Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
The NIH Big Data to Knowledge (BD2K) Center of Excellence in Biomedical Computing at UCLA, Los Angeles, CA 90095, USA; Department of Physiology, University of California at Los Angeles, Los Angeles, CA 90095, USA.
J Mol Cell Cardiol. 2018 Aug;121:163-172. doi: 10.1016/j.yjmcc.2018.07.126. Epub 2018 Jul 19.
Cardiac remodeling (CR) is a complex dynamic process common to many heart diseases. CR is characterized as a temporal progression of global adaptive and maladaptive perturbations. The complex nature of this process clouds a comprehensive understanding of CR, 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), to quantitate the newly-synthesized protein (NSP) changes during the progression of isoproterenol (ISO)-induced CR 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 CR. We also combined the PALM dataset with our published protein turnover rate dataset to identify putative biochemical mechanisms underlying CR. 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.
心脏重构（CR）是许多心脏病共有的复杂动态过程。CR 的特征是全局适应性和失调性干扰的时间进展。这一过程的复杂性阻碍了对 CR 的全面理解，但对这些过程和机制的更深入了解有可能确定新的治疗靶点。为了更深入地了解这一重要的心脏过程，我们应用了一种新的蛋白质组学技术 PALM（哺乳动物脉冲叠氮同型半胱氨酸），来定量分析异丙肾上腺素（ISO）诱导的小鼠左心室 CR 进展过程中新合成的蛋白质（NSP）的变化。该分析揭示了在急性和慢性时间点适应性和失调性改变的复杂组合，包括鉴定以前与 CR 无关的蛋白质。我们还将 PALM 数据集与我们已发表的蛋白质周转率数据集相结合，以确定 CR 潜在的生化机制。分析 NSP 及其蛋白质周转率的新方法表明，特定生物途径（如炎症和氧化应激）的改变是通过蛋白质合成和降解的差异调节产生的。
