AltitudeOmics: Red Blood Cell Metabolic Adaptation to High Altitude Hypoxia.
AltitudeOmics: Red Blood Cell Metabolic Adaptation to High Altitude Hypoxia.
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DOI：
10.1021/acs.jproteome.6b00733
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发表时间：
2016-10-07
影响因子：
4.4
通讯作者：
Roach RC
中科院分区：
文献类型：
--
作者：
D'Alessandro A;Nemkov T;Sun K;Liu H;Song A;Monte AA;Subudhi AW;Lovering AT;Dvorkin D;Julian CG;Kevil CG;Kolluru GK;Shiva S;Gladwin MT;Xia Y;Hansen KC;Roach RC
红细胞（rbc）是全身氧运输的关键参与者。红细胞通过所谓的氧依赖性代谢调节对体外缺氧作出反应，这涉及脱氧血红蛋白和糖酵解酶与带3的n端胞质结构域的竞争性结合。该机制促进2,3- dpg的积累，稳定血红蛋白的脱氧状态，以及细胞质酸化，通过玻尔效应触发氧卸载。尽管有体外研究，但体内对缺氧的适应尚未完全阐明。在海拔组学研究的框架内，采集了21名健康志愿者在海拔（5260米）暴露1、7和16天后，以及在海拔1525米暴露7天后的红细胞。UHPLC-MS代谢组学结果与生理和运动性能参数相关。在海拔5000m的几小时内就发现了立即的代谢适应，并在高海拔维持了16天。与体外机制一致，缺氧促进糖酵解，解除戊糖磷酸途径、嘌呤分解代谢、谷胱甘肽稳态、精氨酸/一氧化氮和硫/H2S代谢的调控。在下降一周后，代谢适应得以保留，与第一次上升相比，身体表现也有所改善，这表明代谢记忆的机制存在。
Red blood cells (RBCs) are key players in systemic oxygen transport. RBCs respond to in vitro hypoxia through the so-called oxygen-dependent metabolic regulation, which involves the competitive binding of deoxyhemoglobin and glycolytic enzymes to the N-terminal cytosolic domain of band 3. This mechanism promotes the accumulation of 2,3-DPG, stabilizing the deoxygenated state of hemoglobin, and cytosol acidification, triggering oxygen off-loading through the Bohr effect. Despite in vitro studies, in vivo adaptations to hypoxia have not yet been completely elucidated. Within the framework of the AltitudeOmics study, erythrocytes were collected from 21 healthy volunteers at sea level, after exposure to high altitude (5260m) for 1, 7 and 16days, and following reascent after 7days at 1525m. UHPLC-MS metabolomics results were correlated to physiological and athletic performance parameters. Immediate metabolic adaptations were noted as early as a few hours from ascending to >5000m, and maintained for 16 days at high altitude. Consistent with the mechanisms elucidated in vitro, hypoxia promoted glycolysis and deregulated the pentose phosphate pathway, as well purine catabolism, glutathione homeostasis, arginine/nitric oxide and sulphur/H2S metabolism. Metabolic adaptations were preserved one week after descent, consistently with improved physical performances in comparison to the first ascendance, suggesting a mechanism of metabolic memory.
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影响因子：
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作者：
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通讯作者：
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