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(2+) signaling in liver cells. Regucalcin was shown to play a multifunctional role in cell regulation, such as maintainance of intracellular Ca(2+) 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(2+) concentration by the Ca(2+) 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(2+)-ATPase activity and ATP-dependent Ca(2+) uptake and mitochondrial Ca(2+)-ATPase activity. Regucalcin was also shown to suppress Ca(2+)-dependent protein tyrosine phosphatase, Ca(2+)/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(2+) 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(2+) signaling in the heart.