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Plasma protein(s)-based conceptual diagnostic tool for assessing high-altitude acclimation in humans.
Functional & Integrative Genomics ( IF 3.9 ) Pub Date : 2019-08-24 , DOI: 10.1007/s10142-019-00712-0
Subhojit Paul 1 , Anamika Gangwar 1 , Kalpana Bhargava 1 , Nilofar Khan 1 , Pankaj Khurana 1 , Yasmin Ahmad 1
Affiliation  

Exposure to high altitude above 3000 m leads to two outcomes—acclimation or high-altitude maladies. To reach a particular outcome, the plasma proteome is modified differentially, either in context of an acclimation response or mal-acclimation response leading to disease. This ensures that hypoxia-responsive plasma protein trends reflect acclimation in acclimated individuals when compared with their levels prior to acclimation. Such protein trends could be used to assess acclimation in an individual and any significant deviation from this trend may indicate non-acclimation, thereby preventing high-altitude illnesses before they manifest. In this study, we investigate and statistically evaluate the trendlines of various hypoxia-responsive plasma protein levels, reported significantly perturbed in our previous studies, in individuals (male; n = 20) exposed to 3520 m at high-altitude day 1 (HAD1), HAD4, and HAD7L and to 4420 m at HAD7H, HAD30, and HAD120. We observe that thioredoxin (Trx), glutathione peroxidase 3 (GPx-3), and apolipoprotein AI (Apo-AI) are statistically robust markers to assess acclimation across the exposure duration while sulfotransferase 1A1 (ST1A1) is a capable negative control whose levels increase only in cases of HAPE. We also observe exposure day-specific and resident altitude-specific proteins capable of accurately assessing acclimation when compared with baseline levels or the lower altitude zone.

中文翻译:

基于血浆蛋白的概念诊断工具,用于评估人的高海拔适应性。

暴露在3000 m以上的高海拔地区会导致两个结果-适应或高海拔疾病。为了达到特定的结果,在适应疾病或导致疾病的适应不良的情况下,对血浆蛋白质组进行差异修饰。与适应之前的水平相比,这确保了低氧反应性血浆蛋白趋势反映了适应的个体的适应。此类蛋白质趋势可用于评估个体的适应能力,并且与该趋势的任何重大偏离都可能表明没有适应能力,从而可以在高海拔疾病发作之前预防它们。在这项研究中,我们调查并统计学评估了各种低氧反应性血浆蛋白水平的趋势线,这些趋势在我们先前的研究中被报告对个体(男性;n  = 20)在高海拔第1天(HAD1),HAD4和HAD7L暴露于3520 m,在HAD7H,HAD30和HAD120暴露于4420 m。我们观察到,硫氧还蛋白(Trx),谷胱甘肽过氧化物酶3(GPx-3)和载脂蛋白AI(Apo-AI)是统计学上可靠的标记,可评估暴露持续时间的适应性,而磺基转移酶1A1(ST1A1)是水平升高的有效阴性对照仅在HAPE的情况下。我们还观察到与基线水平或较低海拔地区相比,特定暴露天数和特定海拔高度居民蛋白质能够准确评估环境适应性。
更新日期:2019-08-24
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