Meyer-Roxlau, Stefanie and Laemmle, Simon and Opitz, Annett and Kuenzel, Stephan and Joos, Julius P. and Neef, Stefan and Sekeres, Karolina and Sosalla, Samuel T. and Schoendube, Friedrich and Alexiou, Konstantin and Maier, Lars S. and Dobrev, Dobromir and Guan, Kaomei and Weber, Silvio and El-Armouche, Ali (2017) Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation. BASIC RESEARCH IN CARDIOLOGY, 112 (4): 43. ISSN 0300-8428, 1435-1803
Full text not available from this repository. (Request a copy)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 PP1 alpha, beta, and gamma in human heart failure (HF) and atrial fibrillation (AF) and addressed the consequences of beta-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 alpha and gamma but unaltered PP1 beta 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 PP1 alpha abundance and activity, as indicated by higher phosphorylation of the PP1 alpha-specific substrate eIF2 alpha. Greater eIF2 alpha 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 PP1 alpha activity may be a novel and innovative therapeutic strategy for the treatment of human cardiac diseases by reducing ER stress conditions.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOPLASMIC-RETICULUM STRESS; SERINE/THREONINE PHOSPHATASES; CATALYTIC SUBUNITS; HYPERTROPHY; INHIBITION; EXPRESSION; DISEASE; MUSCLE; Protein phosphatase 1 (PP1) isoforms; Human heart failure; Atrial fibrillation; Beta-blocker; Endoplasmic reticulum stress response |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:16 |
| Last Modified: | 18 Feb 2019 15:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/1625 |
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