Redox–Oligomeric State of Peroxiredoxin-2 and Glyceraldehyde-3-Phosphate Dehydrogenase in Obstructive Sleep Apnea Red Blood Cells under Positive Airway Pressure Therapy

Cristina Valentim-Coelho,Sofia Neves,Deborah Penque,Hugo Osório,Paula Pinto,Cristina Bárbara,Inês L Martins,Fátima Vaz,Amélia Feliciano,Marília Antunes

doi:10.3390/antiox9121184

Abstract

In this study, we examined the effect of six months of positive airway pressure (PAP) therapy on Obstructive Sleep Apnea (OSA) red blood cell (RBC) proteome by two dimensional difference gel electrophoresis (2D-DIGE) - based proteomics followed by Western blotting (WB) validation. The discovered dysregulated proteins/proteoforms are associated with cell death, H2O2 catabolic/metabolic process, stress response, and protein oligomerization. Validation by nonreducing WB was performed for peroxiredoxin-2 (PRDX2) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by using antibodies against the sulfinylated/sulfonylated cysteine of these proteins to better evaluate their redox–oligomeric states under OSA and/or in response to PAP therapy. The results indicated that the redox–oligomeric state of GAPDH and PRDX2 involving overoxidation by sulfinic/sulfonic acids were differentially modulated in OSA RBC, which might be compromising RBC homeostasis. PAP therapy by restoring this modulation induced a higher oligomerization of overoxidized GAPDH and PRDX2 in some patients that could be associated with eryptosis and the chaperone “gain” of function, respectively. This varied response following PAP may result from the complex interplay between OSA and OSA metabolic comorbidity. Hence, information on the redox status of PRDX2 and GAPDH in RBC will help to better recognize OSA subtypes and predict the therapeutic response in these patients. GAPDH monomer combined with body mass index (BMI) and PRDX2 S-S dimer combined with homeostatic model assessment for insulin resistance (HOMA-IR) showed to be very promising biomarkers to predict OSA and OSA severity, respectively.

Highlights

Obstructive Sleep Apnea (OSA) has emerged as a major public health issue with a high proportion of socio-economic burden
By two dimensional difference gel electrophoresis (2D-DIGE) proteomics, we demonstrated that OSA induces differential changes in red blood cell (RBC) cytoplasmic proteome [10,11], in which redox-regulators such as peroxiredoxin-2 (PRDX2) are the most dysregulated
The redox–oligomeric states of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and PRDX2 involving overoxidation by sulfinic/sulfonic acids were differentially modulated in OSA RBC probably due to the nocturnal apnea-induced intermittent hypoxia that was chronically experienced by these patients

Summary

Introduction

Obstructive Sleep Apnea (OSA) has emerged as a major public health issue with a high proportion of socio-economic burden. OSA is characterized by repetitive upper airway apnea/hypopnea during sleep leading to intermittent hypoxemia, sleep fragmentation, and homeostasis perturbation [1,2,3]. More than 200 million people worldwide may be affected by OSA, but the majority (60–90%) remains undiagnosed and untreated [4]. The gold-standard diagnosis of OSA, the overnight lab-based polysomnography (PSG) is expensive, cumbersome, and not widely available [1,2,3]. The effective treatment for OSA is the nasal (continuous) positive airway pressure (PAP) [6], negative results have been reported, and not all patients benefit from it [7]

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Results

Discussion

Conclusion