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杂合β地中海贫血供者贮存 RBC 膜和囊泡的蛋白质组。

Proteome of Stored RBC Membrane and Vesicles from Heterozygous Beta Thalassemia Donors.

机构信息

Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), 15784 Athens, Greece.

Department of Biochemistry and Molecular Genetics, School of Medicine-Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA.

出版信息

Int J Mol Sci. 2021 Mar 25;22(7):3369. doi: 10.3390/ijms22073369.

DOI:10.3390/ijms22073369
PMID:33806028
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8037027/
Abstract

Genetic characteristics of blood donors may impact the storability of blood products. Despite higher basal stress, red blood cells (RBCs) from eligible donors that are heterozygous for beta-thalassemia traits (βThal) possess a differential nitrogen-related metabolism, and cope better with storage stress compared to the control. Nevertheless, not much is known about how storage impacts the proteome of membrane and extracellular vesicles (EVs) in βThal. For this purpose, RBC units from twelve βThal donors were studied through proteomics, immunoblotting, electron microscopy, and functional ELISA assays, versus units from sex- and aged-matched controls. βThal RBCs exhibited less irreversible shape modifications. Their membrane proteome was characterized by different levels of structural, lipid raft, transport, chaperoning, redox, and enzyme components. The most prominent findings include the upregulation of myosin proteoforms, arginase-1, heat shock proteins, and protein kinases, but the downregulation of nitrogen-related transporters. The unique membrane proteome was also mirrored, in part, to that of βThal EVs. Network analysis revealed interesting connections of membrane vesiculation with storage and stress hemolysis, along with proteome control modulators of the RBC membrane. Our findings, which are in line with the mild but consistent oxidative stress these cells experience in vivo, provide insight into the physiology and aging of stored βThal RBCs.

摘要

献血者的遗传特征可能会影响血液产品的储存能力。尽管具有β地中海贫血特征（βThal）的合格献血者的红细胞（RBC）基础应激较高，但它们具有不同的氮相关代谢，并且与对照相比，能更好地应对储存应激。然而，对于储存如何影响βThal 中的膜和细胞外囊泡（EV）的蛋白质组，我们知之甚少。为此，通过蛋白质组学、免疫印迹、电子显微镜和功能 ELISA 检测，对来自 12 名βThal 供体的 RBC 单位与来自性别和年龄匹配的对照的 RBC 单位进行了研究。βThal RBC 表现出较少的不可逆形状改变。它们的膜蛋白质组具有不同水平的结构、脂筏、运输、伴侣蛋白、氧化还原和酶成分。最显著的发现包括肌球蛋白蛋白形式、精氨酸酶-1、热休克蛋白和蛋白激酶的上调，但氮相关转运蛋白的下调。βThal EV 的膜蛋白质组也部分反映了这一点。网络分析显示，膜囊泡与储存和应激溶血之间存在有趣的联系，以及 RBC 膜的蛋白质组控制调节剂。我们的研究结果与这些细胞在体内经历的轻度但持续的氧化应激一致，为储存的βThal RBC 的生理学和衰老提供了深入的了解。

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