Aryl hydrocarbon hydroxylases. Medical search

Cytoplasmic proteins that bind certain aryl hydrocarbons, translocate to the nucleus, and activate transcription of particular DNA segments. AH receptors are identified by their high-affinity binding to several carcinogenic or teratogenic environmental chemicals including polycyclic aromatic hydrocarbons found in cigarette smoke and smog, heterocyclic amines found in cooked foods, and halogenated hydrocarbons including dioxins and polychlorinated biphenyls. No endogenous ligand has been identified, but an unknown natural messenger with a role in cell differentiation and development is suspected.

A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides.

A chemical by-product that results from burning or incinerating chlorinated industrial chemicals and other hydrocarbons. This compound is considered an environmental toxin, and may pose reproductive, as well as, other health risks for animals and humans.

Aryl hydrocarbon receptor nuclear translocator is a basic HELIX-LOOP-HELIX MOTIF containing protein that forms a complex with DIOXIN RECEPTOR. The complex binds xenobiotic regulatory elements and activates transcription of a variety of genes including UDP GLUCURONOSYLTRANSFERASE. AhR nuclear translocator is also a subunit of HYPOXIA-INDUCIBLE FACTOR 1.

A liver microsomal cytochrome P-450 monooxygenase capable of biotransforming xenobiotics such as polycyclic hydrocarbons and halogenated aromatic hydrocarbons into carcinogenic or mutagenic compounds. They have been found in mammals and fish. This enzyme, encoded by CYP1A1 gene, can be measured by using ethoxyresorufin as a substrate for the ethoxyresorufin O-deethylase activity.

A major group of unsaturated cyclic hydrocarbons containing two or more rings. The vast number of compounds of this important group, derived chiefly from petroleum and coal tar, are rather highly reactive and chemically versatile. The name is due to the strong and not unpleasant odor characteristic of most substances of this nature. (From Hawley's Condensed Chemical Dictionary, 12th ed, p96)

A mixed-function oxygenase that catalyzes the hydroxylation of a prolyl-glycyl containing peptide, usually in PROTOCOLLAGEN, to a hydroxyprolylglycyl-containing-peptide. The enzyme utilizes molecular OXYGEN with a concomitant oxidative decarboxylation of 2-oxoglutarate to SUCCINATE. The enzyme occurs as a tetramer of two alpha and two beta subunits. The beta subunit of procollagen-proline dioxygenase is identical to the enzyme PROTEIN DISULFIDE-ISOMERASES.

Chlorinated hydrocarbons containing heteroatoms that are present as contaminants of herbicides. Dioxins are carcinogenic, teratogenic, and mutagenic. They have been banned from use by the FDA.

Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.

A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke.

A carcinogen that is often used in experimental cancer studies.

Organic compounds containing carbon and hydrogen in the form of an unsaturated, usually hexagonal ring structure. The compounds can be single ring, or double, triple, or multiple fused rings.

Four fused benzyl rings with three linear and one angular, that can be viewed as a benzyl-phenanthrenes. Compare with NAPHTHACENES which are four linear rings.

Enzymes that specifically hydroxylate PROLINE residues on proteins.

Dioxygenase enzymes that specifically hydroxylate a PROLINE residue on the HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT. They are OXYGEN-dependent enzymes that play an important role in mediating cellular adaptive responses to HYPOXIA.

Cytochrome P-450 monooxygenases (MIXED FUNCTION OXYGENASES) that are important in steroid biosynthesis and metabolism.

Substances or energies, for example heat or light, which when introduced into the air, water, or land threaten life or health of individuals or ECOSYSTEMS.

An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.

Compounds consisting of two or more fused ring structures.

A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.

Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)

A polyaromatic hydrocarbon inducer of P4501A1 and P4501A2 cytochromes. (Proc Soc Exp Biol Med 1994 Dec:207(3):302-308)

Organic compounds containing a BENZENE ring attached to a flavone group. Some of these are potent arylhydrocarbon hydroxylase inhibitors. They may also inhibit the binding of NUCLEIC ACIDS to BENZOPYRENES and related compounds. The designation includes all isomers; the 7,8-isomer is most frequently encountered.

A class of chemicals that contain an anthracene ring with a naphthalene ring attached to it.

Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.

A drug-metabolizing, cytochrome P-448 (P-450) enzyme which catalyzes the hydroxylation of benzopyrene to 3-hydroxybenzopyrene in the presence of reduced flavoprotein and molecular oxygen. Also acts on certain anthracene derivatives. An aspect of EC 1.14.14.1.

The generic name for the group of aliphatic hydrocarbons Cn-H2n+2. They are denoted by the suffix -ane. (Grant & Hackh's Chemical Dictionary, 5th ed)

Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants.

A family of DNA-binding transcription factors that contain a basic HELIX-LOOP-HELIX MOTIF.

Hydrocarbon compounds with one or more of the hydrogens replaced by CHLORINE.

Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.

An agent that causes the production of physical defects in the developing embryo.

A basic helix-loop-helix transcription factor that plays a role in APOPTOSIS. It is composed of two subunits: ARYL HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR and HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT.

A cytochrome P450 enzyme subtype that has specificity for relatively planar heteroaromatic small molecules, such as CAFFEINE and ACETAMINOPHEN.

A P450 oxidoreductase that catalyzes the hydroxylation of the terminal carbon of linear hydrocarbons such as octane and FATTY ACIDS in the omega position. The enzyme may also play a role in the oxidation of a variety of structurally unrelated compounds such as XENOBIOTICS, and STEROIDS.

RNA 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.

A family of compounds containing an oxo group with the general structure of 1,5-pentanedioic acid. (From Lehninger, Principles of Biochemistry, 1982, p442)

A mixed-function oxygenase that catalyzes the hydroxylation of peptidyllysine, usually in protocollagen, to peptidylhydroxylysine. The enzyme utilizes molecular oxygen with concomitant oxidative decarboxylation of the cosubstrate 2-oxoglutarate to succinate. EC 1.14.11.4.

An aldehyde oxidoreductase expressed predominantly in the LIVER; LUNGS; and KIDNEY. It catalyzes the oxidation of a variety of organic aldehydes and N-heterocyclic compounds to CARBOXYLIC ACIDS, and also oxidizes quinoline and pyridine derivatives. The enzyme utilizes molybdenum cofactor and FAD as cofactors.

Non-heme iron-containing enzymes that incorporate two atoms of OXYGEN into the substrate. They are important in biosynthesis of FLAVONOIDS; GIBBERELLINS; and HYOSCYAMINE; and for degradation of AROMATIC HYDROCARBONS.

A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.

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.

Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.

An enzyme of the oxidoreductase class that catalyzes the formation of L-TYROSINE, dihydrobiopterin, and water from L-PHENYLALANINE, tetrahydrobiopterin, and oxygen. Deficiency of this enzyme may cause PHENYLKETONURIAS and PHENYLKETONURIA, MATERNAL. EC 1.14.16.1.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.

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)

An NAPH-dependent cytochrome P450 enzyme that catalyzes the oxidation of the side chain of sterol intermediates such as the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol.

A cell line derived from cultured tumor cells.

ACNE-like skin eruptions caused by exposure to CHLORINE-containing compounds. Exposure can be by inhalation, ingestion, or through the skin. Chloracne is often seen in people who have occupational contact with chlorinated pesticides, wood preservatives, and sealants.

Elimination of ENVIRONMENTAL POLLUTANTS; PESTICIDES and other waste using living organisms, usually involving intervention of environmental or sanitation engineers.

Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.

Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants.

Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.

A group of condensed ring hydrocarbons.

Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.

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.

Substances which pollute the soil. Use for soil pollutants in general or for which there is no specific heading.

7,12-Dimethylbenzanthracene. Polycyclic aromatic hydrocarbon found in tobacco smoke that is a potent carcinogen.

Steroids which are substituted with one or more fluorine atoms in any position.

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.

A condition of decreased oxygen content at the cellular level.

An enzyme that catalyzes the hydroxylation of TRYPTOPHAN to 5-HYDROXYTRYPTOPHAN in the presence of NADPH and molecular oxygen. It is important in the biosynthesis of SEROTONIN.

The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.

An enzyme that catalyzes the oxidation of XANTHINE in the presence of NAD+ to form URIC ACID and NADH. It acts also on a variety of other purines and aldehydes.

Compounds that contain a BENZENE ring fused to a furan ring.

Established cell cultures that have the potential to propagate indefinitely.

A metallic element with the atomic symbol Mo, atomic number 42, and atomic weight 95.94. It is an essential trace element, being a component of the enzymes xanthine oxidase, aldehyde oxidase, and nitrate reductase. (From Dorland, 27th ed)

An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

Congenital absence of or defects in structures of the jaw.

Family of small, surface-dwelling fish that inhabit fresh and brackish waters, and coastal marine areas.

Chemical compounds which pollute the water of rivers, streams, lakes, the sea, reservoirs, or other bodies of water.

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.

The products of chemical reactions that result in the addition of extraneous chemical groups to DNA.

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.

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.

Relatively complete absence of oxygen in one or more tissues.

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

A drug-metabolizing enzyme found in the hepatic, placental and intestinal microsomes that metabolizes 7-alkoxycoumarin to 7-hydroxycoumarin. The enzyme is cytochrome P-450- dependent.

Carcinogenic substances that are found in the environment.

The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.

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 genus of gram-negative, aerobic, spherical cells usually occurring in pairs. The resting stage is considered a cyst. (From Bergey's Manual of Determinative Bacteriology, 9th ed)

The relationship between the dose of an administered drug and the response of the organism to the drug.

The rate dynamics in chemical or physical systems.

A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys.

A class of MOLECULAR CHAPERONES whose members act in the mechanism of SIGNAL TRANSDUCTION by STEROID RECEPTORS.

Steroids which are substituted with one or more chlorine atoms in any position.

The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.

Recurring supersecondary structures characterized by 20 amino acids folding into two alpha helices connected by a non-helical "loop" segment. They are found in many sequence-specific DNA-BINDING PROTEINS and in CALCIUM-BINDING PROTEINS.

A ubiquitin-protein ligase that mediates OXYGEN-dependent polyubiquitination of HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT. It is inactivated in VON HIPPEL-LINDAU SYNDROME.

Reduction of pharmacologic activity or toxicity of a drug or other foreign substance by a living system, usually by enzymatic action. It includes those metabolic transformations that make the substance more soluble for faster renal excretion.

A group of phenyl benzopyrans named for having structures like FLAVONES.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)

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 main structural component of the LIVER. They are specialized EPITHELIAL CELLS that are organized into interconnected plates called lobules.

The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.

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.

Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.

Organic compounds composed exclusively of carbon and hydrogen. Three or more carbon atoms are arranged in a cyclic structure and they possess aliphatic properties.

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.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

Unsaturated hydrocarbons of the type Cn-H2n, indicated by the suffix -ene. (Grant & Hackh's Chemical Dictionary, 5th ed, p408)

Organic compounds composed exclusively of carbon and hydrogen where no carbon atoms join to form a ring structure.

Benzoate derivatives substituted by one or more hydroxy groups in any position on the benzene ring.

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.

Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.

The species Delphinapterus leucas, in the family Monodontidae, found primarily in the Arctic Ocean and adjoining seas. They are small WHALES lacking a dorsal fin.

A pituitary tumor that secretes GROWTH HORMONE. In humans, excess HUMAN GROWTH HORMONE leads to ACROMEGALY.

A natural product that has been considered as a growth factor for some insects.

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

The simultaneous or sequential binding of multiple cell surface receptors to different ligands resulting in coordinated stimulation or suppression of signal transduction.

The monitoring of the level of toxins, chemical pollutants, microbial contaminants, or other harmful substances in the environment (soil, air, and water), workplace, or in the bodies of people and animals present in that environment.

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.

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.

Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.

Experimentally induced tumors of the LIVER.

A mitochondrial cytochrome P450 enzyme that catalyzes the 1-alpha-hydroxylation of 25-hydroxyvitamin D3 (also known as 25-hydroxycholecalciferol) in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme, encoded by CYP27B1 gene, converts 25-hydroxyvitamin D3 to 1-alpha,25-dihydroxyvitamin D3 which is the active form of VITAMIN D in regulating bone growth and calcium metabolism. This enzyme is also active on plant 25-hydroxyvitamin D2 (ergocalciferol).

A group of 4-keto-FLAVONOIDS.

Complex petroleum hydrocarbons consisting mainly of residues from crude oil distillation. These liquid products include heating oils, stove oils, and furnace oils and are burned to generate energy.

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.

Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.

7,8,8a,9a-Tetrahydrobenzo(10,11)chryseno (3,4-b)oxirene-7,8-diol. A benzopyrene derivative with carcinogenic and mutagenic activity.

An exotic species of the family CYPRINIDAE, originally from Asia, that has been introduced in North America. They are used in embryological studies and to study the effects of certain chemicals on development.

Steroids which are substituted with one or more bromine atoms in any position.

A human liver tumor cell line used to study a variety of liver-specific metabolic functions.

A species of gram-negative, aerobic bacteria isolated from soil and water as well as clinical specimens. Occasionally it is an opportunistic pathogen.

A flavoprotein that catalyzes the synthesis of protocatechuic acid from 4-hydroxybenzoate in the presence of molecular oxygen. EC 1.14.13.2.

The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.

The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.

Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc.

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.

Elements of limited time intervals, contributing to particular results or situations.

A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.

The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.

Organic compounds that contain 1,2-diphenylethylene as a functional group.

Proteins prepared by recombinant DNA technology.

A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis.

Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.

A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).

1,2-Benzphenanthrenes. POLYCYCLIC COMPOUNDS obtained from coal tar.

A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).

Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.

A hydroxylated form of the imino acid proline. A deficiency in ASCORBIC ACID can result in impaired hydroxyproline formation.

Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.

Amino acids containing an aromatic side chain.

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.

Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.

Release of oil into the environment usually due to human activity.

A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.

The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)

Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

An enzyme that catalyzes the reversible hydration of fumaric acid to yield L-malic acid. It is one of the citric acid cycle enzymes. EC 4.2.1.2.

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.

Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.

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.

Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.

A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17.

Used in the form of its salts as a dye and as an intermediate in manufacture of Acid Yellow, diazo dyes, and indulines.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

Blocking the process leading to OVULATION. Various factors are known to inhibit ovulation, such as neuroendocrine, psychological, and pharmacological agents.

A group of FLAVONOLS based on kaempferol. They are derived from naringenin and can be hydroxylated to QUERCETIN or reduced to leucopelargonidin.

Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.

Derivatives of adipic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a 1,6-carboxy terminated aliphatic structure.

Compounds based on pyrazino[2,3-d]pyrimidine which is a pyrimidine fused to a pyrazine, containing four NITROGEN atoms.

Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)

A flavoprotein that reversibly catalyzes the oxidation of NADH or NADPH by various quinones and oxidation-reduction dyes. The enzyme is inhibited by dicoumarol, capsaicin, and caffeine.

A by-product of the destructive distillation of coal used as a topical antieczematic. It is an antipruritic and keratoplastic agent used also in the treatment of psoriasis and other skin conditions. Occupational exposure to soots, tars, and certain mineral oils is known to be carcinogenic according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985) (Merck Index, 11th ed).

3-Hydroxy-4-oxo-1(4H)-pyridinealanine. An antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca.

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.

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).)

A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds.

A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.

A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.

A liver microsomal cytochrome P450 enzyme that catalyzes the 16-alpha-hydroxylation of a broad spectrum of steroids, fatty acids, and xenobiotics in the presence of molecular oxygen and NADPH-FERRIHEMOPROTEIN REDUCTASE. This enzyme is encoded by a number of genes from several CYP2 subfamilies.

The relationships of groups of organisms as reflected by their genetic makeup.

A condensation product of riboflavin and adenosine diphosphate. The coenzyme of various aerobic dehydrogenases, e.g., D-amino acid oxidase and L-amino acid oxidase. (Lehninger, Principles of Biochemistry, 1982, p972)

Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.

Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.

A residue of coal, left after dry (destructive) distillation, used as a fuel.

An antiseptic and disinfectant aromatic alcohol.

Derivatives of the dimethylisoalloxazine (7,8-dimethylbenzo[g]pteridine-2,4(3H,10H)-dione) skeleton. Flavin derivatives serve an electron transfer function as ENZYME COFACTORS in FLAVOPROTEINS.

The process by which two molecules of the same chemical composition form a condensation product or polymer.

The science of drugs prepared from natural-sources including preparations from PLANTS, animals, and other organisms as well as MINERALS and other substances included in MATERIA MEDICA. The therapeutic usage of plants is PHYTOTHERAPY.

A genus of brown-rot fungi in the family Coriolaceae. The biologically active ingredients of its species have potential pharmaceutical value.

A widely used industrial solvent.

A concave exterior region on some POLYCYCLIC AROMATIC HYDROCARBONS that have three phenyl rings in a non-linear arrangement.

An investigation into the binding of the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one to DNA in vitro. (1/3060)

After metabolic activation the carcinogen 15,16-dihydro-11-[3H]methylcyclopenta[a]phenanthren-17-one binds to DNA in vitro, and this binding is prevented by 7,8-benzoflavone. Radioactivity cannot be removed from the DNA with organic solvents or by chromatography on Sephadex G-50, even after heat denaturation of the DNA. Enzymatic hydrolysis yields radioactive fractions, which elute from a column of Sephadex LH-20 immediately after the natural nucleosides. At least two species of reactive metabolites are involved in this bending, those with a half-life of a few hr and others with greater stability. After extraction from the aqueous incubation mixture, they could be detected in discrete polar fractions from separations of the complex metabolite mixture by high-pressure liquid chromatography. Their ability to bind to DNA decreased with time at ambient temperature, and they were rapidly deactivated by acid. 7,8-Benzolflavone acted by suppressing the formation of polar metabolites derived from enzymatic oxidation of the aromatic double bonds. The inhibitor had no effect on the enzymes hydroxylating saturated carbon; hence it is unlikely that metabolism of the methyl group is important in conversion of this carcinogen to its proximate form, although the presence of the 11-methyl group is essential for carcinogenic activity in this series. (+info)

The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene. (2/3060)

The endogenous CYP2B6 gene becomes phenobarbital (PB) inducible in androstenol-treated HepG2 cells either transiently or stably transfected with a nuclear receptor CAR expression vector. The PB induction mediated by CAR is regulated by a conserved 51-base pair element called PB-responsive enhancer module (PBREM) that has now been located between -1733 and -1683 bp in the gene's 5'-flanking region. An in vitro translated CAR acting as a retinoid X receptor alpha heterodimer binds directly to the two nuclear receptor sites NR1 and NR2 within PBREM. In a stably transfected HepG2 cell line, both PBREM and NR1 are activated by PB and PB-type compounds such as chlorinated pesticides, polychlorinated biphenyls and chlorpromazine. In addition to PBREM, CAR also transactivates the steroid/rifampicin-response element of the human CYP3A4 gene in HepG2 cells. Thus, activation of the repressed nuclear receptor CAR appears to be a versatile mediator that regulates PB induction of the CYP2B and other genes. (+info)

Induction of hepatic cytochromes P450 in dogs exposed to a chronic low dose of polychlorinated biphenyls. (3/3060)

Induction of cytochrome P450 isoforms, specifically CYP1A1, and their catalytic activities are potential biomarkers of environmental contamination by polychlorinated biphenyls (PCBs). In this study, dogs were exposed to 25 ppm or 5 ppm Aroclor 1248 (PCB mixture) daily in their diet for 10 or 20 weeks, respectively. Relative to controls, hepatic microsomes from dogs dosed with PCBs had higher levels of CYP1A1 detected in immunoblots and higher levels of EROD activity, but low levels of induction for CYP2B and PROD activity. Concentrations of 96 PCB congeners in serum and liver were evaluated using capillary chromatography. Results showed that all dogs exposed to PCB mixtures had higher levels of PCB in serum and liver. Dogs preferentially sequestered highly chlorinated PCB congeners in liver relative to serum. With these experiments, we demonstrated that EROD activity was a potentially sensitive marker of PCB exposure at 5 and 25 ppm. Furthermore, CYP1A1 and EROD activity were maximally induced in dogs consuming dietary concentrations only 2.5 times the maximal permissible level for human food (FDA). The value of CYP1A1 induction as a biomarker of PCB exposure was tenuous because neither CYP1A1 levels nor EROD activity correlated with total PCB body burden. However, a small subset of congeners were identified in liver that may strongly influence EROD and PROD induction. Finally, two dogs in the 25 ppm dose group were fasted for 48 h. After 24 h of fasting, several new congeners appeared in the serum and remained in the serum for the remainder of the fast. The fast caused a 293% increase in PCB concentration in serum. This increase has strong implications regarding mobilization of toxic PCBs in wildlife during fasting (e.g., migration, hibernation). (+info)

Regulation of cytochrome P-450 (CYP) 1B1 in mouse Hepa-1 variant cell lines: A possible role for aryl hydrocarbon receptor nuclear translocator (ARNT) as a suppressor of CYP1B1 gene expression. (4/3060)

Cytochrome P-450 (CYP) 1B1 expression in mouse hepatoma (Hepa-1) wild-type (WT) cells was compared with responses in Hepa-1 variants LA1 and LA2, which, respectively, exhibit low aryl hydrocarbon receptor (AhR) level and defective AhR nuclear translocator (ARNT) protein. 10T1/2 mouse embryo fibroblasts express predominantly CYP1B1 and at a 100 times higher level than in Hepa-1 cells, whereas they express about 300-fold lower CYP1A1 than Hepa-1 cells. The expression of CYP1B1 in WT and LA1 variant, although at a much lower level, follows that of CYP1A1, reflecting their common regulation through the AhR. The LA2 (ARNT-defective) cells showed a major difference between CYP1B1 and CYP1A1 expression. Although CYP1A1 mRNA levels in LA2 were extremely low and unresponsive to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), basal CYP1B1 mRNA and protein were expressed at levels similar to those seen in TCDD-induced WT. The elevated basal CYP1B1 mRNA in LA2 cells decreased by 50% after transient transfection of ARNT cDNA, in parallel with substantial restoration of CYP1A1 induction. This implicates ARNT as a suppressor of CYP1B1 basal expression in Hepa cells. In transient CYP1B1-luciferase constructs in LA2 cells, ARNT shows stimulatory effects in the enhancer region but an inhibitory effect on the proximal promoter. Two CYP1B1 enhancer elements [xenobiotic-responsive element (XRE) 1/2 and XRE4] formed TCDD-unresponsive complexes of similar mobility to TCDD-stimulated AhR-ARNT complex with XRE5. However, because these two complexes were formed to the same extent in LA2 as in WT cells, they cannot be due to ARNT or contribute to ARNT-regulated suppression. (+info)

Cytochrome P450 CYP1B1 determines susceptibility to 7, 12-dimethylbenz[a]anthracene-induced lymphomas. (5/3060)

CYP1B1-null mice, created by targeted gene disruption in embryonic stem cells, were born at the expected frequency from heterozygous matings with no observable phenotype, thus establishing that CYP1B1 is not required for mouse development. CYP1B1 was not detectable in cultured embryonic fibroblast (EF) or in different tissues, such as lung, of the CYP1B1-null mouse treated with the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin whereas the equivalent wild-type EF cells express basal and substantial inducible CYP1B1 and lung expresses inducible CYP1B1. CYP1A1 is induced to far higher levels than CYP1B1 in liver, kidney, and lung in wild-type mice and is induced to a similar extent in CYP1B1-null mice. 7,12-dimethylbenz[a]anthracene (DMBA) was toxic in wild-type EFs that express CYP1B1 but not CYP1A1. These cells effectively metabolized DMBA, consistent with CYP1B1 involvement in producing the procarcinogenic 3,4-dihydrodiol as a major metabolite, whereas CYP1B1-null EF showed no significant metabolism and were resistant to DMBA-mediated toxicity. When wild-type mice were administered high levels of DMBA intragastrically, 70% developed highly malignant lymphomas whereas only 7.5% of CYP1B1-null mice had lymphomas. Skin hyperplasia and tumors were also more frequent in wild-type mice. These results establish that CYP1B1, located exclusively at extrahepatic sites, mediates the carcinogenicity of DMBA. Surprisingly, CYP1A1, which has a high rate of DMBA metabolism in vitro, is not sufficient for this carcinogenesis, which demonstrates the importance of extrahepatic P450s in determining susceptibility to chemical carcinogens and validates the search for associations between P450 expression and cancer risk in humans. (+info)

Effect of cryopreservation on cytochrome P-450 enzyme induction in cultured rat hepatocytes. (6/3060)

In the present study, we evaluated the inducibility of cytochrome P-450 (CYP) CYP1A, CYP2B, CYP3A, and CYP4A by beta-naphthoflavone, phenobarbital, dexamethasone, and clofibric acid, respectively, in primary hepatocyte cultures prepared from both fresh and cryopreserved rat hepatocytes. Rat hepatocytes were successfully thawed and cultured after cryopreservation in liquid nitrogen for up to 1 month. Percentage of total recovery, viable cell recovery, and final viability of the cells were 68%, 72%, and 85%, respectively. Regardless of whether they were cryopreserved or not, cultured hepatocytes exhibited near-normal morphology. Treatment of cryopreserved hepatocytes with beta-naphthoflavone caused an 8-fold increase in 7-ethoxyresorufin O-dealkylase (CYP1A1/2) activity, with an EC50 of 1.5 microM; treatment with phenobarbital caused a 26-fold increase in 7-pentoxyresorufin O-dealkylase (CYP2B1/2) activity, with an EC50 of 10 microM; treatment with dexamethasone caused a 10-fold increase in testosterone 6beta-hydroxylase (CYP3A1/2) activity, with an EC50 of 1.3 microM, whereas treatment with clofibric acid caused a 3-fold increase in lauric acid 12-hydroxylase (CYP4A1-3) activity, with an EC50 of 170 microM. The induction of CYP1A, CYP2B, CYP3A, and CYP4A enzymes by these inducers was confirmed by Western immunoblotting. The patterns of P-450 induction in cryopreserved rat hepatocytes, in terms of concentration response, reproducibility, magnitude, and specificity of response, were similar to those observed in freshly isolated hepatocytes. Additionally, the magnitude and specificity of induction was similar to that observed in vivo in rats. In conclusion, under the conditions examined, cryopreserved rat hepatocytes appear to be a suitable in vitro system for evaluating xenobiotics as inducers of P-450 enzymes. (+info)

The aromatase inactivator 4-hydroxyandrostenedione (4-OH-A) inhibits tamoxifen metabolism by rat hepatic cytochrome P-450 3A: potential for drug-drug interaction of tamoxifen and 4-OH-A in combined anti-breast cancer therapy. (7/3060)

Tamoxifen (tam), an anti-breast cancer agent, is metabolized into tam-N-oxide by the hepatic flavin-containing monooxygenase and into N-desmethyl- and 4-hydroxy-tam by cytochrome P-450s (CYPs). Additionally, tam is metabolically activated by hepatic CYP3A, forming a reactive intermediate that binds covalently to proteins. Tam and 4-hydroxyandrostenedione (4-OH-A) are currently used to treat breast cancer, and it has been contemplated that 4-OH-A be given concurrently with tam to contravene potential tumor resistance to tam. Because alterations in tam metabolism may influence its therapeutic efficacy, the effect of 4-OH-A on tam metabolism was examined. Incubation of tam with liver microsomes from phenobarbital-treated rats, in the presence of 4-OH-A (10-100 microM), resulted in marked inhibition of tam-N-demethylation and tam covalent binding and in decreased tam-N-oxide accumulation; however, there was no inhibition of the formation of 4-hydroxy-tam and of 3,4-dihydroxytamoxifen. These findings indicate that 4-OH-A inhibits CYP3A, but not P-450(s) that catalyze tam 4-hydroxylation. The diminished tam-N-oxide accumulation could be due to decreased N-oxide formation and/or due to increased N-oxide reduction. Incubation of tam-N-oxide with liver microsomes containing heat-inactivated flavin-containing monooxygenase demonstrated that 4-OH-A increases the accumulation of tam, possibly by diminishing its P-450-mediated metabolism. Kinetic studies indicate that 4-OH-A is a competitive inhibitor of CYP3A, but not a time-dependent inactivator. Consequently, the concurrent treatment of tam and 4-OH-A may result in increased tam half-life and thus could potentiate the therapeutic efficacy of tam and diminish the potential side effects of tam by inhibiting its covalent binding to proteins and possibly to DNA. (+info)

Quantitative analysis of constitutive and 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytochrome P450 1B1 expression in human lymphocytes. (8/3060)

Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) results in a broad spectrum of biological responses, including altered metabolism, disruption of normal hormone signaling pathways, reproductive and developmental effects, and cancer. Cytochrome P450 1B1 (CYP1B1) is a dioxin-inducible gene that is active in the formation of 4-hydroxyestradiol, a potentially genotoxic catechol estrogen. Therefore, the analysis of CYP1B1 in humans may be useful in establishing relationships between dioxin exposure and adverse health effects. In this study, we examined the expression of CYP1B1 in human peripheral blood lymphocytes of unexposed individuals using a quantitative reverse transcription-PCR method. Absolute CYP1B1 RNA levels varied more than 30-fold in uncultured mononuclear cells obtained from 10 individuals. In vitro treatment of mitogen-stimulated lymphocytes with TCDD for 1-5 days of culture resulted in a peak induction of CYP1B1 after 3 days. The induction of CYP1B1 RNA levels after 3 days of culture was dose-dependent, exhibited a maximum response above 10 nM TCDD, and varied greatly among different individuals. However, the half maximal dose required for this induction was similar between individuals and comparable to that observed in the MCF-7 and HepG2 human cell lines. These observations indicate that CYP1B1 exhibits variable constitutive expression and is inducible in vitro by TCDD in human lymphocytes and that the magnitude of induction varies within the population. These data define the suitability of CYP1B1 for use as a mechanistically based biomarker in ongoing molecular epidemiological studies of human populations exposed to dioxins and related chemicals that bind the aromatic hydrocarbon receptor. (+info)

Treatment of the rats with 3-methylcholanthrene induced the nuclear aryl hydrocarbon hydroxylase (AHH) activity and also ... Treatment of the rats with 3-methylcholanthrene induced the nuclear aryl hydrocarbon hydroxylase (AHH) activity and also ... Treatment of the rats with 3-methylcholanthrene induced the nuclear aryl hydrocarbon hydroxylase (AHH) activity and also ... Treatment of the rats with 3-methylcholanthrene induced the nuclear aryl hydrocarbon hydroxylase (AHH) activity and also ...

https://www.researchwithrutgers.com/en/publications/binding-of-metabolically-activated-benzoapyrene-to-nuclear-macrom

Adult African Americans Aged Aged, 80 and over Anticoagulants Aryl Hydrocarbon Hydroxylases Calcium-Binding Proteins Cytochrome ...

https://labnodes.vanderbilt.edu/member/publication/id/10351/keyword_id/11866/keyword_name/Models,%20Genetic/pmid/22329724/pmid/32016367

Aryl hydrocarbon receptor (Ahr) can be a ligand-dependent transcriptional element, which features as an environmental sensor to ... 11-?? Hydroxylase *11??-Hydroxysteroid Dehydrogenase *14.3.3 Proteins *5-HT Receptors *5-HT Transporters ...

http://ourworldisblue.com/%EF%BB%BFunlike-adaptive-immune-system-cells-that-require-antigen-recognition-and-functional-maturation-during-infection-innate-lymphoid-cells-ilcs-usually-respond-to-pathogens-promptly-and-serve-a/

Beta-defensin 1, aryl hydrocarbon receptor and plasma kynurenine in major depressive disorder: metabolomics-informed genomics. ... A radiometric assay for kynurenine 3-hydroxylase based on the release of 3H2O during hydroxylation of L-[3,5-3H]kynurenine. ...

https://scholars.duke.edu/display/meshD007737

Aryls. *Anhydrides. *Amines. *Amidines. *Amides. *Alkynyls. *Alkyls. *Alkenyls. *Aliphatic Cyclic Hydrocarbons. *Aliphatic ...

https://a2bchem.com/Gepirone.html

Aryl hydrocarbon hydroxylase (AHH) was induced 15-fold in Ambystoma tigrinum by intraperitoneal injection of 3-methylcholanthrene in corn oil, or 10-fold by addition of aromatic polycyclic hydrocarbons to the aqueous environment of the neotene animal. (unt.edu)
In the AhAh or Ahah mouse but not in the ahah mouse, the hydroxylase is induced by a variety of aromatic compounds: polycyclic hydrocarbons such as 3-methylcholanthrene or benz[ a ]anthracene, flavones, and 2-phenylbenzothiazoles. (aspetjournals.org)
The effects of in vivo administration of polycyclic aromatic hydrocarbons on the levels of aryl hydrocarbon hydroxylase (AHH) activity in aromatic hydrocarbon (Ah) responsive and non-responsive strains of mice were studied using the hepatic microsomal fraction. (elsevier.com)
[5] Many species are also capable of oxidizing polycyclic aromatic hydrocarbons , a class of stable organic molecules that tends to persist in the environment and contains many known carcinogenic and mutagenic compounds. (wikipedia.org)
This protein localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. (genecards.org)
In addition, a variety of substances such as fuel, water, antifreeze, dust, and various combustion products such as polycyclic aromatic hydrocarbons (PAHs), metals, and metallic oxides accumulate in the oil. (cdc.gov)
We carried out a clinic-based case-control study specifically designed to address the hypothesis that dietary intake of polycyclic aromatic hydrocarbons (PAH) is associated with colorectal adenoma risk. (aacrjournals.org)
It is unclear, however, whether cancer risk is related to the amount of red meat consumption per se or to certain meat-cooking practices, which produce mutagens and carcinogens such as heterocyclic amines (HCA), polycyclic aromatic hydrocarbons (PAH), and possibly other agents ( 2 - 6 ). (aacrjournals.org)
Polycyclic aromatic hydrocarbons (PAHs), carcinogen mainly from cigarette smoking and air pollution, have been proved to be related to the development of COPD [ 10 , 11 ]. (hindawi.com)
It is involved in the metabolic activation of aromatic hydrocarbons (polycyclic aromatic hydrocarbons, PAH), for example, benzo[a]pyrene (BaP), by transforming it to an epoxide. (wikipedia.org)
Sediments from these sites exhibited a wide range in concentrations of xenobiotic compounds (e.g. concentrations of polycyclic aromatic hydrocarbons (PAHs) ranged from 20 to 50,000 ng/g dry weight and concentrations of polychlorinated biphenyls (PCBs) ranged from 2 to 1,400 ng/g dry weight), with the sites in Boston Harbor and Raritan Bay the most heavily contaminated. (noaa.gov)
Polycyclic aromatic hydrocarbons (PAHs) and cigarette smoke induce tumors of the respiratory organs in the pulmonary peripheral region in rats, in the pulmonary hilar region in humans and in the upper respiratory tract in Syrian hamsters (see review by Mohr and Dungworth, 1988). (springer.com)
Embryos from a population of the teleost fish, Fundulus heteroclitus , inhabiting a clean estuary do not survive when exposed to sediment extract from a site highly contaminated with polycyclic aromatic hydrocarbons (PAHs) while embryos derived from a population inhabiting a PAH polluted estuary are remarkably resistant to the polluted sediment extract. (biomedcentral.com)
Coho salmon and starry flounder Platichthys stellatus , exposed to 200 ppb of cadmium or lead in seawater at l0°C, were fed a model mixture of polycyclic aromatic hydrocarbons (PAHs) consisting of 2-nethylnaphthalene, 2,6-dimethylnaphthalene, and phenanthrene. (noaa.gov)
The strongest carcinogens present in tobacco smoke are polycyclic aromatic hydrocarbons (PAH), N -nitrosamines, aromatic amines, aldehydes, benzene and butadiene. (mdpi.com)
In the present study, to analyze the mechanism of CYP1A2 induction by phenobarbital, we examined whether there is any strain difference in this phenomenon and in particular, any correlation between the induction of CYP1A2 by phenobarbital and the induction of CYP1A1 by polycyclic aryl hydrocarbons. (aspetjournals.org)
CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. (nature.com)
The cytochrome P4501A1 encoded by the gene CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons such as benzo(a)pyrene. (nature.com)
The present study has been undertaken to examine whether exposure to benzo(a)pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH) compound influences the metabolism of fluoranthene (FLA), another PAH compound. (pubmedcentralcanada.ca)
One family of these chemicals that are ubiquitous in the environment is polycyclic aromatic hydrocarbons (PAHs), which are released into the environment as a result of petrogenic and pyrolytic processes. (pubmedcentralcanada.ca)
Alphla-nalphthoflavone also inhibits the aryl hydrocarbon hydroxylase activity in homogenates of induced hamster embryo cells and in liver microsomes from rats previously treated with polycyclic aromatic hydrocarbons, but not in microsomes from control rats. (sciencemag.org)
The leachability of polycyclic aromatic hydrocarbons from coal ash into aqueous systems was studied. (worldwidescience.org)

Because aryl hydrocarbon hydroxylase (AHH) is considered to be responsible for the activation of benzo(a)pyrene and other polyaromatic hydrocarbons in cigarette smoke to carcinogens, it is important to examine CYP1A1 (AHH) activity in the determination of susceptibility to lung cancer. (elsevier.com)
CYP1A1‐dependent aryl hydrocarbon hydroxylase activity is not inducible by 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin or 3‐methylcholanthrene in these two cell lines. (elsevier.com)
Diseases associated with CYP1A1 include Aryl Hydrocarbon Hydroxylase Inducibility and Ehrlich Tumor Carcinoma . (genecards.org)
CYP1A1 is also known as AHH (aryl hydrocarbon hydroxylase). (wikipedia.org)
The expression of the CYP1A1 gene, along with that of CYP1A2/1B1 genes, is regulated by a heterodimeric transcription factor that consist of the aryl hydrocarbon receptor, a ligand activated transcription factor, and the aryl hydrocarbon receptor nuclear translocator. (wikipedia.org)
Hepa-1c1c7 has high CYP1A1-dependent aryl hydrocarbon hydroxylase (AHH) activity. (atcc.org)
The transactivating domain of NFI/CTF was found to act in synergy with the arylhydrocarbon receptor pathway during the induction of CYP1A1 by 2,3,7,8-tetrachloro- p -dibenzodioxin. (asm.org)
CYP1A1 is a ubiquitous member of the P450 superfamily which is among the products of the aryl hydrocarbon (Ah)-inducible gene battery (reference 50 and references therein). (asm.org)
CYP1A1 debrisoquine 4-hydroxylase was inhibited by the CYP1A1 inhibitor α-naphthoflavone and the CYP1A1 substrate 7-ethoxyresorufin. (aspetjournals.org)
Anti-CYP1A1 monoclonal antibody (mAb) 1-7-1 abolished CYP1A1 debrisoquine hydroxylase and anti-CYP2D6 mAb 50-1-3 eradicated CYP2D6 debrisoquine 4-hydroxylase. (aspetjournals.org)

Aryl hydrocarbon hydroxylase (AHH) activity in two cell lines - Hepa-1c1 and H4IIE-C3 was induced to similar levels by benzo(a)-anthracence. (uwindsor.ca)
Aryl hydrocarbon (benzo[a]pyrene) hydroxylases in liver from rats of different age, sex and nutritional status. (semanticscholar.org)
It is highly inducible by the persistent environmental contaminant 2,3,7,8-tetrachloro- p -dibenzodioxin (TCDD) and by planar aromatic hydrocarbons, such as 3-methylcholanthrene or benzo(a)pyrene (BP) ( 24 , 44 , 59 ). (asm.org)
I. J. Sadowski, J. A. Wright and L. G. Israels, A permeabilized cell system for studying regulation of aryl hydrocarbon hydroxylase: NADPH as rate limiting factor in benzo(a)pyrene metabolism, Int. J. Biochem. (springer.com)

Induction of both diphenylhydantoin hydroxylase and aryl hydrocarbon hydroxylase occurs in the liver of 3-methylcholanthrene-treated Osborne-Mendel rats. (aspetjournals.org)
Previous kinetic studies have identified a high-affinity (S)-warfarin 7-hydroxylase present in human liver microsomes which appears to be responsible for the termination of warfarin's biological activity. (nih.gov)
Of the 11 forms examined only 2C9 displayed the regioselectivity and stereoselectivity appropriate for the high-affinity human liver microsomal (S)-7-hydroxylase. (nih.gov)
Chinook salmon Oncorhynchus tshawytscha , maintained in seawater at 13°C and fed mixtures of chlorobiphenyls and petroleum hydrocarbons separately and together, were examined for changes in hepatic microsomal AHH activity and for alterations in the morphology of liver, kidney, intestine, gill and skin tissues. (noaa.gov)
Liver aryl hydrocarbon hydroxylase (AHH) specific activity was low in the young NZB, increased gradually with age, and was higher in the female mice. (worldwidescience.org)
Effect of topical application of defined constituents of coal tar on skin and liver aryl hydrocarbon hydroxylase and 7-ethoxycoumarin deethylase activities. (cdc.gov)
Cytochrome P450 and aryl hydrocarbon hydroxylase (AHH) were present in liver and small intestinal mucosa from normal animals, but were undetectable in colon and rectum. (soton.ac.uk)

The present research was directed toward elucidating the effect of xenobiotics which alter the metabolism and toxicity of aromatic hydrocarbons by marine fish, as evinced through biochemical changes and altered cellular morphology. (noaa.gov)
Part II discusses the bioaccumulation and metabolism of hydrocarbons by marine organisms. (elsevier.com)

Distribution of aryl hydrocarbon hydroxylase inducibility in cultured" by B Paigen, J Minowada et al. (jax.org)
Distribution of aryl hydrocarbon hydroxylase inducibility in cultured human lymphocytes. (jax.org)

in any mouse homozygous or heterozygous for the allele Ah , the monooxygenase activity is generally induced by aromatic hydrocarbons in many tissues regularly containing the inducible enzyme system. (aspetjournals.org)
It is inhibited by hesperetin (a flavonoid found in lime, sweet orange), fluoroquinolones and macrolides and induced by aromatic hydrocarbons. (wikipedia.org)

Induction of hydroxylase activity by 3-methylcholanthrene administration to C57BL/6N mice is associated with an approximately equal conversion of hepatic type b to type a P-450, as measured by n -octylamine binding to the cytochrome. (aspetjournals.org)
Genetic regulation of aryl hydrocarbon hydroxylase induction. (jax.org)
These results indicate that CYP1A2 is a member of the family of phenobarbital-inducible genes in mice and suggest that the aryl hydrocarbon receptor-dependent induction pathway is not involved in the induction of CYP1A2. (aspetjournals.org)
The resistance is accompanied by reduced sensitivity to induction of cytochrome P450 1A (CYP1A), a widely used biomarker of aromatic hydrocarbon exposure and effect, but whether the reduced sensitivity is specific to CYP1A or reflects a genome-wide reduction in responsiveness to all AHR-mediated changes in gene expression is unknown. (biomedcentral.com)

These results suggest that CYP1B1 with polymorphic inducibility by dioxins is involved in aromatic hydrocarbon hydroxylase activities in human lymphocytes. (aacrjournals.org)

Hankinson O. Single-step selection of clones of a mouse hepatoma line deficient in aryl hydrocarbon hydroxylase. (atcc.org)

Among its related pathways are Estrogen Receptor Pathway and Aryl Hydrocarbon Receptor . (genecards.org)
Populations of Atlantic killifish ( Fundulus heteroclitus ) have evolved resistance to the embryotoxic effects of polychlorinated biphenyls (PCBs) and other halogenated and nonhalogenated aromatic hydrocarbons that act through an aryl hydrocarbon receptor (AHR)-dependent signaling pathway. (biomedcentral.com)
We sought to determine if genetic polymorphisms in the aryl hydrocarbon receptor signaling pathway are associated with menopausal hot flashes via hormone levels. (cdc.gov)

We measured aryl hydrocarbon hydroxylase (AHH) in cultured human lymphocytes. (jax.org)

A potent epoxide hydrase and aryl hydrocarbon hydroxylase inhibitor. (curehunter.com)

and for possible changes in the activities of hepatic microsomal aryl hydrocarbon hydroxylase (AHH). (noaa.gov)

The aryl-hydrocarbon receptor (AHR), a ligand activated PAS superfamily transcription factor, mediates most, if not all, of the toxicity induced upon exposure to various dioxins, dibenzofurans, and planar polyhalogenated biphenyls. (hindawi.com)
Blood carboxyhemoglobin, total particulate matter (TPM) intake, and pulmonary aryl hydrocarbon hydroxylase values indicated effective exposure of animals to cigarette smoke. (epa.gov)
10. The Effects of Petroleum Hydrocarbon Exposure on the Structure of Fish Tissues. (elsevier.com)
Journal Article] Fetal exposure to 2,3,7,8 'tetrachlorodibenzo-p-dioxin transactivates aryl hydrocarbon receptor-responsive element Ill in the tyrosine hydroxylase immunoreactive neurons of the mouse midbrain. (nii.ac.jp)
A marked decrease in biological concentrations of trimethylcyclohexane during the initial phase of exposure indicates that this hydrocarbon is capable of inducing its own metabolic conversion resulting in lower steady state levels. (europa.eu)

5. Biotransformation of Petroleum Hydrocarbons in Marine Organisms Indigenous to the Arctic and Subarctic. (elsevier.com)

It is unclear as yet whether these findings have implications for the relationship between CYP2D6 genotype and in vivo debrisoquine 4-hydroxylase activity. (aspetjournals.org)

The half life of enzyme activity induced in vivo was related to the excretion of hydrocarbon metabolites. (unt.edu)
Estradiol-2/4-hydroxylase (E-2/4-H) activity was determined in the mouse uterus during early pregnancy as well as in ovarian steroid hormone-treated ovariectomized uterus. (biomedsearch.com)
Phenobarbital induced the expression of CYP1A2 at the levels of mRNA, protein, and enzyme activity (methoxyresorufin O -demethylation and metabolic activation of 2-amino-3-methylimidazo[4,5- f ]quinoline) in both aryl hydrocarbon-responsive [C57BL/6NCrj (C57BL/6), C3H/HeJSlc] and -nonresponsive (DBA/2NCrj, AKR/JSea, NZB/NSlc) mouse strains. (aspetjournals.org)

In addition, the activities of hepatic AHH were induced by mixtures of the chlorobiphenyls and petroleum hydrocarbons, but not by the chlorobiphenyls alone or hydrocarbons alone. (noaa.gov)
The differences for the coho and chinook salmon in terms of the responses of the hepatic AHH systems to petroleum hydrocarbons and chlorobiphenyls may have been caused by differences due to seasonal parameters between the two experiments. (noaa.gov)
Fate and Effects of Petroleum Hydrocarbons in Marine Organisms and Ecosystems is a collection of papers presented at the international symposium by the same title, held at the Olympic Hotel in Seattle, Washington on November 10-12, 1976. (elsevier.com)
Part I deals with the inputs and physical transport processes influencing the distribution and composition of petroleum hydrocarbons in marine systems. (elsevier.com)
4. Biodegradation of Aromatic Petroleum Hydrocarbons. (elsevier.com)
6. Accumulation and Turnover of Petroleum Hydrocarbons in Marine Organisms. (elsevier.com)
9. Responses to Sublethal Levels of Petroleum Hydrocarbons: Are they Sensitive Indicators and do they Correlate with Tissue Contamination? (elsevier.com)
11. The Effects of Petroleum Hydrocarbons on Marine Populations and Communities. (elsevier.com)
17. The Effect of Petroleum Hydrocarbons on the Survival and Life History of Polychaetous Annelids. (elsevier.com)

Using chinook salmon microsomes, AHH activities were found depressed for all fish treated with either the chlorobiphenyls or the hydrocarbon mixture. (noaa.gov)

28. Arctic Hydrocarbon Biodegradation. (elsevier.com)

The aryl hydrocarbon receptor (AHR) plays a central role not only in the toxicity of dioxins and other xenobiotics ( 1 - 3 ) but also in normal physiology ( 4 - 6 ). (pubmedcentralcanada.ca)

Many of these exposures include ligands of the aryl hydrocarbon receptor (AHR), a transcription factor expressed by immune and nonimmune cells. (physiology.org)
Aryl hydrocarbon hydroxylase (AHH) activities are lower in G6PD-deficient cells, when tested in the absence of exogenous NADPH 2 . (springer.com)

Phenobarbital treatment of AhAh Ahah , or ahah mice similarly induces the hepatic aryl hydrocarbon hydroxylase system about 100% and causes identical increases of about 65% in both type a and b P-450. (aspetjournals.org)

AHR-mediated signaling starts in the cytoplasm, where the receptor can be found in a complex with the heat shock protein of 90 kDa (Hsp90) and the immunophilin-like protein, aryl-hydrocarbon receptor-interacting protein (AIP). (hindawi.com)
Upon ligand binding the AHR translocates to the nucleus and binds its heterodimeric partner, the aryl-hydrocarbon receptor nuclear translocator (ARNT) protein. (hindawi.com)
Heterologous expression of CYP2K1 and identification of the expressed protein (Bv-2K1) as lauric acid (omega-1)-hydroxylase and aflatoxin B1 exo-epoxidase. (zfin.org)

The Ah receptor (AhR), once activated by ligands such as TCDD or planar aromatic hydrocarbons, translocates from the cytosol into the nucleus, heterodimerizes with Arnt (AhR nuclear translocator), and binds to a class of promoter DNA sequences called xenobiotic-responsive elements (XRE) (references 17 and 48 and references therein). (asm.org)

Some of the developmental insults that have been associated with altered responses to infection later in life contain ligands for the aryl hydrocarbon receptor (AHR). (physiology.org)

the concentrations of the hydrocarbons were below detection limits, suggesting that they were metabolized and/or excreted by the fish. (noaa.gov)

Based on the data from the constituents, C9-C14 aliphatic, 2-25% aromatic hydrocarbon fluids, can be absorbed when inhaled, ingested, or when dermally exposed. (europa.eu)

Statistical eliminative process shows 3:4- benzopyrene (BP) to be the hydrocarbon of prime importance in lung cancer and bronchitis, with 1:12 benzoperylene contributing. (worldwidescience.org)

Immunohistochemistry and autoradiography were used to identify sites of the cytochrome P450 enzymes (P450) 1A1 and 1B1 expression and activation of 7,12-dimethylbenz(a)anthracene (DMBA), in the brain of rodents pretreated with the aryl hydrocarbon receptor (AhR) agonists beta-naphthoflavone (BNF), 3,3',4,4',5-pentachlorobiphenyl or vehicle. (diva-portal.org)

Anatomy13

Organisms12

Diseases5

Chemicals and Drugs141

Analytical, Diagnostic and Therapeutic Techniques and Equipment17

Phenomena and Processes41

Disciplines and Occupations1

Information Science4

Health Care9

An investigation into the binding of the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one to DNA in vitro. (1/3060)

The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene. (2/3060)

Induction of hepatic cytochromes P450 in dogs exposed to a chronic low dose of polychlorinated biphenyls. (3/3060)

Regulation of cytochrome P-450 (CYP) 1B1 in mouse Hepa-1 variant cell lines: A possible role for aryl hydrocarbon receptor nuclear translocator (ARNT) as a suppressor of CYP1B1 gene expression. (4/3060)

Cytochrome P450 CYP1B1 determines susceptibility to 7, 12-dimethylbenz[a]anthracene-induced lymphomas. (5/3060)

Effect of cryopreservation on cytochrome P-450 enzyme induction in cultured rat hepatocytes. (6/3060)

The aromatase inactivator 4-hydroxyandrostenedione (4-OH-A) inhibits tamoxifen metabolism by rat hepatic cytochrome P-450 3A: potential for drug-drug interaction of tamoxifen and 4-OH-A in combined anti-breast cancer therapy. (7/3060)

Quantitative analysis of constitutive and 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytochrome P450 1B1 expression in human lymphocytes. (8/3060)

Receptors, Aryl Hydrocarbon

Aryl Hydrocarbon Hydroxylases

Hydrocarbons

Tetrachlorodibenzodioxin

Aryl Hydrocarbon Receptor Nuclear Translocator

Cytochrome P-450 CYP1A1

Polycyclic Hydrocarbons, Aromatic

Procollagen-Proline Dioxygenase

Dioxins

Mixed Function Oxygenases

Benzo(a)pyrene

Methylcholanthrene

Hydrocarbons, Aromatic

Benz(a)Anthracenes

Prolyl Hydroxylases

Hypoxia-Inducible Factor-Proline Dioxygenases

Steroid Hydroxylases

Environmental Pollutants

Enzyme Induction

Polycyclic Compounds

Cytochrome P-450 Enzyme System

Hydroxylation

beta-Naphthoflavone

Benzoflavones

Benzopyrenes

Hypoxia-Inducible Factor 1, alpha Subunit

Hydrocarbons, Halogenated

Benzopyrene Hydroxylase

Alkanes

Polychlorinated Biphenyls

Basic Helix-Loop-Helix Transcription Factors

Hydrocarbons, Chlorinated

Xenobiotics

Teratogens

Hypoxia-Inducible Factor 1

Cytochrome P-450 CYP1A2

Alkane 1-Monooxygenase

RNA, Messenger

Ketoglutaric Acids

Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase

Aldehyde Oxidase

Dioxygenases

Liver

Molecular Sequence Data

Carcinogens

Phenylalanine Hydroxylase

Gene Expression Regulation, Enzymologic

Ligands

Cholestanetriol 26-Monooxygenase

Mice, Inbred C57BL

Cell Line, Tumor

Chloracne

Biodegradation, Environmental

Transcription Factors

Petroleum

Microsomes, Liver

Pyrenes

Oxygenases

Amino Acid Sequence

Soil Pollutants

9,10-Dimethyl-1,2-benzanthracene

Steroids, Fluorinated

Gene Expression Regulation

Cell Hypoxia

Tryptophan Hydroxylase

Transcription, Genetic

Xanthine Dehydrogenase

Benzofurans

Cell Line

Molybdenum

Oxygen

Base Sequence

Jaw Abnormalities

Fundulidae

Water Pollutants, Chemical

Signal Transduction

DNA Adducts

Cells, Cultured

Reverse Transcriptase Polymerase Chain Reaction

Anoxia