One of the PPAR nuclear transcription factors.
A nuclear transcription factor. It is activated by PROSTACYCLIN.
Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons.
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.
Uptake of substances through the SKIN.
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.
The application of drug preparations to the surfaces of the body, especially the skin (ADMINISTRATION, CUTANEOUS) or mucous membranes. This method of treatment is used to avoid systemic side effects when high doses are required at a localized area or as an alternative systemic administration route, to avoid hepatic processing for example.
A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.
The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. Proteolytic processing of the precursor form by CASPASE 1 results in release of the active form of interleukin-1beta from the membrane.
Drugs that bind to and activate dopamine receptors.
An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.
One of two major pharmacologically defined classes of adrenergic receptors. The beta adrenergic receptors play an important role in regulating CARDIAC MUSCLE contraction, SMOOTH MUSCLE relaxation, and GLYCOGENOLYSIS.
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).
Endogenous compounds and drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA).
The relationship between the dose of an administered drug and the response of the organism to the drug.
An integrin beta subunit of approximately 85-kDa in size which has been found in INTEGRIN ALPHAIIB-containing and INTEGRIN ALPHAV-containing heterodimers. Integrin beta3 occurs as three alternatively spliced isoforms, designated beta3A-C.
Drugs that selectively bind to and activate beta-adrenergic receptors.
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.
Drugs that bind to and activate nicotinic cholinergic receptors (RECEPTORS, NICOTINIC). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission.
Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.
Drugs that bind to and activate adrenergic receptors.
Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate.
A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-2 receptors are more sensitive to EPINEPHRINE than to NOREPINEPHRINE and have a high affinity for the agonist TERBUTALINE. They are widespread, with clinically important roles in SKELETAL MUSCLE; LIVER; and vascular, bronchial, gastrointestinal, and genitourinary SMOOTH MUSCLE.
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.
Established cell cultures that have the potential to propagate indefinitely.
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.
Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.
A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT2 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT2 receptor subtypes.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT1 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT1 receptor subtypes.
Drugs that bind to and activate histamine receptors. Although they have been suggested for a variety of clinical applications histamine agonists have so far been more widely used in research than therapeutically.
Compounds that bind to and activate ADRENERGIC BETA-3 RECEPTORS.
Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.
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.
Endogenous compounds and drugs that bind to and activate GABA-A RECEPTORS.
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.
Also known as CD104 antigen, this protein is distinguished from other beta integrins by its relatively long cytoplasmic domain (approximately 1000 amino acids vs. approximately 50). Five alternatively spliced isoforms have been described.
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)
Drugs that bind to and activate cholinergic receptors.
Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.
A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The adrenergic beta-1 receptors are equally sensitive to EPINEPHRINE and NOREPINEPHRINE and bind the agonist DOBUTAMINE and the antagonist METOPROLOL with high affinity. They are found in the HEART, juxtaglomerular cells, and in the central and peripheral nervous systems.
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.
Integrin beta chains combine with integrin alpha chains to form heterodimeric cell surface receptors. Integrins have traditionally been classified into functional groups based on the identity of one of three beta chains present in the heterodimer. The beta chain is necessary and sufficient for integrin-dependent signaling. Its short cytoplasmic tail contains sequences critical for inside-out signaling.
An antilipemic agent which reduces both CHOLESTEROL and TRIGLYCERIDES in the blood.
Compounds that bind to and activate ADRENERGIC ALPHA-1 RECEPTORS.
Drugs that selectively bind to and activate alpha adrenergic receptors.
A 44-kDa highly glycosylated plasma protein that binds phospholipids including CARDIOLIPIN; APOLIPOPROTEIN E RECEPTOR; membrane phospholipids, and other anionic phospholipid-containing moieties. It plays a role in coagulation and apoptotic processes. Formerly known as apolipoprotein H, it is an autoantigen in patients with ANTIPHOSPHOLIPID ANTIBODIES.
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.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
Drugs that bind to and activate excitatory amino acid receptors.
A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). The beta-3 adrenergic receptors are the predominant beta-adrenergic receptor type expressed in white and brown ADIPOCYTES and are involved in modulating ENERGY METABOLISM and THERMOGENESIS.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
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.
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.
Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).
Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.
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.
The rate dynamics in chemical or physical systems.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Benzopyrans saturated in the 2 and 3 positions.
Compounds that interact with and stimulate the activity of CANNABINOID RECEPTORS.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
One of the ESTROGEN RECEPTORS that has greater affinity for ISOFLAVONES than ESTROGEN RECEPTOR ALPHA does. There is great sequence homology with ER alpha in the DNA-binding domain but not in the ligand binding and hinge domains.
A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.
Proteins prepared by recombinant DNA technology.
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.
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.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
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.
Drugs that selectively bind to and activate ADENOSINE A3 RECEPTORS.
AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives.
A class of opioid receptors recognized by its pharmacological profile. Kappa opioid receptors bind dynorphins with a higher affinity than endorphins which are themselves preferred to enkephalins.
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.
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.
Elements of limited time intervals, contributing to particular results or situations.
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.
Integrin beta-1 chains which are expressed as heterodimers that are noncovalently associated with specific alpha-chains of the CD49 family (CD49a-f). CD29 is expressed on resting and activated leukocytes and is a marker for all of the very late activation antigens on cells. (from: Barclay et al., The Leukocyte Antigen FactsBook, 1993, p164)
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
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.
An antilipemic agent that lowers CHOLESTEROL and TRIGLYCERIDES. It decreases LOW DENSITY LIPOPROTEINS and increases HIGH DENSITY LIPOPROTEINS.
A class of opioid receptors recognized by its pharmacological profile. Delta opioid receptors bind endorphins and enkephalins with approximately equal affinity and have less affinity for dynorphins.
Endogenous compounds and drugs that bind to and activate GABA-B 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.
Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT4 RECEPTORS.
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.
Partially saturated 1,2,3,4-tetrahydronaphthalene compounds.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
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.
Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.
Substances which lower blood glucose levels.
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.
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.-.
A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D2-class receptor genes contain INTRONS, and the receptors inhibit ADENYLYL CYCLASES.
A short-acting beta-2 adrenergic agonist that is primarily used as a bronchodilator agent to treat ASTHMA. Albuterol is prepared as a racemic mixture of R(-) and S(+) stereoisomers. The stereospecific preparation of R(-) isomer of albuterol is referred to as levalbuterol.
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.
Peptides composed of between two and twelve amino acids.
A nucleoside that is composed of ADENINE and D-RIBOSE. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter.
An enkephalin analog that selectively binds to the MU OPIOID RECEPTOR. It is used as a model for drug permeability experiments.
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.
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.
Compounds that bind to and activate PURINERGIC RECEPTORS.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives.
A family of hexahydropyridines.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Cell membrane proteins that bind opioids and trigger intracellular changes which influence the behavior of cells. The endogenous ligands for opioid receptors in mammals include three families of peptides, the enkephalins, endorphins, and dynorphins. The receptor classes include mu, delta, and kappa receptors. Sigma receptors bind several psychoactive substances, including certain opioids, but their endogenous ligands are not known.
Compounds having the cannabinoid structure. They were originally extracted from Cannabis sativa L. The most pharmacologically active constituents are TETRAHYDROCANNABINOL; CANNABINOL; and CANNABIDIOL.
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.
Drugs that bind to but do not activate serotonin receptors, thereby blocking the actions of serotonin or SEROTONIN RECEPTOR AGONISTS.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Adherence of cells to surfaces or to other cells.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
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.
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.
Compounds that bind to and activate ADRENERGIC BETA-1 RECEPTORS.
A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)
Agents that increase calcium influx into calcium channels of excitable tissues. This causes vasoconstriction in VASCULAR SMOOTH MUSCLE and/or CARDIAC MUSCLE cells as well as stimulation of insulin release from pancreatic islets. Therefore, tissue-selective calcium agonists have the potential to combat cardiac failure and endocrinological disorders. They have been used primarily in experimental studies in cell and tissue culture.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.
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.
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.
An adrenergic beta-2 agonist that is used as a bronchodilator and tocolytic.
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.
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic.
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.
A moderately lipophilic beta blocker (ADRENERGIC BETA-ANTAGONISTS). It is non-cardioselective and has intrinsic sympathomimetic actions, but little membrane-stabilizing activity. (From Martindale, The Extra Pharmocopoeia, 30th ed, p638)
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
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).
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.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
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.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.
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.
A selective D1 dopamine receptor agonist used primarily as a research tool.
A multi-functional catenin that participates in CELL ADHESION and nuclear signaling. Beta catenin binds CADHERINS and helps link their cytoplasmic tails to the ACTIN in the CYTOSKELETON via ALPHA CATENIN. It also serves as a transcriptional co-activator and downstream component of WNT PROTEIN-mediated SIGNAL TRANSDUCTION PATHWAYS.
An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.
Compounds with BENZENE fused to AZEPINES.
A class of cell surface receptors that prefer ADENOSINE to other endogenous PURINES. Purinergic P1 receptors are widespread in the body including the cardiovascular, respiratory, immune, and nervous systems. There are at least two pharmacologically distinguishable types (A1 and A2, or Ri and Ra).
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.
Brain waves with frequency between 15-30 Hz seen on EEG during wakefulness and mental activity.
Drugs that mimic the effects of parasympathetic nervous system activity. Included here are drugs that directly stimulate muscarinic receptors and drugs that potentiate cholinergic activity, usually by slowing the breakdown of acetylcholine (CHOLINESTERASE INHIBITORS). Drugs that stimulate both sympathetic and parasympathetic postganglionic neurons (GANGLIONIC STIMULANTS) are not included here.
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.
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
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.
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
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.
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.
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.
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.
A dopamine D2/D3 receptor agonist.
A class of saturated compounds consisting of two rings only, having two or more atoms in common, containing at least one hetero atom, and that take the name of an open chain hydrocarbon containing the same total number of atoms. (From Riguady et al., Nomenclature of Organic Chemistry, 1979, p31)
A cell line derived from cultured tumor cells.
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.
A substituted phenylaminoethanol that has beta-2 adrenomimetic properties at very low doses. It is used as a bronchodilator in asthma.
Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.
A disulfide opioid pentapeptide that selectively binds to the DELTA OPIOID RECEPTOR. It possesses antinociceptive activity.
Substances that lower the levels of certain LIPIDS in the BLOOD. They are used to treat HYPERLIPIDEMIAS.
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).)
An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.
A DNA repair enzyme that catalyzes DNA synthesis during base excision DNA repair. EC
A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system.
A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research.
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.
One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology.
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.
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.
A subfamily of G-PROTEIN-COUPLED RECEPTORS that bind the neurotransmitter DOPAMINE and modulate its effects. D1-class receptor genes lack INTRONS, and the receptors stimulate ADENYLYL CYCLASES.
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.
Compounds bind to and activate ADRENERGIC BETA-2 RECEPTORS.
Agents inhibiting the effect of narcotics on the central nervous system.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
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.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.
Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)
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.
Billin AN (October 2008). "PPAR-beta/delta agonists for Type 2 diabetes and dyslipidemia: an adopted orphan still looking for a ... 1,000 fold selectivity over PPARα and PPARγ. In rats, binding of GW501516 to PPARδ recruits the coactivator PGC-1α. The PPARδ/ ... GW501516 is a selective agonist (activator) of the PPARδ receptor. It displays high affinity (Ki = 1 nM) and potency (EC50 = 1 ... a PPAR delta agonist (PDF). 48th Annual Meeting of the Society of Toxicology. Baltimore: Society of Toxicology. p. 105. ...
... (also known as GW610742) is a PPARδ/β agonist that is investigated for drug use by GlaxoSmithKline. GW501516 Elafibranor ... July 2009). "Peroxisome proliferator-activated receptor beta stimulation induces rapid cardiac growth and angiogenesis via ... "Novel selective small molecule agonists for peroxisome proliferator-activated receptor δ (PPARδ)--synthesis and biological ... July 2008). "Modulation of LPS-induced pulmonary neutrophil infiltration and cytokine production by the selective PPARbeta/ ...
Both PPAR-β/δ and AMPK agonists are regarded as exercise mimetics. In adipose tissue PPAR-β/δ increases both oxidation as well ... Peroxisome proliferator-activated receptor beta or delta (PPAR-β or PPAR-δ), also known as NR1C2 (nuclear receptor subfamily 1 ... PPARδ favours tumour angiogenesis. Several high affinity ligands for PPARδ have been developed, including GW501516 and GW0742, ... 2001). "Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)α and PPARβ mutant mice". J. Cell Biol ...
PPAR-alpha agonists may carry therapeutic value for the treatment of non-alcoholic fatty liver disease. PPAR-alpha may also be ... tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat". Endocrinology. 137 (1): 354-66. doi:10.1210/endo.137.1. ... Staels B, Maes M, Zambon A (September 2008). "Peroxisome Fibrates and future PPARα agonists in the treatment of cardiovascular ... PPAR-α is a transcription factor and a major regulator of lipid metabolism in the liver. PPAR-alpha is activated under ...
Chigurupati S, Dhanaraj SA, Balakumar P (May 2015). "A step ahead of PPARγ full agonists to PPARγ partial agonists: therapeutic ... "15-hydroxyeicosatetraenoic acid is a preferential peroxisome proliferator-activated receptor beta/delta agonist". Molecular ... Three subtypes of PPARs are known: PPAR-alpha, PPAR-delta, and PPAR-gamma. The protein encoded by this gene is PPAR-gamma and ... PPAR-gamma agonists have been used in the treatment of hyperlipidaemia and hyperglycemia. PPAR-gamma decreases the inflammatory ...
... is a peroxisome proliferator-activated receptor alpha (PPARα) agonist that is under experimental investigation ... tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat". Endocrinology. 137 (1): 354-66. 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 ... PPARα, a PPAR subtype, controls the expression of genes involved in cardiac fatty acid utilization, and its activation, ...
... and 15-HpETE activate to varying degrees PPAR alpha, beta/delta, and gamma. PPARγ activation by agonist RS5444 may inhibit ... After PPARδ (delta) was identified in humans in 1992, it turned out to be closely related to the PPARβ (beta) previously ... 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: ...
Adiponectin induces ABCA1-mediated reverse cholesterol transport by activation of PPAR-γ and LXRα/β. LXR agonists are effective ... Treatment with T0901317 decreases amyloidal beta production in an Alzheimer's disease mouse model. However, both T0901317 and ... Some synthetic LXR agonists have been developed, including nonsteroidal LXR agonists T0901317 and GW3965. The hexacyclic ... The LXR/RXR heterodimer can be activated with either an LXR agonist (oxysterols) or a RXR agonist (9-cis-13,14-dihydroretinoic ...
Based on its mechanism, PEA may be considered likely to interact with other PPARagonists used to treat high triglycerides; ... Its activity as an inhibitor of inflammation counteracts reactive astrogliosis induced by beta-amyloid peptide, in a model ... the latter related to PEA as an endogenous PPAR-alpha agonist. In 2012 it became clear that PEA can also reduce reperfusion ... A main target of PEA is proposed to be the peroxisome proliferator-activated receptor alpha (PPAR-α). PEA also has affinity to ...
Staels B, Maes M, Zambon A (September 2008). "Peroxisome Fibrates and future PPARα agonists in the treatment of cardiovascular ... 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 ...
These drugs act as agonists of the PPAR-γ receptor leading to insulin sensitizing effects that can improve glycemic control and ... preserves intact glucose-dependent insulinotropic peptide and improves abnormal glucose tolerance in minipigs with reduced beta ... Substances, such a xenobiotics that target and act as agonists of PPARα, typically act to reduce overall serum concentrations ... Substances that target and act as agonists of PPARγ/RXR complex typically act to increase overall serum concentrations of ...
Specific epoxidation of EET sites produces endogenous PPARα agonists. Decrease release of somatostatin, insulin and glucagon ... EETs are also inactivated by being further metabolized though three other pathways: Beta oxidation, Omega oxidation, and ...
As the beta cells cease to function, insulin and pancreatic GABA are no longer present to suppress the freerunning output of ... Kimball and Murlin coined the term glucagon in 1923 when they initially named the substance the glucose agonist. Cortisol ... PPARγ/retinoid X receptor heterodimer. Increased free fatty acids and keto acids into the blood. Increased urea production ... and alpha cells are distributed throughout the islet in close proximity to beta cells. Glucagon is also produced by alpha cells ...
... or beta-2 agonists (see adrenergic beta-agonist). Andro, DHEA, stanozolol, testosterone, and nandrolone, or derivates (see ... Metabolic modulators including peroxisome proliferator-activated receptor delta (PPARδ) agonists (e.g., GW 1516), PPARδ-AMP- ... Beta-2 agonists can act as bronchodilators and increase heart rates, in addition to their mild androgenic effects. Other banned ... All beta-2 agonists and their D- and L-isomers, are banned. However, formoterol, salbutamol, salmeterol, and terbutaline may be ...
Competitive antagonist Intrinsic sympathomimetic activity of beta blockers Inverse agonist Mixed agonist/antagonist Calvey N, ... a non-adipogenic PPARγ agonist from nature". Biochimica et Biophysica Acta (BBA) - General Subjects. 1830 (10): 4813-9. doi: ... the partial agonist actually acts as a competitive antagonist, competing with the full agonist for receptor occupancy and ... In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the ...
... is also an agonist of the PPARα and PPARγ nuclear receptors. WIN 55,212-2 reduces voluntary wheel running in ... WIN 55,212-2, along with HU-210 and JWH-133, may prevent the inflammation caused by amyloid beta proteins involved in ... WIN 55,212-2 is a potent cannabinoid receptor agonist that has been found to be a potent analgesic in a rat model of ... In the United States, all CB1 receptor agonists of the 3-(1-naphthoyl)indole class such as WIN 55,212-2 are Schedule I ...
These studies determined that PFOA and PFOS acted as peroxisome proliferator-activated receptor (PPAR) agonists, increasing ... Elevated levels of hydrogen sulfide result which reduce beta-oxidation and thus nutrient production leading to a breakdown of ... highlighting significantly reduced PPAR expression and alluding to PPAR independent pathways predominating over lipid ... Both mechanisms start by proposing that PROA exposure results in increased PPAR alpha activation in the liver which increases ...
Low oxygen pressure (hypoxia), fatty acids, and beta-adrenergic agonists stimulate HILPDA expression. Nearly all cells have the ... PPAR) target involved in hepatic triglyceride secretion". J Biol Chem. 289 (28): 19279-93. doi:10.1074/jbc.M114.570044. PMC ...
In this figure, running exercise is shown to suppress MAT despite PPARγ agonist. Fat binder osmium is imaged via μCT (A ) in n ... the role of PPAR-gamma2 transcription factor and TGF-beta/BMP signaling pathways". Aging Cell. 3 (6): 379-89. doi:10.1111/j. ... August 2015). "Exercise Regulation of Marrow Fat in the Setting of PPARγ Agonist Treatment in Female C57BL/6 Mice". ... This aging-related biasing of MSC away from osteoblast lineage may represent higher basal PPARγ expression or decreased Wnt10b ...
... not all PPAR agonists are fibrates, not all triglyceride lowering agents are PPAR agonists, and not all drugs used to treat ... inhibitor Angiotensin II receptor antagonist ACE inhibitor Alpha-adrenergic agonist Beta blocker Dopamine agonist Dopamine ... For receptors, these activities include agonist, antagonist, inverse agonist, or modulator. Enzyme target mechanisms include ... PPAR agonist) and mode of action (reducing blood triglycerides), and that are used to prevent and treat the same disease ( ...
... agonists bind to a membrane GLP receptor. As a consequence, insulin release from the pancreatic beta cells is increased. ... Thiazolidinediones (TZDs), also known as "glitazones," bind to PPARγ, a type of nuclear regulatory protein involved in ... Amylin agonist analogues slow gastric emptying and suppress glucagon. They have all the incretins actions except stimulation of ... Exenatide is not an analogue of GLP but rather a GLP agonist. Exenatide has only 53% homology with GLP, which increases its ...
... has also been identified as a direct agonist of PPARα. An off-target effect has been demonstrated at high ... of etomoxir reveals that carnitine palmitoyltransferase I is essential for cancer cell proliferation independent of beta- ...
PPARγ). This activation does not proceed through OXER1; rather, it involves the direct binding of the oxo analog to PPARγ with ... These compounds are termed 5-oxo-ETE analogs or members of the 5-oxo-ETE family of agonists. 5-HETE and 5-hydroxy-15(S)- ... and G beta-gamma complex (Gβγ). When bound by 5-oxo-ETE, the OXER1 triggers this G protein complex to dissociate into its Gαi ... The Activation of OXER1 receptor and PPARγ by the oxo analogs can have opposing effects on cell function. For example, 5-oxo- ...
"Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review". Biochem Pharmacol. 92 (1): 73- ... The soil bacterium Bacillus cereus can be used to transform resveratrol into piceid (resveratrol 3-O-beta-D-glucoside). Only a ... a structurally related compound that acts as a dual PPARα/δ agonist Trans-diptoindonesin B, a resveratrol trimer Hopeaphenol, a ... In vitro, resveratrol was shown to act as an agonist of Peroxisome proliferator-activated receptor gamma, a nuclear receptor ...
Though it has not yet been FDA-approved, the PPAR modulator (sometimes referred to as a SARM) GW501516, currently a research ... through beta-hydroxybutyrate coupling the Niacin receptor 1. HDL levels can be increased by smoking cessation, or mild to ... "Effects of peroxisome proliferator-activated receptor alpha/delta agonists on HDL-cholesterol in vervet monkeys". J Lipid Res. ...
"Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): A review". Biochemical Pharmacology. 92 ( ... Genistin is the 7-O-beta-D-glucoside of genistein.[citation needed] Wighteone can be described as 6-isopentenyl genistein ... full agonist or partial agonist of ERα agonist of G protein-coupled estrogen receptor (affinity of 133 nM) activation of ... For example, membrane-bound PPARγ-binding assay showed that genistein can directly interact with the PPARγ ligand binding ...
The carotenes alpha-carotene, beta-carotene, gamma-carotene; and the xanthophyll beta-cryptoxanthin (all of which contain beta- ... The heterodimers of RXR with nuclear receptors other than RAR (i.e. TR, VDR, PPAR, LXR) bind to various distinct response ... Agonists: 9CDHRA. *9-cis-Retinoic acid (alitretinoin). *all-trans-Retinoic acid (tretinoin) ... which possess the enzyme beta-carotene 15,15'-dioxygenase which cleaves beta-carotene in the intestinal mucosa and converts it ...
Kharroubi I, Rasschaert J, Eizirik DL, Cnop M (December 2003). "Expression of adiponectin receptors in pancreatic beta cells". ... serve as receptors for globular and full-length adiponectin and mediate increased AMPK and PPAR-α ligand activities, as well as ... "A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity". Nature. 503 (7477): 493-9. Bibcode:2013Natur. ... "Regulation of adiponectin receptor 1 in human hepatocytes by agonists of nuclear receptors". Biochemical and Biophysical ...
Pioglitazone is an example of a PPAR gamma agonist drug that lowers blood sugar and improves lipid levels. As part of PPAR ... and decreased pancreatic beta cell function due to genetic syndromes or surgical excision. High blood pressure can be due to ... Because PPAR gamma agents work by increasing the amount of healthy, functional fat, decreasing the proportion of sick abdominal ... For example, peroxisome proliferator-activated receptor (PPAR) gamma agents are commonly used drugs to treat type 2 diabetes ...
October 2013). "Inverse PPARβ/δ agonists suppress oncogenic signaling to the ANGPTL4 gene and inhibit cancer cell invasion". ... "Induction of cardiac Angptl4 by dietary fatty acids is mediated by peroxisome proliferator-activated receptor beta/delta and ...
Polycyclic aromatic hydrocarbons (e.g., 3-methylcholanthrene, benzo[a]pyrene, benzanthracenes, benzoflavones (e.g., beta- ... Agonists: Arachidonic acid metabolites (e.g., lipoxin A4, prostaglandin G2). *Dietary carotenoids ... PPAR. See here instead.. PXR. See here instead.. Retinoid. See here instead. ...
"Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review". Biochemical Pharmacology. 92 ...
Conversely not all PPAR agonists are fibrates, not all triglyceride lowering agents are PPAR agonists, and not all drugs that ... Beta blocker. *Dopamine agonist. *Dopamine antagonist. *Incretin mimetic. *Nonsteroidal anti-inflammatory drug − cyclooxygenase ... For receptors, these activities include agonist, antagonist, inverse agonist, or modulator. Enzyme target mechanisms include ... PPAR agonist), mode of action (reducing blood triglycerides), and are used to prevent and to treat the same disease ( ...
A mixture of PCBs such as Aroclor may contain PCB compounds which are known estrogen agonists, but on the other hand are not ... Polycyclic aromatic hydrocarbons (e.g., 3-methylcholanthrene, benzo[a]pyrene, benzanthracenes, benzoflavones (e.g., beta- ... It is important to note that TCDD, along with the other PCDDs, PCDFs and dioxin-like coplanar PCBs are not direct agonists or ... which is neither persistent nor an AH receptor agonist.[14] ... PPAR. See here instead.. PXR. See here instead.. Retinoid. See ...
The compound has been found to act as an agonist of the aryl hydrocarbon receptor.[23] ... Polycyclic aromatic hydrocarbons (e.g., 3-methylcholanthrene, benzo[a]pyrene, benzanthracenes, benzoflavones (e.g., beta- ... PPAR. See here instead.. PXR. See here instead.. Retinoid. See here instead. ...
Prevention of the testosterone flare at the start of gonadotropin-releasing hormone agonist (GnRH agonist) therapy[15][16][17][ ... inhibition of the activation of PPARγ and LXRα at a concentration of 10 μM.[58] The researchers stated that, to the best of ... "Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta" ... DES is an estrogen; specifically, it is a highly potent full agonist of both of the estrogen receptors (ERs).[55][56] It has ...
Fiorucci S, Zampella A, Distrutti E (2012). "Development of FXR, PXR and CAR agonists and antagonists for treatment of liver ... Polycyclic aromatic hydrocarbons (e.g., 3-methylcholanthrene, benzo[a]pyrene, benzanthracenes, benzoflavones (e.g., beta- ... "Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII expression". Gastroenterology. 125 (2): 544-55. doi:10.1016/ ... "Farnesoid X receptor agonists attenuate colonic epithelial secretory function and prevent experimental diarrhoea in vivo". Gut ...
... agonist bromocriptine inhibits glucose-stimulated insulin secretion by direct activation of the α2-adrenergic receptors in beta ... Agonists: 25H/NB series (e.g., 25I-NBF, 25I-NBMD, 25I-NBOH, 25I-NBOMe, 25B-NBOMe, 25C-NBOMe, 25TFM-NBOMe, 2CBCB-NBOMe, 25CN- ... Agonists: 2Cs (e.g., 2C-B, 2C-E, 2C-I, 2C-T-2, 2C-T-7, 2C-T-21) ... Dual PPAR agonists. *Aleglitazar†. *Muraglitazar§. * ... Beta blockers (e.g., alprenolol, carteolol, cyanopindolol, iodocyanopindolol, isamoltane, oxprenolol, penbutolol, pindobind, ...
Lymphotoxin beta receptor. *MCM2. *Microphthalmia-associated transcription factor. *Muscarinic acetylcholine receptor M2 ... BH3 interacting-domain death agonist. *BRAF (gene). *Bone morphogenetic protein 10. *C-Met ...
Dual PPAR agonists. *Aleglitazar†. *Muraglitazar§. *Saroglitazar. *Tesaglitazar§. Secretagogues. K+ATP. Sulfonylureas. *1st ...
PPARγ. *Agonists: 5-Oxo-ETE. *5-Oxo-15-hydroxy-ETE. *15-Deoxy-Δ12,14-prostaglandin J2 ... associated with reduced pro-inflammatory IL-6 and IL-1 levels and increased anti-inflammatory tumor necrosis factor-beta.[37] ...
... selectively binds to sulfonylurea receptors (SUR-1) on the surface of the pancreatic beta-cells. It was shown to ... Hyperglycemic action may be caused by danazol, chlorpromazine, glucocorticoids, progestogens, or β-2 agonists. Its hypoglycemic ... "Gliclazide produces high-affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial ...
A non-adipogenic PPARγ agonist from nature". Biochimica et Biophysica Acta (BBA) - General Subjects. 1830 (10): 4813-4819. doi: ... Tricin 4'-O-(erythro-beta-guaiacylglyceryl) ether. *Tricin 4'-O-(threo-beta-guaiacylglyceryl) ether ... Honokiol was shown to normalize blood glucose levels and prevent body weight gain in diabetic mice by acting as agonist of ... honokiol has been shown to achieve anxiolysis with fewer motor or cognitive side effects than GABAA receptor agonists such as ...
Agonist: A drug with a fast association and a fast dissociation.. *Partial-agonist: A drug with an intermediate association and ... This results in a receptor blockade, inhibiting the binding of agonists and inverse agonists. Receptor antagonists can be ... Full) agonists are able to activate the receptor and result in a strong biological response. The natural endogenous ligand with ... Partial agonists do not activate receptors with maximal efficacy, even with maximal binding, causing partial responses compared ...
Agonist ligands work by inducing a conformation of the receptor which favors coactivator binding (see upper half of the figure ... Some of these receptors such as FXR, LXR, and PPAR bind a number of metabolic intermediates such as fatty acids, bile acids and ... "Identification of farnesoid X receptor beta as a novel mammalian nuclear receptor sensing lanosterol". Molecular and Cellular ... Binding of agonist ligands (see section below) to nuclear receptors induces a conformation of the receptor that preferentially ...
Zuo Y, Qiang L, Farmer SR (March 2006). "Activation of CCAAT/enhancer-binding protein (C/EBP) alpha expression by C/EBP beta ... Choi WY, Giraldez AJ, Schier AF (October 2007). "Target protectors reveal dampening and balancing of Nodal agonist and ... and 222 significantly inhibited adipogenesis and repressed induction of the master regulators PPARγ and CCAAT/enhancer-binding ...
There are 3 PPAR isoforms: α, β/δ and . PPAR, the protagonist of this review, is expressed in adipose tissue, large intestine, ... There are three PPAR isoforms: α, β/δ and γ. PPARγ, the protagonist of this review, ... ... The effects of PPARy agonists, known for their positive activity on type II diabetes mellitus, have been explored and present ... It is the aim of this review to help understanding and developing novel CINP therapeutic strategies integrating PPAR signalling ...
Zhang, L.S.; Wang, S.Q.; Xu, W.R.; Wang, R.L.; Wang, J.F. Scaffold-based pan-agonist design for the PPARalpha, PPARbeta and ... Human Chorionic Gonadotropin Beta Subunit Genes CGB1 and CGB2 are Transcriptionally Active in Ovarian Cancer ... Ma, Y.; Wang, S.Q.; Xu, W.R.; Wang, R.L.; Chou, K.C. Design novel dual agonists for treating type-2 diabetes by targeting ...
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 ... P. Balakumar, M. Rose, S. S. Ganti, P. Krishan, and M. Singh, "PPAR dual agonists: are they opening Pandoras Box?" ... PPARα-PPARγ coactivator), and lipin-1 refers to them as therapeutic targets in the prevention of dyslipidemia [51]. It was ...
PPAR-gamma agonist attenuates renal interstitial fibrosis and inflammation through reduction of TGF-beta. Lab Invest. 2009; 89 ... 37 PPARagonists modulate multiple cellular functions both in a PPAR-γ-dependent and PPAR-γ-independent manner as indicated ... A PPAR-Gamma Agonist Rosiglitazone Suppresses Fibrotic Response in Human Pterygium Fibroblasts by Modulating the p38 MAPK ... A PPAR-Gamma Agonist Rosiglitazone Suppresses Fibrotic Response in Human Pterygium Fibroblasts by Modulating the p38 MAPK ...
Billin AN (October 2008). "PPAR-beta/delta agonists for Type 2 diabetes and dyslipidemia: an adopted orphan still looking for a ... 1,000 fold selectivity over PPARα and PPARγ. In rats, binding of GW501516 to PPARδ recruits the coactivator PGC-1α. The PPARδ/ ... GW501516 is a selective agonist (activator) of the PPARδ receptor. It displays high affinity (Ki = 1 nM) and potency (EC50 = 1 ... a PPAR delta agonist (PDF). 48th Annual Meeting of the Society of Toxicology. Baltimore: Society of Toxicology. p. 105. ...
2010). GW0742, a high affinity PPAR-beta/delta agonist reduces lung inflammation induced by bleomycin instillation in mice. Int ... 1997). Transforming growth factors-beta 1, -beta 2, and -beta 3 stimulate fibroblast procollagen production in vitro but are ... Willis, B. C., and Borok, Z. (2007). TGF-beta-induced EMT: mechanisms and implications for fibrotic lung disease. Am. J. ... Derynck, R., and Zhang, Y. E. (2003). Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425, ...
Apoptotic effect of the selective PPARbeta/delta agonist GW501516 in invasive bladder cancer cells. Tumour Biol. 2016. Abstract ... Meta-analysis of studies with bivariate binary outcomes: a marginal beta-binomial model approach. Stat Med. 2016;35:21-40. ... FOXA1, GATA3 and PPAR Cooperate to Drive Luminal Subtype in Bladder Cancer: A Molecular Analysis of Established Human Cell ...
PPAR Research; Biological sciences Antilipemic agents B cells Development and progression Physiological aspects Cardiovascular ... 4. PPAR[beta]/[delta] Role in Metabolic Diseases The dual PPAR[alpha]/[delta] agonist (GFT-505-Elafibranor) seems to have ... 7. PPAR[gamma] and Tumorigenesis PPAR[gamma] or dual PPAR [alpha]/[gamma] agonists, in rodent carcinogenicity studies, were ... Currently, we know of three different types of PPARs (PPAR[alpha], PPAR[beta]/[delta], and PPAR[gamma]), which present many ...
Di Loreto S, DAngelo B, DAmico MA et al (2007) PPAR beta agonists trigger neuronal differentiation in the human neuroblastoma ... Human microglia expressed PPAR-β and -γ, but not PPAR-α. Interestingly, either antisense knockdown of PPAR-β or antagonism of ... Oxidative metabolism of linoleic acid modulates PPAR-beta/delta suppression of PPAR-gamma activity. Oncogene 25:1225-1241PubMed ... Buchan KW, Hassall DG (2000) PPAR agonists as direct modulators of the vessel wall in cardiovascular disease. Med Res Rev 20: ...
Effect of topical PPARbeta/delta and PPARgamma agonists on plaque psoriasis. A pilot study. Kuenzli, S., Saurat, J.H. ... The present work shows that when mitochondrial beta-oxidation is stimulated by the hypolipemic, non-beta-oxidizable fatty acid ... TTA also activates the other PPARs (e.g., PPAR delta) and this might compensate for deficiency of PPAR alpha [25]. ... Antiproliferative effects of a non-beta-oxidizable fatty acid, tetradecylthioacetic acid, in native human acute myelogenous ...
GW0742, a selective PPAR-beta/delta agonist, contributes to the resolution of inflammation after gut ischemia/reperfusion ... Three isotypes are named by PPARα, PPARβ/δ, and PPARγ. It is reported recently that PPARγ protects against the development of ... Recently, Aleshin et al24,25 considered that PPARβ/δ linked to PPARα and PPARγ and regulated their expression, which ... Peroxisome proliferator-activated receptor (PPAR)β/δ, a possible nexus of PPARα- and PPARγ-dependent molecular pathways in ...
... a PPARα agonist (Berger and Moller, 2002). PPARα is a nuclear hormone receptor that is activated by long chain unsaturated ... 2008) Growth of beta(2)-microglobulin-related amyloid fibrils by non-esterified fatty acids at a neutral pH The Biochemical ... PPARγ agonists accelerate oligodendrocyte maturation (De Nuccio et al., 2011). Both GW7647 and oleic acid function as PPAR ... 2007) PPARbeta agonists trigger neuronal differentiation in the human neuroblastoma cell line SH-SY5Y Journal of Cellular ...
Effects of PPAR agonists on the rate of glucose uptake in VECs.. The potential role of PPARα, -γ, or -δ in the regulation of ... mediator 4-hydroxynonenal is an intracellular agonist of the nuclear receptor peroxisome proliferator-activated receptor-beta/ ... anti-PPARα, -PPARγ, and -PPARδ (Cayman Chemicals, Ann Arbor, MI); anti-PPARδ (H-74; Santa Cruz Biotechnology, Santa Cruz, CA); ... Recently, Gross and Staels (40) have stressed the need for the development of novel PPARα and PPARγ agonists for the treatment ...
Effects of the PPARbeta agonist GW501516 in an in vitro model of brain inflammation and antibody‐induced demyelination. J. ... Astrocyte‐derived ATP induces vesicle shedding and IL‐1 beta release from microglia. J. Immunol. 174:7268‐7277. ...
PPAR-gamma activation degrades amyloid-beta plaque, a key molecule linked to the development of Alzheimers disease. ... This is one of the reasons why cannabidiol, a PPAR-gamma agonist, may be a useful remedy for Alzheimers patients. ... Polymorphisms or mutations in the gene encoding PPAR-alpha can result in deficient PPAR-alpha signaling, which has been linked ... As an aside, PPAR receptors also regulate genes that are involved in energy homeostasis, lipid uptake, insulin sensitivity, and ...
PPAR-Alpha. PPAR-alpha regulates the expression of genes involved in fatty acid beta-oxidation and is a major regulator of ... SesaGLOW is a PPAR-alpha agonist, which means that (simply put) SesaGlow will help regulate and enhance your results during a ... Helps Increase Peroxisomal Beta Oxidation. - Effective When Cutting or Bulking. - Helps Maintain Healthy Lipid Profile. - ... Sesamins unique effects on PPAR-alpha and prostoglandins classify it as a Nutrient Partitioning agent / compound.. Hormone ...
Effect of PPAR-beta/delta agonist GW0742 treatment in the acute phase response and blood-brain barrier permeability following ... PPAR agonists as therapeutics for CNS trauma and neurological diseases. ASN Neuro 2013;5(5):e00129.CrossRefPubMedPubMedCentral ... Rosiglitazone, a PPAR gamma agonist, attenuates inflammation after surgical brain injury in rodents (Volume 1215) (2008).Google ... Gautier S, Ouk T, Pétrault M, Pétrault O, Bérézowski V, Bordet R. PPAR-alpha agonist used at the acute phase of experimental ...
The PPAR beta/delta Agonist GW0742 Relaxes Pulmonary Vessels and Limits Right Heart Hypertrophy in Rats with Hypoxia-Induced ...
These data identify PPARβ/δ and PPARγ as putative mammalian 3OC12-HSL receptors and suggest that PPARγ agonists may be employed ... Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and - ... RT-PCR assays were performed using primers specific for three PPAR (PPARα, PPARβ/δ, and PPARγ) genes (NR1C1, NR1C2, and NR1C3 ... PPARβ/δ) and PPARγ were expressed. 3OC12-HSL functioned as an agonist of PPARβ/δ transcriptional activity and an antagonist of ...
... in a beta-scintillation counter (Tri-Carb 2300TR; Packard Instrument Company Inc.). We calculated TG-specific radioactivity ... reported that fenofibrate, a PPARα agonist, lowered apoC-III production in humans (71). Effects of PPARγ agonists on apoC-III ... LPL is a PPARγ-responsive gene (56), and the PPARγ agonist troglitazone has been demonstrated to increase postheparin plasma ... it is known that apoC-III gene expression is suppressed by PPARα agonists (67), possibly via direct binding of activated PPARα ...
Regulation of Glial Cell Functions by PPAR-gamma Natural and Synthetic Agonists. PPAR Res 2008: 864140. Berry KP, Nedivi E. ... Repression of beta-catenin signaling by PPAR gamma ligands. Eur J Pharmacol 636: 198-202. Lu M, Sarruf DA, Talukdar S, Sharma S ... All three PPAR subtype (PPAR-α, PPAR-β/δ, PPAR-γ) levels were significantly reduced in the SN and the ventral tegmental area ( ... PPAR Agonists and Metabolic Syndrome: An Established Role? Int J Mol Sci 19. Botteri G, Salvado L, Guma A, Lee Hamilton D, ...
We profile changes of histone marks at enhancers under hypoxia, PPARβ/δ agonist and dual stimulations and these suggest that ... Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of ... PPAR) β/δ and HIF signaling axes. A migration assay shows a synergistic interaction between these two stimuli, and we identify ...
5-cholesten, 3.beta.,25-diol, disulfate (25HCDS) has been found to be an authentic PPAR.gamma. agonist and LXR antagonist, and ... Opioid receptor ligands (ORLs) that are multifunctional having agonist activity at mu opioid receptor (MOR), agonist activity ... The template-fixed .beta.-hairpin peptidomimetics Cyclo(-Tyr-His-Cys-Ser-Ala-.sup.DPro-Dab-Arg-Tyr-Cys-Tyr-Gln-Lys-.sup.D-P- ro ... The present disclosure provides simple .beta.-hairpin peptides in linear and cyclic form that specifically bind to HIV-1 Trans- ...
... show that PPAR beta specific agonist failed to inhibit lesion formation.. ... Deletion of PPAR-beta/delta from foam cells increases the availability of inflammatory suppressors, which in turn reduces ... Agonist Comments. Endogenous fatty acid full agonists have also been reported with pIC50 values of 5.2 for the human isoform [ ... Tan NS, Michalik L, Desvergne B, Wahli W. (2003) Peroxisome proliferator-activated receptor (PPAR)-beta as a target for wound ...
Cellular and Biophysical Pipeline for the Screening of Peroxisome Proliferator-Activated Receptor Beta/Delta Agonists: Avoiding ... PPAR-Gamma Agonist Pioglitazone Reduced CD68+ but Not CD163+ Macrophage Dermal Infiltration in Obese Psoriatic Patients ... Inhibitory Effects of a Novel PPARAgonist MEKT1 on Pomc Expression/ACTH Secretion in AtT20 Cells ... A Reduction in ADAM17 Expression Is Involved in the Protective Effect of the PPAR-α Activator Fenofibrate on Pressure Overload- ...
... beta-adrenergic hormones, retinoids, PPARγ and PPARα agonists, and the liver X receptor.. Exercise and peroxisome proliferator- ... Beta-3-adrenoceptors. Octopamine is one of the only known selective agonists of the mammalian beta-3 adrenergic receptor (β3 ... Lipomorph: 5 reasons why BETA is BETTER. * Beta-aminoisobutyric acid. Antaeus Labs LipoMorph is the only supplement to contain ... Liver X Receptor Beta (LXRβ). The Kuding in LipoMorph suppresses lipogenesis through antagonism of LXRβ.. * Beta- ...
... mediator 4-hydroxynonenal is an intracellular agonist of the nuclear receptor peroxisome proliferator-activated receptor-beta/ ... delta (PPARbeta/delta). Free Radic Biol Med. 2007 Apr 15;42(8):1155-64. Epub 2007 Jan 8. ... phthalate is a highly potent agonist for the human constitutive androstane receptor splice variant, CAR2. Mol. Pharmacol. Feb ... of chemically induced skin carcinogenesis by sulindac is independent of peroxisome proliferator-activated receptor-beta/delta ( ...
PPARβ/δ) for inducing genes related to FAO. The treatment of exogenous RA, on the other hand, significantly increased adipocyte ... the expression of pro-inflammatory genes in RAW264.7 macrophages stimulated with adipocyte-conditioned media by increasing PPAR ... which is a potential endogenous agonist of the transcriptional factor peroxisome proliferator-activated receptor beta/delta ( ... which is a potential endogenous agonist of the transcriptional factor peroxisome proliferator-activated receptor beta/delta ( ...
PPAR) {alpha} and {gamma} agonists on 11{beta}-hydroxysteroid dehydrogenase type 1 in subcutaneous adipose tissue in men. J ... Hughes KA, Webster SP, Walker BR: 11-Beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) inhibitors in type 2 diabetes ... evidence for conversion of cortisone to cortisol via the 11-beta hydroxysteroid dehydrogenase (11beta-hsd) type 1 pathway. ...
A hypothesis for insulin resistance in primary human adipocytes involving MRTF-A and suppression of PPAR γ. ... Agonist-induced membrane nanodomain clustering drives GLP-1 receptor responses in pancreatic beta cells. *. ... We have previously highlighted the relevance of this process in fine-tuning GLP-1R responses in pa ncreatic beta cells to ... Biased GLP-1R agonists and small molecule allosteric modulation both influence GLP-1R palmitoylation, clustering, nanodomain ...
  • The observed antifibrotic effect of rosiglitazone was not affected by the PPAR-γ antagonist GW9662, indicating it is not PPAR-γ dependent. (
  • Interestingly, either antisense knockdown of PPAR-β or antagonism of PPAR-β by a specific chemical antagonist abrogated gemfibrozil-mediated inhibition of microglial activation. (
  • RESULTS Using GW501516 (PPARδ agonist) and GSK0660 (PPARδ antagonist), we discovered that high-glucose-induced downregulation of the glucose transport system in VECs is mediated by PPARδ. (
  • 3OC 12 -HSL functioned as an agonist of PPARβ/δ transcriptional activity and an antagonist of PPARγ transcriptional activity and inhibited the DNA binding ability of PPARγ. (
  • RGZ-induced ENaC activation was PPARγ-dependent since the PPARγ antagonist GW9662 blocked the activation. (
  • Acetylcholine-induced endothelium-dependent relaxation in mouse thoracic aortic (MTA) rings was measured using wire myography, and mouse aortic endothelial cell (MAEC) function was assessed in the presence or absence of palmitate, with or without the PPARβ agonist and antagonist, GW0742(1 µM), or GSK0660(1 µM) respectively. (
  • Blockade of PPARγ activation by the PPARγ antagonist GW9662 markedly inhibited irbesartan-induced adiponectin expression. (
  • The irreversible PPAR-γ antagonist GW9662 was used to investigate whether the effect of PPAR-γ agonists was PPAR-γ dependent. (
  • These findings classify ST247 as an inverse agonist, whereas PT-S58 is the first pure PPARβ/δ antagonist described to date. (
  • Treatment of the seipin -KO mice with the PPARγ agonist rosiglitazone (rosi) could prevent Aβ 25-35/1-42 -induced neuroinflammation and neurotoxicity, which was blocked by the PPARγ antagonist GW9962. (
  • They found that pioglitazone, a PPARγ agonist, inhibited aromatase expression by inhibition of PGE 2 signaling and upregulation of BRCA1. (
  • In this issue of the journal, Subbaramaiah and colleagues ( 23 ) report for the first time that pioglitazone, a PPARγ agonist, inhibits aromatase expression via inhibiting prostaglandin E 2 (PGE 2 ) signaling and upregulating BRCA1 in vitro and in vivo . (
  • The addition of the PPAR-gamma agonist pioglitazone to levothyroxine decreased thyroid-stimulating hormone levels and improved insulin resistance in patients with hypothyroidism, according to data presented at EASD 2013. (
  • We also present novel data indicating pioglitazone as a drug with ability to decrease HbA1c, improve HOMA-IR index by lowering insulin and glucose without influence on HOMA-beta in hypothyroid patients. (
  • Therefore, our study suggests that PPAR-gamma receptors play a role in pathogenesis of hypothyroidism and PPAR-gamma agonist pioglitazone may have new indication to be used," the researchers wrote. (
  • In addition to various targets, THC and CBD are also well-known agonists of peroxisome proliferator-activated receptor gamma (PPARγ), a nuclear receptor involved in energy homeostasis and lipid metabolism. (
  • Studies in mice have shown that PPARα is an important regulator of lipid metabolism in liver and key transcription factor involved in the adaptive response to fasting. (
  • Many genes induced by PPARα activation were involved in lipid metabolism (ACSL5, AGPAT9, FADS1, SLC27A4), xenobiotic metabolism (POR, ABCC2, CYP3A5) or the unfolded protein response, whereas most of the downregulated genes were involved in immune-related pathways. (
  • In addition to the role of PPARγ in glucose and lipid metabolism, PPARγ stimulated adipocyte differentiation ( 9, 10 ), and inhibition of PPARγ attenuated adipocyte differentiation induced by breast cancer epithelial cells ( 11 ). (
  • Lipid homeostasis is controlled by the peroxisome proliferator-activated receptors (PPARalpha, -beta/delta, and -gamma) that function as fatty acid-dependent DNA-binding proteins that regulate lipid metabolism. (
  • These neuroprotective effects have been attributed 27 largely to PPARα's antioxidant and anti-inflammatory properties, although its beneficial 28 effects in lipid metabolism and glucose homeostasis may also play a role [7-11]. (
  • Here we identify hypoxia-inducible lipid droplet-associated (Hilpda/Hig2) as a novel PPAR target gene and demonstrate its involvement in hepatic lipid metabolism. (
  • The study, " Mature myelin maintenance requires Qki to coactivate PPARβ-RXRα-mediated lipid metabolism ," was published in The Journal of Clinical Investigation . (
  • Mechanistically, the team believes that Qki serves as a co-activator of a complex made up of peroxisome proliferator-activated receptor beta (PPAR-beta) and retinoid X receptor alpha (RXR-alpha), which controls the activity of several genes involved in lipid metabolism. (
  • Furthermore, a subset of lesions from patient samples with primary progressive multiple sclerosis were characterized by downregulation of key activities in lipid metabolism associated with Qki and PPAR-beta/RXR-alpha. (
  • Synthetic peroxisome proliferator-activated receptor γ (PPAR-γ) ligands have been shown to be effective antifibrotic agents against transforming growth factor β1 (TGF-β1) induced fibrosis in several tissues. (
  • Berger J, Leibowitz MD, Doebber TW et al (1999) Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. (
  • PPARα is activated when bound by endogenous lipid/lipid metabolite ligands or 17 synthetic xenobiotic ligands [2]. (
  • The peroxisome proliferator-activated receptor-γ (PPAR-γ) is a member of the nuclear receptor superfamily that is activated by its ligands. (
  • The property of their antigrowth and prodifferentiation renders natural and synthetic ligands of PPAR-γ as attractive substances in cancer prevention and treatment ( 3 - 6 ). (
  • However, given that PPAR-γ ligands often trigger crosstalk with other signalling pathways ( 6 - 8 ), use of PPAR-γ agonists alone on much more common advanced epithelial malignancies has minimal clinical effect ( 9 ). (
  • Screening for PPAR non-agonist ligands followed by characterization of a hit, AM-879, with additional no-adipogenic and cdk5-mediated phosphorylation inhibition. (
  • Recently, certain ARBs (irbesartan, telmisartan) were identified as ligands of the peroxisome proliferator-activated receptor (PPAR)γ. (
  • It is noteworthy that ST247 and PT-S58 are also effective on PPRE-independent functions of PPARβ/δ: in monocytic cells, both ligands modulate expression of the activation marker CCL2 in the opposite direction as an established PPARβ/δ agonist. (
  • We aimed to investigate the antifibrotic effects of the PPAR-γ ligand rosiglitazone in pterygium fibroblasts and the underlying mechanisms. (
  • The proinflammatory effect of 3OC 12 -HSL in lung epithelial cells was blocked by the PPARγ agonist rosiglitazone, suggesting that 3OC 12 -HSL and rosiglitazone are mutually antagonistic negative and positive regulators of PPARγ activity, respectively. (
  • Here, we show that treating Xenopus laevis oocytes expressing ENaC and PPARγ with the TZD rosiglitazone (RGZ) produced a twofold increase of amiloride-sensitive sodium current (Iam), as measured by two-electrode voltage clamp. (
  • HIFs were treated with TGF-β1 and co-incubated with or without one of two synthetic PPAR-γ agonists, troglitazone or rosiglitazone. (
  • The results identify Lpin2 and St3gal5 as novel PPARbeta/delta target genes and show that upregulation of gene expression by PPARbeta/delta is sensitive to plasma FFA levels. (
  • Finally, several putative new target genes of PPARα were identified that were commonly induced by PPARα activation in the two human liver model systems, including TSKU, RHOF, CA12 and VSIG10L. (
  • PPARγ is a ligand-activated transcription factor, which along with retinoid X receptors (RXR) forms heterodimers that activate transcription of its target genes by binding to PPAR response elements (PPRE) located in the promoter region. (
  • However, relatively little is known about PPARbeta/delta in the context of target tissues, target genes, lipid homeostasis, and functional overlap with PPARalpha and -gamma. (
  • 1 Abstract 2 Peroxisome-Proliferator Activated Receptor-Alpha (PPARα) is a broadly 3 expressed nuclear hormone receptor, and is a transcription factor for diverse target genes 4 possessing a PPAR Response Element (PPRE) in the promoter region. (
  • Once activated, PPARα heterodimerizes with the 18 Retinoid X Receptor (RXR) and binds to PPAR Response Elements (PPREs) in the 19 promoter regions of target genes involved in diverse processes such as energy 20 metabolism, oxidative stress, inflammation, circadian rhythm, immune response and cell 21 differentiation [3-8]. (
  • Furthermore, only in WT-PCLS, CDCA upregulated a subset of known FXR-target genes as well as the regulator of inflammation and mitochondrial functions peroxisome proliferator- activated receptor delta (Ppar delta). (
  • Like the other PPAR subtypes, PPARβ/δ forms heterodimers with the nuclear retinoid X receptor that bind to peroxisome proliferator response elements (PPREs) in target genes. (
  • Pharmaceutical inhibition of PPAR-γ receptor was used to determine the dependency or otherwise of rosiglitazone's action on PPAR-γ signaling. (
  • Inhibition of chemically induced skin carcinogenesis by sulindac is independent of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta). (
  • In numerous tissues, PPAR gamma activation induces inhibition of beta-catenin pathway, while the activation of the canonical WNT/beta-catenin pathway inactivates PPAR gamma. (
  • PPARγ agonists have been shown to lower blood pressure in animals and humans, perhaps by suppressing the renin-angiotensin (Ang)-aldosterone system (RAAS), including the inhibition of Ang II type 1 receptor expression, Ang-II-mediated signaling pathways, and Ang-II-induced adrenal aldosterone synthesis/secretion. (
  • Strategies for peroxisome proliferator-activated receptor (PPAR) activation or survivin inhibition have potential for cancer therapy. (
  • In this study, the combinatory effect of PPAR-γ agonist and survivin inhibition on bladder cancer cells was investigated. (
  • LAZ3 knock-down decreases NRF2 expression and nuclear translocation, while only the PPARa agonist (GW7647) can prevent this inhibition. (
  • PPAR-γ agonists down regulated fibrogenesis, as shown by inhibition of Akt and Smad2 phosphorylation. (
  • One of the innate qualities of a PPAR delta agonist is that it alters the source of fuel for our muscle cells. (
  • We found that PPARbeta/delta agonist and exercise training synergistically increase oxidative myofibers and running endurance in adult mice. (
  • After binding with their agonists (natural or synthetic) in cytoplasm, PPARs heterodimerize with the retinoid acid receptor (RNR or NR2B) and translocate to the nucleus, subsequently binding to specific DNA regions termed peroxisome proliferator response elements (PPREs). (
  • The Cignal PPAR Reporter Assay Kit is designed to measure the transcriptional activity of peroxisome proliferator-activated receptors (PPARs). (
  • Upon ligand binding, PPARs forms a heterodimer with the retinoic acid receptor (RXR) and control the expression of genes that have PPAR response elements. (
  • X-ray structures of PPARs indicate that alpha or beta derivatives of fatty acids would fit into PPARalpha/gamma binding cavity. (
  • We utilize selective PPARalpha, -beta/delta, -gamma, and liver X receptor agonists in skeletal muscle cells to understand the functional role of PPARbeta/delta, and the complementary and/or contrasting roles of PPARs in this major mass peripheral tissue. (
  • Further, our group found that retinal levels of 40 PPARα, but not PPARγ or PPARβ/δ were decreased in diabetes, suggesting that PPARα 41 plays a more crucial role than other PPARs in repressing development of diabetic 42 retinopathy (DR) [15]. (
  • GW501516 (also known as GW-501,516, GW1516, GSK-516, Cardarine, and on the black market as Endurobol) is a PPARδ receptor agonist that was invented in a collaboration between Ligand Pharmaceuticals and GlaxoSmithKline in the 1990s. (
  • The World Anti-Doping Agency (WADA) developed a test for GW501516 and other related PPARδ modulators, and added such drugs to the prohibited list in 2009. (
  • GW501516 is a selective agonist (activator) of the PPARδ receptor. (
  • In rats, binding of GW501516 to PPARδ recruits the coactivator PGC-1α. (
  • GW501516, also known as Cardarine is a PPAR delta/beta agonist that works by activating the transcription of a bunch of genes in different locations in the body. (
  • Activation of PPARbeta/delta by GW501516 in skeletal muscle cells induces the expression of genes involved in preferential lipid utilization, beta-oxidation, cholesterol efflux, and energy uncoupling. (
  • Furthermore, we show that treatment of muscle cells with GW501516 increases apolipoprotein-A1 specific efflux of intracellular cholesterol, thus identifying this tissue as an important target of PPARbeta/delta agonists. (
  • Recently, GW501516, a selective PPARdelta agonist, was reported to increase glucose uptake in human skeletal myotubes by an AMPK-dependent mechanism that may contribute to the improved glucose tolerance. (
  • Peroxisome proliferator-activated receptors (PPAR) are transcription factors belonging to the nuclear receptor super family with diverse effect. (
  • To identify putative 3OC 12 -HSL receptors, we examined the expression patterns of a panel of nuclear hormone receptors in these two cell lines and determined that both peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) and PPARγ were expressed. (
  • These data identify PPARβ/δ and PPARγ as putative mammalian 3OC 12 -HSL receptors and suggest that PPARγ agonists may be employed as anti-inflammatory therapeutics for P. aeruginosa infections. (
  • PPARγ is a member of the PPAR family, including PPAR-α, β/δ, and γ, which belongs to the superfamily of nuclear hormone receptors. (
  • Many of its effects listed below stem from its ability to activate PPAR receptors. (
  • In their final experiments, researchers showed that treating animals lacking Qki with PPAR-beta/RXR-alpha agonists (substances that activate these receptors) lessened their neurological problems and prolonged their survival. (
  • Peroxisome proliferator-activated receptors (PPARα, -β/δ and -γ), members of the nuclear receptor transcription factor superfamily, play important roles in regulating lipid metabolic genes. (
  • Furthermore, our in vivo and in vitro findings indicate that TNFα downregulates the expression of genes related to FAO in adipocytes by suppressing the conversion of retinol (dietary vitamin A) to retinoic acid (RA), which is a potential endogenous agonist of the transcriptional factor peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) for inducing genes related to FAO. (
  • Upon the discovery that bile acids (BA) are endogenous FXR agonists with chonedoexy cholic acid (CDCA) being the most potent FXR agonist, the primary functions of FXR were attributed to the maintenance of BA homeostasis [ 2 ]. (
  • Anandamide, the endogenous cannabinoid, is also a TRPV1 agonist. (
  • Anandamide, the endogenous cannabinoid, is also a TRPV-1 agonist. (
  • MS and AK promoted AMPK phosphorylation, suppressed the steatosis-related mRNA expression and inflammatory cytokines secretion, as well as upregulated farnesoid X receptor (FXR), peroxisome proliferator-activated receptor gamma co-activator (PGC)-1α, and PPARα expression to induce fatty acid oxidation in the liver of mice. (
  • We aimed to analyze the effect of omega-9 supplementation on corticosteroid unbalance, inflammation, bacterial elimination, and peroxisome proliferator-activated receptor (PPAR) gamma expression, an omega-9 receptor and inflammatory modulator. (
  • We measured systemic corticosterone levels, cytokine production, leukocyte and bacterial counts in the peritoneum, and the expression of PPAR gamma in both liver and adipose tissues during experimental sepsis. (
  • Omega-9 also decreased bacterial load in the peritoneal lavage and restored liver and adipose tissue PPAR gamma expression in septic animals. (
  • Our data suggest a beneficial anti-inflammatory role of omega-9 in sepsis, mitigating leukocyte rolling and leukocyte influx, balancing cytokine production, and controlling bacterial growth possibly through a PPAR gamma expression-dependent mechanism. (
  • The alpha isoform is primarily expressed in adipose tissue, liver, and muscle, the beta/delta isoform is widely expressed in all tissues, and the gamma isoform is primarily expressed in adipose tissue and muscle. (
  • Several PPAR gamma agonists were released as pharmaceuticals. (
  • Chraïbi, Ahmed 2010-08-26 00:00:00 Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor gamma (PPARγ) agonists used to treat type 2 diabetes. (
  • But synthetically developed PPARalpha/gamma dual agonists and glitazones are showing side effects such as weight gain and edema. (
  • We focus this review on the interactions between the canonical WNT/beta-catenin pathway and peroxisome proliferator-activated receptor gamma (PPAR gamma) in cancers and their implications from an energetic and metabolic point of view. (
  • In most cancers but not all, PPAR gamma is downregulated while the WNT/beta-catenin pathway is upregulated. (
  • In addition in many cancer cells, PPAR gamma is downregulated. (
  • Moreover, PPAR gamma contributes to regulate some key circadian genes. (
  • Activation of the receptor known as PPAR-gamma has an anti-proliferative effect as well as an ability to induce tumor regression in human lung cancer cell lines. (
  • There are few data on the use of PPAR-gamma agonists in pregnancy. (
  • Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ) expression in intestinal epithelial cells. (
  • Recently, peroxisome proliferator-activated receptor gamma (PPARγ) has been shown to be regulated by a number of bacterial pathogens including Helicobacter pylori and Mycobacterium tuberculosis [17] - [19] , greatly impacting disease severity. (
  • Neuronal knockout of seipin in mice ( seipin -KO mice) reduces the hippocampal peroxisome proliferator-activated receptor gamma (PPARγ) level without the loss of pyramidal cells. (
  • The role of Sgk-1 in the upregulation of transport proteins by PPAR-{gamma} agonists in human proximal tubule cells. (
  • Peroxisome proliferator-activated receptor beta stimulation induces rapid cardiac growth and angiogenesis via direct activation of calcineurin" (PDF). (
  • In cancer cells, upregulation of the WNT/beta-catenin signaling induces dramatic changes in key metabolic enzymes that modify their thermodynamic behavior. (
  • The WNT/beta-catenin pathway induces the transcription of genes involved in cell proliferation, i.e. (
  • GW0742 (1 μM) induces PPARδ protein in neonatal rat cardiomyocytes. (
  • ST247 has a higher affinity to PPARβ/δ than GSK0660, and at equimolar concentrations, it more efficiently 1) induces the interaction with corepressors both in vitro and in vivo, 2) inhibits the agonist-induced transcriptional activity of PPARβ/δ, and 3) down-regulates basal level expression of the peroxisome proliferator responsive element-driven PPARβ/δ target gene ANGPTL4 . (
  • All three PPAR subtype (PPAR-α, PPAR-β/δ, PPAR-γ) levels were significantly reduced in the SN and the ventral tegmental area (VTA) of HFD mice when compared to those in normal-diet controls, and the PPAR-α showed the most prominent reduction. (
  • Supportively, in vivo administration of the LXR ligand to mice and rat primary hepatocytes substantially decreased hepatic mRNA levels of PPARalpha-targeted genes in both basal and PPARalpha agonist-induced conditions. (
  • SCI was induced in mice through a spinal cord compression by the application of vascular clips (force of 24 g) to the dura via a four-level T5 to T8 laminectomy, and PEA (10 mg/kg, intraperitoneally, 1 and 6 hours after SCI) was injected into wildtype mice and into mice lacking PPAR-α (PPAR-αKO). (
  • To deepen the ability of specific PPAR-δ and PPAR-γ antagonists to reverse the effect of PEA, mice were administered GSK0660 or GW9662, 30 minutes before PEA injection. (
  • Genetic ablation of PPAR-α in mice exacerbated spinal cord damage, while PEA-induced neuroprotection seemed be abolished in PPARαKO mice. (
  • In particular, PEA was less effective in PPAR-αKO, GSK0660-treated or GW9662-pretreated mice, as evaluated by the degree of spinal cord inflammation and tissue injury, neutrophil infiltration, proinflammmatory cytokine, inducible nitric oxide synthase expression and motor function. (
  • Further, Pparα −/− mice and age-matched wild-type (WT) mice were used for laser-induced CNV and treated with Feno-FA to explore the underlying mechanism. (
  • Furthermore, Pparα −/− mice developed more severe CNV compared with WT mice, and PPARα knockout abolished the beneficial effects of Feno-FA on CNV. (
  • Hepatic overexpression of HILPDA in mice via adeno-associated virus led to a 4-fold increase in liver triglyceride storage, without any changes in key genes involved in de novo lipogenesis, beta-oxidation, or lipolysis. (
  • The aim was to evaluate the efficacy of the pan-PPAR agonist, bezafibrate, in tafazzin knockdown mice (TazKD), a mouse model of Barth syndrome that exhibits age-dependent dilated cardiomyopathy with left ventricular (LV) dysfunction. (
  • The effect of bezafibrate on cardiac function was evaluated by echocardiography in TazKD mice with or without beta-adrenergic stress. (
  • Without beta-adrenergic stress, TazKD mice develop dilated cardiomyopathy by 7 months of age. (
  • The oxidative stress mediator 4-hydroxynonenal is an intracellular agonist of the nuclear receptor peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta). (
  • Cellular and Biophysical Pipeline for the Screening of Peroxisome Proliferator-Activated Receptor Beta/Delta Agonists: Avoiding False Positives NB Videira, FAH Batista, A Torres Cordeiro, ACM Figueira PPAR Research 2018. (
  • Activated PPAR[alpha] also stimulates the expression of the fibroblast growth factor gene 21 (FGF21) and the angiopoietin-like protein gene 4 (ANGPLT4). (
  • These results highlight the fact that gemfibrozil regulates microglial activation by inhibiting inflammatory gene expression in a PPAR-β dependent pathway and further reinforce its therapeutic application in several neuroinflammatory and neurodegenerative diseases. (
  • Finally, specific binding of PPARδ to a PPAR response element in the promoter region of the calreticulin gene was identified by utilizing a specific chromatin immunoprecipitation assay. (
  • We present a detailed investigation of hypoxia-inducible factor (HIF) 1 dependent gene expression in endothelial cells which suggests the importance of crosstalk between the peroxisome proliferator-activated receptor (PPAR) β/δ and HIF signaling axes. (
  • Multiple coactivators and corepressors interact with PPAR/RXR heterodimers to direct target gene specificity. (
  • QIAGEN provides a broad range of assay technologies for PPAR signaling research that enables analysis of gene expression and regulation, epigenetic modification, genotyping, and signal transduction pathway activation. (
  • In luciferase reporter gene assays, overexpression of LXRalpha or beta suppressed PPARalpha-induced peroxisome proliferator response element-luciferase activity in a dose-dependent manner. (
  • Introduction TGFBI-linked corneal dystrophies are autosomal dominating disorders caused by mutations in transforming growth factor-beta-induced (gene that results in an arginine-to-histidine substitution (R124H) [1]. (
  • Cells were transfected with a peroxisome proliferator response element-AB (rat fatty acyl CoA beta-oxidase response element)-luciferase gene reporter construct. (
  • Here we set out to study the function of PPARα in human liver via analysis of whole genome gene regulation in human liver slices treated with the PPARα agonist Wy14643. (
  • Comparative analysis of gene regulation by Wy14643 between human liver slices and primary human hepatocytes showed that down-regulation of gene expression by PPARα is much better captured by liver slices as compared to primary hepatocytes. (
  • Transactivation studies and chromatin immunoprecipitation showed that Hilpda is a direct PPAR alpha target gene via a conserved PPAR response element located 1200 base pairs upstream of the transcription start site. (
  • We have performed genomewide analyses of agonist-treated and PPARβ/δ-depleted human myofibroblasts to test this hypothesis and to identify global principles of PPARβ/δ-mediated gene regulation. (
  • In humans it binds to the estrogen receptor beta (ERβ) protein-coding gene. (
  • Asayama K, Sandhir R, Sheikh FG, Hayashibe H, Nakane T, Singh I (1999) Increased peroxisomal fatty acid beta-oxidation and enhanced expression of peroxisome proliferator-activated receptor-alpha in diabetic rat liver. (
  • PPAR-alpha regulates the expression of genes involved in fatty acid beta-oxidation and is a major regulator of energy homeostasis. (
  • We found that both MS and AK prevented fatty acid accumulation in hepatocytes by inhibiting fatty acid uptake, lipogenesis, and promoting fatty acid beta-oxidation mediated by activating peroxisome proliferator-activated receptor (PPAR)-α and AMP-activated kinase (AMPK). (
  • Binding of PPARbeta/delta to the Lpin2 and St3gal5 genes followed the plasma free fatty acid (FFA) concentration, consistent with activation of PPARbeta/delta by plasma FFAs. (
  • Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. (
  • Fatty acid metabolism is transcriptionally regulated by two reciprocal systems: peroxisome proliferator-activated receptor (PPAR) alpha controls fatty acid degradation, whereas sterol regulatory element-binding protein-1c activated by liver X receptor (LXR) regulates fatty acid synthesis. (
  • Moreover, we surmise that PPARbeta/delta agonists would increase fatty acid catabolism, cholesterol efflux, and energy expenditure in muscle, and speculate selective activators of PPARbeta/delta may have therapeutic utility in the treatment of hyperlipidemia, atherosclerosis, and obesity. (
  • PPARα has been shown to control transcriptional expression of key enzymes that are involved in fatty acid (FA) uptake and oxidation, triglyceride synthesis, mitochondrial respiration uncoupling, and glucose metabolism. (
  • The nuclear hormone receptor PPARγ is activated by several agonists, including members of the thiazolidinedione group of insulin sensitizers. (
  • Peroxisome proliferator-activated receptor (PPAR)γ is a nuclear hormone receptor that, with the retinoid X receptor (RXR), binds as a heterodimer to the PPAR response element (PPRE), a direct repeat of 'AGGTCA' gapped by a nucleotide. (
  • Peroxisome-Proliferator Activated Receptor-Alpha (PPARα) 15 PPARα is a transcription factor, and belongs to the nuclear receptor superfamily 16 [1]. (
  • Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a ligand-regulated nuclear receptor with essential functions in metabolism and inflammation. (
  • Peroxisome proliferator - activated receptor alpha (PPARalpha) is an important transcription factor in liver that can be activated physiologically by fasting or pharmacologically by using high-affinity synthetic agonists. (
  • In response to PPAR[alpha] activation, production of FGF21 in the liver begins, activating white adipose tissue lipolysis in order to provide nonadipose tissue with fatty acids as well as controlling ketogenesis in the liver with the purpose of procuring energy from fatty acids [11]. (
  • Natural regulators of brown and beige fat include external conditions like cold temperatures, and exercise, as well as internal mechanisms like thyroid hormones, beta-adrenergic hormones, retinoids, PPARγ and PPARα agonists, and the liver X receptor. (
  • However, much less is known about the role of PPARα in human liver. (
  • Quantitative PCR indicated that PPARα is well expressed in human liver and human liver slices and that the classical PPARα targets PLIN2, VLDLR, ANGPTL4, CPT1A and PDK4 are robustly induced by PPARα activation. (
  • In particular, PPARα activation markedly suppressed immunity/inflammation-related genes in human liver slices but not in primary hepatocytes. (
  • Our paper demonstrates the suitability and superiority of human liver slices over primary hepatocytes for studying the functional role of PPARα in human liver. (
  • Our data underscore the major role of PPARα in regulation of hepatic lipid and xenobiotic metabolism in human liver and reveal a marked immuno-suppressive/anti-inflammatory effect of PPARα in human liver slices that may be therapeutically relevant for non-alcoholic fatty liver disease. (
  • Fasting is associated with dramatic changes in lipid handling in the liver, which is coordinated by PPARα. (
  • Microarray analysis revealed that Hilpda is one of the most highly induced genes by the PPAR alpha agonist Wy14643 in mouse precision cut liver slices. (
  • The Human PPAR Targets RT² Profiler PCR Array profiles the expression of 84 key genes involved in peroxisome proliferator-activated receptor (PPAR) activation and response. (
  • These fatty acids act as PPAR agonists that transcript the genes involved in glucose and lipid homeostasis. (
  • This study underlines the importance of PPARβ/δ in mediating the anti-inflammatory effect of gemfibrozil, an FDA-approved lipid-lowering drug, in primary human microglia. (
  • On the other hand, blocking of PPAR-α and -γ had no effect on gemfibrozil-mediated anti-inflammatory effect in microglia. (
  • A PPAR-sensitive luciferase reporter assay in VECs revealed that high glucose markedly increased luciferase activity, while GSK0660 abolished it. (
  • GW0742 is a potent PPARβ and PPARδ agonist, with an IC 50 of 1 nM for human PPARδ in binding assay, and EC 50 s of 1 nM, 1.1 μM and 2 μM for human PPARδ , PPARα, and PPARγ, respectively. (
  • PPAR-γ agonists also inhibited TGF-β1-induced mRNA and protein expressions of procollagen1A1, fibronectin, and α-smooth muscle actin. (
  • DeKeyser JG, Stagliano MC, Auerbach SS, Prabhu KS, Jones AD, and Omiecinski CJ (2009) Di(2-ehtylhexyl)phthalate is a highly potent agonist for the human constitutive androstane receptor splice variant, CAR2. (
  • PPARα has potent protective effects against 8 neuronal cell death and microvascular impairment, which have been attributed in part to 9 its antioxidant and anti-inflammatory properties. (
  • Ligand-mediated regulation of peroxisome proliferator-activated receptor (PPAR) beta/delta: a comparative analysis of PPAR-selective agonists and all-trans retinoic acid. (
  • GW1516, also written GW 50516, is a drug and research chemical developed by pharmaceutical client GlaxoSmithKline, which acts as a PPARδ (peroxisome proliferator activated receptor delta) modulator and selective agonist. (
  • 36 Interestingly, PPARα is down-regulated in the diabetic retina and kidney, and 37 although the regulatory mechanisms responsible for diabetes-induced PPARα down- 38 regulation are unclear, decreased PPARα levels may play a pathological role in diabetic 39 microvascular complications [15, 16]. (
  • Interestingly, this PPARγ down-regulation by S. Typhimurium is independent of TLR-4 signaling but triggers a marked elevation of host innate immune response genes, including that encoding the antimicrobial peptide lipocalin-2 (Lcn2). (
  • The hypothesis that 4-hydroxydodeca-(2 E ,6 Z )-dienal (4-HDDE), the peroxidation product of 12-lipoxygenase, mediates this downregulatory mechanism by activating peroxisome proliferator-activated receptor (PPAR) δ was investigated. (
  • Feno-FA has therapeutic effects on ocular NV in models recapitulating neovascular AMD through a PPARα-dependent mechanism. (
  • ARB-induced adiponectin stimulation is likely to be mediated via PPARγ activation involving a post-transcriptional mechanism. (
  • These data identify PPRE-mediated repression as a major mechanism of transcriptional regulation by PPARβ/δ, but, unexpectedly, also show that only a subset of repressed genes are activated by a ligand-mediated switch. (
  • Our data suggest a mechanism in which S. Typhimurium hijacks the control of host immune response genes such as those encoding PPARγ and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion. (
  • Buchan KW, Hassall DG (2000) PPAR agonists as direct modulators of the vessel wall in cardiovascular disease. (
  • The invention features tetralin and indane compounds, compositions containing them, and methods of using them as PPAR alpha modulators to treat or inhibit the progression of, for example, dyslipidemia. (
  • We have synthesized a new derivative [methyl 3-( N -(4-(hexylamino)-2-methoxyphenyl)sulfamoyl)thiophene-2-carboxylate (ST247) structurally related to the published PPARβ/δ inhibitory ligand methyl 3-( N -(2-methoxy-4-(phenylamino)phenyl)sulfamoyl)thiophene-2-carboxylate (GSK0660). (
  • All three PPAR subtypes are expressed in cardiomyocytes. (
  • There are three PPAR isoforms: α, β/δ and γ. (
  • The 3 PPAR isoforms share similar functions but different tissue distributions. (
  • PPARγ agonists also inhibit the progression of atherosclerosis in animals and humans, possibly through a pathway involving the suppression of RAAS and the thromboxane A 2 system, as well as the protection of endothelial function. (
  • Clearly, additional research into PPAR isoform regulation is necessary to identify the mechanisms for these side effects and ensure avoidance in the future. (
  • These novel cytoprotective effects appear to operate via increased beta-oxidation resulting from CPT-1 up-regulation. (
  • Taken together, our data uncover HILPDA as a novel PPAR target that raises hepatic triglyceride storage via regulation of triglyceride secretion. (
  • Genomewide analyses define different modes of transcriptional regulation by peroxisome proliferator-activated receptor-β/δ (PPARβ/δ). (
  • On the other hand, the role of PPARγ on transcriptional regulation of FA metabolism in the heart remains obscure. (
  • The down-regulation of PPARγ has gained increasing attention in neuroinflammation of Alzheimer's disease (AD). (
  • The effects of PPARγ agonists, known for their positive activity on type II diabetes mellitus, have been explored and present promising effects in the control of neuropathic pain, including CINP, and also cancer. (
  • The PPARδ/coactivator complex in turn upregulates the expression of proteins involved in energy expenditure. (
  • Cimini A, Bernardo A, Cifone MG, Di Marzio L, Di Loreto S (2003) TNFalpha downregulates PPAR delta expression in oligodendrocyte progenitor cells: implications for demyelinating diseases. (
  • RESEARCH DESIGN AND METHODS Effects of 4-HDDE and PPARδ on the glucose transport system and calreticulin expression in primary bovine aortic endothelial cells were evaluated by pharmacological and molecular interventions. (
  • RA treatment also suppressed the expression of pro-inflammatory genes in RAW264.7 macrophages stimulated with adipocyte-conditioned media by increasing PPARβ/δ protein expression in both cell types. (
  • Previous studies have shown that PPARγ activation by TZD enhances the expression or function of the epithelial sodium channel (ENaC) through different mechanisms. (
  • PEA is also able to restore PPAR-δ and PPAR-γ expression in spinal cord tissue. (
  • Due to its ubiquitous expression pattern and diverse cellular actions, no single descriptor appropriately captures the biological function of PPARδ. (
  • Because the renin-angiotensin (Ang)-aldosterone system (RAAS) plays the most important role in the progression of hypertension, we examined the effects of several PPARγ agonists on Ang II type 1 receptor (AT1R) expression in vascular smooth muscle cells (VSMCs). (
  • In this issue of the journal (beginning on p. 1183), Subbaramaiah and colleagues improve our understanding of the molecular mechanisms by which PPARγ inhibits aromatase expression. (
  • Telmisartan also stimulated adiponectin protein expression, whereas the non-PPARγ-activating ARB eprosartan had no effect. (
  • Both PPAR-γ agonists reduced the TGF-β1-induced expression of α-smooth muscle actin which was integrated into stress fibers in HIFs, as determined by actin microfilaments fluorescent staining and α-smooth muscle actin-specific immunocytochemistry. (
  • In addition to those natural roles in beta cell development and maturation, ectopic expression of PDX1, NEUROG3, and/or MAFA has been successfully used to reprogram various cell types into insulin-producing cells in vitro and in vivo, such as pancreatic exocrine cells, hepatocytes, and pluripotent stem cells. (
  • We provided evidence that MS and AK act as PPARα agonists to upregulate AMPK activity and attenuate NAFLD. (
  • GW1516 holds promise for treating obesity and adiposity and has been touted, much like AICAR, as exercise in a pill, etc.[6] In conjunction with AICAR, an AMPK agonist which acts synergistically with GW1516, significant increases in exercise endurance have been demonstrated in animal studies. (
  • Because training activates AMPK and PGC1alpha, we then tested whether the orally active AMPK agonist AICAR might be sufficient to overcome the exercise requirement. (
  • Downstream effe cts on insulin secretion from pancreatic beta cells indicate that these processes are relevant to GLP-1R physiological actions and might be therapeutically targetable. (
  • In vitro protein binding assays demonstrated that activation of LXR by an LXR agonist promoted formation of LXR/RXRalpha and, more importantly, LXR/PPARalpha heterodimers, leading to a reduction of PPARalpha/RXRalpha formation. (
  • Transforming growth factor-beta-induced protein (TGFBIp) is usually ubiquitously expressed in the extracellular matrix (ECM) of various tissues and cell lines. (
  • GW0742 (5 mg/kg/day, i.v.) increases PPARδ protein level in the heart of rats. (
  • Pancreas/duodenum homeobox protein 1 (PDX1), Neurogenin-3 (NEUROG3), and V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAFA) are transcription factors critical for beta cell development and maturation. (
  • Using chromatin immunoprecipitation, Lpin2 and St3gal5 were shown to be direct targets of PPARbeta/delta during fasting, whereas Aldh3a2 and Cpt2 were exclusive targets of PPARalpha. (
  • Further studies on the potential distinctive roles of each PPAR subtype in the heart should provide new therapeutic targets for treating heart disease. (
  • We have previously highlighted the relevance of this process in fine-tuning GLP-1R responses in pa ncreatic beta cells to control insulin secretion. (
  • 6. A combination according to claim 1 wherein the insulin secretion enhancer or a pharmaceutically acceptable salt thereof is selected from the group consisting of sulfonylureas (SU), glinides, DPP-IV inhibitors, GLP1 and GLP1 agonists. (
  • GW0742 (also known as GW610742) is a PPARδ/β agonist that is investigated for drug use by GlaxoSmithKline. (
  • The PPARγ is known as the key transcriptional regulator that drives adipogenesis [ 5 ], the process by which fat cells differentiate from pre-adipocytes into mature adipose cells. (
  • To explore potential interactions between LXR and PPAR, the effect of LXR activation on PPARalpha signaling was investigated. (
  • Results from in vitro studies showed that pterostilbene acts as a PPARalpha agonist and may be a more effective PPARalpha agonist and hypolipidemic agent than resveratrol. (
  • such as fibrates as PPARalpha agonists which lower lipid level, and glitazones as PPARgamma agonists which lower glucose level. (
  • The transcriptional PPARβ/δ network in human macrophages defines a unique agonist-induced activation state. (
  • Biased GLP-1R agonists and small molecule allosteric modulation both influence GLP-1R palmitoylation, clustering, nanodomain signaling, and internalization. (
  • Pleiotropic beneficial effects of these agonists, independent of their blood glucose-lowering effects, have recently been demonstrated in the vasculature. (
  • PPARα has beneficial effects in many diseases, but also plays a 2 22 pathological role in some conditions, for example the development of insulin resistance 23 [3]. (
  • 29 PPARα also has beneficial effects in the vasculature, and plays a more prominent 30 role in the microvasculature than in the macrovasculature. (
  • Indeed, beneficial effects of activation of the PPAR/PGC1α axis have been demonstrated in various mitochondrial disorders. (
  • Methyl 3-( N -(4-( tert -butylamino)-2-methoxyphenyl)sulfamoyl)thiophene-2-carboxylate (PT-S58), another high-affinity derivative from our series, also efficiently inhibits agonist-induced transcriptional activation, but in contrast to ST247, it does not enhance the interaction of PPARβ/δ with corepressors. (
  • CONCLUSIONS Collectively, our data show that 4-HDDE plays a central role in the downregulation of glucose uptake in VECs by activating PPARδ. (
  • In this review, we discuss recent findings regarding the additional beneficial aspects of PPARγ agonists in the vasculature, including conclusions based on our own data. (