The Aryl Hydrocarbon Receptor: A Review of Its Role in the Physiology and Pathology of the Integument and Its Relationship to the Tryptophan Metabolism

Noakes, Rowland

doi:10.4137/ijtr.s19985

Cited by 59 publications

(52 citation statements)

References 121 publications

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“…The process initiates apoptosis and involves damage to nuclear DNA accompanied by mitochondrial dysfunction 10.1029/2018RG000629 (Frauenstein et al, 2013). There is a general consensus that the AhR of modern humans is implicated in DNA repair (Dittmann et al, 2016;Schreck et al, 2009), tumor suppression (Fan et al, 2010;Yu et al, 2017), epidermal barrier function (Noakes, 2015), skin tanning response, and melanocyte homeostasis (Jux et al, 2011;Luecke et al, 2010). Phylogenetic analysis suggested that the ability of vertebrate AhR to sense xenobiotics was acquired at a late stage of evolution, implying that the driving force for evolutionary conservation of AhR lies not only in its role in xenobiotic metabolism but also in normal cell development (Hahn et al, 2017;Hao & Whitelaw, 2013).…”

Section: The Role Of the Ahrmentioning

confidence: 99%

The Role of Geomagnetic Field Intensity in Late Quaternary Evolution of Humans and Large Mammals

Channell

Vigliotti

2019

Reviews of Geophysics

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It has long been speculated that biological evolution was influenced by ultraviolet radiation (UVR) reaching the Earth's surface, despite imprecise knowledge of the timing of both UVR flux and evolutionary events. The past strength of Earth's dipole field provides a proxy for UVR flux because of its role in maintaining stratospheric ozone. The timing of Quaternary evolutionary events has become better constrained by fossil finds, improved radiometric dating, use of dung fungi as proxies for herbivore populations, and improved ages for nodes in human phylogeny from human mitochondrial DNA and Y chromosomes. The demise of Neanderthals at ~41 ka can now be closely tied to the intensity minimum associated with the Laschamp magnetic excursion, and the survival of anatomically modern humans can be attributed to differences in the aryl hydrocarbon receptor that has a key role in the evolutionary response to UVR flux. Fossil occurrences and dung‐fungal proxies in Australia indicate that episodes of Late Quaternary extinction of mammalian megafauna occurred close to the Laschamp and Blake magnetic excursions. Fossil and dung fungal evidence for the age of the Late Quaternary extinction in North America (and Europe) coincide with a prominent decline in geomagnetic field intensity at ~13 ka. Over the last ~200 kyr, phylogeny based on mitochondrial DNA and Y chromosomes in modern humans yields nodes and bifurcations in evolution corresponding to geomagnetic intensity minima, which supports the proposition that UVR reaching Earth's surface influenced mammalian evolution with the loci of extinction controlled by the geometry of stratospheric ozone depletion.

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Section: The Role Of the Ahrmentioning

confidence: 99%

The Role of Geomagnetic Field Intensity in Late Quaternary Evolution of Humans and Large Mammals

Channell

Vigliotti

2019

Reviews of Geophysics

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“…KYNA, whose mammalian brain concentrations in adulthood are in the nanomolar to low micromolar range, exerts neuroactive properties as an antagonist of the alpha 7 nicotinic acetylcholine (α7nACh) receptors (Hilmas et al, 2001) and N-methyl-D-aspartate (NMDA) receptors (Perkins and Stone, 1982). KYNA also acts as a ligand of G protein-coupled receptor (GPR) 35 and the aryl hydrocarbon receptor (AhR), two signaling receptors that are functional in both the brain and peripheral organs (Divorty et al, 2015; Julliard et al, 2014; Mackenzie and Milligan, 2015; Moroni et al, 2012; Noakes, 2015). The second branch of the KP is predominantly metabolized in microglial cells (Guillemin et al, 2001, 2003; Heyes et al, 1996; Saito and Heyes, 1996), where the enzyme kynurenine 3-monooxygenase (KMO) metabolizes kynurenine to 3-hydroxykynurenine (3-HK), and the downstream catabolite 3-hydroxyanthranilic acid is formed by the enzyme kynureninase.…”

Section: Introductionmentioning

confidence: 99%

Elevated kynurenine pathway metabolism during neurodevelopment: Implications for brain and behavior

Notarangelo

Pocivavsek

2017

Neuropharmacology

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The kynurenine pathway (KP) of tryptophan degradation contains several neuroactive metabolites that may influence brain function in health and disease. Mounting focus has been dedicated to investigating the role of these metabolites during neurodevelopment and elucidating their involvement in the pathophysiology of psychiatric disorders with a developmental component, such as schizophrenia. In this review, we describe the changes in KP metabolism in the brain from gestation until adulthood and illustrate how environmental and genetic factors affect the KP during development. With a particular focus on kynurenic acid, the antagonist of α7 nicotinic acetylcholine (α7nACh) and N-methyl-D-aspartate (NMDA) receptors, both implicated in modulating brain development, we review animal models designed to ascertain the role of perinatal KP elevation on long-lasting biochemical, neuropathological, and behavioral deficits later in life. We present new data demonstrating that combining perinatal choline-supplementation, to potentially increase activation of α7nACh receptors during development, with embryonic kynurenine manipulation is effective in attenuating cognitive impairments in adult rat offspring. With these findings in mind, we conclude the review by discussing the advancement of therapeutic interventions that would target not only symptoms, but potentially the root cause of central nervous system diseases that manifest from a perinatal KP insult.

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“…It serves as a cytosolic ligand-activated transcription factor which, upon ligand binding, translocates into the nucleus, where it dimerizes with the AhR nuclear translocator (ARNT) followed by binding to specific sites in target gene promoters [13]. Much research in the last 15 years has revealed that the AhR is involved in various physiological aspects such as cell homeostasis, cell proliferation and differentiation, embryogenesis, carcinogenesis, inflammation, and host immunity [13,14]. Several reports also indicate an important function of the AhR for maintaining the skin barrier [15,16].…”

Section: Doi: 101159/000492162mentioning

confidence: 99%

<b><i>Staphylococcus epidermidis</i></b> Activates Aryl Hydrocarbon Receptor Signaling in Human Keratinocytes: Implications for Cutaneous Defense

Rademacher¹,

Simanski²,

Hesse³

et al. 2018

J Innate Immun

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Bacterial challenge of keratinocytes with the abundant skin commensal Staphylococcus epidermidis induces distinct innate immune responses, but the underlying molecular mechanisms are still emerging. We report that the aryl hydrocarbon receptor (AhR) was activated in human primary keratinocytes infected with S. epidermidis, leading to induction of the AhR-responsive gene cytochrome P450 1A1 (CYP1A1). In addition, functional AhR was required for S. epidermidis-mediated induction of IL-1β expression in keratinocytes. AhR-dependent gene induction of IL-1β and CYP1A1 was mediated by factor(s) < 2 kDa secreted by S. epidermidis. Blockade of the AhR in a 3D organotypic skin equivalent infected with S. epidermidis attenuated the S. epidermidis-induced CYP1A1 and IL-1β expression. Moreover, S. epidermidis also induced expression of IL-1α and of the antimicrobial peptide human β-defensin-3 in an AhR-dependent manner in a 3D skin equivalent. An increased outgrowth of S. epidermidis on the surface of skin explants treated with a specific AhR inhibitor further indicate a pivotal role of the AhR in mediating an epidermal defense response. Taken together, our data expand the role of the AhR in innate immunity and support a previously unappreciated contribution for the AhR in cutaneous defense.

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The Aryl Hydrocarbon Receptor: A Review of Its Role in the Physiology and Pathology of the Integument and Its Relationship to the Tryptophan Metabolism

Cited by 59 publications

References 121 publications

The Role of Geomagnetic Field Intensity in Late Quaternary Evolution of Humans and Large Mammals

The Role of Geomagnetic Field Intensity in Late Quaternary Evolution of Humans and Large Mammals

Elevated kynurenine pathway metabolism during neurodevelopment: Implications for brain and behavior

<b><i>Staphylococcus epidermidis</i></b> Activates Aryl Hydrocarbon Receptor Signaling in Human Keratinocytes: Implications for Cutaneous Defense

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