title: Characterization of human plasma proteome dynamics using deuterium oxide.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: The NHLBI Proteomics Center at UCLA, Los Angeles, CA, USA; Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
authors.forename: Ding
authors.initials: D
authors.lastname: Wang
authors.forename: David A
authors.initials: DA
authors.lastname: Liem
authors.forename: Edward
authors.initials: E
authors.lastname: Lau
authors.forename: Dominic C M
authors.initials: DC
authors.lastname: Ng
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Bleakley
authors.forename: Martin
authors.initials: M
authors.lastname: Cadeiras
authors.forename: Mario C
authors.initials: MC
authors.lastname: Deng
authors.forename: Maggie P Y
authors.initials: MP
authors.lastname: Lam
authors.forename: Peipei
authors.initials: P
authors.lastname: Ping
mesh_terms: D000328:Adult; D001798:Blood Proteins / Q000378:metabolism*; D017666:Deuterium Oxide / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D040901:Proteomics / Q000379:methods*; D055815:Young Adult
chemical_list: D001798:Blood Proteins; D017666:Deuterium Oxide
keywords: Deuterium oxide; Heavy water; Plasma proteome; Protein dynamics; Protein turnover