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

Toru Akaike; Na Du; Gang Lu; Susumu Minamisawa; Yibin Wang; Hongmei Ruan

doi:10.1016/j.jacbts.2016.12.002

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

JACC Basic Transl Sci. 2017 Mar;2(2):160-180. doi: 10.1016/j.jacbts.2016.12.002. Epub 2017 Apr 24.

Authors

Toru Akaike^{1

2}, Na Du¹, Gang Lu¹, Susumu Minamisawa², Yibin Wang¹, Hongmei Ruan¹

Affiliations

¹ Department of Anesthesiology and Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095-1735.
² Department of Cell Physiology, The Jikei University School of Medicine.

Abstract

Phospholamban (PLN) is a key regulator of sarcolemma calcium uptake in cardiomyocyte, its inhibitory activity to SERCA is regulated by phosphorylation. PLN hypophosphorylation is a common molecular feature in failing heart. The current study provided evidence at 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.

Keywords: Phosphalamban; Phosphatase; heart.

Abstract

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