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Library of Congress Cataloging-in-Publication Data: The AH receptor in biology and toxicology / edited by Raimo Pohjanvirta. p. ; cm. Includes bibliographical references and index. ISBN (cloth) 1. Polycyclic aromatic hydrocarbons–Toxicology. 2. Polycyclic aromatic hydrocarbons–Metabolism. 3. Dioxins–Toxicology. 4. Mar 02, · Pink Screen | A Screen Of Pure Pink For 10 Hours | Background | Backdrop | Screensaver | Full HD | - Duration: Pictures of stuff for 10 hours , views. Request PDF on ResearchGate | The AH Receptor in Biology and Toxicology | IntroductionHistory of TEFPrerequisites of the TEF ConceptWHO TEF Assessment and Major Changes to the Previous. Request PDF on ResearchGate | The AH Receptor in Biology and Toxicology | IntroductionOverview of TCDD's Immunomodulatory EffectsReferences. Read "The AH Receptor in Biology and Toxicology" by Raimo Pohjanvirta available from Rakuten Kobo. Sign up today and get $5 off your first purchase. This book provides a thorough and up-to-date overview of the aryl hydrocarbon receptor (AHR) and its unique dual role in Brand: Wiley.The aryl hydrocarbon receptor AhR is a ligand-activated nuclear transcription factor that mediates responses to toxic halogenated aromatic toxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin TCDD , polynuclear aromatic hydrocarbons, combustion products, and numerous phytochemicals such as flavonoids and indolecarbinol I3C. The nuclear AhR complex is a heterodimer containing the AhR and AhR nuclear translocator Arnt proteins, and the molecular mechanism of AhR action is associated with binding of the heterodimer to dioxin responsive elements DREs in regulatory regions of Ah-responsive genes. TCDD, a 'xenodioxin', is a multi-site carcinogen in several species and possibly in humans, whereas natural AhR ligands including I3C and flavonoids tend to protect against cancer. Both TCDD and phytochemicals inhibit estrogen-induced breast and endometrial cancer, and the molecular mechanisms of this common response will be described. Abstract The aryl hydrocarbon receptor AhR is a ligand-activated nuclear transcription factor that mediates responses to toxic halogenated aromatic toxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin TCDD , polynuclear aromatic hydrocarbons, combustion products, and numerous phytochemicals such as flavonoids and indolecarbinol I3C. Publication types Research Support, Non-U. Gov't Research Support, U. Las BRUJAS y el CANIBALISMO The aryl hydrocarbon receptor AhR is a ligand-activated transcription factor that regulates a battery of genes in response to exposure to a broad class of environmental poly aromatic hydrocarbons PAH. AhR is historically characterized for its role in mediating the christliche bilder kostenlos en kader and adaptive responses to bioloby chemicals, however mounting evidence has established a role for it in ligand-independent physiological processes and pathological conditions, including cancer. The AhR is overexpressed and constitutively activated in advanced breast cancer cases and was shown to drive the progression of breast cancer. Zh this article we will review the current state of knowledge on the possible role of AhR in breast cancer and how it will be exploited in targeting AhR for biologt cancer therapy. Breast cancer is the second leading cause of cancer-related death in women in the US [ 1 ]. An estimated 40 percent of breast cancer patients relapse and develop metastatic disease and approximately 40, women die of breast cancer each year [ 2 ]; a mortality rate is largely attributed to the ah receptor in biology and toxicology metastatic hoxicology [ 3 ].
This book provides a thorough and up-to-date overview of the aryl hydrocarbon receptor (AHR) and its unique dual role in toxicology and. This book provides a thorough and up-to-date overview of the aryl hydrocarbon receptor (AHR) and its unique dual role in toxicology and biology. The coverage . The complete guide to the aryl hydrocarbon receptor (AHR)—what it is, what it does, and what it might mean for the future of drug metabolism. Providing a. Request PDF on ResearchGate | The AH Receptor in Biology and Toxicology. Edited by Raimo Pohjanvirta. | Wiley, Hoboken , XIII+ pp., hardcover. Download Citation on ResearchGate | On Nov 10, , Sahoko Ichihara and others published The AH Receptor in Biology and Toxicology.Kopf, J. Luo, Y. Enomoto, H. Huang et al. Hoch, K. more information grammar and punctuation checker Get this from a library! The AH receptor in biology and toxicology. [Raimo Pohjanvirta;] -- This book provides a thorough and up-to-date overview of the aryl hydrocarbon receptor (AHR) and its unique dual role in toxicology and biology. The coverage includes epigenetic mechanisms, gene. The AH Receptor in Biology and Toxicology. The complete guide to the aryl hydrocarbon receptor (AHR)-what it is, what it does, and what it might mean for the future of drug metabolism Providing a thorough and up-to-date overview of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that mediates the induction of d. Dec 20, · inbetatest.website: The AH Receptor in Biology and Toxicology (): Raimo Pohjanvirta: BooksCited by:
The aryl hydrocarbon receptor AhR is a DNA binding protein that acts as a nuclear receptor mediating xenobiotic metabolism and environmental responses. More recently, the functions of AhR in environmental adaption have been examined in the context of the occurrence, development, and therapy of cardiovascular diseases.
Increasing evidence suggests that AhR is involved in maintaining homeostasis or in triggering pathogenesis by modulating the biological responses of critical cell types in the cardiovascular system. Here, we describe the structure, distribution, and ligands of AhR and the AhR signaling pathway and review the impact of AhR on cardiovascular physiology.
We also discuss the potential contribution of AhR as a new potential factor in the targeted treatment of cardiovascular diseases. Traditionally AhR acts as a crucial regulator mediating xenobiotic metabolism and environmental responses, and it was discovered to bind closely with 2,3,7,8-tetrachlorodibenzo-p-dioxin TCDD, dioxin and then was hyperactivated to release a myriad of toxicologic outcomes, which contribute to the potency of TCDD as an inducer or promoter of some carcinogenesis in [ 3 , 4 ].
Thus, for many years, AhR has been almost exclusively studied by the toxicological field for its role in various environmental and food contaminants such as polycyclic aromatic hydrocarbons, polychlorinated biphenyls and dioxins.
Numerous studies have found that cytosolic AhR can be activated by many natural and synthetic ligands, and translocated into the nucleus where it complexes with the AhR nuclear translocator ARNT [ 5 ]. The complex recognizes the specific dioxin-responsive elements DREs and modulates subsequent transcription of its downstream target genes including phase I and phase II metabolic enzymes, which can affect the metabolism of environmental toxicants and chemical substances [ 6 ].
The increasing deterioration of the natural environment is having serious consequences on human health. The circulation system is the major organ exposed xenobiotics and endobiotics during metabolic homeostasis [ 7 ], and long-term exposure to environmental pollutants can drastically alter this system, resulting in cardiovascular diseases such as hypertension, atherosclerosis, and ischemic heart disease [ 8 — 12 ].
Because many environmental pollutants contain exogenous aryl hydrocarbon receptor AhR ligands, increasing attention is being given to the relationship between AhR and cardiovascular diseases. Recent evidence from gene knock-out studies and clinical trials suggests that not only does AhR have a major impact on general physiological functions, including immune responses, reproduction, oxidative stress, tumor promotion, the cell cycle, and proliferation [ 13 , 14 ], but also influences cardiovascular physiological functions [ 15 — 18 ].
In this review, we discuss the progress of AhR biology and toxicology, its pathophysiology roles in the heart and vascular systems, and the prospects as a therapeutic target for cardiovascular diseases, with the aim of providing a potential direction for the prevention and treatment of the diseases. The TAD domain functions as a mediator in transcriptional activation of downstream genes [ 23 ].
AhR is expressed ubiquitously in the fetus and in adults, with the distribution changing significantly with age [ 24 ] Figure 2. In the fetus, there are specific distribution of AhR in the lungs, liver, kidneys, pancreas, testicles, esophagus, thymus glands, retinas, and epithelial cells, and relatively low levels in the heart, brain, choroids, thoracic aorta, and sclera; In adults, AhR is expressed at relatively high levels in the lungs, placenta, spleen, pancreas, and liver, and relatively low levels in the heart, brain, and skeletal muscles [ 25 , 26 ].
AhR exerts diverse physiological effects depending on where it is located in different tissues. AhR ligands can be divided into endogenous ligands and exogenous ligands Figure 3. Endogenous ligands include indigoids, heme metabolites, eicosanoids, tryptophan derivatives, and equilenin [ 27 ]. Exogenous ligands include polycyclic aromatic hydrocarbons, polychlorinated biphenyls, natural compounds, and small molecule compounds [ 28 ].
The different structures and properties of AhR ligands mean that when they combine with AhR they have distinct biological effects. The AhR signaling pathway involves both classical and non-classical signal transduction mechanisms [ 2 , 24 ] Figure 4. In the classical signaling pathway, AhR exists as an AhR molecular chaperone complex comprising an AhR, two heat shock protein 90, and X-associated protein 2 and 23 in the cytosol [ 24 , 29 ].
Being activated by ligands, AhR is translocated from the cytosol to the nucleus where it disassociates from the complex. In the non-classical signaling pathway, the AhR signaling pathway can interact with other pathways by competition for transcriptional coactivators or corepressors [ 30 ]. In the nucleus, sustained AhR activation results in G1 phase cell cycle arrest via hyperphosphorylation of retinoblastoma protein and repression of E2F-dependent transcription [ 31 — 35 ].
AhR also regulates the development of regulatory type 1 T cells by combining with the transcription factor c-Mcf [ 37 ]. Despite low expression levels of AhR in the heart, AhR does have noticeable effects on the physiological functioning of the heart.
It was suggested that the underlying mechanism may be associated with the elevated level of vascular endothelial growth factor VEGF in AhR mice [ 44 ]. In , Vasquez et al. The researchers suggested that AhR deficiency mainly lead to cardiomyocyte hypertrophy, resulting in cardiomyopathy and cardiac hypertrophy [ 45 ]. Paradoxically, another study reported that cardiac hypertrophy in AhR mice was caused by pressure overload and accompanied by evident fibrosis and elevated expression of plasma endothelin-1 ET-1 and angiotensin II Ang II.
Captopril, an angiotensin-converting enzyme inhibitor, was used to alleviate the pressure overload, leading to a lowered expression of plasma ET-1 and Ang II and a delay in the increase of mean arterial pressure [ 16 ]. Subsequent research found that cardiac function in AhR mice could be completely reversed with BQ, an receptor antagonist, indicating that ET-1 could be mediated by AhR and function as the key molecule in the progression of cardiac hypertrophy [ 46 ].
Nevertheless, the specific mechanism has yet to be completely determined. Although there are contradictions among studies, it is evident that AhR signaling in cardiac function is important. The AhR signaling pathway is vital for the development of the heart. These results suggest that AhR mediated the differentiation of P19 mouse embryonic carcinoma cells into cardiomyocytes through the AhR and WNT1 signaling pathways [ 49 ].
Another study found that activation, inhibition, or knockdown of AhR all could affect cardiomyocyte differentiation of mouse embryonic stem cells; the cause of which was connected with AhR-relating incongruous expression of genes, including genes encoding homeobox transcription factors and polycomb and trithorax group genes [ 50 ].
The expression of AhR in the undifferentiated embryonic stem cells impacts their choice of lineage in differentiation, restricting cardiogenesis and commit to a neuroglia cell fate. With regard to self-renewal of embryonic stem cells, a relatively low level of AhR expression was required for cells to retain their stem cell properties. Han et al. Hence, cardiomyocyte differentiation is a carefully regulated process in which AhR plays a crucial role.
Maintenance of the function and structure of blood vessels relies in part on laminar fluid shear stress. Normally, laminar fluid shear stress-activated AhR mediate cell cycle arrest by activating CYP1A1 in human umbilical vein endothelial cells, suggesting the involvement of AhR in the regulation of the vascular microenvironment [ 52 ].
A study reported that there exists abnormal vascular structures in the liver, kidneys, and hyaloids in AhR mice [ 53 ]. A study of hepatic vascular development revealed that hepatic necrosis and decreased perfusion in the fetal liver was the cause of patent ductus venosus and comparatively smaller livers in adult AhR mice [ 54 ].
Ichihara et al. VEGF is necessary for vascularization. In summary, AhR participates in the regulation of vascular physiological functions, including vascular development and angiogenesis. Both deficiency and abnormal activation of AhR give rise to vascular dysfunction, and many vascular diseases. It is reported that AhR-deficient mice showed decreased cardiac output and low systolic and diastolic aortic pressure compared with normal mice of the same age [ 15 ].
In , Zhang et al. ET-1 signaling was also found to be involved in the mediation of hypotension in AhR mice. Importantly, the study reported that the sympathetic nervous system and nitric oxide NO signaling were not involved in the activation of the rennin-angiotensin system and ET-1 [ 62 ].
Captopril could alleviate high blood pressure in AhR mice, in part because of the reduction of Ang II [ 16 ]. However, inhibition of ET-1 could not only lower mean arterial pressure and the levels of ET-1, but also reduce Ang II expression levels in AhR mice with hypertension, indicating involvement of the regulation of the ETAng II axis in hypertension in AhR mice induced by hypoxia [ 65 ].
Sauzeau et al. Taken together, the findings suggest that AhR is involved in the complicated networks that regulate blood pressure, and possible mechanisms should be further studied.
Myocarditis is a significant cause of heart disease, especially in young people[ 66 ]. It can lead to dilated cardiomyopathy, a common precursor of heart failure. Myocarditis can be induced by multiple causes, including infection and auto-immune or auto-inflammatory diseases [ 67 , 68 ]. Infection remains a major factor in myocarditis and is closely associated with the immune and inflammatory responses of the host.
Numerous studies have reported that AhR is a crucial factor in the immune system and is involved in the differentiation of antigen-presenting cells and specific T cell subpopulations [ 69 , 70 ]. AhR participates in the regulation of innate and adaptive immune responses in some models of infection. AhR is also an important protein to limit the inflammatory response.
Deletion of AhR exacerbated the inflammatory response to Listeria monocytogenes , Toxoplasma gondii , and Plasmodium falciparum [ 71 — 73 ], and was confirmed in a model of Leishmania major infection [ 74 ]. There is strong evidence to suggest that AhR is a pivotal molecule in myocarditis.
In , it was first reported that AhR modulated the development of myocarditis during Trypanosoma cruzi infection. When model mice were infected with T.
Viral infection is the most common cause of myocarditis. No study has examined the relationship between AhR and viral myocarditis. However, Coogan et al. It is possible that AhR modulates the inflammatory response in viral myocarditis. AhR is a promising line of research on myocarditis. It has been reported that exposure to environmental pollutants, particularly traffic-related pollutants, could increase the risk for hypertension [ 77 ]; however, causation has not been determined.
One possible mechanism is that AhR, as an important regulator of blood pressure, could be activated by abundant exogenous AhR ligands in environment pollutants, such as TCDD [ 10 ]. Another study suggested that 3-methylcholanthrene, an exogenous AhR agonist, can induce high blood pressure associated with endothelial NO synthase eNOS inactivation [ 78 ].
These findings suggest that AhR could serve as a therapeutic target in hypertension, or other AhR-regulated NO-dependent vascular diseases. Besides endogenous and exogenous ligands, activation of AhR can also be influenced by genetic polymorphisms.
Genetic polymorphisms of the AhR signaling pathway are reported to be closely associated with the pathogenesis of essential hypertension. The genetic environment and gene—gene interactions in the AhR signaling pathway are reported to determine susceptibility to essential hypertension [ 80 ]. Therefore, it is possible that gene therapy targeting AhR signaling could be a potential candidate in the treatment of essential hypertension.
It has recently been reported that AhR is expressed in immune cells such as Th17 cells and dendritic cells [ 70 ]. Mice lacking T cells exhibited reduced blood pressure increases with Ang II infusion [ 82 ]. Whether expression levels of AhR in immune cells influence blood pressure, and possible mechanisms, is an interesting potential area of research.
Atherosclerosis mainly occurs in the intimal layer of the blood vessel wall, and is characterized by subendothelial lipid deposits, vascular smooth muscle cell migration and proliferation, and formation of foam cells in the subendothelial space [ 83 ]. Risk factors for cardiovascular diseases include vascular senescence and obesity. Chronic vascular inflammation and oxidative stress contribute to atherosclerosis [ 84 , 85 ], but the molecular mechanisms are not well understood.
Vascular senescence, a risk factor for cardiovascular diseases, is an important factor in the development of atherosclerosis. Studies suggest that senescent vascular cells are present in human atherosclerotic lesions [ 89 — 91 ]. A study in reported that indoxyl sulfate regulated sirtuin 1 via AhR activation, promoting endothelial senescence [ 92 ].
It was suggested that endothelial senescence in atherosclerosis is linked to AhR activation. Obesity is also a vital contributor to atherosclerosis. Inhibition of AhR, in turn, prevented obesity [ 93 ].
Inflammatory responses contribute to AhR-regulated atherosclerosis. The inflammation-related cytokine monocyte chemoattractant protein-1 MCP-1 , an important endothelium-derived chemokine, was reported to recruit monocytes into the subendothelial space where they differentiated into macrophages, promoting atherosclerotic plaque development [ 94 ]. ROS also play an important role in AhR-related atherosclerosis.
Download Citation on ResearchGate | On Nov 10, , Qiang Ma and others published The AH Receptor in Biology and Toxicology. The AH Receptor in Biology and Toxicology by Raimo Pohjanvirta, , available at Book Depository with free delivery worldwide. Read "The AH Receptor in Biology and Toxicology" by Raimo Pohjanvirta available from Rakuten Kobo. Sign up today and get $5 off your first purchase. Read "The AH Receptor in Biology and Toxicology" by Raimo Pohjanvirta available from Rakuten Kobo. Sign up today and get £3 off your first purchase. This book provides a thorough and up-to-date overview of the aryl hydrocarbon receptor (AHR) and its unique dual role in toxicology and.
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This book provides a thorough and up-to-date overview of the aryl hydrocarbon receptor (AHR) and its unique dual role in toxicology and biology. The coverage includes epigenetic mechanisms, gene expression, reproductive and developmental toxicity. Raimo Pohjanvirta. ISBN: December Pages. This book provides a thorough and up-to-date overview of the aryl hydrocarbon receptor (AHR) and its unique dual role in toxicology and biology. The coverage. The AH Receptor in Biology and Toxicology - Kindle edition by Pohjanvirta, Raimo. Download it once and read it on your Kindle device, PC, phones or tablets. The aryl hydrocarbon receptor (AHR) is an evolutionarily ancient, evidently over million-year-old protein. It is a ligand-activated. Request PDF | On Nov 10, , Hollie Swanson published The AH Receptor in Biology and Toxicology | Find, read and cite all the research. Raimo Pohjanvirta, Editor The AH Receptor in Biology and Toxicology. Hoboken, NJ: John Wiley & Sons, Inc, pp. $ USD. Place of Publication, Hoboken, New Jersey, USA. Publisher, John Wiley & Sons Ltd. Number of pages, ISBN (Print), ISBN (Electronic). E.J. Dougherty, R.S. Pollenz, in Comprehensive Toxicology, The aryl hydrocarbon receptor repressor (AHRR) protein is a bHLH/PAS family (AhR) is a ligand-dependent transcription factor that mediates many of the biological and.This book provides a thorough and up-to-date overview of the aryl hydrocarbon receptor (AHR) and its unique dual role in toxicology and biology. The coverage includes epigenetic mechanisms, gene expression, reproductive and developmental toxicity, signal transduction, and transgenic animal models. Featuring an internationally recognized team of authors at the forefront of AHR research, this. The AH Receptor in Biology and Toxicology - Kindle edition by Pohjanvirta, Raimo. Download it once and read it on your Kindle device, PC, phones or tablets. Use features like bookmarks, note taking and highlighting while reading The AH Receptor in Biology and Toxicology. The AH receptor in biology and toxicology / edited by Raimo Pohjanvirta. p. ; cm. Includes bibliographical references and index. ISBN (cloth) 1. Polycyclic aromatic hydrocarbons–Toxicology. 2. Polycyclic aromatic hydrocarbons–Metabolism. 3. Dioxins–Toxicology. 4. Dioxins–Metabolism. 5. Nuclear receptors (Biochemistry) 6. In book: The AH Receptor in Biology and Toxicology, pp Cite this publication. Sara Brunnberg. Aryl hydrocarbon receptor (AHR) has been identified as a regulator of CD25(+)CD4. In book: The AH Receptor in Biology and Toxicology (pp) Authors: Fumio Matsumura. Aryl hydrocarbon receptor (AhR) activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to. May 21, · IN THIS JOURNAL. Journal Home; Browse Journal. Current Issue; OnlineFirst; All Issues; Submit PaperAuthor: John A. Budny. Oct 19, · Wiley, Hoboken , XIII+ pp., hardcover, $ —ISBN ‐0‐‐‐2Author: Caroline Pot. E.J. Dougherty, R.S. Pollenz, in Comprehensive Toxicology, Aryl Hydrocarbon Receptor Repressor Interactions. The aryl hydrocarbon receptor repressor (AHRR) protein is a bHLH/PAS family member that is missing the second PAS domain (PAS-B) implicated in ligand binding by the AHR (Mimura et al. ).Recent studies suggest that the AHRR is expressed in a tissue-specific manner.