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Obstructive Sleep Apnea: a proteomics study of the effects of positive airway pressure therapy

dc.contributor.authorValentim-Coelho, Cristina
dc.contributor.authorVaz, Fátima
dc.contributor.authorMartins, Inês L.
dc.contributor.authorFeliciano, Amélia
dc.contributor.authorPinto, Paula
dc.contributor.authorCristina, Bárbara
dc.contributor.authorPenque, Deborah
dc.date.accessioned2020-05-22T19:36:38Z
dc.date.available2020-05-22T19:36:38Z
dc.date.issued2019-07-08
dc.description.abstractObstructive Sleep Apnea (OSA) syndrome is a common public health concern characterized by recurrent episodes of apneas and hypopneas during sleep. These obstructive events result in recurrent intermittent hypoxia and sleep fragmentation that can lead to metabolic and cardiovascular diseases. We recently demonstrated that OSA can cause alterations in the red blood cells (RBC) proteome that may be associated with OSA outcomes1,2. Here we intend to investigate whether the first-line therapy for OSA, the positive airway pressure (PAP) can revert or modulate these proteome alterations. RBCs from Snorers and patients with severe OSA before/after 6 months of PAP treatment (n=10/condition) were depleted of hemoglobin, analyzed by 2D-DIGE using Progenesis SameSpotsv4.5. The differentially abundant proteins were identified by MALDI-MS/MS and protein annotations acquired by DAVIDv6.8. Western blotting (WB) validation was performed for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and (overoxidized) GAPDHSO3 on a new Cohort (n=59). SPSS software was used to correlation studies with peroxiredoxin-2 (PRDX2) redox-oligomeric forms and several clinical parameters. Ten protein spots showed significant differences (Anova p<0.05) among groups and were associated with cell death, protein oligomerization and response to stress. Three proteoforms of GAPDH were identified decreased in OSA RBC (Anova p<0.05) and 6 months of PAP treatment increased these GAPDH proteoforms to the control levels. By WB, we confirmed these data by showing that the decreased GAPDH monomeric/tetrameric forms in OSA were increased by PAP treatment. PAP also increased GAPDHSO3 tetramers. In OSA, GAPDH monomers and GAPDHSO3 tetramers correlated positively with the respiratory disturbance index or triglycerides and adrenalin, respectively. After PAP, GAPDHSO3 tetramers correlated positively with PAP-induced PRDX2SO2/3 decameric forms, described having chaperone activity in cell protection. OSA induces alterations in the redox/oligomeric state of GAPDH and PRDX2 that can be reverted/modulated by PAP therapy. The clinical significant of these findings needs further validation and investigation.pt_PT
dc.description.sponsorshipProject partially supported by Harvard Medical School-Portugal Program (HMSP-ICJ/0022/2011) and ToxOmics - Centre for Toxicogenomics and Human Health (FCT-UID/BIM/00009/2013). CVC is recipient of FCT doctoral scholarship FCT-SFRH/BD/133511/2017.pt_PT
dc.description.versionN/Apt_PT
dc.identifier.urihttp://hdl.handle.net/10400.18/6756
dc.language.isoengpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectObstructive Sleep Apneapt_PT
dc.subjectRed Blood Cellspt_PT
dc.subjectProteomept_PT
dc.subjectPositive Arway Pressurept_PT
dc.subjectPRDX2pt_PT
dc.subjectGAPDHpt_PT
dc.subjectGenómica Funcionalpt_PT
dc.subjectGenómica Funcional e Estruturalpt_PT
dc.titleObstructive Sleep Apnea: a proteomics study of the effects of positive airway pressure therapypt_PT
dc.typeconference object
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/HMSP-ICJ%2F0022%2F2011/PT
oaire.citation.conferencePlaceCosta da Caparica, Portugalpt_PT
oaire.citation.title6th International Caparica Conference on Analytical Proteomics, 8-11 July 2019pt_PT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsembargoedAccesspt_PT
rcaap.typeconferenceObjectpt_PT
relation.isProjectOfPublicationa9bad44d-3ec0-4cf1-acdc-ce4155e0f68a
relation.isProjectOfPublication.latestForDiscoverya9bad44d-3ec0-4cf1-acdc-ce4155e0f68a

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