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Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation

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An Erratum to this article was published on 07 July 2017

This article has been updated

Abstract

Protein phosphatase 1 (PP1) is a key regulator of important cardiac signaling pathways. Dysregulation of PP1 has been heavily implicated in cardiac dysfunctions. Accordingly, pharmacological targeting of PP1 activity is considered for therapeutic intervention in human cardiomyopathies. Recent evidence from animal models implicated previously unrecognized, isoform-specific activities of PP1 in the healthy and diseased heart. Therefore, this study examined the expression of the distinct PP1 isoforms PP1α, β, and γ in human heart failure (HF) and atrial fibrillation (AF) and addressed the consequences of β-adrenoceptor blocker (beta-blocker) therapy for HF patients with reduced ejection fraction on PP1 isoform expression. Using western blot analysis, we found greater abundance of PP1 isoforms α and γ but unaltered PP1β levels in left ventricular myocardial tissues from HF patients as compared to non-failing controls. However, expression of all three PP1 isoforms was higher in atrial appendages from patients with AF compared to patients with sinus rhythm. Moreover, we found that in human failing ventricles, beta-blocker therapy was associated with lower PP1α abundance and activity, as indicated by higher phosphorylation of the PP1α-specific substrate eIF2α. Greater eIF2α phosphorylation is a known repressor of protein translation, and accordingly, we found lower levels of the endoplasmic reticulum (ER) stress marker Grp78 in the very same samples. We propose that isoform-specific targeting of PP1α activity may be a novel and innovative therapeutic strategy for the treatment of human cardiac diseases by reducing ER stress conditions.

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  • 07 July 2017

    An erratum to this article has been published.

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Author information

Author notes

  1. Silvio Weber and Ali El-Armouche share senior authorship.

Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Medical Faculty, Technische Universität Dresden, Fetscherstraße 74, Dresden, 01307, Germany

    Stefanie Meyer-Roxlau, Simon Lämmle, Annett Opitz, Stephan Künzel, Julius P. Joos, Karolina Sekeres, Kaomei Guan, Silvio Weber & Ali El-Armouche

  2. Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany

    Stefan Neef, Samuel Sossalla & Lars S. Maier

  3. Department of Thoracic and Cardiovascular Surgery, University Medical Centre Goettingen, Göttingen, Germany

    Friedrich Schöndube

  4. Department of Heart Surgery, Dresden University of Technology, Dresden, Germany

    Konstantin Alexiou

  5. Institute of Pharmacology, West German Heart and Vascular Center, University Duisburg-Essen, Essen, Germany

    Dobromir Dobrev

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  1. Stefanie Meyer-Roxlau
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Corresponding authors

Correspondence to Silvio Weber or Ali El-Armouche.

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Funding

This work was supported by DFG Grant EL270/7-1, DZHK (Grant-Nr.: 81X2800134) (to A. E.-A.), the National Institutes of Health (HL131517 to D.D.) and research stipend of the German Society of Cardiology (to S.W.).

Conflict of interest

The authors declare that they have no conflicts of interest with the contents of this article.

Additional information

The original version of this article was revised: The spelling of the author name Samuel Sossalla was incorrect.

An erratum to this article is available at https://doi.org/10.1007/s00395-017-0638-x.

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Meyer-Roxlau, S., Lämmle, S., Opitz, A. et al. Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation. Basic Res Cardiol 112, 43 (2017). https://doi.org/10.1007/s00395-017-0635-0

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