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Proteomics Clin Appl. 2014 Aug;8(7-8):610-9. doi: 10.1002/prca.201400038.

Characterization of human plasma proteome dynamics using deuterium oxide.

Author information

1
The NHLBI Proteomics Center at UCLA, Los Angeles, CA, USA; Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

Abstract

PURPOSE:

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.

EXPERIMENTAL DESIGN:

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.

RESULTS:

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.

CONCLUSIONS AND CLINICAL RELEVANCE:

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.

KEYWORDS:

Deuterium oxide; Heavy water; Plasma proteome; Protein dynamics; Protein turnover

PMID:
24946186
PMCID:
PMC4764616
DOI:
10.1002/prca.201400038
[Indexed for MEDLINE]
Free PMC Article

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