Institute of Blood Transfusion , Chinese Academy of Medical Sciences & Peking Union Medical College , Chengdu 610052 , China.
Department of Transfusion , Aba Prefecture People's Hospital , Ngawa Tibetan and Qiang Autonomous Prefecture 510530 , China.
J Proteome Res. 2019 May 3;18(5):2021-2031. doi: 10.1021/acs.jproteome.8b00911. Epub 2019 Apr 3.
For individuals migrating to or residing permanently in high-altitude regions, environmental hypobaric hypoxia is a primary challenge that induces several physiological or pathological responses. It is well documented that human beings adapt to hypobaric hypoxia via some protective mechanisms, such as erythropoiesis and overproduction of hemoglobin; however, little is known on the alterations of plasma proteome profiles in accommodation to high-altitude hypobaric hypoxia. In the present study, we investigated differential plasma proteomes of high altitude natives and lowland normal controls by a TMT-based proteomic approach. A total of 818 proteins were identified, of which 137 were differentially altered. Bioinformatics (including GO, KEGG, protein-protein interactions, etc.) analysis showed that the differentially altered proteins were basically involved in complement and coagulation cascades, antioxidative stress, and glycolysis. Validation results demonstrated that CCL18, C9, PF4, MPO, and S100A9 were notably up-regulated, and HRG and F11 were down-regulated in high altitude natives, which were consistent with TMT-based proteomic results. Our findings highlight the contributions of complement and coagulation cascades, antioxidative stress, and glycolysis in acclimatization to hypobaric hypoxia and provide a foundation for developing potential diagnostic or/and therapeutic biomarkers for high altitude hypobaric hypoxia-induced diseases.
对于迁移或永久居住在高海拔地区的个体来说,环境低气压缺氧是一个主要的挑战,会引起多种生理或病理反应。有大量文献记载,人类通过一些保护机制来适应低气压缺氧,例如红细胞生成和血红蛋白的过度产生;然而,对于适应高海拔低气压缺氧时血浆蛋白质组谱的变化知之甚少。在本研究中,我们通过基于 TMT 的蛋白质组学方法研究了高原居民和低地正常对照者的差异血浆蛋白质组。共鉴定出 818 种蛋白质,其中 137 种发生了差异改变。生物信息学(包括 GO、KEGG、蛋白质-蛋白质相互作用等)分析表明,差异改变的蛋白质基本涉及补体和凝血级联、抗氧化应激和糖酵解。验证结果表明,高原居民中 CCL18、C9、PF4、MPO 和 S100A9 明显上调,HRG 和 F11 下调,与 TMT 蛋白质组学结果一致。我们的研究结果强调了补体和凝血级联、抗氧化应激和糖酵解在适应低气压缺氧中的作用,并为开发潜在的诊断或/和治疗高海拔低气压缺氧引起的疾病的生物标志物提供了基础。