Oral Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

The Use of LC/MS and Bio-orthogonal Chemistry to Study Protein Dynamics in Cardiac Remodeling (#159)

John R Yates 1 , Yuanhui Ma 1 , David Liem 2 , Dominic Ng 2 , Peipei Ping 2 , Daniel McClatchy 1
  1. Scripps Research, Lajolla, CA, United States
  2. Department of Physiology, University of California at Los Angeles, Los Angeles, California, USA

Maladaptive cardiac remodeling (MCR) is a complex dynamic process common to many heart diseases. MCR is characterized as a temporal progression of global adaptive and maladaptive perturbations. The complex nature of this process clouds a comprehensive understanding of MCR, but greater insight into the processes and mechanisms has potential to identify new therapeutic targets. To provide a deeper understanding of this important cardiac process, we applied a new proteomic technique, PALM (Pulse Azidohomoalanine in Mammals), together with multi-dimensional LC to quantitate the newly synthesized protein (NSP) changes during the progression of isoproterenol(ISO) induced MCR in the mouse left ventricle. This analysis revealed a complex combination of adaptive and maladaptive alterations at acute and prolonged time points including the identification of proteins not previously associated with MCR. We also combined the PALM dataset with our published protein turnover rate dataset to identify putative biochemical mechanisms underlying MCR. The novel integration of analyzing newly synthesized proteins together with their protein turnover rates demonstrated that alterations in specific biological pathways (e.g. inflammation and oxidative stress) are produced by differential regulation of protein synthesis and degradation.

McClatchy DB, Ma Y, Liem DA, Ng DCM, Ping P, Yates JR 3rd.,Quantitative temporal analysis of protein dynamics in cardiac remodeling., J Mol Cell Cardiol. 2018 Aug;121:163-172. doi: 10.1016/j.yjmcc.2018.07.126.