Identification of proteins responding to adrenergic receptor subtype-specific hypertrophy in cardiomyocytes by proteomic approaches.

The individual signaling pathways underlying cardiac hypertrophy, which is induced by either α or β adrenergic receptor (AR), are different. Activation of different AR subtypes couples to different G proteins and induction of specific signaling pathways, which ultimately results in subtype-specific regulation of cardiac function. We present the first proteomics study identifying proteins that are related to AR subtype-specific hypertrophy in cardiomyocytes by comparing the two-dimensional electrophoresis patterns between neonatal rat cardiomyocytes treated by phenylepinephrin (PE) and by isoproterenol (ISO). An improved 2-DE strategy was used in these comparative experiments. Twenty-five differentially expressed proteins in cardiomyocytes treated by PE or treated by ISO were successfully analyzed and identified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry, especially those that might be responsible to intracellular oxidative stress such as dismutase, peroxiredoxin, and thioredoxin-like protein p46. In addition, induced reactive oxygen species were also found to be AR subtype-specifically relevant to endoplasmic reticulum proteinase ERK1/2 phosphorylation during the development of hypertrophy induced by different AR subtypes. The results will help to better understand the underlying mechanisms of different adrenergic receptor subtype-induced hypertrophy.