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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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