Characterization of the region of the aryl hydrocarbon receptor required for ligand dependency of transactivation using chimeric receptor between Drosophila and Mus musculus

Kudo, Kyoko; Takeuchi, Takeshi; Murakami, Yusuke; Ebina, Masayuki; Kikuchi, Hideaki

doi:10.1016/j.bbagrm.2009.06.003

Cited by 18 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This conserved effect in BXDs across different environmental conditions indicates a constitutive role for Ahr in the regulation of movement in vertebrates as well. The observation that reduction of Ahr orthologs in invertebrates has a consistent effect on movement furthers this hypothesis, as the Drosophila ortholog ( spineless ) is constitutively active [38] and does not appear to be affected by any exogenous ligands [33]. A large number of AHR polymorphisms have been identified in large and diverse human population studies [39], [40], though it remains to be seen if these variants lead to variation in locomotion and/or disposition to exercise in humans as in mice.…”

Section: Discussionmentioning

confidence: 80%

See 1 more Smart Citation

An Evolutionarily Conserved Role for the Aryl Hydrocarbon Receptor in the Regulation of Movement

et al. 2014

View full text Add to dashboard Cite

The BXD genetic reference population is a recombinant inbred panel descended from crosses between the C57BL/6 (B6) and DBA/2 (D2) strains of mice, which segregate for about 5 million sequence variants. Recently, some of these variants have been established with effects on general metabolic phenotypes such as glucose response and bone strength. Here we phenotype 43 BXD strains and observe they have large variation (∼5-fold) in their spontaneous activity during waking hours. QTL analyses indicate that ∼40% of this variance is attributable to a narrow locus containing the aryl hydrocarbon receptor (Ahr), a basic helix-loop-helix transcription factor with well-established roles in development and xenobiotic metabolism. Strains with the D2 allele of Ahr have reduced gene expression compared to those with the B6 allele, and have significantly higher spontaneous activity. This effect was also observed in B6 mice with a congenic D2 Ahr interval, and in B6 mice with a humanized AHR allele which, like the D2 allele, is expressed much less and has less enzymatic activity than the B6 allele. Ahr is highly conserved in invertebrates, and strikingly inhibition of its orthologs in D. melanogaster and C. elegans (spineless and ahr-1) leads to marked increases in basal activity. In mammals, Ahr has numerous ligands, but most are either non-selective (e.g. resveratrol) or highly toxic (e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)). Thus, we chose to examine a major environmental influence—long term feeding with high fat diet (HFD)—to see if the effects of Ahr are dependent on major metabolic differences. Interestingly, while HFD robustly halved movement across all strains, the QTL position and effects of Ahr remained unchanged, indicating that the effects are independent. The highly consistent effects of Ahr on movement indicate that changes in its constitutive activity have a role on spontaneous movement and may influence human behavior.

show abstract

Section: Discussionmentioning

confidence: 80%

“…In Drosophila and C. elegans , the Ahr orthologs are suspected to be exclusively constitutively active [33]. However, this does not indicate whether it is constitutive activity operating in the mice, or if it is an unknown dietary component of the chow diet common to all cohorts, which could influence movement in a ligand-dependent manner.…”

Section: Resultsmentioning

confidence: 98%

An Evolutionarily Conserved Role for the Aryl Hydrocarbon Receptor in the Regulation of Movement

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Additionally, no direct binding of a ligand has ever been shown in C. elegans or Drosophila. In vitro studies showed that the Drosophila AhR is constitutively active which might result in the inability of ligand-dependent activation (Kudo et al, 2009). Recent studies show however that indoles from commensal bacteria extend the lifespan of C. elegans and Drosophila in an AhR-dependent manner (Sonowal et al, 2017).…”

Section: Ahr and Aging In Invertebratesmentioning

confidence: 99%

The Aryl Hydrocarbon Receptor (AhR) in the Aging Process: Another Puzzling Role for This Highly Conserved Transcription Factor

et al. 2020

View full text Add to dashboard Cite

Aging is the most important risk factor for the development of major life-threatening diseases such as cardiovascular disorders, cancer, and neurodegenerative disorders. The aging process is characterized by the accumulation of damage to intracellular macromolecules and it is concurrently shaped by genetic, environmental and nutritional factors. These factors influence the functionality of mitochondria, which play a central role in the aging process. Mitochondrial dysfunction is one of the hallmarks of aging and is associated with increased fluxes of ROS leading to damage of mitochondrial components, impaired metabolism of fatty acids, dysregulated glucose metabolism, and damage of adjacent organelles. Interestingly, many of the environmental (e.g., pollutants and other toxicants) and nutritional (e.g., flavonoids, carotenoids) factors influencing aging and mitochondrial function also directly or indirectly affect the activity of a highly conserved transcription factor, the Aryl hydrocarbon Receptor (AhR). Therefore, it is not surprising that many studies have already indicated a role of this versatile transcription factor in the aging process. We also recently found that the AhR promotes aging phenotypes across species. In this manuscript, we systematically review the existing literature on the contradictory studies indicating either pro-or anti-aging effects of the AhR and try to reconcile the seemingly conflicting data considering a possible dependency on the animal model, tissue, as well as level of AhR expression and activation. Moreover, given the crucial role of mitochondria in the aging process, we summarize the growing body of evidence pointing toward the influence of AhR on mitochondria, which can be of potential relevance for aging.

show abstract

“…Although these AHRs do not appear to bind typical (i.e. vertebrate) AHR ligands [13,16,34] and there is some evidence for constitutive, ligand-independent activity [32,42,50], it is also possible that there are endogenous ligands or other regulatory mechanisms involved [51–53]. Nevertheless, we refer to these proteins as “ protoAHRs ” (Table 1) to highlight the apparently substantial differences in ligand specificity between these proteins and their vertebrate homologs, which function (at least in part) as true “aryl hydrocarbon receptors.” It is important to note, however, that all of the evidence currently available is consistent with the idea that protoAHRs and vertebrate AHRs are true orthologs (i.e.…”

Section: Ahrs In Protostomes: Key Roles In Development Of Sensory mentioning

confidence: 99%

Diversity as opportunity: Insights from 600 million years of AHR evolution

Hahn

Karchner

Merson

2017

Current Opinion in Toxicology

107

111

View full text Add to dashboard Cite

The aryl hydrocarbon receptor (AHR) was for many years of interest only to pharmacologists and toxicologists. However, this protein has fundamental roles in biology that are being revealed through studies in diverse animal species. The AHR is an ancient protein. AHR homologs exist in most major groups of modern bilaterian animals, including deuterostomes (chordates, hemichordates, echinoderms) and the two major clades of protostome invertebrates [ecdysozoans (e.g. arthropods and nematodes) and lophotrochozoans (e.g. molluscs and annelids)]. AHR homologs also have been identified in cnidarians such as the sea anemone Nematostella and in the genome of Trichoplax, a placozoan. Bilaterians, cnidarians, and placozoans form the clade Eumetazoa, whose last common ancestor lived approximately 600 million years ago (MYA). The presence of AHR homologs in modern representatives of all these groups indicates that the original eumetazoan animal possessed an AHR homolog. Studies in invertebrates and vertebrates reveal parallel functions of AHR in the development and function of sensory neural systems, suggesting that these may be ancestral roles. Vertebrate animals are characterized by the expansion and diversification of AHRs, via gene and genome duplications, from the ancestral protoAHR into at least five classes of AHR-like proteins: AHR, AHR1, AHR2, AHR3, and AHRR. The evolution of multiple AHRs in vertebrates coincided with the acquisition of high-affinity binding of halogenated and polynuclear aromatic hydrocarbons and the emergence of adaptive functions involving regulation of xenobiotic-metabolizing enzymes and roles in adaptive immunity. The existence of multiple AHRs may have facilitated subfunction partitioning and specialization of specific AHR types in some taxa. Additional research in diverse model and non-model species will continue to enrich our understanding of AHR and its pleiotropic roles in biology and toxicology.

show abstract

Characterization of the region of the aryl hydrocarbon receptor required for ligand dependency of transactivation using chimeric receptor between Drosophila and Mus musculus

Cited by 18 publications

References 36 publications

An Evolutionarily Conserved Role for the Aryl Hydrocarbon Receptor in the Regulation of Movement

An Evolutionarily Conserved Role for the Aryl Hydrocarbon Receptor in the Regulation of Movement

The Aryl Hydrocarbon Receptor (AhR) in the Aging Process: Another Puzzling Role for This Highly Conserved Transcription Factor

Diversity as opportunity: Insights from 600 million years of AHR evolution

Contact Info

Product

Resources

About