Protein kinetic signatures of the remodeling heart following isoproterenol stimulation

Maggie P.Y. Lam, Ding Wang, Edward Lau, David A. Liem, Allen K. Kim, Dominic C.M. Ng, Xiangbo Liang, Brian J. Bleakley, Chenguang Liu, Jason D. Tabaraki, Martin Cadeiras, Yibin Wang, Mario C. Deng, Peipei Ping

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Protein temporal dynamics play a critical role in time-dimensional pathophysiological processes, including the gradual cardiac remodeling that occurs in early-stage heart failure. Methods for quantitative assessments of protein kinetics are lacking, and despite knowledge gained from single-protein studies, integrative views of the coordinated behavior of multiple proteins in cardiac remodeling are scarce. Here, we developed a workflow that integrates deuterium oxide (2H2O) labeling, high-resolution mass spectrometry (MS), and custom computational methods to systematically interrogate in vivo protein turnover. Using this workflow, we characterized the in vivo turnover kinetics of 2,964 proteins in a mouse model of β-adrenergic-induced cardiac remodeling. The data provided a quantitative and longitudinal view of cardiac remodeling at the molecular level, revealing widespread kinetic regulations in calcium signaling, metabolism, proteostasis, and mitochondrial dynamics. We translated the workflow to human studies, creating a reference dataset of 496 plasma protein turnover rates from 4 healthy adults. The approach is applicable to short, minimal label enrichment and can be performed on as little as a single biopsy, thereby overcoming critical obstacles to clinical investigations. The protein turnover quantitation experiments and computational workflow described here should be widely applicable to large- scale biomolecular investigations of human disease mechanisms with a temporal perspective.

Original languageEnglish (US)
Pages (from-to)1734-1744
Number of pages11
JournalJournal of Clinical Investigation
Volume124
Issue number4
DOIs
StatePublished - Apr 1 2014
Externally publishedYes

Fingerprint

Isoproterenol
Workflow
Proteins
Mitochondrial Dynamics
Deuterium Oxide
Calcium Signaling
Adrenergic Agents
Blood Proteins
Mass Spectrometry
Heart Failure
Biopsy

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lam, M. P. Y., Wang, D., Lau, E., Liem, D. A., Kim, A. K., Ng, D. C. M., ... Ping, P. (2014). Protein kinetic signatures of the remodeling heart following isoproterenol stimulation. Journal of Clinical Investigation, 124(4), 1734-1744. https://doi.org/10.1172/JCI73787

Protein kinetic signatures of the remodeling heart following isoproterenol stimulation. / Lam, Maggie P.Y.; Wang, Ding; Lau, Edward; Liem, David A.; Kim, Allen K.; Ng, Dominic C.M.; Liang, Xiangbo; Bleakley, Brian J.; Liu, Chenguang; Tabaraki, Jason D.; Cadeiras, Martin; Wang, Yibin; Deng, Mario C.; Ping, Peipei.

In: Journal of Clinical Investigation, Vol. 124, No. 4, 01.04.2014, p. 1734-1744.

Research output: Contribution to journalArticle

Lam, MPY, Wang, D, Lau, E, Liem, DA, Kim, AK, Ng, DCM, Liang, X, Bleakley, BJ, Liu, C, Tabaraki, JD, Cadeiras, M, Wang, Y, Deng, MC & Ping, P 2014, 'Protein kinetic signatures of the remodeling heart following isoproterenol stimulation', Journal of Clinical Investigation, vol. 124, no. 4, pp. 1734-1744. https://doi.org/10.1172/JCI73787
Lam, Maggie P.Y. ; Wang, Ding ; Lau, Edward ; Liem, David A. ; Kim, Allen K. ; Ng, Dominic C.M. ; Liang, Xiangbo ; Bleakley, Brian J. ; Liu, Chenguang ; Tabaraki, Jason D. ; Cadeiras, Martin ; Wang, Yibin ; Deng, Mario C. ; Ping, Peipei. / Protein kinetic signatures of the remodeling heart following isoproterenol stimulation. In: Journal of Clinical Investigation. 2014 ; Vol. 124, No. 4. pp. 1734-1744.
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