Abstract P256: Epigenetic Changes by Nuclear Calcium/Calmodulin-Dependent Protein Kinase II in the Heart
Calcium is central in the regulation of many cellular functions and alteration of calcium signaling leads to a variety of cardiac disorders. An important question remaining in cardiac biology is how calcium-dependent mechanisms are regulated and more specifically how calcium activates intracellular signaling pathways and regulates gene activity in the cell nucleus. The nuclear isoform of calcium/calmodulin-dependent protein kinase II (CaMKIIB) plays a protective role in the heart under basal conditions, and alteration of its level or activity is associated with pathological events such as cell death and cardiac hypertrophy. We recently made a novel discovery showing that CaMKIIδB couples calcium signals to the genome by targeting specific histones in chromatin. Our preliminary results show that CaMKIIδB selectively phosphorylates histone H3 in vitro and in primary cardiomyocytes. Activation of CaMK activity after α-adrenergic stimulation of primary cardiac cells increases histone H3 phosphorylation at serine 10 (Ser-10), whereas specific elimination of the kinase has the opposite effect. Enhanced phosphorylation of histone H3 Ser-10 is observed in primary fibroblasts and also in primary ventricular myocytes and culminates at 24 hours of stimulation, suggesting that signaling to histone H3 is not limited to highly dividing cells and is not transient. Importantly, Enhanced histone H3 Ser-10 phosphorylation can be detected in the heart of mice subjected to myocardial infarction. These results reveal a new role for CaMK enzymes in chromatin remodeling the heart and that epigenetic changes may contribute to the development cardiac diseases.
- © 2011 by American Heart Association, Inc.