Correia, Maria JoãoPimpão, António B.Lopes-Coelho, FilipaSequeira, Catarina O.Coelho, Nuno R.Gonçalves-Dias, ClaraBarouki, RobertCoumoul, XavierSerpa, JacintaSerpa, JacintaMorello, JuditMonteiro, Emília C.Monteiro, E.C.Pereira, Sofia A.SA, Pereira2021-11-112021-11-112021-092076-3921PURE: 33949785PURE UUID: f1890f58-851e-4452-a52f-3cb0dd1485f8Scopus: 85115106295PubMed: 34573115ORCID: /0000-0002-8456-9995/work/103030947ORCID: /0000-0002-1548-5907/work/103031161WOS: 000699264100001http://hdl.handle.net/10362/127576Funding Information: Funding: This work was supported by Fundação para Ciência e Tecnologia [PTDC/MED-TOX/30418/2017] and iNOVA4Health [UID/Multi/04462/2013]. M.J.C., F.L.-C., N.R.C., C.G.-D. and J.M. are supported by FCT grants [SFRH/BD/131331/2017, PD/BD/128337/2017, PD/BD/114257/2016, and PD/BD/105892/2014, PTDC/MED-TOX/30418/2017 respectively]. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.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.3393735engAnimal modelsArterial hypertensionCYP1A1CystineEndothelial dysfunctionNon-radical oxidative speciesObstructive sleep apneaPrecision medicineThiolsXCTBiochemistryPhysiologyMolecular BiologyClinical BiochemistryCell BiologySDG 3 - Good Health and Well-beingjournal article10.3390/antiox10091484https://www.scopus.com/pages/publications/85115106295