ARYL HYDROCARBON RECEPTOR IN METABOLISM, CARCINOGENESIS AND DEVELOPMENT

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F19%3AN0000252" target="_blank" >RIV/00027162:_____/19:N0000252 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

ARYL HYDROCARBON RECEPTOR IN METABOLISM, CARCINOGENESIS AND DEVELOPMENT

Popis výsledku v původním jazyce

THE 68th CZECH-SLOVAK PHARMACOLOGICAL DAYS - Hradec Králové, 5.-7.9.2018. The aryl hydrocarbon receptor (AhR) is a cytosolic ligand-activated transcription factor, a member of basic helix-loop-helix/Per Arnt Sim family of transcriptional regulators, which plays a key role in many physiological and pathophysiological processes, including toxicity of persistent polyhalogenated aromatic pollutants (“dioxin-like compounds“) as well as less persistent polycyclic aromatic hydrocarbons (PAHs) and their derivatives. The majority of endogenous AhR ligands described so far, are transient products of e.g. tryptophan and indole metabolism, originating from endogenous metabolic sources, diet or microbiota. A typical feature of these compounds is their limited stability, since they are rapidly metabolized. AhR has been originally studied as a xenobiotic receptor, which plays a key role in metabolism of polyaromatic pollutants. However, today, AhR is viewed as a receptor, which cytosolic protein complex provides a reactive platform for a plethora of distinct aromatic compounds of both endogenous and exogenous origin. AhR may form complexes also with other transcription factors, such as STAT1, STAT5, RELB, KLF6, TCF21, and these interactions can be both ligand- and cell context-dependent. The complexity of AhR signaling is related to the fact that it controls numerous tissue-/cell-specific effects, as illustrated e.g. by the ability of AhR ligands to trigger pro-survival action in one cell type, while simultaneously inducing apoptosis in another one. AhR signaling has been also implicated in the regulation of cell cycle in multiple cell types of various tissue origin, it modulates immune response, intercellular communication, and it participates in the regulation of cellular adaptation to oxidative stress. Aberrant or a sustained activation of AhR signaling pathway, triggered by exogenous toxic compounds such as dioxins or PAHs, is a well-described biological process engaged during tumor initiation and/or promotion in various tissues (e.g. liver, lung, skin). Some toxic AhR ligands are mutagenic compounds acting as genotoxins, via formation of DNA adducts and oxidative stress (e.g. benzo[a]pyrene), while others seem to act primarily as tumor promoters, which do not cause a direct DNA damage. Crosstalk between the AhR and ERα and AhR-dependent catabolism of steroid hormones are examples of involvement of AhR activation in endocrine disruption. Finally, a central role of AhR in regulation of pluripotency and cell differentiation has been reported recently, suggesting that exposure to toxic AhR ligands may disrupt developmental processes.

Název v anglickém jazyce

ARYL HYDROCARBON RECEPTOR IN METABOLISM, CARCINOGENESIS AND DEVELOPMENT

Popis výsledku anglicky

THE 68th CZECH-SLOVAK PHARMACOLOGICAL DAYS - Hradec Králové, 5.-7.9.2018. The aryl hydrocarbon receptor (AhR) is a cytosolic ligand-activated transcription factor, a member of basic helix-loop-helix/Per Arnt Sim family of transcriptional regulators, which plays a key role in many physiological and pathophysiological processes, including toxicity of persistent polyhalogenated aromatic pollutants (“dioxin-like compounds“) as well as less persistent polycyclic aromatic hydrocarbons (PAHs) and their derivatives. The majority of endogenous AhR ligands described so far, are transient products of e.g. tryptophan and indole metabolism, originating from endogenous metabolic sources, diet or microbiota. A typical feature of these compounds is their limited stability, since they are rapidly metabolized. AhR has been originally studied as a xenobiotic receptor, which plays a key role in metabolism of polyaromatic pollutants. However, today, AhR is viewed as a receptor, which cytosolic protein complex provides a reactive platform for a plethora of distinct aromatic compounds of both endogenous and exogenous origin. AhR may form complexes also with other transcription factors, such as STAT1, STAT5, RELB, KLF6, TCF21, and these interactions can be both ligand- and cell context-dependent. The complexity of AhR signaling is related to the fact that it controls numerous tissue-/cell-specific effects, as illustrated e.g. by the ability of AhR ligands to trigger pro-survival action in one cell type, while simultaneously inducing apoptosis in another one. AhR signaling has been also implicated in the regulation of cell cycle in multiple cell types of various tissue origin, it modulates immune response, intercellular communication, and it participates in the regulation of cellular adaptation to oxidative stress. Aberrant or a sustained activation of AhR signaling pathway, triggered by exogenous toxic compounds such as dioxins or PAHs, is a well-described biological process engaged during tumor initiation and/or promotion in various tissues (e.g. liver, lung, skin). Some toxic AhR ligands are mutagenic compounds acting as genotoxins, via formation of DNA adducts and oxidative stress (e.g. benzo[a]pyrene), while others seem to act primarily as tumor promoters, which do not cause a direct DNA damage. Crosstalk between the AhR and ERα and AhR-dependent catabolism of steroid hormones are examples of involvement of AhR activation in endocrine disruption. Finally, a central role of AhR in regulation of pluripotency and cell differentiation has been reported recently, suggesting that exposure to toxic AhR ligands may disrupt developmental processes.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

10601 - Cell biology

Projekt

<a href="/cs/project/GBP503%2F12%2FG147" target="_blank" >GBP503/12/G147: Centrum studií toxických vlastností nanočástic</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů