Comparative iTRAQ analysis of protein abundance in the human sinoatrial node and working cardiomyocytes

Abstract

Our objective was to assess the changes in protein abundance in the human sinoatrial node (SAN) compared with working cardiomyocytes to identify SAN-specific protein signatures. Four pairs of samples (the SAN and working cardiomyocytes) were obtained postmortem from four human donors with no evidence of cardiovascular disease. We performed protein identification and quantitation using two-dimensional chromatography-tandem mass spectrometry with isobaric peptide labeling (iTRAQ). We identified 451 different proteins expressed in both the SAN and working cardiomyocytes, 166 of which were differentially regulated (110 were upregulated in the SAN and 56 in the working cardiomyocytes). We identified sarcomere structural proteins in both tissues, although they were differently distributed among the tested samples. For example, myosin light chain 4, myosin regulatory light chain 2-atrial isoform, and tropomyosin alpha-3 chain levels were twofold higher in the SAN than in working cardiomyocytes, and myosin light chain 3 and myosin regulatory light chain 2-ventricular/cardiac muscle isoform levels were twofold higher in the ventricle tissue than in SAN. We identified many mitochondrial oxidative phosphorylation, β-oxidation, and tricarboxylic acid cycle proteins that were predominantly associated with working cardiomyocytes tissue. We detected upregulation of the fatty acid omega activation pathway proteins in the SAN samples. Some proteins specific for smooth muscle tissue were highly upregulated in the SAN (e.g. transgelin), which indicates that the SAN tissue might act as the bridge between the working myocardium and the smooth muscle. Our results show possible implementation of proteomic strategies to identify in-depth functional differences between various heart sub-structures.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2sYhB39