Browsing by Author "Feliciano, Amélia"
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- Evening and morning alterations in Obstructive Sleep Apnea red blood cell proteomePublication . Feliciano, Amélia; Vaz, Fátima; Valentim-Coelho, Cristina; Torres, Vukosava M.; Silva, Rita; Prosinecki, Vesna; Alexandre, Bruno M.; Almeida, Andreia; Almeida-Marques, Catarina; Carvalho, Ana S.; Matthiesen, Rune; Malhotra, Atul; Pinto, Paula; Bárbara, Cristina; Penque, DeborahThis article presents proteomics data referenced in [1] Using proteomics-based evaluation of red blood cells (RBCs), we have identified differentially abundant proteins associated with Obstructive Sleep Apnea Syndrome (OSA). RBCs were collected from peripheral blood of patients with moderate/severe OSA or snoring at pre- (evening) and post-night (morning) polysomnography, so that proteome variations between these time points could be assessed. RBC cytoplasmic fraction depleted of hemoglobin, using Hemovoid(™) system, were analyzed by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), the 2D image software-based analyzed and relevant differentially abundant proteins identified by mass spectrometry (MS). MS identified 31 protein spots differentially abundant corresponding to 21 unique proteins possibly due to the existence of post-translational modification regulations. Functional analysis by bioinformatics tools indicated that most proteins are associated with catalytic, oxidoreductase, peroxidase, hydrolase, ATPase and anti-oxidant activity. At morning a larger numbers of differential proteins including response to chemical stimulus, oxidation reduction, regulation of catalytic activity and response to stress were observed in OSA. The data might support further research in OSA biomarker discovery and validation.
- Evening and morning peroxiredoxin-2 redox/oligomeric state changes in obstructive sleep apnea red blood cells: Correlation with polysomnographic and metabolic parametersPublication . Feliciano, Amélia; Vaz, Fátima; Torres, Vukosava M.; Valentim-Coelho, Cristina; Silva, Rita; Prosinecki, Vesna; Alexandre, Bruno M.; Carvalho, Ana S.; Matthiesen, Rune; Malhotra, Atul; Pinto, Paula; Bárbara, Cristina; Penque, DeborahWe 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.
- Obstructive Sleep Apnea: a proteomics study of the effects of positive airway pressure therapyPublication . Valentim-Coelho, Cristina; Vaz, Fátima; Martins, Inês L.; Feliciano, Amélia; Pinto, Paula; Cristina, Bárbara; Penque, DeborahObstructive 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.
- Obstructive Sleep Apnea: New insights into antioxidant activity and cellular response to stressPublication . Vaz, Fátima; Feliciano, Amélia; Silva, Ana Rita; Coelho, Cristina; Torres, Vukosava Millic; Bozanic, Vesna; Malhotra, Atul; Pinto, Paula; Bárbara, Cristina; Penque, DeborahObstructive sleep apnea (OSA) is a sleep¬related breathing disorder characterized by recurrent episodes of apnea/and hypopnea during sleep with resultant intermittent hypoxia and sleep fragmentation, leading to cardiometabolic diseases. OSA affects 3.7% to 26% of adult population, but frequently is underdiagnosed. By 2DIGE-proteomics approach, we have investigated red blood cells (RBC) in OSA to uncover new insights into putative chronic stress-induced RBC dysfunction that lead to inflammation and metabolic syndrome associated with OSA. A number of proteins as potential candidate biomarkers for OSA, such as the cytosolic antioxidant regulators, catalase (CAT) and peroxiredoxin2 (PRX2) was identified, needing additional biochemical research validation.
- Overview of proteomics studies in obstructive sleep apneaPublication . Feliciano, Amélia; Torres, Vukosava M.; Vaz, Fatima; Carvalho, Ana Sofia; Matthiesen, Rune; Pinto, Paula; Malhotra, Atul; Bárbara, Cristina; Penque, DeborahObstructive sleep apnea (OSA) is an underdiagnosed common public health concern causing deleterious effects on metabolic and cardiovascular health. Although much has been learned regarding the pathophysiology and consequences of OSA in the past decades, the molecular mechanisms associated with such processes remain poorly defined. The advanced high-throughput proteomics-based technologies have become a fundamental approach for identifying novel disease mediators as potential diagnostic and therapeutic targets for many diseases, including OSA. Here, we briefly review OSA pathophysiology and the technological advances in proteomics and the first results of its application to address critical issues in the OSA field.
- Proteoforms of transthyretin - candidate biomarkers in diagnosis of obstructive sleepPublication . Torres, VM; Feliciano, Amélia; Antunes, Marilia; Vaz, Fatima; Penque, DeborahObstructive sleep apnea (OSA) is a common sleep-related breathing disorder which is characterized by recurrent occurrence of partial or complete closure of the upper airway during sleep, despite ongoing efforts to breathe. The majority of patients with OSA remain undiagnosed since most of them only come to the attention of a clinician when they complain of daytime sleepiness or when their bed partners report loud snoring or witnessed apnea episodes.Epidemiological studies have indicated that OSA affects 6–13% of the adult population. OSA is multifactorial disease, also considered as metabolic syndrome, which diagnosis in early stages is challenging thus often remain undiagnosed. Recently was found connection between transthyretin (TTR) protein modifications present in human plasma samples and appearance of sleep apnea syndrome1,2 . Mass Spectrometric Immunoassay (MSIA) was successfully applied previously on identification of and quantification of TTR variants present in human serum3. We took advantage on this powerful method to investigate possible modifications of TTR proteoforms in patients with OSAS.
- Redox–Oligomeric State of Peroxiredoxin-2 and Glyceraldehyde-3-Phosphate Dehydrogenase in Obstructive Sleep Apnea Red Blood Cells under Positive Airway Pressure TherapyPublication . Valentim-Coelho, Cristina; Vaz, Fátima; Antunes, Marília; Neves, Sofia; Martins, Inês L.; Osório, Hugo; Feliciano, Amélia; Pinto, Paula; Bárbara, Cristina; Penque, DeborahIn 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.