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Aryl hydrocarbon receptor and cysteine redox dynamics underlie (Mal)adaptive mechanisms to chronic intermittent hypoxia in kidney cortex

2021-09Artigo científico Acesso aberto
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dc.contributor.authorCorreia, Maria João
dc.contributor.authorPimpão, António B.
dc.contributor.authorLopes-Coelho, Filipa
dc.contributor.authorSequeira, Catarina O.
dc.contributor.authorCoelho, Nuno R.
dc.contributor.authorGonçalves-Dias, Clara
dc.contributor.authorBarouki, Robert
dc.contributor.authorCoumoul, Xavier
dc.contributor.authorSerpa, Jacinta
dc.contributor.authorSerpa, Jacinta
dc.contributor.authorMorello, Judit
dc.contributor.authorMonteiro, Emília C.
dc.contributor.authorMonteiro, E.C.
dc.contributor.authorPereira, Sofia A.
dc.contributor.authorSA, Pereira
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.pblMDPI - Multidisciplinary Digital Publishing Institute
dc.date.accessioned2021-11-11T23:38:43Z
dc.date.available2021-11-11T23:38:43Z
dc.date.issued2021-09
dc.descriptionFunding 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.
dc.description.abstractWe 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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent3393735
dc.identifier.doi10.3390/antiox10091484
dc.identifier.issn2076-3921
dc.identifier.otherPURE: 33949785
dc.identifier.otherPURE UUID: f1890f58-851e-4452-a52f-3cb0dd1485f8
dc.identifier.otherScopus: 85115106295
dc.identifier.otherPubMed: 34573115
dc.identifier.otherORCID: /0000-0002-8456-9995/work/103030947
dc.identifier.otherORCID: /0000-0002-1548-5907/work/103031161
dc.identifier.otherWOS: 000699264100001
dc.identifier.urihttp://hdl.handle.net/10362/127576
dc.identifier.urlhttps://www.scopus.com/pages/publications/85115106295
dc.language.isoeng
dc.peerreviewedyes
dc.subjectAnimal models
dc.subjectArterial hypertension
dc.subjectCYP1A1
dc.subjectCystine
dc.subjectEndothelial dysfunction
dc.subjectNon-radical oxidative species
dc.subjectObstructive sleep apnea
dc.subjectPrecision medicine
dc.subjectThiols
dc.subjectXCT
dc.subjectBiochemistry
dc.subjectPhysiology
dc.subjectMolecular Biology
dc.subjectClinical Biochemistry
dc.subjectCell Biology
dc.subjectSDG 3 - Good Health and Well-being
dc.titleAryl hydrocarbon receptor and cysteine redox dynamics underlie (Mal)adaptive mechanisms to chronic intermittent hypoxia in kidney cortexen
dc.typejournal article
degois.publication.issue9
degois.publication.titleAntioxidants
degois.publication.volume10
dspace.entity.typePublication
person.familyNameSerpa
person.familyNameMonteiro
person.familyNamede Azeredo Pereira
person.givenNameJacinta
person.givenNameEmília Carreira
person.givenNameSofia
person.identifier562223
person.identifier.ciencia-id2610-7C0D-38F2
person.identifier.ciencia-id5918-54A6-FAA0
person.identifier.ciencia-id6B13-7601-73A2
person.identifier.orcid0000-0002-1548-5907
person.identifier.orcid0000-0002-0570-0765
person.identifier.orcid0000-0002-8456-9995
person.identifier.ridO-8942-2014
person.identifier.ridM-2976-2019
person.identifier.scopus-author-id6601922586
person.identifier.scopus-author-id7102113853
person.identifier.scopus-author-id35190948700
rcaap.rightsopenAccess
relation.isAuthorOfPublication5f6eaca2-f01f-4894-8da2-688671913214
relation.isAuthorOfPublication631292a4-58bc-4ec4-97ee-1143e44df2c0
relation.isAuthorOfPublicationf4809377-832b-40b5-92ca-0bb1c6fe14f3
relation.isAuthorOfPublication.latestForDiscoveryf4809377-832b-40b5-92ca-0bb1c6fe14f3

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