Endogenous regulation of the Akt pathway by the aryl hydrocarbon receptor (AhR) in lung fibroblasts

Abstract The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor known to mediate toxic responses to dioxin. However, the role of the AhR in the regulation of cellular physiology has only recently been appreciated, including its ability to control cell cycle progression and ap...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Fangyi Shi, Noof Aloufi, Hussein Traboulsi, Jean-François Trempe, David H. Eidelman, Carolyn J. Baglole
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/427f81613c934d70ab473eef83a88388
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:427f81613c934d70ab473eef83a88388
record_format	dspace
spelling	oai:doaj.org-article:427f81613c934d70ab473eef83a883882021-12-05T12:14:06ZEndogenous regulation of the Akt pathway by the aryl hydrocarbon receptor (AhR) in lung fibroblasts10.1038/s41598-021-02339-32045-2322https://doaj.org/article/427f81613c934d70ab473eef83a883882021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02339-3https://doaj.org/toc/2045-2322Abstract The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor known to mediate toxic responses to dioxin. However, the role of the AhR in the regulation of cellular physiology has only recently been appreciated, including its ability to control cell cycle progression and apoptosis by unknown mechanisms. We hypothesized that the AhR enhances the activation of the AKT serine/threonine kinase (Akt) pathway to promote cell survival. Utilizing AhR knock-out (Ahr −/−) and wild-type (Ahr +/+) mouse lung fibroblasts (MLFs), we found that Ahr −/− MLFs have significantly higher basal Akt phosphorylation but that AhR did not affect Akt phosphorylation in MLFs exposed to growth factors or AhR ligands. Basal Akt phosphorylation was dependent on PI3K but was unaffected by changes in intracellular glutathione (GSH) or p85α. There was no significant decrease in cell viability in Ahr −/− MLFs treated with LY294002—a PI3K inhibitor—although LY294002 did attenuate MTT reduction, indicating an affect on mitochondrial function. Using a mass spectrometry (MS)-based approach, we identified several proteins that were differentially phosphorylated in the Ahr −/− MLFs compared to control cells, including proteins involved in the regulation of extracellular matrix (ECM), focal adhesion, cytoskeleton remodeling and mitochondrial function. In conclusion, Ahr ablation increased basal Akt phosphorylation in MLFs. Our results indicate that AhR may modulate the phosphorylation of a variety of novel proteins not previously identified as AhR targets, findings that help advance our understanding of the endogenous functions of AhR.Fangyi ShiNoof AloufiHussein TraboulsiJean-François TrempeDavid H. EidelmanCarolyn J. BagloleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fangyi Shi Noof Aloufi Hussein Traboulsi Jean-François Trempe David H. Eidelman Carolyn J. Baglole Endogenous regulation of the Akt pathway by the aryl hydrocarbon receptor (AhR) in lung fibroblasts
description	Abstract The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor known to mediate toxic responses to dioxin. However, the role of the AhR in the regulation of cellular physiology has only recently been appreciated, including its ability to control cell cycle progression and apoptosis by unknown mechanisms. We hypothesized that the AhR enhances the activation of the AKT serine/threonine kinase (Akt) pathway to promote cell survival. Utilizing AhR knock-out (Ahr −/−) and wild-type (Ahr +/+) mouse lung fibroblasts (MLFs), we found that Ahr −/− MLFs have significantly higher basal Akt phosphorylation but that AhR did not affect Akt phosphorylation in MLFs exposed to growth factors or AhR ligands. Basal Akt phosphorylation was dependent on PI3K but was unaffected by changes in intracellular glutathione (GSH) or p85α. There was no significant decrease in cell viability in Ahr −/− MLFs treated with LY294002—a PI3K inhibitor—although LY294002 did attenuate MTT reduction, indicating an affect on mitochondrial function. Using a mass spectrometry (MS)-based approach, we identified several proteins that were differentially phosphorylated in the Ahr −/− MLFs compared to control cells, including proteins involved in the regulation of extracellular matrix (ECM), focal adhesion, cytoskeleton remodeling and mitochondrial function. In conclusion, Ahr ablation increased basal Akt phosphorylation in MLFs. Our results indicate that AhR may modulate the phosphorylation of a variety of novel proteins not previously identified as AhR targets, findings that help advance our understanding of the endogenous functions of AhR.
format	article
author	Fangyi Shi Noof Aloufi Hussein Traboulsi Jean-François Trempe David H. Eidelman Carolyn J. Baglole
author_facet	Fangyi Shi Noof Aloufi Hussein Traboulsi Jean-François Trempe David H. Eidelman Carolyn J. Baglole
author_sort	Fangyi Shi
title	Endogenous regulation of the Akt pathway by the aryl hydrocarbon receptor (AhR) in lung fibroblasts
title_short	Endogenous regulation of the Akt pathway by the aryl hydrocarbon receptor (AhR) in lung fibroblasts
title_full	Endogenous regulation of the Akt pathway by the aryl hydrocarbon receptor (AhR) in lung fibroblasts
title_fullStr	Endogenous regulation of the Akt pathway by the aryl hydrocarbon receptor (AhR) in lung fibroblasts
title_full_unstemmed	Endogenous regulation of the Akt pathway by the aryl hydrocarbon receptor (AhR) in lung fibroblasts
title_sort	endogenous regulation of the akt pathway by the aryl hydrocarbon receptor (ahr) in lung fibroblasts
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/427f81613c934d70ab473eef83a88388
work_keys_str_mv	AT fangyishi endogenousregulationoftheaktpathwaybythearylhydrocarbonreceptorahrinlungfibroblasts AT noofaloufi endogenousregulationoftheaktpathwaybythearylhydrocarbonreceptorahrinlungfibroblasts AT husseintraboulsi endogenousregulationoftheaktpathwaybythearylhydrocarbonreceptorahrinlungfibroblasts AT jeanfrancoistrempe endogenousregulationoftheaktpathwaybythearylhydrocarbonreceptorahrinlungfibroblasts AT davidheidelman endogenousregulationoftheaktpathwaybythearylhydrocarbonreceptorahrinlungfibroblasts AT carolynjbaglole endogenousregulationoftheaktpathwaybythearylhydrocarbonreceptorahrinlungfibroblasts
_version_	1718372128769703936

Endogenous regulation of the Akt pathway by the aryl hydrocarbon receptor (AhR) in lung fibroblasts

Ejemplares similares