Tropomyosin Phosphorylation in Healthy and Diseased Hearts

Abstract

Tropomyosin (Tm) is an alpha‐helical coiled coil dimer involved in regulating striated muscle contraction. Although sarcomeric Tm is known to be phosphorylated at the penultimate amino acid Ser‐283, little is known regarding its phosphorylation levels in healthy and cardiac diseased states. The objective of this study was to study Tm phosphorylation levels with respect to age in wild type mice and in mice with familial hypertrophic cardiomyopathy (FHC). Phosphorylation levels were determined by western blotting of 2‐D gel electrophoresis of myofibrillar protein preparations. Results show that cardiac Tm phosphorylation is high during the perinatal period and decreases throughout adulthood in wild type mice. We also found that walls of the different cardiac chambers exhibit differential Tm phosphorylation.Two transgenic mouse models harboring FHC mutations in alpha‐Tm (Glu180Gly, and Asp175Asn) were studied to determine the effect of this disease on cardiac Tm phosphorylation. Results show that Tm phosphorylation is altered in both FHC models. Unlike in wild type mice, Tm phosphorylation levels do not decrease after birth, but rather remain constant. Depending on the role of Tm phosphorylation, modulation of phosphorylation levels in FHC patients may be potentially of therapeutic value.This project was funded by NHLBI HL81680 grant to DFW. HNS was supported by a fellowship from Dubai Medical College.