Characterization of human plasma proteome dynamics using deuterium oxide. Issue 7 (August 2014)

• Record Type: Journal Article
• Authors: 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; Ge, Ying; Van Eyk, Jennifer
• Is Part Of: Proteomics. Volume 8:Issue 7/8(2014)
• Page Start: 610
• Page End: 619
• Publication Date: 2014-08
• Subjects: Proteomics -- Periodicals; 572.605
• DOI: 10.1002/prca.201400038
• Languages: English
• ISSNs: 1862-8346

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="prca1559-sec-0010" sec-type="section"> <title>Purpose</title> <p>High‐throughput quantification of human protein turnover via in vivo administration of deuterium oxide (<sup>2</sup>H<sub>2</sub>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 <sup>2</sup>H<sub>2</sub>O to human subjects.</p> </sec> <sec id="prca1559-sec-0020" sec-type="section"> <title>Experimental design</title> <p>We recruited ten healthy human subjects with a broad demographic variety to evaluate the safety, feasibility, efficacy, and reproducibility of <sup>2</sup>H<sub>2</sub>O intake for studying protein dynamics. We designed a protocol where each subject orally consumed weight‐adjusted doses of 70% <sup>2</sup>H<sub>2</sub>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.</p> </sec> <sec id="prca1559-sec-0030" sec-type="section"> <title>Results</title> <p>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 <sup>2</sup>H<sub>2</sub>O consumption.</p> </sec> <sec id="prca1559-sec-0040" sec-type="section"> <title>Conclusions and clinical relevance</title> <p>Our investigation supports the utility of a <sup>2</sup>H<sub>2</sub>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.</p> </sec> </abstract>