Penque, DeborahDias, DeodáliaAntunes, Marília Cristina de SousaValentim-Coelho, Cristina2025-06-062025-03-282024-07-16http://hdl.handle.net/10400.5/101427Obstructive 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.engObstructive sleep apnea (OSA)positive airway pressure (PAP)biomarkersSíndrome da apneia obstrutiva do sono (SAOS)pressão positiva nas vias aéreas superiores (PAP)biomarcadoresdoctoral thesis101613059