Wang Ding, Liem David A, Lau Edward, Ng Dominic C M, Bleakley Brian J, Cadeiras Martin, Deng Mario C, Lam Maggie P Y, Ping Peipei
The NHLBI Proteomics Center at UCLA, Los Angeles, CA, USA; Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Proteomics Clin Appl. 2014 Aug;8(7-8):610-9. doi: 10.1002/prca.201400038.
High-throughput quantification of human protein turnover via in vivo administration of deuterium oxide ((2) H2 O) is a powerful new approach to examine potential disease mechanisms. Its immediate clinical translation is contingent upon characterizations of the safety and hemodynamic effects of in vivo administration of (2) H2 O to human subjects.
We recruited ten healthy human subjects with a broad demographic variety to evaluate the safety, feasibility, efficacy, and reproducibility of (2) H2 O intake for studying protein dynamics. We designed a protocol where each subject orally consumed weight-adjusted doses of 70% (2) H2 O daily for 14 days to enrich body water and proteins with deuterium. Plasma proteome dynamics was measured using a high-resolution MS method we recently developed.
This protocol was successfully applied in ten human subjects to characterize the endogenous turnover rates of 542 human plasma proteins, the largest such human dataset to-date. Throughout the study, we did not detect physiological effects or signs of discomfort from (2) H2 O consumption.
Our investigation supports the utility of a (2) H2 O intake protocol that is safe, accessible, and effective for clinical investigations of large-scale human protein turnover dynamics. This workflow shows promising clinical translational value for examining plasma protein dynamics in human diseases.
通过向体内注射氧化氘（(2)H2O）对人体蛋白质周转率进行高通量定量分析，是一种研究潜在疾病机制的强有力的新方法。其直接的临床转化取决于对向人体受试者体内注射(2)H2O的安全性和血流动力学效应的表征。
我们招募了10名具有广泛人口统计学特征的健康人类受试者，以评估摄入(2)H2O用于研究蛋白质动力学的安全性、可行性、有效性和可重复性。我们设计了一个方案，让每个受试者每天口服经体重调整的70% (2)H2O剂量，持续14天，以使体内水分和蛋白质富含氘。使用我们最近开发的一种高分辨率质谱方法测量血浆蛋白质组动力学。
该方案成功应用于10名人类受试者，以表征542种人类血浆蛋白的内源性周转率，这是迄今为止最大的此类人类数据集。在整个研究过程中，我们未检测到因摄入(2)H2O而产生的生理效应或不适迹象。
我们的研究支持了一种摄入(2)H2O方案的实用性，该方案对于大规模人类蛋白质周转动力学的临床研究是安全、可行且有效的。这种工作流程对于研究人类疾病中的血浆蛋白动力学具有良好的临床转化价值。
