Aryl Hydrocarbon Receptor Expression and Activity in Cerebellar Granule Neuroblasts: Implications for Development and Dioxin Neurotoxicity

Williamson, Mary A.; Gasiewicz, Thomas A.; Opanashuk, Lisa A.

doi:10.1093/toxsci/kfi031

Cited by 105 publications

(89 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2,4 Furthermore, AhR is postulated to play important roles in normal cell physiology and function, as demonstrated by the phenotype observed in the AhR knockout mice 5 and by different studies that link AhR activation by endogenous or naturally occurring ligands to vascular and cardiac homeostasis, 6 immune system function 7 and tumor development. 8 Although AhR and its target genes are widely expressed in different brain regions, including cerebellum, ventrolateral medulla, hippocampus, and cortex, [9][10][11] little is known about its role in brain physiology and pathology. Of note, AhR inhibition has been shown to protect against N-methyl-d-aspartate excitotoxicity 12 and to decrease apoptosis in cortical neurons, 13 suggesting its potential involvement in neurological insults such as stroke.…”

Section: Editorial See P 2002 Clinical Perspective On P 2051mentioning

confidence: 99%

L-Kynurenine/Aryl Hydrocarbon Receptor Pathway Mediates Brain Damage After Experimental Stroke

et al. 2014

View full text Add to dashboard Cite

Background-Aryl hydrocarbon receptor (AhR) is a transcription factor that belongs to the basic helix-loop-helix PAS (PerArnt-Sim homology domain) family known to mediate the toxic and carcinogenic effects of xenobiotics. Interestingly, AhR is widely expressed in the central nervous system, but its physiological and pathological roles are still unclear. Methods and Results-To define the role of AhR in stroke, we used middle cerebral artery occlusion in mice and oxygenglucose deprivation in rat cortical neurons. The results presented here show that the ischemic insult increases total and nuclear AhR levels and AhR transcriptional activity in neurons in vivo and in vitro. We also show that AhR has a causal role in acute ischemic damage because pharmacological or genetic loss-of-function approaches result in neuroprotection. Inhibition of cAMP response element-binding protein-dependent signaling may participate in the deleterious actions of AhR. Finally, we have also found that L-kynurenine, a tryptophan metabolite with AhR agonistic properties, is an endogenous ligand that mediates AhR activation in the brain after middle cerebral artery occlusion. Conclusions-Our data demonstrate that an L-kynurenine/AhR pathway mediates acute brain damage after stroke and open new possibilities for the diagnosis and treatment of this pathology.

show abstract

Section: Editorial See P 2002 Clinical Perspective On P 2051mentioning

confidence: 99%

L-Kynurenine/Aryl Hydrocarbon Receptor Pathway Mediates Brain Damage After Experimental Stroke

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Relative expression levels were further normalized by defining the average expression level of each gene in the small intestine of Arnt F/F (FVB/N) mice (for the analysis of Arnt F/F and Arnt ΔIE mice) or Hif-1α F/F mice (for the analysis of Hif-1α F/F and Hif-1α ΔIE mice) fed a normal chow diet as 1.0. Primers were designed using Primer Express 2.0.2 software (Applied Biosystems) and validated by homology search by nucleotide BLAST (http://nciarray.nci.nih.gov/), while other primers were described in an earlier report (49). Primer sequences used were as follows (gene symbol: forward, reverse): Arnt: 5ʹ-CAAGCCATCTTTCCTCACT-GATC-3ʹ, 5ʹ-ACACCACCCGTCCAGTCTCA-3ʹ; AhR: 5ʹ-CGGCTTCTT-GCAAAACACAGT-3ʹ, 5ʹ-GTAAATGCTCTCGTCCTTCTTCATC-3ʹ (49); Hif-1α: 5ʹ-ATAGCTTCGCAGAATGCTCAGA-3ʹ, 5ʹ-CAGTCACCTG-GTTGCTGCAA-3ʹ; Cyp1a1: 5ʹ-GGTTAACCATGACCGGGAACT-3ʹ, 5ʹ-TGCCCAAACCAAAGAGAGTGA-3ʹ; Cyp1a2: 5ʹ-GGAGAATGTCACCT-CAGGGAAT-3ʹ, 5ʹ-CGAAGTTATCATTGAAGGTCTTAAACC-3ʹ; Cyp1b1: 5ʹ-CCCCCCAAAACAAAAACAGAT-3ʹ, 5ʹ-AGAGTGTGCTAATATTTCA-CAGGTCAA-3ʹ; Egln3: 5ʹ-GTCCCGTGGCTCAGTTTTGT-3ʹ, 5ʹ-GGCAT-CACAGGCTAAAGAGACA-3ʹ; Mt1: 5ʹ-CCAGGGCTGTGTCTGCAAA-3ʹ, 5ʹ-TGGGTTGGTCCGATACTATTTACA-3ʹ; β-actin: 5ʹ-TATTGGCAAC-GAGCGGTTCC-3ʹ, 5ʹ-GGCATAGAGGTCTTTACGGATGTC-3ʹ.…”

Section: Animals and Dietsmentioning

confidence: 99%

Dietary phytochemicals regulate whole-body CYP1A1 expression through an arylhydrocarbon receptor nuclear translocator–dependent system in gut

Ito¹,

Chen²,

Satoh³

et al. 2007

J. Clin. Invest.

View full text Add to dashboard Cite

Cytochrome P450 1A1 (CYP1A1) is one of the most important detoxification enzymes due to its broad substrate specificity and wide distribution throughout the body. On the other hand, CYP1A1 can also produce highly carcinogenic intermediate metabolites through oxidation of polycyclic aromatic hydrocarbons. We describe what we believe to be a novel regulatory system for whole-body CYP1A1 expression by a factor originating in the gut. A mutant mouse was generated in which the arylhydrocarbon receptor nuclear translocator (Arnt) gene is disrupted predominantly in the gut epithelium. Surprisingly, CYP1A1 mRNA expression and enzymatic activities were markedly elevated in almost all non-gut tissues in this mouse line. The induction was even observed in early-stage embryos in pregnant mutant females. Interestingly, the upregulation was CYP1A1 selective and lost upon administration of a synthetic purified diet. Moreover, the increase was recovered by addition of the natural phytochemical indole-3-carbinol to the purified diet. These results suggest that an Arnt-dependent pathway in gut has an important role in regulation of the metabolism of dietary CYP1A1 inducers and whole-body CYP1A1 expression. This machinery might be involved in naturally occurring carcinogenic processes and/or other numerous biological responses mediated by CYP1A1 activity.

show abstract

“…All genes were analyzed with the SYBR green detection method by using the Applied Biosystems 7500 real-time PCR machine. The forward and reverse primer sequences were obtained from published studies (37,38). Each PCR was run in duplicate with two different cDNA templates.…”

mentioning

confidence: 99%

Pancreatic exocrine insufficiency in LXRβ ^−/− mice is associated with a reduction in aquaporin-1 expression

Gabbi

Kim

Hultenby

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Liver X receptors (LXRs) ␣ and ␤ are nuclear oxysterol receptors with a key role in cholesterol, triglyceride, and glucose metabolism. In LXR␤ ؊/؊ mice on a normal diet, there is a reduction in size of perigonadal fat pad and, on high-fat diet there is resistance to obesity. In the present study, we investigated the reason for the resistance of LXR␤ ؊/؊ mice to weight gain. In LXR␤ ؊/؊ mice we found pancreatic exocrine insufficiency with reduced serum levels of amylase and lipase, reduced proteolytic activity in feces, chronic inflammatory infiltration, and, in the ductal epithelium, an increased apoptosis without compensatory proliferation. Electron microscopy revealed ductal dilatation with intraductal laminar structures characteristic of cystic fibrosis. To investigate the relationship between LXR␤ and pancreatic secretion, we studied the expression of LXR␤ and the water channel, aquaporin-1 (AQP1), in the ductal epithelium of the pancreas. In WT mice, ductal epithelial cells expressed LXR␤ in the nuclei and AQP1 on the plasma membrane. In LXR␤ ؊/؊ mice neither LXR␤ nor AQP1 was detectable. Moreover, in WT mice the LXR agonist (T2320) increased AQP1 gene expression. These data demonstrate that in LXR␤ ؊/؊ mice dietary resistance to weight gain is caused by pancreatic insufficiency and that LXR␤ regulates pancreatic exocrine secretion through the control of AQP1 expression. Pancreatic exocrine insufficiency is the main cause of malabsorption syndrome responsible for weight loss in adults and growth failure in children. Several genes are known to be involved in the pathogenesis and susceptibility to pancreatic insufficiency. LXR␤ should be included in that list.pancreas ͉ malabsorption ͉ cystic fibrosis ͉ amylase ͉ lipase

show abstract

Aryl Hydrocarbon Receptor Expression and Activity in Cerebellar Granule Neuroblasts: Implications for Development and Dioxin Neurotoxicity

Cited by 105 publications

References 30 publications

L-Kynurenine/Aryl Hydrocarbon Receptor Pathway Mediates Brain Damage After Experimental Stroke

L-Kynurenine/Aryl Hydrocarbon Receptor Pathway Mediates Brain Damage After Experimental Stroke

Dietary phytochemicals regulate whole-body CYP1A1 expression through an arylhydrocarbon receptor nuclear translocator–dependent system in gut

Pancreatic exocrine insufficiency in LXRβ ^−/− mice is associated with a reduction in aquaporin-1 expression

Contact Info

Product

Resources

About

Aryl Hydrocarbon Receptor Expression and Activity in Cerebellar Granule Neuroblasts: Implications for Development and Dioxin Neurotoxicity

Cited by 105 publications

References 30 publications

L-Kynurenine/Aryl Hydrocarbon Receptor Pathway Mediates Brain Damage After Experimental Stroke

L-Kynurenine/Aryl Hydrocarbon Receptor Pathway Mediates Brain Damage After Experimental Stroke

Dietary phytochemicals regulate whole-body CYP1A1 expression through an arylhydrocarbon receptor nuclear translocator–dependent system in gut

Pancreatic exocrine insufficiency in LXRβ −/− mice is associated with a reduction in aquaporin-1 expression

Contact Info

Product

Resources

About

Pancreatic exocrine insufficiency in LXRβ ^−/− mice is associated with a reduction in aquaporin-1 expression