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

2025-03-04Artigo científico Acesso aberto
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datacite.subject.fosCiências Naturais::Ciências Biológicas
dc.contributor.authorValentim-Coelho, Cristina
dc.contributor.authorSaraiva, Joana
dc.contributor.authorOsório, Hugo
dc.contributor.authorAntunes, Marília
dc.contributor.authorVaz, Fátima
dc.contributor.authorNeves, Sofia
dc.contributor.authorPinto, Paula
dc.contributor.authorBárbara, Cristina
dc.contributor.authorPenque, Deborah
dc.date.accessioned2026-01-20T13:42:05Z
dc.date.available2026-01-20T13:42:05Z
dc.date.issued2025-03-04
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.eng
dc.description.abstractHighlights: - Glycolysis and PPP main enzymes showed significant alterations in Severe OSA RBCs. - Mild OSA presented significant changes in the Rapoport-Luebering glycolytic shunt. - Immunoproteasome, a cellular homeostasis player, was upregulated in Severe OSA RBCs. - UPS pathway, an ATP-dependent proteasome system, was upregulated in Mild OSA RBCs. - PAP treatment reverted some proteins alterations in OSA RBCs.eng
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.
dc.identifier.citationBiochim Biophys Acta Mol Basis Dis. 2025 Jun;1871(5):167767. doi: 10.1016/j.bbadis.2025.167767. Epub 2025 Mar 4
dc.identifier.doi10.1016/j.bbadis.2025.167767
dc.identifier.eissn1879-260X
dc.identifier.issn0925-4439
dc.identifier.urihttp://hdl.handle.net/10400.18/10723
dc.language.isoeng
dc.peerreviewedyes
dc.publisherElsevier
dc.relationProteome Profiling in Obstructive Sleep Apnea Severity and Treatment Response Towards Early Diagnosis and Prognosis Prediction
dc.relationCentre of Statistics and its Applications
dc.relationCOVID-19 Vaccination - Emerging role of Red Blood Cells as immunomodulators
dc.relation.hasversionhttps://www.sciencedirect.com/science/article/pii/S0925443925001127?via%3Dihub
dc.relation.ispartofseries167767
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectGlycolysis
dc.subjectObstructive Sleep Apnea (OSA) Severity
dc.subjectPentose Phosphate Pathway (PPP)
dc.subjectPositive Airway Pressure (PAP)
dc.subjectProteasome System
dc.subjectRed Blood Cells
dc.subjectGenómica Funcional e Estrutural
dc.titleRed blood cell proteomic profiling in mild and severe obstructive sleep apnea patients before and after positive airway pressure treatmenteng
dc.typejournal article
dcterms.referenceshttps://ars.els-cdn.com/content/image/1-s2.0-S0925443925001127-mmc1.docx
dcterms.referenceshttps://ars.els-cdn.com/content/image/1-s2.0-S0925443925001127-mmc2.docx
dspace.entity.typePublication
oaire.awardTitleProteome Profiling in Obstructive Sleep Apnea Severity and Treatment Response Towards Early Diagnosis and Prognosis Prediction
oaire.awardTitleCentre of Statistics and its Applications
oaire.awardTitleCOVID-19 Vaccination - Emerging role of Red Blood Cells as immunomodulators
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F133511%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00006%2F2020/PT
oaire.awardURIhttp://hdl.handle.net/10400.18/10716
oaire.citation.issue5
oaire.citation.titleBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
oaire.citation.volume1871
oaire.fundingStreamOE
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
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
relation.isProjectOfPublication39802557-af64-4b35-834f-3e015a20919e
relation.isProjectOfPublication1828b27c-0dae-4001-a56b-8e520a5b181e
relation.isProjectOfPublication3c67c2b0-43d0-4eb7-a0c3-22209a9ea4f5
relation.isProjectOfPublication.latestForDiscovery39802557-af64-4b35-834f-3e015a20919e

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