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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 evi...

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Autores principales: Akaike, Toru, Du, Na, Lu, Gang, Minamisawa, Susumu, Wang, Yibin, Ruan, Hongmei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648354/
https://www.ncbi.nlm.nih.gov/pubmed/29057374
http://dx.doi.org/10.1016/j.jacbts.2016.12.002
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author Akaike, Toru
Du, Na
Lu, Gang
Minamisawa, Susumu
Wang, Yibin
Ruan, Hongmei
author_facet Akaike, Toru
Du, Na
Lu, Gang
Minamisawa, Susumu
Wang, Yibin
Ruan, Hongmei
author_sort Akaike, Toru
collection PubMed
description 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.
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spelling pubmed-56483542017-10-20 A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart Akaike, Toru Du, Na Lu, Gang Minamisawa, Susumu Wang, Yibin Ruan, Hongmei JACC Basic Transl Sci PRECLINICAL RESEARCH 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. Elsevier 2017-04-24 /pmc/articles/PMC5648354/ /pubmed/29057374 http://dx.doi.org/10.1016/j.jacbts.2016.12.002 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle PRECLINICAL RESEARCH
Akaike, Toru
Du, Na
Lu, Gang
Minamisawa, Susumu
Wang, Yibin
Ruan, Hongmei
A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart
title A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart
title_full A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart
title_fullStr A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart
title_full_unstemmed A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart
title_short A Sarcoplasmic Reticulum Localized Protein Phosphatase Regulates Phospholamban Phosphorylation and Promotes Ischemia Reperfusion Injury in the Heart
title_sort sarcoplasmic reticulum localized protein phosphatase regulates phospholamban phosphorylation and promotes ischemia reperfusion injury in the heart
topic PRECLINICAL RESEARCH
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648354/
https://www.ncbi.nlm.nih.gov/pubmed/29057374
http://dx.doi.org/10.1016/j.jacbts.2016.12.002
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