Proteomics of Obstructive Sleep Apnea with type 2 Diabetes Mellitus

Vaz, Fátima; Valentim-Coelho, Cristina; Neves, Sofia; Penque, Deborah

http://hdl.handle.net/10400.18/6413

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Authors

Vaz, Fátima

Valentim-Coelho, Cristina

Neves, Sofia

Penque, Deborah

Abstract(s)

Background: We previously showed that Obstructive sleep apnea (OSA), a common public health concern causing deleterious cardiometabolic dysfunction, induces alterations in red blood cell (RBC) proteome (Feliciano et al 2017). Herein, we aimed to investigate redox state of PRDX2 in OSA patients with Type 2 Diabetes Mellitus before and after positive airway pressure (PAP) treatment to better understand the basic mechanisms associated with OSA and OSA outcomes. Methods: RBC samples from control snorers (n=22 being 3 diabetics) and OSA patients before and after six month of PAP-treatment (n=29 being 8 diabetics) were analysed by non-reducing western blot using antibody against PRDX2 or PRDXSO2 to measure the total and overoxidized levels of monomeric/dimeric/multimeric forms of PRDX2. Non-reducing SDS-PAGE coomassie gel band corresponding to PRDX2 monomers from the different groups where trypsinized and investigation by LC/MS/MS for additional post-translational modifications (PTMs) are under process. Results: We confirmed previously data showing higher overoxidation on monomeric forms of PRDX2 in OSA RBC without comorbidity compared to Snorer controls. After PAP treatment, this overoxidation decreased followed by an increase of multimeric-overoxidized forms associated with chaperone protective function. In contrast, the level of PRDX2 monomers in RBC diabetic OSA, although the most abundant its overoxidation level was much lower than OSA without comorbidity and did not significant change after treatment. Moreover, the level of PAP-induced PRDX2-overoxidized-multimers was also lower in these diabetic OSA patients. The level of PRDX2 overoxidized monomeric/dimeric forms in RBC correlated negatively with levels of insulin / triglycerides and HbA1C, respectively.After PAP, PRDX2SO2 / 3 decamer levels correlated positively with adrenaline levels. Conclusions: The redox/oligomeric state of RBC PRDX2 regulated by overoxidation of the active cysteines were differentially modulated in diabetic OSA patients compared to OSA without this comorbidity. PAP-induced overoxidized oligo forms of PRDX2 associated with chaperone protective function showed decreased in OSA patients with diabetes. Preliminary data pointed to polyglutamylation on PRDX2 glutamic acid91 that can be differentially modulated in OSA with and without diabetes and/or in response to PAP treatment. The clinical impact of these findings needs further investigation and validation. My perspective future encompasses the complete identification of these PTM by MS based strategies and validation by SRM approaches.