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Protein kinetic signatures of the remodeling heart following isoproterenol stimulation.

Publication ,  Journal Article
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
Published in: J Clin Invest
April 2014

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.

Duke Scholars

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Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

April 2014

Volume

124

Issue

4

Start / End Page

1734 / 1744

Location

United States

Related Subject Headings

  • Proteins
  • Myocardium
  • Muscle Proteins
  • Mitochondria, Heart
  • Mice, Inbred ICR
  • Mice
  • Mass Spectrometry
  • Male
  • Kinetics
  • Isoproterenol
 

Citation

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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. J Clin Invest, 124(4), 1734–1744. https://doi.org/10.1172/JCI73787
Lam, Maggie P. Y., Ding Wang, Edward Lau, David A. Liem, Allen K. Kim, Dominic C. M. Ng, Xiangbo Liang, et al. “Protein kinetic signatures of the remodeling heart following isoproterenol stimulation.J Clin Invest 124, no. 4 (April 2014): 1734–44. https://doi.org/10.1172/JCI73787.
Lam MPY, Wang D, Lau E, Liem DA, Kim AK, Ng DCM, et al. Protein kinetic signatures of the remodeling heart following isoproterenol stimulation. J Clin Invest. 2014 Apr;124(4):1734–44.
Lam, Maggie P. Y., et al. “Protein kinetic signatures of the remodeling heart following isoproterenol stimulation.J Clin Invest, vol. 124, no. 4, Apr. 2014, pp. 1734–44. Pubmed, doi:10.1172/JCI73787.
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. Protein kinetic signatures of the remodeling heart following isoproterenol stimulation. J Clin Invest. 2014 Apr;124(4):1734–1744.

Published In

J Clin Invest

DOI

EISSN

1558-8238

Publication Date

April 2014

Volume

124

Issue

4

Start / End Page

1734 / 1744

Location

United States

Related Subject Headings

  • Proteins
  • Myocardium
  • Muscle Proteins
  • Mitochondria, Heart
  • Mice, Inbred ICR
  • Mice
  • Mass Spectrometry
  • Male
  • Kinetics
  • Isoproterenol