A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart

Phospholamban (PLN) is a key regulator of sarcolemma calcium uptake in cardiomyocyte; its inhibitory activity to sarcolemma-endoplasmic reticulum calcium ATPase is regulated by phosphorylation. PLN hypophosphorylation is a common molecular feature in the failing heart. The current study provided evidence at the molecular, cellular, and whole-heart levels to implicate a sarcolemma membrane-targeted protein phosphatase, PP2Ce, as a specific and potent PLN phosphatase. PP2Ce expression was elevated in failing human heart and induced acutely at protein level by β-adrenergic stimulation or oxidative stress in cardiomyocytes. PP2Ce expression in mouse heart blunted β-adrenergic response and exacerbated ischemia/reperfusion injury. Therefore, PP2Ce is a new regulator for cardiac function and pathogenesis.