and immune function, and has been implicated in skeletal MYOGENESIS; NEURAL CREST migration and proliferation, lymphocyte maturation and morphogenesis of the PLACENTA and HEART.Interleukin-1alpha: An interleukin-1 subtype that occurs as a membrane-bound pro-protein form that is cleaved by proteases to form a secreted mature form. Unlike INTERLEUKIN-1BETA both membrane-bound and secreted forms of interleukin-1alpha are biologically active.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.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.Interferon-gamma: The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.RNA: A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Multienzyme Complexes: Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.Integrin alpha2beta1: An integrin found on fibroblasts, platelets, endothelial and epithelial cells, and lymphocytes where it functions as a receptor for COLLAGEN and LAMININ. Although originally referred to as the collagen receptor, it is one of several receptors for collagen. Ligand binding to integrin alpha2beta1 triggers a cascade of intracellular signaling, including activation of p38 MAP kinase.Receptors, Adrenergic, alpha-1: A subclass of alpha-adrenergic receptors that mediate contraction of SMOOTH MUSCLE in a variety of tissues such as ARTERIOLES; VEINS; and the UTERUS. They are usually found on postsynaptic membranes and signal through GQ-G11 G-PROTEINS.Integrin alpha5: This integrin alpha subunit combines with INTEGRIN BETA1 to form a receptor (INTEGRIN ALPHA5BETA1) that binds FIBRONECTIN and LAMININ. It undergoes posttranslational cleavage into a heavy and a light chain that are connected by disulfide bonds.Integrin alpha1beta1: Integrin alpha1beta1 functions as a receptor for LAMININ and COLLAGEN. It is widely expressed during development, but in the adult is the predominant laminin receptor (RECEPTORS, LAMININ) in mature SMOOTH MUSCLE CELLS, where it is important for maintenance of the differentiated phenotype of these cells. Integrin alpha1beta1 is also found in LYMPHOCYTES and microvascular endothelial cells, and may play a role in angiogenesis. In SCHWANN CELLS and neural crest cells, it is involved in cell migration. Integrin alpha1beta1 is also known as VLA-1 and CD49a-CD29.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.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.Receptors, Adrenergic, alpha-2: A subclass of alpha-adrenergic receptors found on both presynaptic and postsynaptic membranes where they signal through Gi-Go G-PROTEINS. While postsynaptic alpha-2 receptors play a traditional role in mediating the effects of ADRENERGIC AGONISTS, the subset of alpha-2 receptors found on presynaptic membranes signal the feedback inhibition of NEUROTRANSMITTER release.Integrin alpha6beta1: A cell surface receptor mediating cell adhesion to the EXTRACELLULAR MATRIX and to other cells via binding to LAMININ. It is involved in cell migration, embryonic development, leukocyte activation and tumor cell invasiveness. Integrin alpha6beta1 is the major laminin receptor on PLATELETS; LEUKOCYTES; and many EPITHELIAL CELLS, and ligand binding may activate a number of signal transduction pathways. Alternative splicing of the cytoplasmic domain of the alpha6 subunit (INTEGRIN ALPHA6) results in the formation of A and B isoforms of the heterodimer, which are expressed in a tissue-specific manner.Macromolecular Substances: Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.PPAR-beta: One of the PPAR nuclear transcription factors.Kinetics: The rate dynamics in chemical or physical systems.Lipolysis: The metabolic process of breaking down LIPIDS to release FREE FATTY ACIDS, the major oxidative fuel for the body. Lipolysis may involve dietary lipids in the DIGESTIVE TRACT, circulating lipids in the BLOOD, and stored lipids in the ADIPOSE TISSUE or the LIVER. A number of enzymes are involved in such lipid hydrolysis, such as LIPASE and LIPOPROTEIN LIPASE from various tissues.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Integrin alpha6beta4: This intrgrin is a key component of HEMIDESMOSOMES and is required for their formation and maintenance in epithelial cells. Integrin alpha6beta4 is also found on thymocytes, fibroblasts, and Schwann cells, where it functions as a laminin receptor (RECEPTORS, LAMININ) and is involved in wound healing, cell migration, and tumor invasiveness.TriglyceridesIntegrins: A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.Integrin alpha Chains: The alpha subunits of integrin heterodimers (INTEGRINS), which mediate ligand specificity. There are approximately 18 different alpha chains, exhibiting great sequence diversity; several chains are also spliced into alternative isoforms. They possess a long extracellular portion (1200 amino acids) containing a MIDAS (metal ion-dependent adhesion site) motif, and seven 60-amino acid tandem repeats, the last 4 of which form EF HAND MOTIFS. The intracellular portion is short with the exception of INTEGRIN ALPHA4.Tumor Necrosis Factor-alpha: Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.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.Alpha Rhythm: Brain waves characterized by a relatively high voltage or amplitude and a frequency of 8-13 Hz. They constitute the majority of waves recorded by EEG registering the activity of the parietal and occipital lobes when the individual is awake, but relaxed with the eyes closed.Protein Subunits: Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.Chromans: Benzopyrans saturated in the 2 and 3 positions.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.Integrin alpha1: An integrin alpha subunit that binds COLLAGEN and LAMININ though its I domain. It combines with INTEGRIN BETA1 to form the heterodimer INTEGRIN ALPHA1BETA1.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)Receptors, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.Luciferases: Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.Integrin alpha3: An integrin alpha subunit that occurs as alternatively spliced isoforms. The isoforms are differentially expressed in specific cell types and at specific developmental stages. Integrin alpha3 combines with INTEGRIN BETA1 to form INTEGRIN ALPHA3BETA1 which is a heterodimer found primarily in epithelial cells.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.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.alpha 1-Antitrypsin Deficiency: Deficiency of the protease inhibitor ALPHA 1-ANTITRYPSIN that manifests primarily as PULMONARY EMPHYSEMA and LIVER CIRRHOSIS.Adrenergic alpha-Agonists: Drugs that selectively bind to and activate alpha adrenergic receptors.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.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 Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Dinoprost: A naturally occurring prostaglandin that has oxytocic, luteolytic, and abortifacient activities. Due to its vasocontractile properties, the compound has a variety of other biological actions.Receptors, GABA-A: Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Adrenergic alpha-Antagonists: Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma.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.Bezafibrate: An antilipemic agent that lowers CHOLESTEROL and TRIGLYCERIDES. It decreases LOW DENSITY LIPOPROTEINS and increases HIGH DENSITY LIPOPROTEINS.DNA: 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).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.Adipocytes: Cells in the body that store FATS, usually in the form of TRIGLYCERIDES. WHITE ADIPOCYTES are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. BROWN ADIPOCYTES are thermogenic cells that can be found in newborns of some species and hibernating mammals.Prostaglandin D2: The principal cyclooxygenase metabolite of arachidonic acid. It is released upon activation of mast cells and is also synthesized by alveolar macrophages. Among its many biological actions, the most important are its bronchoconstrictor, platelet-activating-factor-inhibitory, and cytotoxic effects.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Hepatocyte Nuclear Factor 1-alpha: Hepatocyte nuclear factor 1-alpha is a transcription factor found in the LIVER; PANCREAS; and KIDNEY that regulates HOMEOSTASIS of GLUCOSE.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Transforming Growth Factor alpha: An EPIDERMAL GROWTH FACTOR related protein that is found in a variety of tissues including EPITHELIUM, and maternal DECIDUA. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form which binds to the EGF RECEPTOR.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.alpha 1-Antichymotrypsin: Glycoprotein found in alpha(1)-globulin region in human serum. It inhibits chymotrypsin-like proteinases in vivo and has cytotoxic killer-cell activity in vitro. The protein also has a role as an acute-phase protein and is active in the control of immunologic and inflammatory processes, and as a tumor marker. It is a member of the serpin superfamily.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.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.Protein 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).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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.alpha Karyopherins: Nucleocytoplasmic transport molecules that bind to the NUCLEAR LOCALIZATION SIGNALS of cytoplasmic molecules destined to be imported into the CELL NUCLEUS. Once attached to their cargo they bind to BETA KARYOPHERINS and are transported through the NUCLEAR PORE COMPLEX. Inside the CELL NUCLEUS alpha karyopherins dissociate from beta karypherins and their cargo. They then form a complex with CELLULAR APOPTOSIS SUSCEPTIBILITY PROTEIN and RAN GTP-BINDING PROTEIN which is exported to the CYTOPLASM.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Adrenergic alpha-1 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS.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.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.Mice, Inbred BALB CGuanosine 5'-O-(3-Thiotriphosphate): Guanosine 5'-(trihydrogen diphosphate), monoanhydride with phosphorothioic acid. A stable GTP analog which enjoys a variety of physiological actions such as stimulation of guanine nucleotide-binding proteins, phosphoinositide hydrolysis, cyclic AMP accumulation, and activation of specific proto-oncogenes.Interleukin-1: A soluble factor produced by MONOCYTES; MACROPHAGES, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. Interleukin-1 is a general term refers to either of the two distinct proteins, INTERLEUKIN-1ALPHA and INTERLEUKIN-1BETA. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.6-Ketoprostaglandin F1 alpha: The physiologically active and stable hydrolysis product of EPOPROSTENOL. Found in nearly all mammalian tissue.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Antigens, CD: Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.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.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.)GTP-Binding Protein gamma Subunits: Heterotrimeric GTP-binding protein subunits that tightly associate with GTP-BINDING PROTEIN BETA SUBUNITS. A dimer of beta and gamma subunits is formed when the GTP-BINDING PROTEIN ALPHA SUBUNIT dissociates from the GTP-binding protein heterotrimeric complex. The beta-gamma dimer can play an important role in signal transduction by interacting with a variety of second messengers.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.Hypoglycemic Agents: Substances which lower blood glucose levels.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)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.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.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Cell Line, Tumor: A cell line derived from cultured tumor cells.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.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Peptide Elongation Factor 1: Peptide elongation factor 1 is a multisubunit protein that is responsible for the GTP-dependent binding of aminoacyl-tRNAs to eukaryotic ribosomes. The alpha subunit (EF-1alpha) binds aminoacyl-tRNA and transfers it to the ribosome in a process linked to GTP hydrolysis. The beta and delta subunits (EF-1beta, EF-1delta) are involved in exchanging GDP for GTP. The gamma subunit (EF-1gamma) is a structural component.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.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.Clonidine: An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.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.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.AnilidesGTP-Binding Protein alpha Subunits, Gi-Go: A family of heterotrimeric GTP-binding protein alpha subunits that were originally identified by their ability to inhibit ADENYLYL CYCLASES. Members of this family can couple to beta and gamma G-protein subunits that activate POTASSIUM CHANNELS. The Gi-Go part of the name is also spelled Gi/Go.Phospholipase C gamma: A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.Retinoid X Receptor alpha: A nuclear transcription factor. Heterodimerization with PPAR GAMMA is important in regulation of GLUCOSE metabolism and CELL GROWTH PROCESSES.Receptors, Fc: Molecules found on the surface of some, but not all, B-lymphocytes, T-lymphocytes, and macrophages, which recognize and combine with the Fc (crystallizable) portion of immunoglobulin molecules.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Molecular Weight: The sum of the weight of all the atoms in a molecule.Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of ERECTILE DYSFUNCTION.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Muscle, Skeletal: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.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)Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.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.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.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cell Movement: The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.3T3-L1 Cells: A continuous cell line that is a substrain of SWISS 3T3 CELLS developed though clonal isolation. The mouse fibroblast cells undergo an adipose-like conversion as they move to a confluent and contact-inhibited state.Adrenergic alpha-2 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.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.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.Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.Hepatocyte Nuclear Factor 4: A subfamily of nuclear receptors that regulate GENETIC TRANSCRIPTION of a diverse group of GENES involved in the synthesis of BLOOD COAGULATION FACTORS; and in GLUCOSE; CHOLESTEROL; and FATTY ACIDS metabolism.Acyl-CoA Oxidase: An enzyme that catalyzes the first and rate-determining steps of peroxisomal beta-oxidation of fatty acids. It acts on COENZYME A derivatives of fatty acids with chain lengths from 8 to 18, using FLAVIN-ADENINE DINUCLEOTIDE as a cofactor.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
"Structure of the intact PPAR-gamma-RXR-alpha nuclear receptor complex on DNA". Nature. 456 (7220): 350-356. doi:10.1038/ ... The structure of the LBD is referred to as an alpha helical sandwich fold in which three anti parallel alpha helices (the " ... Some of these receptors such as FXR, LXR, and PPAR bind a number of metabolic intermediates such as fatty acids, bile acids and ... Retinoids can bind mammalian receptors other than RAR and RXR such as, PPAR, RORb, or COUP-TFII. Furthermore, RXR is sensitive ...
PPAR alpha and delta were found to upregulate PDK4 mRNA, but PPAR gamma activation downregulated expression. PDK4 is relevant ... Hypoxia is shown to induce PDK4 gene expression through the ERR gamma mechanism. Conversely, PDK4 is downregulated in cardiac ... Kwon HS, Huang B, Unterman TG, Harris RA (Apr 2004). "Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 ...
... like peroxisome proliferator-activated receptor gamma(PPAR-γ) and coactivator 1 alpha(PGC-1α). The hypermethylation of these ... Exercise is a way to prevent and treat these effects by helping to hypomethylate PPAR-γ and PGC-1α. Additionally, exercise also ...
... tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat". Endocrinology. 137 (1): 354-366. doi:10.1210/endo.137.1 ... PPARs are a family of ligand activated receptors which include PPARα, PPARδ and PPARγ subtypes that are expressed in varying ... Pirinixic acid is a peroxisome proliferator-activated receptor alpha (PPARα) agonist that is under experimental investigation ... PPARα, a PPAR subtype, controls the expression of genes involved in cardiac fatty acid utilization, and its activation, ...
... alpha) and γ (gamma) of the peroxisome proliferator-activated receptor (PPAR). Agonist action at PPARα lowers high blood ... Being a dual PPAR agonist, Saroglitazar (Lipaglyn) helps in controlling blood glucose and Lipid parameters especially high ... Saroglitazar is novel first in class drug which acts as a dual PPAR agonist at the subtypes α ( ... triglycerides, and agonist action on PPARγ improves insulin resistance and consequently lowers blood sugar. ...
PPAR-alpha and PPAR-gamma are the molecular targets of a number of marketed drugs. The main classes of PPAR agonists are: PPARα ... PPARγ (gamma) is the main target of the drug class of thiazolidinediones (TZDs), used in diabetes mellitus and other diseases ... PPARδ (delta) is the main target of a research chemical named GW501516. It has been shown that agonism of PPARδ changes the ... A fourth class of dual PPAR agonists, so-called glitazars, which bind to both the α and γ PPAR isoforms, are currently under ...
PPAR gamma and RXR alpha". Nucleic Acids Res. 22 (25): 5628-34. doi:10.1093/nar/22.25.5628. PMC 310126 . PMID 7838715. Lee JW, ... PPAR gamma and RXR alpha". Nucleic Acids Res. 22 (25): 5628-34. doi:10.1093/nar/22.25.5628. PMC 310126 . PMID 7838715. Berger J ... Retinoid X receptor alpha (RXR-alpha), also known as NR2B1 (nuclear receptor subfamily 2, group B, member 1) is a nuclear ... "Entrez Gene: RXRA retinoid X receptor, alpha". "Retinoic acid receptor RXR-alpha - Homo sapiens (Human)". UniProt. Na SY, Choi ...
"PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ... Liver X receptor alpha (LXR-alpha) is a nuclear receptor protein that in humans is encoded by the NR1H3 gene (nuclear receptor ... and peroxisome proliferator-activated receptor alpha (PPARalpha ) in HEK293 cells". The Journal of Biological Chemistry. 277 ( ... "The atypical interaction of peroxisome proliferator-activated receptor alpha with liver X receptor alpha antagonizes the ...
Together with peroxisome proliferator-activated receptor delta and peroxisome proliferator-activated receptor gamma, PPAR-alpha ... PPAR-alpha is a transcription factor and a major regulator of lipid metabolism in the liver. PPAR-alpha is activated under ... PPAR-alpha agonists may carry therapeutic value for the treatment of non-alcoholic fatty liver disease. PPAR-alpha may also be ... Lower PPAR-alpha expression levels are found in small and large intestine, skeletal muscle and adrenal gland. Human PPAR-alpha ...
PPAR-alpha, PPAR-delta, PPAR-beta and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and is a regulator of ... PPAR-gamma agonists have been used in the treatment of hyperlipidaemia and hyperglycemia. PPAR-gamma decreases the inflammatory ... Puigserver P, Spiegelman BM (2003). "Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): ... a unique traditional antidiabetic medicine with dual PPAR-alpha/-gamma activator properties". Diabetes Obes Metab. 10 (1): 10-7 ...
... expression is also induced in white adipose tissue by PPAR-gamma, which may indicate it also regulates metabolism in the ... In mice FGF21 is strongly induced in liver by prolonged fasting via PPAR-alpha and in turn induces the transcriptional ... In liver FGF21 expression is regulated by PPARα and levels rise substantially with both fasting and consumption of ketogenic ...
PPAR) gamma target gene and promotes PPARgamma-induced adipocyte differentiation". The Journal of Biological Chemistry. 278 (39 ... Lazar MA, Hodin RA, Cardona G, Chin WW (Aug 1990). "Gene expression from the c-erbA alpha/Rev-ErbA alpha genomic locus. ... Chawla A, Lazar MA (Aug 1993). "Induction of Rev-ErbA alpha, an orphan receptor encoded on the opposite strand of the alpha- ... Delerive P, Chin WW, Suen CS (Sep 2002). "Identification of Reverb(alpha) as a novel ROR(alpha) target gene". The Journal of ...
PPARγ) post-transcriptionally, as well as C/EBP alpha in the case of miR-27b. miR-27 can be identified both as an adipogenic ... to negatively regulate adipocyte differentiation through regulation of the peroxisome proliferator-activated receptor gamma ( ... alpha} Expression and Hormone Responsiveness in MCF-7 Breast Cancer Cells". Endocrinology. 151 (6): 2462-73. doi:10.1210/en. ...
PPARγ), PR domain containing 16 (PRDM16), and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α). ... "Exercise Regulation of Marrow Fat in the Setting of PPARγ Agonist Treatment in Female C57BL/6 Mice". Endocrinology. 156 (8): ... These include peroxisome proliferator-activated receptor gamma ( ...
There are three retinoic X receptors (RXR): RXR-alpha, RXR-beta, and RXR-gamma, encoded by the RXRA, RXRB, RXRG genes, ... RXR heterodimerizes with subfamily 1 nuclear receptors including CAR, FXR, LXR, PPAR, PXR, RAR, TR, and VDR. As with other type ... Retinoic acid receptor Retinoid X receptor alpha Retinoid X receptor beta Retinoid X receptor gamma Germain P, Chambon P, ... Plutzky J (April 2011). "The PPAR-RXR transcriptional complex in the vasculature: energy in the balance". Circ. Res. 108 (8): ...
... and 15-HpETE activate to varying degrees PPAR alpha, beta/delta, and gamma. PPARγ activation by agonist RS5444 may inhibit ... Three types of PPARs have been identified: alpha, gamma, and delta (beta): α (alpha) - expressed in liver, kidney, heart, ... PPARα and PPARγ are the molecular targets of a number of marketed drugs. For instance the hypolipidemic fibrates activate PPARα ... "PPAR-gamma Agonists and Their Effects on IGF-I Receptor Signaling: Implications for Cancer". PPAR Res. 2009: 830501. doi: ...
Dalen KT, Ulven SM, Arntsen BM, Solaas K, Nebb HI (May 2006). "PPARalpha activators and fasting induce the expression of ... At 251 position , serine residue was substituted by proline which results in the disruption of predicted alpha helical ... protein adipophilin is expressed in human trophoblasts and is regulated by peroxisomal proliferator-activated receptor-gamma/ ...
... increasing expression of the anti-apoptotic factor PCP4 and antagonizing PPAR-gamma signaling. Progesterone is thought to ... and promotes survival through up-regulating Bcl-2 expression and down-regulating TNF-alpha. Progesterone is believed to ...
... proliferator activated receptor gamma coactivator 1) PPARGC1A (PPARGC1A) PPARGC1B (PPARGC1B) PNRC (proline-rich nuclear ... a novel human coregulator of estrogen receptor alpha". J Biol Chem. 276 (41): 38272-9. doi:10.1074/jbc.M103783200. PMID ... "Structural basis for antagonist-mediated recruitment of nuclear co-repressors by PPARalpha". Nature. 415 (6873): 813-7. doi: ...
... tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat.". Endocrinology 137 (1): 354-66. PMID 8536636. doi: ... O receptor activado polo proliferador do peroxisoma alfa (PPAR-α, PPAR-alfa), tamén chamado NR1C1 (receptor nuclear subfamilia ... O PPAR-alfa é un factor de transcrición e un importante regulador do metabolismo lipídico no fígado. O PPAR-alfa actívase en ... Os agonistas do PPAR-alfa poden ter valor terapéutico para o tratamento da enfermidade do fígado graxo non alcohólica. O PPAR- ...
Zhang R, Zheng F (Sep 2008). "PPAR-gamma and aging: one link through klotho?". Kidney International. 74 (6): 702-4. doi:10.1038 ... Nabeshima Y (Jul 2008). "[Discovery of alpha-Klotho and FGF23 unveiled new insight into calcium and phosphate homeostasis]". ... "alpha-Klotho as a regulator of calcium homeostasis". Science. 316 (5831): 1615-8. Bibcode:2007Sci...316.1615I. doi:10.1126/ ...
Puigserver P, Spiegelman BM (2003). "Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): ... An independent study confirmed the effect of PGC-1 on polarisation of macrophages towards M2 via STAT6/PPAR gamma and ... Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) is a protein that in humans is encoded by the ... "Entrez Gene: PPARGC1A peroxisome proliferator-activated receptor gamma, coactivator 1 alpha". Liang H, Ward WF (December 2006 ...
... of apoptotic cells in mice with macrophage peroxisome proliferator-activated receptor gamma or retinoid X receptor alpha ... Nov 2009). "PPAR-delta senses and orchestrates clearance of apoptotic cells to promote tolerance". Nat Med. 15 (11): 1266-72. ...
The interaction of CaMKK2 with AMPK only involves the alpha and beta subunits of AMPK (AMPK gamma is absent from the CaMKK2 ... PPARalpha, PGC-1, UCP-3, cytochrome C and TFAM. AMPK activity increases with exercise and the LKB1/MO25/STRAD complex is ... STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade". J. Biol. 2 (4): 28. doi ... Cheung PC, Salt IP, Davies SP, Hardie DG, Carling D (March 2000). "Characterization of AMP-activated protein kinase gamma- ...
... gamma) and retinoic acid receptors (-alpha,-beta,-gamma) in normal human skin: an immunohistological evaluation". Histochem. J ... Wang Q, Fujii H, Knipp GT (2003). "Expression of PPAR and RXR isoforms in the developing rat and human term placentas". ... Retinoic acid receptor gamma (RXR-gamma), also known as NR2B3 (nuclear receptor subfamily 2, group B, member 3) is a nuclear ... "Immunohistochemical detection of the retinoid X receptors alpha, beta, and gamma in human prostate". J. Androl. 24 (1): 113-9. ...
"Assignment of the human genes for hepatocyte nuclear factor 3-alpha, -beta, and -gamma (HNF3A, HNF3B, HNF3G) to 14q12-q13, ... Hepatocyte nuclear factor 3-gamma (HNF-3G), also known as forkhead box protein A3 (FOXA3) or transcription factor 3G (TCF-3G) ... regulation of human CYP3A4 basal expression by CCAAT enhancer-binding protein alpha and hepatocyte nuclear factor-3 gamma". Mol ...
... which are all downstream targets of PPAR-alpha or PPAR-gamma, in patients with type 2 diabetes. ... Introduction: Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-alpha agonist which showed beneficial effects ...
PPAR-alpha) and PPAR-gamma: effect of PPAR-alpha activation on abnormal lipid metabolism in liver of Zucker fatty rats. ... a dual activator of PPAR-alpha and PPAR-gamma. Eur. J. Pharmacol., 491 (2-3): 195-206. [PMID:15140637] ... 2001) Disturbances in the normal regulation of SREBP-sensitive genes in PPAR alpha-deficient mice. J. Lipid Res., 42 (3): 328- ... peroxisome proliferator activated receptor alpha 32. Rat. 468. 7q34. Ppara peroxisome proliferator activated receptor alpha 26 ...
Peroxisome proliferator-activated receptor gamma coactivator 1-beta (PPAR gamma coactivator-1beta) (PPARGC-1-beta) (PGC-1-beta ... Actin, alpha cardiac muscle 1 (Alpha-cardiac actin). [Source:Uniprot/SWISSPROT;Acc:P68035]. ... Double C2-like domain-containing protein alpha (Doc2-alpha). [Source:Uniprot/SWISSPROT;Acc:P70611]. ... sodium channel, voltage-gated, type VIII, alpha polypeptide [Source:RefSeq_peptide;Acc:NP_062139]. ...
Increases mRNA Levels of PPAR Gamma and Inhibits Alpha Amylase and Alpha Glucosidase. David Mizael Ortíz-Martinez,1 Catalina ... on mRNA expression of PPARγ on cell line 3T3-L1, its effect on alpha amylase and alpha glucosidase, lipid accumulation during ... C. Janani and B. D. Ranjitha, "PPAR gamma gene-a review," Diabetes and Metabolic Syndrome: Clinical Research and Reviews, vol. ... The search for new drugs that act against peroxisome proliferator-activated receptor gamma (PPARγ) is very important because ...
RXR alpha Nuclear Receptor Complex on DNA bound with Rosiglitazone, 9-cis Retinoic Acid and NCOA2 Peptide ... PPAR-gamma and RXR-alpha form a non-symmetric complex, allowing the ligand-binding domain (LBD) of PPAR-gamma to contact ... Three interfaces link PPAR-gamma and RXR-alpha, including some that are DNA dependent. The PPAR-gamma LBD cooperates with both ... Intact PPAR gamma - RXR alpha Nuclear Receptor Complex on DNA bound with Rosiglitazone, 9-cis Retinoic Acid and NCOA2 Peptide. ...
PPAR-alpha is involved in the regulation of fatty acid (FA) uptake and oxidation, inflam.. ... Synthetic PPAR-alpha or PPAR-gamma agonists have been widely used in the treatment of dyslipidaemia, hyperglycaemia and their ... Given the favourable metabolic effects of both PPAR-alpha and PPAR-gamma activators, as well as their potential to modulate ... To date, a medication that may combine the beneficial metabolic effects of PPAR-alpha and PPAR-gamma activation with fewer ...
... alpha/delta/gamma protein expressions were detected by immunohistochemistry. The retina of control rats was thicker than that ... obviously increased both PPARalpha and PPARdelta expressions in diabetic retina. Berberine modulates PPARalpha/delta/gamma ... Effect of berberine on PPARalpha/delta/gamma expression in type 2 diabetic rat retinae Yao Xue Xue Bao. 2007 Dec;42(12):1243-9. ...
PPAR-alpha) and PPAR-gamma: effect of PPAR-alpha activation on abnormal lipid metabolism in liver of Zucker fatty rats.. ... PPAR-alpha) and PPAR-gamma: effect of PPAR-alpha activation on abnormal lipid metabolism in liver of Zucker fatty rats. ... PPAR-alpha) and PPAR-gamma: effect of PPAR-alpha activation on abnormal lipid metabolism in liver of Zucker fatty rats. ... PPAR-alpha) and PPAR-gamma: effect of PPAR-alpha activation on abnormal lipid metabolism in liver of Zucker fatty rats. ...
GENFIT: Risk of confusion between PPAR alpha/delta Phase 3 drug candidate elafibranor and PPAR a/d/gamma Phase 2 compound ... but is pharmacologically inactive on PPAR gamma, whereas lanifibranor is a PPAR alpha/delta/gamma. The suffix -fibranor, ... Elafibranor (INN granted in 2015), first-in-class PPAR alpha/delta dual agonist, has shown no PPAR gamma activity nor side ... GENFIT: Risk of confusion between PPAR alpha/delta Phase 3 drug candidate elafibranor and PPAR a/d/gamma Phase 2 compound ...
... ... PPARα and PPARγ are the molecular targets of a number of marketed drugs for the treatment of metabolic syndrome. Green coffee ... Administration of green coffe extract for 9 weeks have beneficial effect in improvement of PPARα and PPARγ gene expression in ... This study aimed to investigate the effect of green coffee extract administration on PPARα and PPARγ gene expression in ...
Conclusion: The sensitivity of aortic rings to alpha-1 and alpha-2 adrenoceptors was decreased in the presence of pioglitazone ... Concomitant use of PPAR-gamma agonists, thiazolidinediones, and angiotensin receptor blockers may be effective treatment for ... and the alpha-2 agonist, clonidine, in L-NAME-induced hypertensive, STZ-induced diabetic, and hypertensive diabetic rats. ... study was to investigate the effects of pioglitazone and losartan pre-treatment on the aortic contractile response to the alpha ...
In cell-based assays, MK-0767 produced potent activation of human PPARgamma and PPARalpha with a gamma:alpha potency ratio of ... We conclude that MK-0767 is a potent dual PPARalpha/gamma agonist with robust insulin sensitizing and hypolipidemic activities. ... approximately 2. The dual agonist induced high affinity interactions of PPARalpha and PPARgamma with the transcriptional ... In cell-based assays, MK-0767 produced potent activation of human PPARgamma and PPARalpha with a gamma:alpha potency ratio of ...
Peroxisome proliferator activated receptor-gamma, leptin and tumor necrosis factor-alpha mRNA expression during very low ... but in which PPARγ1 was found to increase in BAT, was called the PPARγ hypomorphic mouse (PPARγhyp/hyp) 186. PPAR hyp/hyp mice ... Alternative promoter usage gives rise to two PPARγ isoforms. PPARγ1 is the ubiquitous isoform found in all PPARγ-expressing ... In the studies discussed above, both isoforms PPARγ1 and PPARγ2 were deleted. When PPARγ2 alone is selectively disrupted, the ...
Mouse monoclonal PPAR gamma 1+2 antibody [A3409A]. Validated in WB, IP, ELISA, IHC, ChIP and tested in Mouse, Rat, Human. Cited ... The primary ab2779 PPAR alpha antibody [3B6/PPAR] The secondary Ab DyLight® 488 goat anti-mouse IgG (H+L) (ab96879) Isotype ... Immunoprecipitation analysis using Fluorescence labeled PPAR gamma generated in vitro translation. Anti-PPAR gamma antibody ( ... Now I would like to expand my experiment and analyse PPAR-delta and PPAR-gamma in the same cells and I will use flow cytometry ...
3B6/PPAR). Validated: WB, ChIP, Flow, GS, ICC/IF, IHC, IHC-P, IP. Tested Reactivity: Human, Mouse, Rat, and more. 100% ... PGC-1 alpha (PGC1A or PPAR gamma coactivator 1-alpha) is a transcriptional co-activator for steroid receptors and nuclear ... Home » PPAR alpha/NR1C1 » PPAR alpha/NR1C1 Antibodies » PPAR alpha/NR1C1 Antibody (3B6/PPAR) ... Additional PPAR alpha/NR1C1 Products. PPAR alpha/NR1C1 NB300-537 * PPAR alpha/NR1C1 Antibodies ...
PPAR-alpha and PPAR-gamma are the molecular targets of a number of marketed drugs. The main classes of PPAR agonists are: PPARα ... PPARγ (gamma) is the main target of the drug class of thiazolidinediones (TZDs), used in diabetes mellitus and other diseases ... PPARδ (delta) is the main target of a research chemical named GW501516. It has been shown that agonism of PPARδ changes the ... A fourth class of dual PPAR agonists, so-called glitazars, which bind to both the α and γ PPAR isoforms, are currently under ...
PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ... PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ... Research presented concerns the expression of peroxisome proliferator-activated receptors (PPAR)- alpha and gamma in human ... The role of PPAR-gamma in macrophage differentiation and cholesterol uptake. Article Abstract:. Research presented concerns the ...
The peroxisome proliferator-activated receptor (PPAR) gamma co-activator 1 alpha (PGC-1 ), a signal-sensing transcriptional co- ... Long-term caloric restriction up-regulates PPAR gamma co-activator 1 alpha (PGC-1 ) expression in mice. ... Long-term caloric restriction up-regulates PPAR gamma co-activator 1 alpha (PGC-1 ) expres ...
The estrogen-related receptor alpha (ERR alpha) functions in PPAR gamma coactivator 1 alpha (PGC-1 alpha)-induced mitochondrial ... Estrogen-related receptor alpha (ERRalpha) is one of the first orphan nuclear receptors to be identified, yet its physiological ... peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha], and that it regulates the expression of genes ...
There was an improvement in glucose homeostasis and pro-inflammatory profile-related overexpression of PPAR-γ. Our data ... inflammation and insulin resistance associated with the induction of PPAR-alpha and PPAR-gamma expression.. mai 13, 2013. av ... There was an improvement in glucose homeostasis and pro-inflammatory profile-related overexpression of PPAR-γ.» ...
Pharmacologic and stress induced regulation of the mitochondrial biogenesis regulator PPAR-[gamma]-coactivator-1[alpha] in ... Pharmacologic and stress induced regulation of the mitochondrial biogenesis regulator PPAR-[gamma]-coactivator-1[alpha] in ... Add tags for Pharmacologic and stress induced regulation of the mitochondrial biogenesis regulator PPAR-[gamma]-coactivator-1[ ... Post a Comment for Pharmacologic and stress induced regulation of the mitochondrial biogenesis regulator PPAR-[gamma]- ...
PPAR alpha / genetics * PPAR gamma / genetics * Prostaglandin-Endoperoxide Synthases / metabolism * RNA, Messenger / analysis ...
"Structure of the intact PPAR-gamma-RXR-alpha nuclear receptor complex on DNA". Nature. 456 (7220): 350-356. doi:10.1038/ ... The structure of the LBD is referred to as an alpha helical sandwich fold in which three anti parallel alpha helices (the " ... Some of these receptors such as FXR, LXR, and PPAR bind a number of metabolic intermediates such as fatty acids, bile acids and ... Retinoids can bind mammalian receptors other than RAR and RXR such as, PPAR, RORb, or COUP-TFII. Furthermore, RXR is sensitive ...
Based on PPAR reporter assays, VPA is classified as a "triple ppar-alpha, -beta/delta, -gamma agonist" [45]. Ppard regulates ... PPARα, PPARβ/δ (PPARD), and PPARγ, each having different expression and biological activities [48]. PPARα is mainly expressed ... Peroxisome proliferative activated receptor, gamma, coactivator 1 alpha. 10548996. 0.062377. 2.0. Slco1a4. Solute carrier ... PPARα-PPARγ coactivator), and lipin-1 refers to them as therapeutic targets in the prevention of dyslipidemia [51]. It was ...
PPAR-gamma coactivator-1-alpha expression. [ Time Frame: One to eight months. ]. ...
  • The sensitivity of aortic rings to alpha-1 and alpha-2 adrenoceptors was decreased in the presence of pioglitazone and/or losartan in diabetic and hypertensive rats. (journals.co.za)
  • We conclude that even though WY14643 and pioglitazone, representing PPAR-alpha and PPAR-gamma activation, respectively, may alter muscle lipid supply by different mechanisms, both significantly improve muscle insulin action in the high fat-fed rat model of insulin resistance, and this effect is proportional to the degree to which they reduce muscle lipid accumulation. (garvan.org.au)
  • We show here that ERRalpha is an effector of the transcriptional coactivator PGC-1alpha [peroxisome proliferator-activated receptor gamma (PPARgamma) coactivator 1alpha], and that it regulates the expression of genes involved in oxidative phosphorylation and mitochondrial biogenesis. (scripps.edu)
  • Title: PGC-1 alpha regulates HO-1 expression, mitochondrial dynamics and biogenesis: Role of epoxyeicosatrienoic acid. (nih.gov)
  • Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPAR γ modulators. (nature.com)