Regulatory role of regucalcin in heart calcium signaling: Insight into cardiac failure (Review).

Regucalcin was first identified in 1978 as a regulatory protein of Ca signaling in liver cells. Regucalcin was shown to play a multifunctional role in cell regulation, such as maintainance of intracellular Ca homeostasis and suppression of signal transduction, protein synthesis, nuclear function, cell proliferation and apoptosis in various types of cells and tissues. Cardiac excitation-contraction coupling is based on the regulation of intracellular Ca concentration by the Ca pump in the sarcoplasmic reticulum of heart muscle cells. Regucalcin, which is expressed in the heart, was found to increase rat heart sarcoplasmic reticulum Ca-ATPase activity and ATP-dependent Ca uptake and mitochondrial Ca-ATPase activity. Regucalcin was also shown to suppress Ca-dependent protein tyrosine phosphatase, Ca/calmodulin-dependent protein phosphatase (calcineurin) and nitric oxide (NO) synthase activity in the heart cytoplasm. Moreover, regucalcin was found to activate superoxide dismutase (SOD), which plays a significant role in the prevention of cell death and apoptosis in the heart. Regucalcin may be a key molecule in heart muscle cell regulation through Ca signaling. Regucalcin may also play a pathophysiological role in heart failure. The aim of this study was to review the recent findings regarding the role of regucalcin in Ca signaling in the heart.