Aryl Hydrocarbon Receptor Nuclear Translocator
Receptors, Aryl Hydrocarbon
Tetrachlorodibenzodioxin
Cytochrome P-450 CYP1A1
Dioxins
Helix-Loop-Helix Motifs
Hypoxia-Inducible Factor 1
Hypoxia-Inducible Factor 1, alpha Subunit
Basic Helix-Loop-Helix Transcription Factors
Transcription Factors
DNA-Binding Proteins
Hydrocarbons
RNA, Messenger
Transcriptional Activation
Nuclear Proteins
Aryl Hydrocarbon Hydroxylases
Molecular Sequence Data
Polycyclic Hydrocarbons, Aromatic
Environmental Pollutants
Benzo(a)pyrene
Promoter Regions, Genetic
Xenobiotics
beta-Naphthoflavone
Benzoflavones
Enzyme Induction
Polychlorinated Biphenyls
Dimerization
Transcription, Genetic
AhR, ARNT, and CYP1A1 mRNA quantitation in cultured human embryonic palates exposed to TCDD and comparison with mouse palate in vivo and in culture. (1/421)
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is developmentally toxic in many species and induces cleft palate in the C57BL/6N mouse embryo. Palatogenesis in mouse and human embryos involves homologous processes at the morphological, cellular, and molecular levels. In organ culture, mouse and human palates respond similarly to TCDD. The present study quantitates the expression of AhR, ARNT, and CYP1A1 mRNA in human embryonic palates in organ culture. Palatal tissues were exposed to 1 x 10(-10), 1 x 10(-9), or 1 x 10(-8) M TCDD or control medium and sampled at 0, 2, 4, and 6 hours for quantitative RT-PCR using a synthetic RNA internal standard. Similar measurements of CYP1A1 gene expression were collected for mouse palates cultured in this model. In human palates, AhR expression correlated with ARNT and CYP1A1 mRNA expression. TCDD induction of CYP1A1 was time- and concentration-dependent. The expression of these genes presented a uniform and continuous distribution across the group of embryos, with no subset of either high or low expressors/responders. The ratio of AhR to ARNT was approximately 4:1. AhR mRNA increased during the culture period in both treated and control subjects; however, ARNT expression was relatively constant. TCDD did not alter either AhR or ARNT expression in a consistent dose- or time-related manner. Comparison of human and mouse data showed a high correlation across species for the induction of CYP1A1. Human embryos expressed approximately 350 times less AhR mRNA than the mouse, and in earlier studies it was shown that human palates required 200 times more TCDD to produce the same effects. When the morphological, cellular, and molecular responses to TCDD between mouse and human are compared, it seems highly unlikely that human embryos could be exposed to sufficient TCDD to achieve changes in palatal differentiation that would lead to cleft palate. (+info)RT-PCR quantification of AHR, ARNT, GR, and CYP1A1 mRNA in craniofacial tissues of embryonic mice exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and hydrocortisone. (2/421)
C57BL/6N mouse embryos exposed to hydrocortisone (HC) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) develop cleft palate. An interaction between these agents produces clefts at doses which alone are not teratogenic. The glucocorticoid receptor (GR) and dioxin receptor (AhR) mediated these responses and their gene expression was altered by TCDD and/or HC in palates examined on gestation day (GD) 14 by Northern blot analysis and in situ hybridization. The present study quantifies AhR, AhR nuclear translocator (ARNT), and GR mRNA at 4, 12, 24, and 48 h after exposure (time 0 = dose administration at 8 A.M. on gestation day 12) on GD12 to TCDD (24 micrograms/kg), HC (100 mg/kg) or HC (25 mg/kg) + TCDD (3 micrograms/kg). The induction of CYP1A1 mRNA was also quantified at 2, 4, 6, 12, 24, and 48 h for control and TCDD-exposed samples. Total RNA was prepared from midfacial tissue of 4-6 embryos/litter at each time and dose. An RNA internal standard (IS) for each gene was synthesized, which included the gene's primer sequences separated by a pUC19 plasmid sequence. Reverse transcription-polymerase chain reaction (RT-PCR) was performed on total RNA + IS using a range of 5-7 IS concentrations across a constant level of total RNA. PCR products were separated in gels (mRNA and IS-amplified sequences differed by 30-50 bases), ethidium bromide-stained, imaged (Hamamatsu Photonics Systems, Bridgewater, NJ), and quantified with NIH Image. CYP1A1 mRNA was significantly induced in the TCDD-exposed samples at all time points examined (p = 0.005 at 2 h and 0.001 after 2 h). During palatal shelf outgrowth on GD12, AhR mRNA levels increased significantly and this was not affected by treatment with TCDD or HC + TCDD. A significant increase in GR was detected at 24 h (p < 0.05) and this was unaffected by any of the exposures. Expression of ARNT increased at 12 h (p < 0.001); however, treatment with HC or HC + TCDD blocked this increase (p < 0.05). At 24 h, the TCDD-treated embryos had significantly lower ARNT mRNA compared with controls (p < 0.001). The relative overall expression level of the genes was AhR > ARNT > GR. Within individuals, expression of AhR and/or ARNT was highly correlated with GR level. In conclusion, CYP1A1 mRNA was expressed in developing craniofacial tissue and was highly induced by TCDD exposure. AhR, ARNT, and GR mRNA are upregulated in early palatogenesis, although not on the same schedule. The TCDD-induced decrease in ARNT at 24 h after dosing and the HC and HC + TCDD-induced delay in upregulation of ARNT may affect the dynamics of heterodimer formation between AhR and ARNT. The changes in ARNT mRNA level could also affect availability of this transcriptional regulator to interact with other potential partners, and these effects, separately or in combination, may be involved in disruption of normal embryonic development. (+info)Inhibition of hypoxia-inducible factor 1 activation by carbon monoxide and nitric oxide. Implications for oxygen sensing and signaling. (3/421)
It has been proposed that cells sense hypoxia by a heme protein, which transmits a signal that activates the heterodimeric transcription factor hypoxia-inducible factor 1 (HIF-1), thereby inducing a number of physiologically relevant genes such as erythropoietin (Epo). We have investigated the mechanism by which two heme-binding ligands, carbon monoxide and nitric oxide, affect oxygen sensing and signaling. Two concentrations of CO (10 and 80%) suppressed the activation of HIF-1 and induction of Epo mRNA by hypoxia in a dose-dependent manner. In contrast, CO had no effect on the induction of HIF-1 activity and Epo expression by either cobalt chloride or the iron chelator desferrioxamine. The affinity of CO for the putative sensor was much lower than that of oxygen (Haldane coefficient, approximately 0.5). Parallel experiments were done with 100 microM sodium nitroprusside, a nitric oxide donor. Both NO and CO inhibited HIF-1 DNA binding by abrogating hypoxia-induced accumulation of HIF-1alpha protein. Moreover, both NO and CO specifically targeted the internal oxygen-dependent degradation domain of HIF-1alpha, and also repressed the C-terminal transactivation domain of HIF-1alpha. Thus, NO and CO act proximally, presumably as heme ligands binding to the oxygen sensor, whereas desferrioxamine and perhaps cobalt appear to act at a site downstream. (+info)Induction and nuclear translocation of hypoxia-inducible factor-1 (HIF-1): heterodimerization with ARNT is not necessary for nuclear accumulation of HIF-1alpha. (4/421)
Hypoxia-inducible factor-1 (HIF-1) is a master regulator of mammalian oxygen homeostasis. HIF-1 consists of two subunits, HIF-1alpha and the aryl hydrocarbon receptor nuclear translocator (ARNT). Whereas hypoxia prevents proteasomal degradation of HIF-1alpha, ARNT expression is thought to be oxygen-independent. We and others previously showed that ARNT is indispensable for HIF-1 DNA-binding and transactivation function. Here, we have used ARNT-mutant mouse hepatoma and embryonic stem cells to examine the requirement of ARNT for accumulation and nuclear translocation of HIF-1alpha in hypoxia. As shown by immunofluorescence, HIF-1alpha accumulation in the nucleus of hypoxic cells was independent of the presence of ARNT, suggesting that nuclear translocation is intrinsic to HIF-1alpha. Co-immunoprecipitation of HIF-1alpha together with ARNT could be performed in nuclear extracts but not in cytosolic fractions, implying that formation of the HIF-1 complex occurs in the nucleus. A proteasome inhibitor and a thiol-reducing agent could mimic hypoxia by inducing HIF-1alpha in the nucleus, indicating that escape from proteolytic degradation is sufficient for accumulation and nuclear translocation of HIF-1alpha. During biochemical separation, both HIF-1alpha and ARNT tend to leak from the nuclei in the absence of either subunit, suggesting that heterodimerization is required for stable association within the nuclear compartment. Nuclear stabilization of the heterodimer might also explain the hypoxically increased total cellular ARNT levels observed in some of the cell lines examined. (+info)Protein kinase C modulates aryl hydrocarbon receptor nuclear translocator protein-mediated transactivation potential in a dimer context. (5/421)
Protein kinase C (PKC)- and protein kinase A (PKA)-mediated modulation of the transactivation potential of human aryl hydrocarbon receptor nuclear translocator (hARNT), a basic helix-loop-helix (bHLH)-PAS transcription factor, and the bHLH-ZIP transcription factors USF-1 (for upstream regulatory factor 1) and c-Myc were examined. An 81 nM dose of the PKC activator phorbol-12-myristate-13-acetate (PMA), shown here to specifically activate PKC in COS-1 cells, or a 1 nM dose of the PKA activator 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP) results in 2. 6- and 1.9-fold enhancements, respectively, in hARNT-mediated transactivation of the class B, E-box-driven reporter pMyc3E1bLuc relative to identically transfected, carrier solvent-treated COS-1 cells. In contrast, 81 nM PMA and 1 nM 8-Br-cAMP did not enhance transactivation of pMyc3E1bLuc-driven by USF-1 and c-Myc expression relative to identically transfected, carrier-treated COS-1 cells. Co-transfection of pcDNA3/ARNT-474-Flag, expressing a hARNT carboxyl-terminal transactivation domain deletion, and pMyc3E1bLuc does not result in induction of reporter activity, suggesting PMA's effects do not involve formation of unknown hARNT-protein heterodimers. Additionally, PMA had no effect on hARNT expression relative to Me2SO-treated cells. Metabolic 32P labeling of hARNT in cells treated with carrier solvent or 81 nM PMA demonstrates that PMA does not increase the overall phosphorylation level of hARNT. These results demonstrate, for the first time, that the transactivation potential of ARNT in a dimer context can be specifically modulated by PKC or PKA stimulation and that the bHLH-PAS and bHLH-ZIP transcription factors are differentially regulated by these pathways in COS-1 cells. (+info)Repression of dioxin signal transduction in fibroblasts. Identification Of a putative repressor associated with Arnt. (6/421)
Heterodimeric complexes of basic helix-loop-helix/PAS transcription factors are involved in regulation of diverse physiological phenomena such as circadian rhythms, reaction to low oxygen tension, and detoxification. In fibroblasts, the basic helix-loop-helix/PAS heterodimer consisting of the ligand-inducible dioxin receptor and Arnt shows DNA-binding activity, and the receptor and Arnt are able to activate transcription when fused to a heterologous DNA-binding domain. However, fibroblasts are nonresponsive to dioxin with regard to induction mediated by the DNA response element recognized by the receptor and Arnt. Here we demonstrate that Arnt is associated with a fibroblast-specific factor, forming a complex that is capable of binding the dioxin response element. This factor may function as a repressor since negative regulation of target gene induction appears to be abolished by inhibition of histone deacetylase activity by trichostatin A. Finally, the negative regulatory function of this factor appears to be restricted for dioxin signaling since Arnt was able to mediate, together with hypoxia-inducible factor-1alpha, transcriptional activation in hypoxic cells. Taken together, these data suggest that fibroblast-specific inhibition of dioxin responsiveness involves recruitment by Arnt of a cell type- and signaling pathway-specific corepressor associated with a histone deacetylase. (+info)Aromatic hydrocarbon nuclear translocator as a common component for the hypoxia- and dioxin-induced gene expression. (7/421)
Aromatic hydrocarbon nuclear translocator (Arnt) is an ubiquitously expressed protein that contains basic helix-loop-helix (bHLH) and Per-AhR-Arnt-Sim (PAS) motifs. Other bHLH-PAS proteins, hypoxia-inducible factor-1alpha (HIF-1alpha) and aromatic hydrocarbon receptor (AhR) mediate hypoxia- and dioxin-signal pathway, respectively. Arnt has been identified as a heterodimerization partner for AhR. AhR/Arnt heterodimer binds the regulatory region of xenobiotic-induced genes and activates their transcription. Here, in vivo results provide evidence that Arnt is involved in not only xenobiotic- but also hypoxia-induced transcriptional activation. In hypoxic condition, Arnt dimerizes with HIF-1alpha to make HIF-1alpha/Arnt heterodimer which is able to bind hypoxia-responsive DNA elements. The HIF-1alpha/Arnt heterodimer functions as a transactivator for hypoxia-inducible genes. Given that the expression of Arnt is limited, HIF-1alpha may compete with AhR for recruiting Arnt as a heteromeric partner. Consistent with this idea, the results indicate that the hypoxic activation of HIF-1alpha reduces dioxin-induced AhR's function on the dioxin-responsive reporter gene and the endogenous gene. (+info)Expression of CYP1A1 and CYP1B1 depends on cell-specific factors in human breast cancer cell lines: role of estrogen receptor status. (8/421)
The impact of estrogen receptor (ER) was examined for expression and activity of cytochrome P4501B1 (CYP1B1) and cytochrome P4501A1 (CYP1A1) in two pairs of ER+/ER- human breast epithelial cell lines derived from single lineages, and representing earlier (T47D) or later (MDA-MB-231) stages of tumorigenesis. Acute loss of ER was evaluated using the anti-estrogen ICI 182,780 (ICI). In all lines, CYP1B1 was expressed constitutively and was induced by 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD), whereas CYP1A1 was expressed only following induction. Expression of each CYP (with or without TCDD) was greater in T47D cells than MDA cells. The ER impacted expression of these genes in opposite directions. The ER- phenotype was associated with less TCDD-induced CYP1A1 expression, but greater basal and induced CYP1B1 expression. A 48 h treatment of ER+ cells with ICI did not revert the P450 expression pattern to that of ER- cells. Based on activities of recombinant enzyme and expression levels, differences in 7,2-dimethylbenz [a]anthracene (DMBA) metabolism between the cell lines were consistent with differences in CYP1A1 and CYP1B1 expression. In T47D lines, basal microsomal DMBA metabolism was primarily due to CYP1B1, based on regioselective metabolite distribution and inhibition by anti-CYP1B1 antibodies (>80%). Metabolism in TCDD-induced microsomes was mostly due to CYP1A1 and was inhibited by anti-CYP1A1 antibody (>50%). TCDD-induced MDA+ cells demonstrated CYP1A1 activity, whereas TCDD-induced MDA- cells displayed CYP1B1 activity. Aryl hydrocarbon receptor (AhR) levels, but not AhR nuclear translocator protein (ARNT) levels were highly dependent on cell type; AhR was high and ER-independent in MDA, and low and ER-linked in T47D. AhR levels were insensitive to ICI. ER does not directly modulate the expression of CYP1A1, CYP1B1 or AhR. Indeed, factors that have replaced ER in growth regulation during clonal selection predominate in this regulation. Characteristics unique to each cell line, including ER status, determine CYP1A1 and CYP1B1 expression. (+info)The Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) is a protein that plays a crucial role in the functioning of the aryl hydrocarbon receptor (AhR) signaling pathway. The AhR signaling pathway is involved in various biological processes, including the regulation of xenobiotic metabolism and cellular responses to environmental contaminants such as polycyclic aromatic hydrocarbons (PAHs) and dioxins.
The ARNT protein forms a heterodimer with the AhR protein upon ligand binding, which then translocates into the nucleus. Once in the nucleus, this complex binds to specific DNA sequences called xenobiotic response elements (XREs), leading to the activation or repression of target genes involved in various cellular processes such as detoxification, cell cycle regulation, and immune responses.
Therefore, the ARNT protein is an essential component of the AhR signaling pathway, and its dysregulation has been implicated in several diseases, including cancer, autoimmune disorders, and neurodevelopmental disorders.
Aryl hydrocarbon receptors (AhRs) are a type of intracellular receptor that play a crucial role in the response to environmental contaminants and other xenobiotic compounds. They are primarily found in the cytoplasm of cells, where they bind to aromatic hydrocarbons, including polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), which are common environmental pollutants.
Once activated by ligand binding, AhRs translocate to the nucleus, where they dimerize with the AhR nuclear translocator (ARNT) protein and bind to specific DNA sequences called xenobiotic response elements (XREs). This complex then regulates the expression of a variety of genes involved in xenobiotic metabolism, including those encoding cytochrome P450 enzymes.
In addition to their role in xenobiotic metabolism, AhRs have been implicated in various physiological processes, such as immune response, cell differentiation, and development. Dysregulation of AhR signaling has been associated with the pathogenesis of several diseases, including cancer, autoimmune disorders, and neurodevelopmental disorders.
Therefore, understanding the mechanisms of AhR activation and regulation is essential for developing strategies to prevent or treat environmental toxicant-induced diseases and other conditions linked to AhR dysfunction.
Tetrachlorodibenzodioxin (TCDD) is not a common medical term, but it is known in toxicology and environmental health. TCDD is the most toxic and studied compound among a group of chemicals known as dioxins.
Medical-related definition:
Tetrachlorodibenzodioxin (TCDD) is an unintended byproduct of various industrial processes, including waste incineration, chemical manufacturing, and pulp and paper bleaching. It is a highly persistent environmental pollutant that accumulates in the food chain, primarily in animal fat. Human exposure to TCDD mainly occurs through consumption of contaminated food, such as meat, dairy products, and fish. TCDD is a potent toxicant with various health effects, including immunotoxicity, reproductive and developmental toxicity, and carcinogenicity. The severity of these effects depends on the level and duration of exposure.
Cytochrome P-450 CYP1A1 is an enzyme that is part of the cytochrome P450 family, which are a group of enzymes involved in the metabolism of drugs and other xenobiotics (foreign substances) in the body. Specifically, CYP1A1 is found primarily in the liver and lungs and plays a role in the metabolism of polycyclic aromatic hydrocarbons (PAHs), which are chemicals found in tobacco smoke and are produced by the burning of fossil fuels and other organic materials.
CYP1A1 also has the ability to activate certain procarcinogens, which are substances that can be converted into cancer-causing agents (carcinogens) within the body. Therefore, variations in the CYP1A1 gene may influence an individual's susceptibility to cancer and other diseases.
The term "P-450" refers to the fact that these enzymes absorb light at a wavelength of 450 nanometers when they are combined with carbon monoxide, giving them a characteristic pink color. The "CYP" stands for "cytochrome P," and the number and letter designations (e.g., 1A1) indicate the specific enzyme within the family.
Dioxins are a group of chemically-related compounds that are primarily formed as unintended byproducts of various industrial, commercial, and domestic processes. They include polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and certain polychlorinated biphenyls (PCBs). Dioxins are highly persistent environmental pollutants that accumulate in the food chain, particularly in animal fat. Exposure to dioxins can cause a variety of adverse health effects, including developmental and reproductive problems, immune system damage, hormonal disruption, and cancer. The most toxic form of dioxin is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Helix-loop-helix (HLH) motifs are structural domains found in certain proteins, particularly transcription factors, that play a crucial role in DNA binding and protein-protein interactions. These motifs consist of two amphipathic α-helices connected by a loop region. The first helix is known as the "helix-1" or "recognition helix," while the second one is called the "helix-2" or "dimerization helix."
In many HLH proteins, the helices come together to form a dimer through interactions between their hydrophobic residues located in the core of the helix-2. This dimerization enables DNA binding by positioning the recognition helices in close proximity to each other and allowing them to interact with specific DNA sequences, often referred to as E-box motifs (CANNTG).
HLH motifs can be further classified into basic HLH (bHLH) proteins and HLH-only proteins. bHLH proteins contain a basic region adjacent to the N-terminal end of the first helix, which facilitates DNA binding. In contrast, HLH-only proteins lack this basic region and primarily function as dimerization partners for bHLH proteins or participate in other protein-protein interactions.
These motifs are involved in various cellular processes, including cell fate determination, differentiation, proliferation, and apoptosis. Dysregulation of HLH proteins has been implicated in several diseases, such as cancer and neurodevelopmental disorders.
Hypoxia-Inducible Factor 1 (HIF-1) is a transcription factor that plays a crucial role in the cellular response to low oxygen levels, also known as hypoxia. It is a heterodimeric protein composed of two subunits: HIF-1α and HIF-1β.
Under normoxic conditions (adequate oxygen supply), HIF-1α is constantly produced but rapidly degraded by proteasomes due to the action of prolyl hydroxylases, which mark it for destruction in the presence of oxygen. However, under hypoxic conditions, the activity of prolyl hydroxylases is inhibited, leading to the stabilization and accumulation of HIF-1α.
Once stabilized, HIF-1α translocates to the nucleus and forms a complex with HIF-1β. This complex then binds to hypoxia-responsive elements (HREs) in the promoter regions of various genes involved in angiogenesis, glucose metabolism, erythropoiesis, cell survival, and other processes that help cells adapt to low oxygen levels.
By activating these target genes, HIF-1 plays a critical role in regulating the body's response to hypoxia, including promoting the formation of new blood vessels (angiogenesis), enhancing anaerobic metabolism, and inhibiting cell proliferation and apoptosis under low oxygen conditions. Dysregulation of HIF-1 has been implicated in several diseases, such as cancer, cardiovascular disease, and ischemic disorders.
Hypoxia-Inducible Factor 1 (HIF-1) is a transcription factor that plays a crucial role in the body's response to low oxygen levels, also known as hypoxia. HIF-1 is a heterodimeric protein composed of two subunits: an alpha subunit (HIF-1α) and a beta subunit (HIF-1β).
The alpha subunit, HIF-1α, is the regulatory subunit that is subject to oxygen-dependent degradation. Under normal oxygen conditions (normoxia), HIF-1α is constantly produced in the cell but is rapidly degraded by proteasomes due to hydroxylation of specific proline residues by prolyl hydroxylase domain-containing proteins (PHDs). This hydroxylation reaction requires oxygen as a substrate, and under hypoxic conditions, the activity of PHDs is inhibited, leading to the stabilization and accumulation of HIF-1α.
Once stabilized, HIF-1α translocates to the nucleus, where it heterodimerizes with HIF-1β and binds to hypoxia-responsive elements (HREs) in the promoter regions of target genes. This binding results in the activation of gene transcription programs that promote cellular adaptation to low oxygen levels. These adaptive responses include increased erythropoiesis, angiogenesis, glucose metabolism, and pH regulation, among others.
Therefore, HIF-1α is a critical regulator of the body's response to hypoxia, and its dysregulation has been implicated in various pathological conditions, including cancer, cardiovascular disease, and neurodegenerative disorders.
Basic Helix-Loop-Helix (bHLH) transcription factors are a type of proteins that regulate gene expression through binding to specific DNA sequences. They play crucial roles in various biological processes, including cell growth, differentiation, and apoptosis. The bHLH domain is composed of two amphipathic α-helices separated by a loop region. This structure allows the formation of homodimers or heterodimers, which then bind to the E-box DNA motif (5'-CANNTG-3') to regulate transcription.
The bHLH family can be further divided into several subfamilies based on their sequence similarities and functional characteristics. Some members of this family are involved in the development and function of the nervous system, while others play critical roles in the development of muscle and bone. Dysregulation of bHLH transcription factors has been implicated in various human diseases, including cancer and neurodevelopmental disorders.
Transcription factors are proteins that play a crucial role in regulating gene expression by controlling the transcription of DNA to messenger RNA (mRNA). They function by binding to specific DNA sequences, known as response elements, located in the promoter region or enhancer regions of target genes. This binding can either activate or repress the initiation of transcription, depending on the properties and interactions of the particular transcription factor. Transcription factors often act as part of a complex network of regulatory proteins that determine the precise spatiotemporal patterns of gene expression during development, differentiation, and homeostasis in an organism.
DNA-binding proteins are a type of protein that have the ability to bind to DNA (deoxyribonucleic acid), the genetic material of organisms. These proteins play crucial roles in various biological processes, such as regulation of gene expression, DNA replication, repair and recombination.
The binding of DNA-binding proteins to specific DNA sequences is mediated by non-covalent interactions, including electrostatic, hydrogen bonding, and van der Waals forces. The specificity of binding is determined by the recognition of particular nucleotide sequences or structural features of the DNA molecule.
DNA-binding proteins can be classified into several categories based on their structure and function, such as transcription factors, histones, and restriction enzymes. Transcription factors are a major class of DNA-binding proteins that regulate gene expression by binding to specific DNA sequences in the promoter region of genes and recruiting other proteins to modulate transcription. Histones are DNA-binding proteins that package DNA into nucleosomes, the basic unit of chromatin structure. Restriction enzymes are DNA-binding proteins that recognize and cleave specific DNA sequences, and are widely used in molecular biology research and biotechnology applications.
Cell hypoxia, also known as cellular hypoxia or tissue hypoxia, refers to a condition in which the cells or tissues in the body do not receive an adequate supply of oxygen. Oxygen is essential for the production of energy in the form of ATP (adenosine triphosphate) through a process called oxidative phosphorylation. When the cells are deprived of oxygen, they switch to anaerobic metabolism, which produces lactic acid as a byproduct and can lead to acidosis.
Cell hypoxia can result from various conditions, including:
1. Low oxygen levels in the blood (hypoxemia) due to lung diseases such as chronic obstructive pulmonary disease (COPD), pneumonia, or high altitude.
2. Reduced blood flow to tissues due to cardiovascular diseases such as heart failure, peripheral artery disease, or shock.
3. Anemia, which reduces the oxygen-carrying capacity of the blood.
4. Carbon monoxide poisoning, which binds to hemoglobin and prevents it from carrying oxygen.
5. Inadequate ventilation due to trauma, drug overdose, or other causes that can lead to respiratory failure.
Cell hypoxia can cause cell damage, tissue injury, and organ dysfunction, leading to various clinical manifestations depending on the severity and duration of hypoxia. Treatment aims to correct the underlying cause and improve oxygen delivery to the tissues.
I'm sorry for any confusion, but "hydrocarbons" is not a term that has a specific medical definition. Hydrocarbons are organic compounds consisting entirely of hydrogen and carbon. They are primarily used in industry as fuel, lubricants, and as raw materials for the production of plastics, fibers, and other chemicals.
However, in a broader scientific context, hydrocarbons can be relevant to medical discussions. For instance, in toxicology, exposure to certain types of hydrocarbons (like those found in gasoline or solvents) can lead to poisoning and related health issues. In environmental medicine, the pollution of air, water, and soil with hydrocarbons is a concern due to potential health effects.
But in general clinical medicine, 'hydrocarbons' wouldn't have a specific definition.
Messenger RNA (mRNA) is a type of RNA (ribonucleic acid) that carries genetic information copied from DNA in the form of a series of three-base code "words," each of which specifies a particular amino acid. This information is used by the cell's machinery to construct proteins, a process known as translation. After being transcribed from DNA, mRNA travels out of the nucleus to the ribosomes in the cytoplasm where protein synthesis occurs. Once the protein has been synthesized, the mRNA may be degraded and recycled. Post-transcriptional modifications can also occur to mRNA, such as alternative splicing and addition of a 5' cap and a poly(A) tail, which can affect its stability, localization, and translation efficiency.
Transcriptional activation is the process by which a cell increases the rate of transcription of specific genes from DNA to RNA. This process is tightly regulated and plays a crucial role in various biological processes, including development, differentiation, and response to environmental stimuli.
Transcriptional activation occurs when transcription factors (proteins that bind to specific DNA sequences) interact with the promoter region of a gene and recruit co-activator proteins. These co-activators help to remodel the chromatin structure around the gene, making it more accessible for the transcription machinery to bind and initiate transcription.
Transcriptional activation can be regulated at multiple levels, including the availability and activity of transcription factors, the modification of histone proteins, and the recruitment of co-activators or co-repressors. Dysregulation of transcriptional activation has been implicated in various diseases, including cancer and genetic disorders.
Nuclear proteins are a category of proteins that are primarily found in the nucleus of a eukaryotic cell. They play crucial roles in various nuclear functions, such as DNA replication, transcription, repair, and RNA processing. This group includes structural proteins like lamins, which form the nuclear lamina, and regulatory proteins, such as histones and transcription factors, that are involved in gene expression. Nuclear localization signals (NLS) often help target these proteins to the nucleus by interacting with importin proteins during active transport across the nuclear membrane.
Aryl hydrocarbon hydroxylases (AHH) are a group of enzymes that play a crucial role in the metabolism of various aromatic and heterocyclic compounds, including potentially harmful substances such as polycyclic aromatic hydrocarbons (PAHs) and dioxins. These enzymes are primarily located in the endoplasmic reticulum of cells, particularly in the liver, but can also be found in other tissues.
The AHH enzymes catalyze the addition of a hydroxyl group (-OH) to the aromatic ring structure of these compounds, which is the first step in their biotransformation and eventual elimination from the body. This process can sometimes lead to the formation of metabolites that are more reactive and potentially toxic than the original compound. Therefore, the overall impact of AHH enzymes on human health is complex and depends on various factors, including the specific compounds being metabolized and individual genetic differences in enzyme activity.
Molecular sequence data refers to the specific arrangement of molecules, most commonly nucleotides in DNA or RNA, or amino acids in proteins, that make up a biological macromolecule. This data is generated through laboratory techniques such as sequencing, and provides information about the exact order of the constituent molecules. This data is crucial in various fields of biology, including genetics, evolution, and molecular biology, allowing for comparisons between different organisms, identification of genetic variations, and studies of gene function and regulation.
Polycyclic aromatic hydrocarbons (PAHs) are a group of organic compounds characterized by the presence of two or more fused benzene rings. They are called "polycyclic" because they contain multiple cyclic structures, and "aromatic" because these structures contain alternating double bonds that give them distinctive chemical properties and a characteristic smell.
PAHs can be produced from both natural and anthropogenic sources. Natural sources include wildfires, volcanic eruptions, and the decomposition of organic matter. Anthropogenic sources include the incomplete combustion of fossil fuels, such as coal, oil, and gasoline, as well as tobacco smoke, grilled foods, and certain industrial processes.
PAHs are known to be environmental pollutants and can have harmful effects on human health. They have been linked to an increased risk of cancer, particularly lung, skin, and bladder cancers, as well as reproductive and developmental toxicity. PAHs can also cause skin irritation, respiratory problems, and damage to the immune system.
PAHs are found in a variety of environmental media, including air, water, soil, and food. They can accumulate in the food chain, particularly in fatty tissues, and have been detected in a wide range of foods, including meat, fish, dairy products, and vegetables. Exposure to PAHs can occur through inhalation, ingestion, or skin contact.
It is important to limit exposure to PAHs by avoiding tobacco smoke, reducing consumption of grilled and smoked foods, using ventilation when cooking, and following safety guidelines when working with industrial processes that produce PAHs.
Environmental pollutants are defined as any substances or energy (such as noise, heat, or light) that are present in the environment and can cause harm or discomfort to humans or other living organisms, or damage the natural ecosystems. These pollutants can come from a variety of sources, including industrial processes, transportation, agriculture, and household activities. They can be in the form of gases, liquids, solids, or radioactive materials, and can contaminate air, water, and soil. Examples include heavy metals, pesticides, volatile organic compounds (VOCs), particulate matter, and greenhouse gases.
It is important to note that the impact of environmental pollutants on human health and the environment can be acute (short-term) or chronic (long-term) and it depends on the type, concentration, duration and frequency of exposure. Some common effects of environmental pollutants include respiratory problems, cancer, neurological disorders, reproductive issues, and developmental delays in children.
It is important to monitor, control and reduce the emissions of these pollutants through regulations, technology advancements, and sustainable practices to protect human health and the environment.
Teratogens are substances, such as certain medications, chemicals, or infectious agents, that can cause birth defects or abnormalities in the developing fetus when a woman is exposed to them during pregnancy. They can interfere with the normal development of the fetus and lead to a range of problems, including physical deformities, intellectual disabilities, and sensory impairments. Examples of teratogens include alcohol, tobacco smoke, some prescription medications, and infections like rubella (German measles). It is important for women who are pregnant or planning to become pregnant to avoid exposure to known teratogens as much as possible.
Promoter regions in genetics refer to specific DNA sequences located near the transcription start site of a gene. They serve as binding sites for RNA polymerase and various transcription factors that regulate the initiation of gene transcription. These regulatory elements help control the rate of transcription and, therefore, the level of gene expression. Promoter regions can be composed of different types of sequences, such as the TATA box and CAAT box, and their organization and composition can vary between different genes and species.
Xenobiotics are substances that are foreign to a living organism and usually originate outside of the body. This term is often used in the context of pharmacology and toxicology to refer to drugs, chemicals, or other agents that are not naturally produced by or expected to be found within the body.
When xenobiotics enter the body, they undergo a series of biotransformation processes, which involve metabolic reactions that convert them into forms that can be more easily excreted from the body. These processes are primarily carried out by enzymes in the liver and other organs.
It's worth noting that some xenobiotics can have beneficial effects on the body when used as medications or therapeutic agents, while others can be harmful or toxic. Therefore, understanding how the body metabolizes and eliminates xenobiotics is important for developing safe and effective drugs, as well as for assessing the potential health risks associated with exposure to environmental chemicals and pollutants.
Beta-Naphthoflavone is a type of compound known as an aromatic hydrocarbon receptor (AHR) agonist. It is often used in research to study the effects of AHR activation on various biological processes, including the regulation of gene expression and the development of certain diseases such as cancer.
In the medical field, beta-Naphthoflavone may be used in experimental settings to investigate its potential as a therapeutic agent or as a tool for understanding the mechanisms underlying AHR-mediated diseases. However, it is not currently approved for use as a medication in humans.
Benzoflavones are a type of chemical compound that consist of a benzene ring (a basic unit of organic chemistry made up of six carbon atoms arranged in a flat, hexagonal shape) fused to a flavone structure. Flavones are a type of flavonoid, which is a class of plant pigments widely present in fruits and vegetables. Benzoflavones have been studied for their potential medicinal properties, including anti-inflammatory, antioxidant, and anticancer activities. However, more research is needed to fully understand their effects and safety profile in humans.
Methylcholanthrene is a polycyclic aromatic hydrocarbon that is used in research to induce skin tumors in mice. It is a potent carcinogen and mutagen, and exposure to it can increase the risk of cancer in humans. It is not typically found in medical treatments or therapies.
Enzyme induction is a process by which the activity or expression of an enzyme is increased in response to some stimulus, such as a drug, hormone, or other environmental factor. This can occur through several mechanisms, including increasing the transcription of the enzyme's gene, stabilizing the mRNA that encodes the enzyme, or increasing the translation of the mRNA into protein.
In some cases, enzyme induction can be a beneficial process, such as when it helps the body to metabolize and clear drugs more quickly. However, in other cases, enzyme induction can have negative consequences, such as when it leads to the increased metabolism of important endogenous compounds or the activation of harmful procarcinogens.
Enzyme induction is an important concept in pharmacology and toxicology, as it can affect the efficacy and safety of drugs and other xenobiotics. It is also relevant to the study of drug interactions, as the induction of one enzyme by a drug can lead to altered metabolism and effects of another drug that is metabolized by the same enzyme.
Polychlorinated biphenyls (PCBs) are a group of man-made organic chemicals consisting of 209 individual compounds, known as congeners. The congeners are formed by the combination of two benzene rings with varying numbers and positions of chlorine atoms.
PCBs were widely used in electrical equipment, such as transformers and capacitors, due to their non-flammability, chemical stability, and insulating properties. They were also used in other applications, including coolants and lubricants, plasticizers, pigments, and copy oils. Although PCBs were banned in many countries in the 1970s and 1980s due to their toxicity and environmental persistence, they still pose significant health and environmental concerns because of their continued presence in the environment and in products manufactured before the ban.
PCBs are known to have various adverse health effects on humans and animals, including cancer, immune system suppression, reproductive and developmental toxicity, and endocrine disruption. They can also cause neurological damage and learning and memory impairment in both human and animal populations. PCBs are highly persistent in the environment and can accumulate in the food chain, leading to higher concentrations in animals at the top of the food chain, including humans.
Dimerization is a process in which two molecules, usually proteins or similar structures, bind together to form a larger complex. This can occur through various mechanisms, such as the formation of disulfide bonds, hydrogen bonding, or other non-covalent interactions. Dimerization can play important roles in cell signaling, enzyme function, and the regulation of gene expression.
In the context of medical research and therapy, dimerization is often studied in relation to specific proteins that are involved in diseases such as cancer. For example, some drugs have been developed to target and inhibit the dimerization of certain proteins, with the goal of disrupting their function and slowing or stopping the progression of the disease.
Genetic transcription is the process by which the information in a strand of DNA is used to create a complementary RNA molecule. This process is the first step in gene expression, where the genetic code in DNA is converted into a form that can be used to produce proteins or functional RNAs.
During transcription, an enzyme called RNA polymerase binds to the DNA template strand and reads the sequence of nucleotide bases. As it moves along the template, it adds complementary RNA nucleotides to the growing RNA chain, creating a single-stranded RNA molecule that is complementary to the DNA template strand. Once transcription is complete, the RNA molecule may undergo further processing before it can be translated into protein or perform its functional role in the cell.
Transcription can be either "constitutive" or "regulated." Constitutive transcription occurs at a relatively constant rate and produces essential proteins that are required for basic cellular functions. Regulated transcription, on the other hand, is subject to control by various intracellular and extracellular signals, allowing cells to respond to changing environmental conditions or developmental cues.
A base sequence in the context of molecular biology refers to the specific order of nucleotides in a DNA or RNA molecule. In DNA, these nucleotides are adenine (A), guanine (G), cytosine (C), and thymine (T). In RNA, uracil (U) takes the place of thymine. The base sequence contains genetic information that is transcribed into RNA and ultimately translated into proteins. It is the exact order of these bases that determines the genetic code and thus the function of the DNA or RNA molecule.
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Aryl hydrocarbon receptor nuclear translocator - Wikipedia
Repression of Aryl Hydrocarbon Receptor (AHR) Signaling by AHR Repressor: Role of DNA Binding and Competition for AHR Nuclear...
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REGULATOR: a database of metazoan transcription factors and maternal factors for developmental studies
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Arnt11
- The ARNT gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor (AhR), and is required for receptor function. (wikipedia.org)
- The AHR repressor (AHRR) inhibits AHR signaling through a proposed mechanism involving competition with AHR for dimerization with AHR nuclear translocator (ARNT) and binding to AHR-responsive enhancer elements (AHREs). (oregonstate.edu)
- Responsiveness of the adult male rat reproductive tract to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: Ah receptor and ARNT expression, CYP1A1 induction, and Ah receptor down-regulation. (nih.gov)
- Because TCDD toxicity could possibly be the result of alterations in gene transcription mediated by the TCDD/aryl hydrocarbon receptor (AhR)/AhR nuclear translocator (ARNT) complex, the presence of the AhR and ARNT in the various organs of the adult male reproductive tract was examined using Western blotting. (nih.gov)
- The cytochrome P450 family 1 (CYP1 or Cyp1) is composed of three functional human members: CYP1A1, CYP1A2 and CYP1B1, which are regulated by the aryl hydrocarbon receptor (AhR), ligand-activated transcriptional factor that dimerizes with AhR nuclear translocator (ARNT). (nih.gov)
- HIF1 is a heterodimeric basic helix-loop-helix structure[11] that is composed of HIF1A, the alpha subunit (this protein), and the aryl hydrocarbon receptor nuclear translocator (Arnt), the beta subunit. (hif-signal.com)
- Class II members include the aryl hydrocarbon receptor nuclear translocator (ARNT, also called HIF-1β), ARNT2, brain and muscle ARNT-like protein 1 (BMAL1, also called ARNTL), and BMAL2 (ARNTL2). (ox.ac.uk)
- Gel shift analysis determined that a potent tandem AHR binding site ~3.1 kb upstream from the transcriptional start site can efficiently bind the AHR/ARNT (aryl hydrocarbon receptor/AHR nuclear translocator) heterodimer upon activation with a number of AHR agonists. (princeton.edu)
- The crystal structures of all three HIF-α proteins have been elucidated, revealing their bHLH and tandem PAS domains are used to engage their dimerization partner aryl hydrocarbon receptor nuclear translocator (ARNT, also called HIF-1β). (ox.ac.uk)
- The heterodimer on the transcription variables circadian locomotor output cycles kaput (CLOCK) and brain and muscle ARNT (aryl hydrocarbon receptor nuclear translocator)-like 1 (BMAL1) stimulate gene transcription by binding to response components (E-boxes) present within the clock-controlled gene promoters. (ephb4inhibitor.com)
- SRC-1 and several other members of the SRC family of coactivators have both a basic-helix-loop-helix (bHLH) domain and a periodicity/aryl hydrocarbon receptor nuclear translocator (ARNT)/single-minded (PAS) domain (Leo and Chen 2000) (Figure 1), which are found in the AhR, ARNT, and hypoxia inducible factor 1 α (HIF1α). (ojinka.com)
Androgen receptor1
- The androgen receptor ( AR ), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor [9] that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, [10] in the cytoplasm and then translocating into the nucleus. (ojinka.com)
Polycyclic4
- Binding of ligand, which includes dioxin and polycyclic aromatic hydrocarbons, results in translocation of the ligand-binding subunit only into the nucleus. (wikipedia.org)
- Another important risk factor, in particular with regards to occupational settings, is the chronic exposure to polycyclic aromatic hydrocarbons (PAH) which are formed during incomplete combustion of organic material and thus can be found in coal tar, creosote, bitumen and related working materials. (frontiersin.org)
- Subsequent expression analysis of genes in the polycyclic aromatic hydrocarbon bioactivation pathway was conducted with Real-Time RT-PCR. (nih.gov)
- Recent studies have provided strong evidence that exposure to carcinogens, such as polycyclic aromatic hydrocarbons, heterocyclic amines and others in the diet, influences the risk of developing colorectal cancer (CRC) [ 1 - 3 ]. (biomedcentral.com)
BMAL11
- The stimuli are received by the central circadian clock in suprachiasmatic nucleus of the brain, regulating the transcriptional-translational feedback loop between the core components of the circadian clock: circadian locomotor output cycles kaput (CLOCK), aryl hydrocarbon receptor nuclear translocator-like (BMAL1), cryptochrome (CRY) and period (PER). (biomedcentral.com)
Proteins1
- Current evidence suggests novel mechanisms of circadian regulation including the interaction with the circadian clock proteins with nuclear receptors along with the existence of co-regulatory mechanisms (Lamia et al. (ephb4inhibitor.com)
Transcriptional3
- 5. Transcriptional activation of the oxytocin promoter by oestrogens uses a novel non-classical mechanism of oestrogen receptor action. (nih.gov)
- The Nuclear Receptor PPARγ Controls Progressive Macrophage Polarization as a Ligand-Insensitive Epigenomic Ratchet of Transcriptional Memory. (ox.ac.uk)
- Northern blot hybridization and nuclear run-on assays demonstrated that transcriptional activation of these genes was suppressed in stably transfected cultures expressing an Ha-ras oncogene (the MCF10A-NeoT line). (utmb.edu)
CYP1A11
- 18. Aryl hydrocarbon receptor mediates laminar fluid shear stress-induced CYP1A1 activation and cell cycle arrest in vascular endothelial cells. (nih.gov)
Protein that forms a complex1
- Aryl hydrocarbon receptor nuclear translocator is a basic HELIX-LOOP-HELIX MOTIF containing protein that forms a complex with DIOXIN RECEPTOR . (bvsalud.org)
Translocation3
- AHRR1 neither blocked AHR nuclear translocation nor reduced the levels of AHR2 protein. (oregonstate.edu)
- Using AHR mutants, it was determined that nuclear translocation and heterodimerization with AHR-nuclear translocator are essential, but DNA binding is not involved in AHR-mediated Saa repression. (psu.edu)
- Western blot analyses and immunofluorescence microscopy demonstrated that the lack of inducibility in MDF10A-NeoT cells reflected neither reductions in aryl hydrocarbon receptor (AHR) and aryl hydrocarbon nuclear translocator protein nor prevention of TCDD-induced AHR translocation to the nucleus. (utmb.edu)
Genes1
- We investigated the potential of the aryl hydrocarbon receptor (AHR) to suppress NF-B regulated-gene expression, especially acute-phase genes, such as serum amyloid A (Saa). (psu.edu)
TCDD1
- 1994. Ah receptor in embryonic mouse palate and effects of TCDD on receptor expression. (cdc.gov)
Transcription3
- Induction and superinduction of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible ioly(ADP-ribose) polymerase: role of the aryl hydrocarbon receptor/aryl hydrocarbon receptor nuclear translocator transcription activation domains and a labile transcription repressor. (cdc.gov)
- Aryl hydrocarbon receptor (AHR) is a transcription factor that regulates the activity of multiple innate and adaptive immune cells subsequent to binding to numerous endogenous and exogenous ligands. (aacrjournals.org)
- 1991 HIF-1 is normally a heterodimeric transcription aspect comprising an oxygen-sensitive α subunit and a constitutive β subunit with apparent molecular public of 120-130 kD and 91-94 kD respectively (Wang and Semenza 1995 Nuclear series analysis uncovered that both subunits contain bHLH and Rac1 PAS domains. (cell-signaling-pathways.com)
Hypoxia2
- AhR nuclear translocator is also a subunit of HYPOXIA-INDUCIBLE FACTOR 1. (bvsalud.org)
- Two examples are Belzutifan, targeting hypoxia-inducible factor (HIF)-2α, and Tapinarof, targeting the aryl hydrocarbon receptor (AHR), both of which have gained regulatory approval recently. (ox.ac.uk)
Activation1
- Activation of the aryl hydrocarbon receptor (AHR) by 2,3,7,8-tetrachlorodibenzo-p-dioxin causes altered gene expression and toxicity. (oregonstate.edu)
CYP1A21
- 12. Microtubules-interfering agents restrict aryl hydrocarbon receptor-mediated CYP1A2 induction in primary cultures of human hepatocytes via c-jun-N-terminal kinase and glucocorticoid receptor. (nih.gov)
Ligand3
- The ligand-free, cytosolic form of the aryl hydrocarbon receptor is complexed to heat shock protein 90. (wikipedia.org)
- The functional heterodimers formed in this family bring together four distinct ligand-binding pockets, twice the number in nuclear receptor heterodimers. (ox.ac.uk)
- The chemokine (c-c motif) ligand 20 (CCL20) plays a nonredundant role in the chemoattraction of C-C motif receptor 6 expressing cells (eg, T cells and others). (princeton.edu)
Enzymes1
- The aryl hydrocarbon receptor (AhR) is involved in the induction of several enzymes that participate in xenobiotic metabolism. (wikipedia.org)
Cytochrome1
- 16. Cytochrome P450 gene regulation and physiological functions mediated by the aryl hydrocarbon receptor. (nih.gov)
Regulation3
- 9. Regulation of oestrogen receptor gene expression: new insights and novel mechanisms. (nih.gov)
- 15. Regulation of aryl hydrocarbon receptor activity in porcine cumulus-oocyte complexes in physiological and toxicological conditions: the role of follicular fluid. (nih.gov)
- The Ah receptor (AHR) is directly involved in the regulation of both innate and adaptive immunity. (princeton.edu)
Repression3
- Repression of aryl hydrocarbon receptor (AHR) signaling by AHR repressor: role of DNA binding and competition for AHR nuclear translocator. (oregonstate.edu)
- An AHRR1 point mutant (AHRR1-Y9F) that could not bind to AHREs but that retained its nuclear localization was only slightly reduced in its ability to repress AHR2, demonstrating that AHRR repression does not occur solely through competition for AHREs. (oregonstate.edu)
- Repression of the nuclear factor-B (NF-B) pathway has been extensively researched because of its pivotal role in inflammation. (psu.edu)
Pathways2
- 4. Targeted salmon gene array (SalArray): a toxicogenomic tool for gene expression profiling of interactions between estrogen and aryl hydrocarbon receptor signalling pathways. (nih.gov)
- Integrin alpha (ITGA)6 and 2 were enriched in several pathways, including focal adhesion and extracellular matrix‑receptor interaction. (spandidos-publications.com)
19992
- 1999. Adverse reproductive outcomes in the transgenic Ah receptor-deficient mouse. (cdc.gov)
- 1999. Transactivation activity of human, zebrafish, and rainbow trout aryl hydrocarbon receptors expressed in COS-7 cells: Greater insight into species differences in toxic potency of polychlorinated dibenzo- p -dioxin, dibenzofuran, and biphenyl congeners. (cdc.gov)
Dioxin1
- 2. Modulation of oestrogen receptor signalling by association with the activated dioxin receptor. (nih.gov)
Polychlorinated biphenyls1
- 1991. Effects of polychlorinated biphenyls with Ah receptor affinity on lymphoid development in the thymus and the bursa of Fabricius on chick embryos in ovo and in mouse thymus anlagen in vitro . (cdc.gov)
Myeloid1
- Interestingly E2A −/− , Ebf1 −/− , and Pax5 −/− pro-B cells all overexpress the myeloid cytokine receptor gene MCSFR (macrophage-colony stimulating factor receptor). (hindawi.com)
Gene expression2
Activity2
Cell2
- 1997 TGF-β exerts its biological results through a cell surface area receptor complicated the TGF-β type I and type II receptors TβRI and TβRII. (cell-signaling-pathways.com)
- Powerful staining of nuclear p53 was accompanied by beta catenin from the cell borders. (chk1inhibitor.com)
Nucleus1
- P53s presence from the nucleus was also confirmed with western blots of cytoplasmic and nuclear fractions. (chk1inhibitor.com)
Mouse1
- 1991. Promotion of mouse lung tumors by bioaccumulated polychlorinated aromatic hydrocarbons. (cdc.gov)
Experiments1
- Profiling experiments demonstrated that a multitude of nuclear receptors had been shown to exhibit rhythmic oscillations in adipose, liver, and muscle tissue (Yang et al. (ephb4inhibitor.com)
Role1
- 1. Oestrogen-receptors (ER) are likely to be promiscuous: wider role for oestrogens and mimics. (nih.gov)