Abstract 16660: Estradiol-Induced Phosphorylation of Myosin Regulatory Light Chain Leads to Increased Female Cardiomyocyte Contractility
Myosin regulatory light chain (Mrlc) controls actin/myosin interactions and modulation of contraction by Mrlc in the heart has been well documented. Notably, mutant mice for Mrlc phosphorylation show defects in cardiac contraction. The sex steroid hormone 17β-estradiol (E2) has been shown to exert several cardioprotective actions. However, little is known about the effects of E2 on the regulation of Mrlc and contractile function. Here, we tested the hypothesis that E2 increases the phosphorylation of Mrlc, which in turn leads to improved cardiomyocyte contractile function. One set of 14-month old female C57BL/6J mice were injected intraperitonealy with 0.2 mg/kg E2 (n = 8) or vehicle (Ctrl; n = 5). Five hours after injection, cardiomyocytes (CMs) were enzymatically isolated with the Langendorff-perfusion system, which were used for unloaded cell shortening measurements. Another set of female mice with the same age and strain (n = 6 per group) were treated in exactly the same manner and left ventricles were collected for protein extraction. Western blot analysis revealed that E2-treated CMs had higher levels of phosphorylated Mrlc than Ctrl CMs. Recordings of unloaded cell shortening at 1, 2 and 4 Hz demonstrated that the treatment with E2 improved CM contractile function compared to Ctrl CMs. In particular, at 1 Hz there was a 29.6% increase (adjusted P = 0.005), at 2 Hz a 31.5% increase (adjusted P = 0.009) and at 4 Hz a 29.3% increase (adjusted P = 0.01). For each frequency, 37 E2-treated and 45 Ctrl CMs were measured. Similarly, there was a significant increase in the rate of contraction of E2-treated CMs compared to controls. To our knowledge, our present work is the first to implicate E2 in the modulation of Mrlc phosphorylation leading to improved contractile function.
- © 2011 by American Heart Association, Inc.