Quantitative Temporal Analysis of Protein Dynamics in Maladaptive Cardiac Remodeling
| Autor: | Dominic C. M. Ng, John R. Yates, David A. Liem, Peipei Ping, Yuanhui Ma, Daniel B. McClatchy |
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| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
Cardiac process Protein dynamics Protein turnover Differential regulation Inflammation Computational biology 030204 cardiovascular system & hematology Biology Biological pathway 03 medical and health sciences 0302 clinical medicine medicine Protein biosynthesis medicine.symptom hormones hormone substitutes and hormone antagonists 030304 developmental biology |
| Popis: | 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 the 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), 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 NSPs 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. |
| Databáze: | OpenAIRE |
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