Repository logo
 
Publication

Proteome profiling in obstructive sleep apnea severity and treatment response towards early diagnosis and prognosis prediction

2025-03-28Doctoral thesis Embargoed access
Simple item page
datacite.subject.fosCiências Naturais::Ciências Biológicaspt_PT
dc.contributor.advisorPenque, Deborah
dc.contributor.advisorDias, Deodália
dc.contributor.advisorAntunes, Marília Cristina de Sousa
dc.contributor.authorValentim-Coelho, Cristina
dc.date.accessioned2025-06-06T16:58:35Z
dc.date.embargo2028-04
dc.date.issued2025-03-28
dc.date.submitted2024-07-16
dc.description.abstractObstructive Sleep Apnea (OSA) is characterized by recurrent episodes of apneas/hypopneas during sleep, leading to intermittent hypoxia and sleep fragmentation that can result in cardiometabolic diseases. A Proteomic approach was applied to investigate RBC homeostasis regulation in the context of OSA, before (t0) and after six months (t6) of PAP treatment. This work aims the discovery of candidate blood biomarkers for the diagnosis/prognosis of OSA and/or the monitoring/effectiveness of therapy. RBC samples were analysed through 2D-DIGE and the differentially expressed protein spots identified by MALDI-TOF/TOF MS. Three GAPDH-proteoforms were detected as decreased in OSA RBCs when compared to control ones that after PAP increased. An acidic PRDX2-proteoform, reported as hyperoxidized, showed changes between groups. By Western-Blot the results indicated that the redox-oligomeric state of GAPDH and PRDX2 may be compromising the homeostasis of OSA RBCs. The GAPDH monomer combined with BMI and the PRDX2 S-S dimer combined with the HOMA-IR showed to be promising biomarkers for predicting OSA and the severity of OSA, respectively. A Shotgun LC-MS/MS study was also performed on RBCs from patients with Mild and Severe OSA, before and after six months of PAP, using Snorers as controls. Dysregulation in Glycolysis and Pentose Phosphate pathways was observed in Severe OSA RBCs. Mild OSA showed a decrease in the Rapoport-Luebering shunt, which is associated with increased affinity for Hb-O2. Proteins of the immunoproteasome were upregulated in Severe OSA RBCs maybe to respond to severe oxidative stress. In Mild OSA RBCs, proteins related to the ubiquitination/neddylation-(Ub/Ned)-dependent proteasome system were up-regulated. After PAP, proteins of Glycolysis and Ub/Ned-dependent proteasome system showed reactivated in Severe OSA RBC. In Mild-OSA RBC, 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.pt_PT
dc.identifier.tid101613059pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.5/101427
dc.language.isoengpt_PT
dc.relationProteome Profiling in Obstructive Sleep Apnea Severity and Treatment Response Towards Early Diagnosis and Prognosis Prediction
dc.subjectObstructive sleep apnea (OSA)pt_PT
dc.subjectpositive airway pressure (PAP)pt_PT
dc.subjectbiomarkerspt_PT
dc.subjectSíndrome da apneia obstrutiva do sono (SAOS)pt_PT
dc.subjectpressão positiva nas vias aéreas superiores (PAP)pt_PT
dc.subjectbiomarcadorespt_PT
dc.titleProteome profiling in obstructive sleep apnea severity and treatment response towards early diagnosis and prognosis predictionpt_PT
dc.typedoctoral thesis
dspace.entity.typePublication
oaire.awardTitleProteome Profiling in Obstructive Sleep Apnea Severity and Treatment Response Towards Early Diagnosis and Prognosis Prediction
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F133511%2F2017/PT
oaire.fundingStreamOE
person.familyNameValentim Coelho
person.givenNameCristina
person.identifier.ciencia-idFD16-2D05-23E5
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsembargoedAccesspt_PT
rcaap.typedoctoralThesispt_PT
relation.isAuthorOfPublication4fc6385e-eb7f-493f-a5b1-f38c95ed05f4
relation.isAuthorOfPublication.latestForDiscovery4fc6385e-eb7f-493f-a5b1-f38c95ed05f4
relation.isProjectOfPublicationb4bcf936-107d-4f85-bb2c-8841dbbcff50
relation.isProjectOfPublication.latestForDiscoveryb4bcf936-107d-4f85-bb2c-8841dbbcff50
thesis.degree.nameTese de doutoramento, Biologia (Biologia Molecular), Universidade de Lisboa, Faculdade de Ciências, 2025pt_PT

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
scnd990026354742649_td_Cristina_Coelho.pdf
Size:
4.16 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.2 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

FC - Teses de Doutoramento