Phospholipase C-δ1 rescues intracellular Ca²⁺ overload in ischemic heart and hypoxic neonatal cardiomyocytes

Ischemia and simulated ischemic conditions cause intracellular Ca ²⁺ overload in the myocardium. The relationship between ischemia injury and Ca²⁺ overload has not been fully characterized. The aim of the present study was to investigate the expression and characteristics of PLC isozymes in myocardial infarction-induced cardiac remodeling and heart failure. In normal rat heart tissue, PLC-δ1 (about 44 ng/mg of heart tissue) was most abundant isozymes compared to PLC-γ1 (6.8 ng/mg) and PLC-β1 (0.4 ng/mg). In ischemic heart and hypoxic neonatal cardiomyocytes, PLC-δ1, but not PLC-β1 and PLC-γ1, was selectively degraded, a response that could be inhibited by the calpain inhibitor, calpastatin, and by the caspase inhibitor, zVAD-fmk. Overexpression of the PLC-δ1 in hypoxic neonatal cardiomyocytes rescued intracellular Ca²⁺ overload by ischemic conditions. In the border zone and scar region of infarcted myocardium, and in hypoxic neonatal cardiomyocytes, the selective degradation of PLC-δ1 by the calcium sensitive proteases may play important roles in intracellular Ca²⁺ regulations under the ischemic conditions. It is suggested that PLC isozyme-changes may contribute to the alterations in calcium homeostasis in myocardial ischemia.