Author(s): Valentim-Coelho, Cristina ; Saraiva, Joana ; Osorio, Hugo ; Antunes, Marília ; Vaz, Fátima ; Neves, Sofia ; Pinto, Paula ; Bárbara, Cristina ; Penque, Deborah
Date: 2025
Persistent ID: http://hdl.handle.net/10362/181550
Origin: Repositório Institucional da UNL
Subject(s): Glycolysis; Obstructive sleep apnea (OSA) severity; Pentose phosphate pathway (PPP); Positive airway pressure (PAP); Proteasome system; Red blood cells; Molecular Medicine; Molecular Biology
Funding Information: Project partially supported by Harvard Medical School \u2013 Portugal Program ( HMSPICJ/0022/2011 ), Instituto Nacional de Sa\u00FAde Dr. Ricardo Jorge \u2013 INSA, Centro de Toxicogen\u00F3mica e Sa\u00FAde Humana \u2013 ToxOmics, Rede Nacional de Espectrometria de Massa \u2013 RNEM, FCT /Poly-Annual Funding Program and FEDER /Sa\u00FAde XXI Program, Portugal. Cristina Coelho (SFRH/BD/133511/2017) and Joana Saraiva (2022.14435.BD) were granted with PhD fellowships from Funda\u00E7\u00E3o para a Ci\u00EAncia e a Tecnologia \u2013 FCT. Research by Mar\u00EDlia Antunes is partially financed by national funds through FCT under the project UIDB/00006/2020 - ( doi:10.54499/UIDB/00006/2020 ). Publisher Copyright: © 2025
Obstructive 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.
