Abstract
Purpose: High-throughput quantification of human protein turnover via in vivo administration of deuterium oxide (2H2O) 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 2H2O 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 2H2O intake for studying protein dynamics. We designed a protocol where each subject orally consumed weight-adjusted doses of 70% 2H2O 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 2H2O consumption. Conclusions and clinical relevance: Our investigation supports the utility of a 2H2O 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 610-619 |
| Number of pages | 10 |
| Journal | Proteomics - Clinical Applications |
| Volume | 8 |
| Issue number | 7-8 |
| DOIs | |
| State | Published - Aug 2014 |
| Externally published | Yes |
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Keywords
- Deuterium oxide
- Heavy water
- Plasma proteome
- Protein dynamics
- Protein turnover
ASJC Scopus subject areas
- Clinical Biochemistry
Cite this
Characterization of human plasma proteome dynamics using deuterium oxide. / 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.
In: Proteomics - Clinical Applications, Vol. 8, No. 7-8, 08.2014, p. 610-619.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characterization of human plasma proteome dynamics using deuterium oxide
AU - Wang, Ding
AU - Liem, David A.
AU - Lau, Edward
AU - Ng, Dominic C.M.
AU - Bleakley, Brian J.
AU - Cadeiras, Martin
AU - Deng, Mario C.
AU - Lam, Maggie P.Y.
AU - Ping, Peipei
PY - 2014/8
Y1 - 2014/8
N2 - Purpose: High-throughput quantification of human protein turnover via in vivo administration of deuterium oxide (2H2O) 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 2H2O 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 2H2O intake for studying protein dynamics. We designed a protocol where each subject orally consumed weight-adjusted doses of 70% 2H2O 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 2H2O consumption. Conclusions and clinical relevance: Our investigation supports the utility of a 2H2O 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.
AB - Purpose: High-throughput quantification of human protein turnover via in vivo administration of deuterium oxide (2H2O) 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 2H2O 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 2H2O intake for studying protein dynamics. We designed a protocol where each subject orally consumed weight-adjusted doses of 70% 2H2O 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 2H2O consumption. Conclusions and clinical relevance: Our investigation supports the utility of a 2H2O 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.
KW - Deuterium oxide
KW - Heavy water
KW - Plasma proteome
KW - Protein dynamics
KW - Protein turnover
UR - http://www.scopus.com/inward/record.url?scp=84906058520&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906058520&partnerID=8YFLogxK
U2 - 10.1002/prca.201400038
DO - 10.1002/prca.201400038
M3 - Article
C2 - 24946186
AN - SCOPUS:84906058520
VL - 8
SP - 610
EP - 619
JO - Proteomics - Clinical Applications
JF - Proteomics - Clinical Applications
SN - 1862-8346
IS - 7-8
ER -