Red blood cell proteomic profiling in mild and severe obstructive sleep apnea patients before and after positive airway pressure treatment

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-03-04 DOI:10.1016/j.bbadis.2025.167767

Cristina Valentim-Coelho , Joana Saraiva , Hugo Osório , Marília Antunes , Fátima Vaz , Sofia Neves , Paula Pinto , Cristina Bárbara , Deborah Penque

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Abstract

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.

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阻塞性睡眠呼吸暂停（OSA）的特点是睡眠中反复发作的呼吸暂停/低通气，导致反复间歇性缺氧和睡眠破碎。在这项研究中，我们采用霰弹枪蛋白质组学策略，深入研究了红细胞（RBC）在 OSA 严重程度下的稳态调节及其对 6 个月气道正压（PAP）治疗的反应。研究人员选取了气道正压治疗前/后的轻度/重度 OSA 患者和单纯打鼾对照组患者的红细胞样本。质谱仪原始数据由 MaxQuant 进行蛋白质鉴定/定量分析，然后分别采用统计线性模型（LM）和线性混合模型（LMM）研究 OSA 严重程度的影响以及与 PAP 的交互作用。结果表明，Embden-Meyerhof-Parnas（EMP）-糖酵解和磷酸戊糖通路（PPP）的关键酶在重度OSA中发生了不同程度的变化，这表明在这些患者中，由于严重的间歇性缺氧/复氧诱导的氧化应激事件，通过EMP和PPP的O2依赖性代谢通量可能受到损害。雷波波特-卢伯林-糖酵解分流在不同严重程度的 OSA 中都出现了明显的下调，这可能是为了增加血红蛋白与氧气的亲和力，以适应肺中氧气供应不足的情况，但只有在严重-OSA 中 EMP-糖酵解才出现下降。在轻度-OSA 中，与泛素化/去乙酰化-（Ub/Ned）依赖性蛋白酶体系统相关的蛋白质上调。在 PAP 后，糖酵解和 Ub/Ned 依赖性蛋白酶体系统的蛋白质在重度-OSA 中重新激活。在轻度-OSA患者中，PAP诱导免疫蛋白酶体蛋白上调，表明这种治疗可能会增加这些患者的氧化应激。这些蛋白一旦得到验证，就有可能成为 OSA 或 OSA 治疗反应的候选生物标记物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.