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Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex
We hypothesized that an interplay between aryl hydrocarbon receptor (AhR) and cysteine-related thiolome at the kidney cortex underlies the mechanisms of (mal)adaptation to chronic intermittent hypoxia (CIH), promoting arterial hypertension (HTN). Using a rat model of CIH-HTN, we investigated the imp...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469308/ https://www.ncbi.nlm.nih.gov/pubmed/34573115 http://dx.doi.org/10.3390/antiox10091484 |
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author | Correia, Maria João Pimpão, António B. Lopes-Coelho, Filipa Sequeira, Catarina O. Coelho, Nuno R. Gonçalves-Dias, Clara Barouki, Robert Coumoul, Xavier Serpa, Jacinta Morello, Judit Monteiro, Emília C. Pereira, Sofia A. |
author_facet | Correia, Maria João Pimpão, António B. Lopes-Coelho, Filipa Sequeira, Catarina O. Coelho, Nuno R. Gonçalves-Dias, Clara Barouki, Robert Coumoul, Xavier Serpa, Jacinta Morello, Judit Monteiro, Emília C. Pereira, Sofia A. |
author_sort | Correia, Maria João |
collection | PubMed |
description | We hypothesized that an interplay between aryl hydrocarbon receptor (AhR) and cysteine-related thiolome at the kidney cortex underlies the mechanisms of (mal)adaptation to chronic intermittent hypoxia (CIH), promoting arterial hypertension (HTN). Using a rat model of CIH-HTN, we investigated the impact of short-term (1 and 7 days), mid-term (14 and 21 days, pre-HTN), and long-term intermittent hypoxia (IH) (up to 60 days, established HTN) on CYP1A1 protein level (a sensitive hallmark of AhR activation) and cysteine-related thiol pools. We found that acute and chronic IH had opposite effects on CYP1A1 and the thiolome. While short-term IH decreased CYP1A1 and increased protein-S-thiolation, long-term IH increased CYP1A1 and free oxidized cysteine. In addition, an in vitro administration of cystine, but not cysteine, to human endothelial cells increased Cyp1a1 expression, supporting cystine as a putative AhR activator. This study supports CYP1A1 as a biomarker of obstructive sleep apnea (OSA) severity and oxidized pools of cysteine as risk indicator of OSA-HTN. This work contributes to a better understanding of the mechanisms underlying the phenotype of OSA-HTN, mimicked by this model, which is in line with precision medicine challenges in OSA. |
format | Online Article Text |
id | pubmed-8469308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84693082021-09-27 Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex Correia, Maria João Pimpão, António B. Lopes-Coelho, Filipa Sequeira, Catarina O. Coelho, Nuno R. Gonçalves-Dias, Clara Barouki, Robert Coumoul, Xavier Serpa, Jacinta Morello, Judit Monteiro, Emília C. Pereira, Sofia A. Antioxidants (Basel) Article We hypothesized that an interplay between aryl hydrocarbon receptor (AhR) and cysteine-related thiolome at the kidney cortex underlies the mechanisms of (mal)adaptation to chronic intermittent hypoxia (CIH), promoting arterial hypertension (HTN). Using a rat model of CIH-HTN, we investigated the impact of short-term (1 and 7 days), mid-term (14 and 21 days, pre-HTN), and long-term intermittent hypoxia (IH) (up to 60 days, established HTN) on CYP1A1 protein level (a sensitive hallmark of AhR activation) and cysteine-related thiol pools. We found that acute and chronic IH had opposite effects on CYP1A1 and the thiolome. While short-term IH decreased CYP1A1 and increased protein-S-thiolation, long-term IH increased CYP1A1 and free oxidized cysteine. In addition, an in vitro administration of cystine, but not cysteine, to human endothelial cells increased Cyp1a1 expression, supporting cystine as a putative AhR activator. This study supports CYP1A1 as a biomarker of obstructive sleep apnea (OSA) severity and oxidized pools of cysteine as risk indicator of OSA-HTN. This work contributes to a better understanding of the mechanisms underlying the phenotype of OSA-HTN, mimicked by this model, which is in line with precision medicine challenges in OSA. MDPI 2021-09-17 /pmc/articles/PMC8469308/ /pubmed/34573115 http://dx.doi.org/10.3390/antiox10091484 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Correia, Maria João Pimpão, António B. Lopes-Coelho, Filipa Sequeira, Catarina O. Coelho, Nuno R. Gonçalves-Dias, Clara Barouki, Robert Coumoul, Xavier Serpa, Jacinta Morello, Judit Monteiro, Emília C. Pereira, Sofia A. Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex |
title | Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex |
title_full | Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex |
title_fullStr | Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex |
title_full_unstemmed | Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex |
title_short | Aryl Hydrocarbon Receptor and Cysteine Redox Dynamics Underlie (Mal)adaptive Mechanisms to Chronic Intermittent Hypoxia in Kidney Cortex |
title_sort | aryl hydrocarbon receptor and cysteine redox dynamics underlie (mal)adaptive mechanisms to chronic intermittent hypoxia in kidney cortex |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469308/ https://www.ncbi.nlm.nih.gov/pubmed/34573115 http://dx.doi.org/10.3390/antiox10091484 |
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