Benzo(a)pyrene triggers desensitization of β2-adrenergic pathway

Abstract Exposure to environmental polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (B(a)P), has been linked to several health-threatening risks. PAHs were also shown to hinder adrenergic receptor (ADR) responses. As we previously demonstrated that B(a)P can directly interact with the...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Abdullah Mayati, Normand Podechard, Manuelle Rineau, Lydie Sparfel, Dominique Lagadic-Gossmann, Olivier Fardel, Eric Le Ferrec
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c8613d3a23d14ba8b04f0210cc5654ff
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c8613d3a23d14ba8b04f0210cc5654ff
record_format	dspace
spelling	oai:doaj.org-article:c8613d3a23d14ba8b04f0210cc5654ff2021-12-02T15:05:31ZBenzo(a)pyrene triggers desensitization of β2-adrenergic pathway10.1038/s41598-017-03646-42045-2322https://doaj.org/article/c8613d3a23d14ba8b04f0210cc5654ff2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03646-4https://doaj.org/toc/2045-2322Abstract Exposure to environmental polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (B(a)P), has been linked to several health-threatening risks. PAHs were also shown to hinder adrenergic receptor (ADR) responses. As we previously demonstrated that B(a)P can directly interact with the β2ADR, we investigated here whether B(a)P could decrease β2ADR responsiveness by triggering receptor desensitization phenomena. We firstly showed that exposure to B(a)P reduced β2ADR-mediated epinephrine-induced induction of NR4A gene mRNAs and of intracellular cAMP. Analysis of β2ADR protein expression demonstrated that B(a)P rapidly decreased membrane expression of β2ADR with a subsequent degradation of receptor protein. B(a)P exposure concomitantly rapidly increased the β2ADR mRNA levels. The use of the β-blockers, propranolol and ICI 118.551, demonstrated the involvement of β2ADR itself in this increase. However, sustained exposure to B(a)P induced a diminution of β2ADR mRNA steady-state as a result of the acceleration of its degradation. Together, these results show that, beside the well-known activation of the aryl hydrocarbon receptor, PAH deleterious effects may involve the dysfunction of adrenergic responses through, in part, the desensitization of β2ADR. This may be taken in consideration when β2-agonists/antagonists are administered in patients exposed to important concentrations of PAHs, e.g. in cigarette smokers.Abdullah MayatiNormand PodechardManuelle RineauLydie SparfelDominique Lagadic-GossmannOlivier FardelEric Le FerrecNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Abdullah Mayati Normand Podechard Manuelle Rineau Lydie Sparfel Dominique Lagadic-Gossmann Olivier Fardel Eric Le Ferrec Benzo(a)pyrene triggers desensitization of β2-adrenergic pathway
description	Abstract Exposure to environmental polycyclic aromatic hydrocarbons (PAHs), such as benzo(a)pyrene (B(a)P), has been linked to several health-threatening risks. PAHs were also shown to hinder adrenergic receptor (ADR) responses. As we previously demonstrated that B(a)P can directly interact with the β2ADR, we investigated here whether B(a)P could decrease β2ADR responsiveness by triggering receptor desensitization phenomena. We firstly showed that exposure to B(a)P reduced β2ADR-mediated epinephrine-induced induction of NR4A gene mRNAs and of intracellular cAMP. Analysis of β2ADR protein expression demonstrated that B(a)P rapidly decreased membrane expression of β2ADR with a subsequent degradation of receptor protein. B(a)P exposure concomitantly rapidly increased the β2ADR mRNA levels. The use of the β-blockers, propranolol and ICI 118.551, demonstrated the involvement of β2ADR itself in this increase. However, sustained exposure to B(a)P induced a diminution of β2ADR mRNA steady-state as a result of the acceleration of its degradation. Together, these results show that, beside the well-known activation of the aryl hydrocarbon receptor, PAH deleterious effects may involve the dysfunction of adrenergic responses through, in part, the desensitization of β2ADR. This may be taken in consideration when β2-agonists/antagonists are administered in patients exposed to important concentrations of PAHs, e.g. in cigarette smokers.
format	article
author	Abdullah Mayati Normand Podechard Manuelle Rineau Lydie Sparfel Dominique Lagadic-Gossmann Olivier Fardel Eric Le Ferrec
author_facet	Abdullah Mayati Normand Podechard Manuelle Rineau Lydie Sparfel Dominique Lagadic-Gossmann Olivier Fardel Eric Le Ferrec
author_sort	Abdullah Mayati
title	Benzo(a)pyrene triggers desensitization of β2-adrenergic pathway
title_short	Benzo(a)pyrene triggers desensitization of β2-adrenergic pathway
title_full	Benzo(a)pyrene triggers desensitization of β2-adrenergic pathway
title_fullStr	Benzo(a)pyrene triggers desensitization of β2-adrenergic pathway
title_full_unstemmed	Benzo(a)pyrene triggers desensitization of β2-adrenergic pathway
title_sort	benzo(a)pyrene triggers desensitization of β2-adrenergic pathway
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c8613d3a23d14ba8b04f0210cc5654ff
work_keys_str_mv	AT abdullahmayati benzoapyrenetriggersdesensitizationofb2adrenergicpathway AT normandpodechard benzoapyrenetriggersdesensitizationofb2adrenergicpathway AT manuellerineau benzoapyrenetriggersdesensitizationofb2adrenergicpathway AT lydiesparfel benzoapyrenetriggersdesensitizationofb2adrenergicpathway AT dominiquelagadicgossmann benzoapyrenetriggersdesensitizationofb2adrenergicpathway AT olivierfardel benzoapyrenetriggersdesensitizationofb2adrenergicpathway AT ericleferrec benzoapyrenetriggersdesensitizationofb2adrenergicpathway
_version_	1718388792517197824

Benzo(a)pyrene triggers desensitization of β2-adrenergic pathway

Ejemplares similares