title: Evening and morning peroxiredoxin-2 redox/oligomeric state changes in obstructive sleep apnea red blood cells: Correlation with polysomnographic and metabolic parameters.
abstract: We have examined the effects of Obstructive Sleep Apnea (OSA) on red blood cell (RBC) proteome variation at evening/morning day time to uncover new insights into OSA-induced RBC dysfunction that may lead to OSA manifestations. Dysregulated proteins mainly fall in the group of catalytic enzymes, stress response and redox regulators such as peroxiredoxin 2 (PRDX2). Validation assays confirmed that at morning the monomeric/dimeric forms of PRDX2 were more overoxidized in OSA RBC compared to evening samples. Six month of positive airway pressure (PAP) treatment decreased this overoxidation and generated multimeric overoxidized forms associated with chaperone/transduction signaling activity of PRDX2. Morning levels of overoxidized PRDX2 correlated with polysomnographic (PSG)-arousal index and metabolic parameters whereas the evening level of disulfide-linked dimer (associated with peroxidase activity of PRDX2) correlated with PSG parameters. After treatment, morning overoxidized multimer of PRDX2 negatively correlated with fasting glucose and dopamine levels. Overall, these data point toward severe oxidative stress and altered antioxidant homeostasis in OSA RBC occurring mainly at morning time but with consequences till evening. The beneficial effect of PAP involves modulation of the redox/oligomeric state of PRDX2, whose mechanism and associated chaperone/transduction signaling functions deserves further investigation. RBC PRDX2 is a promising candidate biomarker for OSA severity and treatment monitoring, warranting further investigation and validation.
authors.affiliation: Serviço de Pneumologia, Centro Hospitalar Lisboa Norte (CHLN), Lisboa, Portugal; Laboratório de Proteómica, Departamento de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa 1640-016, Portugal.
authors.forename: Amélia
authors.initials: A
authors.lastname: Feliciano
authors.affiliation: Laboratório de Proteómica, Departamento de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa 1640-016, Portugal; ToxOmics- Centre of Toxicogenomics and Human Health, Universidade Nova de Lisboa, Portugal.
authors.forename: Fátima
authors.initials: F
authors.lastname: Vaz
authors.affiliation: Laboratório de Proteómica, Departamento de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa 1640-016, Portugal; ToxOmics- Centre of Toxicogenomics and Human Health, Universidade Nova de Lisboa, Portugal.
authors.forename: Vukosava M
authors.initials: VM
authors.lastname: Torres
authors.affiliation: Laboratório de Proteómica, Departamento de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa 1640-016, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Valentim-Coelho
authors.affiliation: Laboratório de Proteómica, Departamento de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa 1640-016, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Silva
authors.affiliation: Laboratório de Proteómica, Departamento de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa 1640-016, Portugal.
authors.forename: Vesna
authors.initials: V
authors.lastname: Prosinecki
authors.affiliation: Laboratório de Proteómica, Departamento de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa 1640-016, Portugal.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Alexandre
authors.affiliation: Departamento da Promoção da Saúde, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa 1640-016, Portugal.
authors.forename: Ana S
authors.initials: AS
authors.lastname: Carvalho
authors.affiliation: Departamento da Promoção da Saúde, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa 1640-016, Portugal.
authors.forename: Rune
authors.initials: R
authors.lastname: Matthiesen
authors.affiliation: Pulmonary, Critical Care and Sleep Medicine Division, University of California San Diego, CA, USA.
authors.forename: Atul
authors.initials: A
authors.lastname: Malhotra
authors.affiliation: Serviço de Pneumologia, Centro Hospitalar Lisboa Norte (CHLN), Lisboa, Portugal; Instituto de Saúde Ambiental (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Portugal.
authors.forename: Paula
authors.initials: P
authors.lastname: Pinto
authors.affiliation: Serviço de Pneumologia, Centro Hospitalar Lisboa Norte (CHLN), Lisboa, Portugal; Instituto de Saúde Ambiental (ISAMB), Faculdade de Medicina, Universidade de Lisboa, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bárbara
authors.affiliation: Laboratório de Proteómica, Departamento de Genética Humana, Instituto Nacional de Saúde Dr Ricardo Jorge, Lisboa 1640-016, Portugal; ToxOmics- Centre of Toxicogenomics and Human Health, Universidade Nova de Lisboa, Portugal.. Electronic address: deborah.penque@insa.min-saude.pt.
authors.forename: Deborah
authors.initials: D
authors.lastname: Penque
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D045422:Continuous Positive Airway Pressure; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000378:metabolism*; D017440:Photoperiod; D017286:Polysomnography; D055503:Protein Multimerization; D020543:Proteome / Q000378:metabolism; D012720:Severity of Illness Index; D020181:Sleep Apnea, Obstructive / Q000378:metabolism* / Q000628:therapy
chemical_list: D015415:Biomarkers; D020543:Proteome; D054464:Peroxiredoxins
keywords: Biomarkers; Obstructive sleep apnea; Peroxiredeoxin-2; Red blood cells