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Red blood cell proteomic profiling in mild and severe obstructive sleep apnea patients before and after positive airway pressure treatment

2025Journal article Open access
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dc.contributor.authorValentim-Coelho, Cristina
dc.contributor.authorSaraiva, Joana
dc.contributor.authorOsório, Hugo
dc.contributor.authorAntunes, Marilia
dc.contributor.authorVaz, Fátima
dc.contributor.authorNeves, Sofia
dc.contributor.authorPinto, Paula
dc.contributor.authorBárbara, Cristina
dc.contributor.authorPenque, Deborah
dc.date.accessioned2025-03-06T14:35:18Z
dc.date.available2025-03-06T14:35:18Z
dc.date.issued2025
dc.description© 2025 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)pt_PT
dc.description.abstractObstructive Sleep Apnea (OSA) is characterized by recurrent-episodes of apneas/hypopneas during sleep, leading to recurrent intermittent-hypoxia and sleep fragmentation. Non-treated OSA can result in cardiometabolic diseases. In this study, we applied a shotgun-proteomics strategy to deeper investigate the red blood cell-(RBC) homeostasis regulation in the context of OSA-severity and their response to six months of positive airway pressure (PAP)-treatment. RBC-samples from patients with Mild/Severe-OSA before/after-PAP treatment and patients as simple-snoring controls were selected. The mass-spectrometry raw-data was analysed by MaxQuant for protein identification/quantification followed by statistical Linear Models-(LM) and Linear Mixed Models-(LMM) to investigate OSA-severity effect and interaction with PAP, respectively. The functional/biological network analysis were performed by DAVID-platform. The results indicated that key-enzymes of the Embden-Meyerhof-Parnas (EMP)-glycolysis and pentose phosphate pathway-(PPP) were differentially changed in Severe-OSA, suggesting that the O2-dependent metabolic flux through EMP and PPP maybe compromised in these cells due to severe intermittent hypoxia/reoxygenation-induced oxidative-stress events in these patients. The Rapoport-Luebering-glycolytic shunt showed a significant downregulation across OSA-severity maybe to increase hemoglobin-O2 affinity to adapt to O2 low availability in the lung, although EMP-glycolysis showed decreased only in Severe-OSA. Proteins of the immunoproteasome were upregulated in Severe-OSA maybe to respond to severe oxidative-stress. In Mild-OSA, proteins related to the ubiquitination/neddylation-(Ub/Ned)-dependent proteasome system were upregulated. After PAP, proteins of Glycolysis and Ub/Ned-dependent proteasome system showed reactivated in Severe-OSA. In Mild-OSA, PAP induced upregulation of immunoproteasome proteins, suggesting that this treatment may increase oxidative-stress in these patients. Once validated these proteins maybe candidate biomarkers for OSA or OSA-therapy response.pt_PT
dc.description.sponsorshipProject partially supported by Harvard Medical School – Portugal Program (HMSPICJ/0022/2011), Instituto Nacional de Saúde Dr. Ricardo Jorge – INSA, Centro de Toxicogenómica e Saúde Humana – ToxOmics, Rede Nacional de Espectrometria de Massa – RNEM, FCT/Poly-Annual Funding Program and FEDER/Saúde XXI Program, Portugal. Cristina Coelho (SFRH/BD/133511/2017) and Joana Saraiva (2022.14435.BD) were granted with PhD fellowships from Fundação para a Ciência e a Tecnologia – FCT. Research by Marília Antunes is partially financed by national funds through FCT under the project UIDB/00006/2020 - (doi:10.54499/UIDB/00006/2020).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBiochim Biophys Acta Mol Basis Dis. 2025 Mar 4;1871(5):167767pt_PT
dc.identifier.doi10.1016/j.bbadis.2025.167767pt_PT
dc.identifier.eissn1879-260X
dc.identifier.issn0925-4439
dc.identifier.urihttp://hdl.handle.net/10400.5/99042
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationCentre of Statistics and its Applications
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/biochimica-et-biophysica-acta-bba-molecular-basis-of-diseasept_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectGlycolysispt_PT
dc.subjectObstructive sleep apnea (OSA) severitypt_PT
dc.subjectPentose phosphate pathway (PPP)pt_PT
dc.subjectPositive airway pressure (PAP)pt_PT
dc.subjectProteasome systempt_PT
dc.subjectRed blood cellspt_PT
dc.titleRed blood cell proteomic profiling in mild and severe obstructive sleep apnea patients before and after positive airway pressure treatmentpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCentre of Statistics and its Applications
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F133511%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/2022.14435.BD/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00006%2F2020/PT
oaire.citation.issue5pt_PT
oaire.citation.titleBiochimica et Biophysica Acta (BBA) - Molecular Basis of Diseasept_PT
oaire.citation.volume1871pt_PT
oaire.fundingStreamOE
oaire.fundingStream6817 - DCRRNI ID
person.familyNamede Sousa Antunes
person.familyNamePinto
person.familyNameBárbara
person.givenNameMarilia Cristina
person.givenNamePaula Maria Gonçalves
person.givenNameCristina
person.identifierG-8864-2015
person.identifier1330713
person.identifier.ciencia-id1A16-4A6A-A8F9
person.identifier.ciencia-idF01D-6AFB-DFFD
person.identifier.ciencia-id171F-DE21-B23B
person.identifier.orcid0000-0002-1257-2829
person.identifier.orcid0000-0003-2301-2752
person.identifier.orcid0000-0003-0915-4105
person.identifier.scopus-author-id16300632900
person.identifier.scopus-author-id24074744900
person.identifier.scopus-author-id6701574502
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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