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Contributions of Nitric Oxide to AHR-Ligand-Mediated Keratinocyte Differentiation

Activation of the aryl hydrocarbon receptor (AHR) in normal human epidermal keratinocytes (NHEKs) accelerates keratinocyte terminal differentiation through metabolic reprogramming and reactive oxygen species (ROS) production. Of the three NOS isoforms, NOS3 is significantly increased at both the RNA...

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Autores principales: Sutter, Carrie Hayes, Rainwater, Haley M., Sutter, Thomas R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460822/
https://www.ncbi.nlm.nih.gov/pubmed/32784365
http://dx.doi.org/10.3390/ijms21165680
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author Sutter, Carrie Hayes
Rainwater, Haley M.
Sutter, Thomas R.
author_facet Sutter, Carrie Hayes
Rainwater, Haley M.
Sutter, Thomas R.
author_sort Sutter, Carrie Hayes
collection PubMed
description Activation of the aryl hydrocarbon receptor (AHR) in normal human epidermal keratinocytes (NHEKs) accelerates keratinocyte terminal differentiation through metabolic reprogramming and reactive oxygen species (ROS) production. Of the three NOS isoforms, NOS3 is significantly increased at both the RNA and protein levels by exposure to the very potent and selective ligand of the AHR, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Inhibition of NOS with the chemical N-nitro-l-arginine methyl ester (l-NAME) reversed TCDD-induced cornified envelope formation, an endpoint of terminal differentiation, as well as the expression of filaggrin (FLG), a marker of differentiation. Conversely, exposure to the NO-donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), increased the number of cornified envelopes above control levels and augmented the levels of cornified envelopes formed in response to TCDD treatment and increased the expression of FLG. This indicates that nitric oxide signaling can increase keratinocyte differentiation and that it is involved in the AHR-mediated acceleration of differentiation. As the nitrosylation of cysteines is a mechanism by which NO affects the structure and functions of proteins, the S-nitrosylation biotin switch technique was used to measure protein S-nitrosylation. Activation of the AHR increased the S-nitrosylation of two detected proteins of about 72 and 20 kD in size. These results provide new insights into the role of NO and protein nitrosylation in the process of epithelial cell differentiation, suggesting a role of NOS in metabolic reprogramming and the regulation of epithelial cell fate.
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spelling pubmed-74608222020-09-03 Contributions of Nitric Oxide to AHR-Ligand-Mediated Keratinocyte Differentiation Sutter, Carrie Hayes Rainwater, Haley M. Sutter, Thomas R. Int J Mol Sci Article Activation of the aryl hydrocarbon receptor (AHR) in normal human epidermal keratinocytes (NHEKs) accelerates keratinocyte terminal differentiation through metabolic reprogramming and reactive oxygen species (ROS) production. Of the three NOS isoforms, NOS3 is significantly increased at both the RNA and protein levels by exposure to the very potent and selective ligand of the AHR, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Inhibition of NOS with the chemical N-nitro-l-arginine methyl ester (l-NAME) reversed TCDD-induced cornified envelope formation, an endpoint of terminal differentiation, as well as the expression of filaggrin (FLG), a marker of differentiation. Conversely, exposure to the NO-donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), increased the number of cornified envelopes above control levels and augmented the levels of cornified envelopes formed in response to TCDD treatment and increased the expression of FLG. This indicates that nitric oxide signaling can increase keratinocyte differentiation and that it is involved in the AHR-mediated acceleration of differentiation. As the nitrosylation of cysteines is a mechanism by which NO affects the structure and functions of proteins, the S-nitrosylation biotin switch technique was used to measure protein S-nitrosylation. Activation of the AHR increased the S-nitrosylation of two detected proteins of about 72 and 20 kD in size. These results provide new insights into the role of NO and protein nitrosylation in the process of epithelial cell differentiation, suggesting a role of NOS in metabolic reprogramming and the regulation of epithelial cell fate. MDPI 2020-08-08 /pmc/articles/PMC7460822/ /pubmed/32784365 http://dx.doi.org/10.3390/ijms21165680 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sutter, Carrie Hayes
Rainwater, Haley M.
Sutter, Thomas R.
Contributions of Nitric Oxide to AHR-Ligand-Mediated Keratinocyte Differentiation
title Contributions of Nitric Oxide to AHR-Ligand-Mediated Keratinocyte Differentiation
title_full Contributions of Nitric Oxide to AHR-Ligand-Mediated Keratinocyte Differentiation
title_fullStr Contributions of Nitric Oxide to AHR-Ligand-Mediated Keratinocyte Differentiation
title_full_unstemmed Contributions of Nitric Oxide to AHR-Ligand-Mediated Keratinocyte Differentiation
title_short Contributions of Nitric Oxide to AHR-Ligand-Mediated Keratinocyte Differentiation
title_sort contributions of nitric oxide to ahr-ligand-mediated keratinocyte differentiation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7460822/
https://www.ncbi.nlm.nih.gov/pubmed/32784365
http://dx.doi.org/10.3390/ijms21165680
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