Dioxin- and Ah receptor-dependent protein binding to xenobiotic responsive elements and G-rich DNA studied by in vivo footprinting.

Watson, Andrea; Hankinson, Oliver

doi:10.1016/s0021-9258(19)50509-9

Cited by 76 publications

(9 citation statements)

References 36 publications

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“…Once bound to TCDD, AhR dissociates from some of the proteins in the inactive complex and translocates to the nucleus where it dimerizes with Arnt (Reyes et al, 1992). The AhR/Arnt heterodimer activates the transcription of xenobiotic-metabolizing genes (Fujii-Kuriyama et al, 1992;Watson and Hankinson, 1992), some of which encode proteins involved in growth control, cytokines, nuclear transcription, and regulators of extracellular matrix proteolysis (Sutter et al, 1991;Yin et al, 1994). Therefore, the AhR pathway may be involved in the effects of tobacco smoke on skin.…”

Section: Tobacco Smoke and The Aryl Hydrocarbon Receptormentioning

confidence: 99%

Molecular Basis of Tobacco Smoke-Induced Premature Skin Aging

Morita

Torii

Maeda

et al. 2009

Journal of Investigative Dermatology Symposium Proceedings

104

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Although it is now widely recognized that tobacco smoke has negative effects on the skin, the molecular mechanisms underlying its skin-aging effects remain uncertain. Epidemiological studies indicate that tobacco smoking is a strong independent predictor of facial wrinkle formation and other aspects of premature skin aging. Recent in vivo studies in humans and mice provided the first direct evidence that tobacco smoke causes premature skin aging, and they have begun to reveal the molecular changes in the skin that occur in response to it. Water-soluble tobacco smoke extract, which predominantly produces oxidative stress when applied topically to cultured skin fibroblasts, impairs collagen biosynthesis. Matrix metalloproteinases, which degrade collagen, are induced dose-dependently by tobacco smoke extract as well as by other constituents that trigger the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor that mediates the toxicity of several environmental contaminants, including photoproducts in the body generated by UVB radiation. Tobacco smoke also contains many non-water-soluble constituents that activate the AhR pathway. Our most recent studies using hexane-soluble tobacco extract indicate that activation of the AhR pathway may play a role in the premature skin-aging effects of tobacco smoke exposure.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 53-55; doi:10.1038/jidsymp.2009.13.

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Section: Tobacco Smoke and The Aryl Hydrocarbon Receptormentioning

confidence: 99%

Molecular Basis of Tobacco Smoke-Induced Premature Skin Aging

Morita

Torii

Maeda

et al. 2009

Journal of Investigative Dermatology Symposium Proceedings

104

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“…ARNT also belongs to the bHLH family and directly binds to DRE [12]. In vivo DNA footprinting showed that AhR binds to the 5 -CACGCNA/T-3 , and ARNT with 5 -GTG-3 [13]. The molecular mechanisms underlying the action of dioxin on the cell are still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Meta-Analysis of Transcriptome Data Detected New Potential Players in Response to Dioxin Exposure in Humans

Ощепкова

Sizentsova

Wiebe

et al. 2020

IJMS

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Dioxins are one of the most potent anthropogenic poisons, causing systemic disorders in embryonic development and pathologies in adults. The mechanism of dioxin action requires an aryl hydrocarbon receptor (AhR), but the downstream mechanisms are not yet precisely clear. Here, we performed a meta-analysis of all available transcriptome datasets taken from human cell cultures exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Differentially expressed genes from different experiments overlapped partially, but there were a number of those genes that were systematically affected by TCDD. Some of them have been linked to toxic dioxin effects, but we also identified other attractive targets. Among the genes that were affected by TCDD, there are functionally related gene groups that suggest an interplay between retinoic acid, AhR, and Wnt signaling pathways. Next, we analyzed the upstream regions of differentially expressed genes and identified potential transcription factor (TF) binding sites overrepresented in the genes responding to TCDD. Intriguingly, the dioxin-responsive element (DRE), the binding site of AhR, was not overrepresented as much as other cis-elements were. Bioinformatics analysis of the AhR binding profile unveils potential cooperation of AhR with E2F2, CTCFL, and ZBT14 TFs in the dioxin response. We discuss the potential implication of these predictions for further dioxin studies.

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“…The mechanism by which AHR ligands affect physiological processes appears to involve multiple interactions between AHR and other signaling pathways (reviewed extensively by [3,4,10,11]) or may be a consequence of a change in the activity of metabolic enzymes and transporters, which are AHR target genes that modify the availability and disposition of endogenous metabolites (e.g., estrogen, arachidonic acid, melatonin) [19][20][21]. AHR target genes include several drug-metabolizing enzymes belonging to the cytochrome P450, like cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1), CYP1A2 and CYP1B1, aldehyde dehydrogenase 3 (ALDH3), and UDP glucuronosyltransferase family 1 member A1 (UGT1A1) [22][23][24] and transporters such as the ATP binding cassette subfamily B member 1 (ABCB1) [25].…”

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confidence: 99%