Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation
| العنوان: | Differential regulation of protein phosphatase 1 (PP1) isoforms in human heart failure and atrial fibrillation |
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| المؤلفون: | Lars S. Maier, Stefan Neef, Kaomei Guan, Julius P. Joos, Silvio Weber, Ali El-Armouche, Simon Lämmle, Friedrich A. Schöndube, Samuel Sossalla, Annett Opitz, Konstantin Alexiou, Karolina Sekeres, Dobromir Dobrev, Stefanie Meyer-Roxlau, Stephan R Künzel |
| المصدر: | Basic Research in Cardiology. 112 |
| بيانات النشر: | Springer Science and Business Media LLC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Physiology, Eukaryotic Initiation Factor-2, Medizin, 030204 cardiovascular system & hematology, Ventricular Function, Left, Substrate Specificity, 0302 clinical medicine, Heart Rate, Protein Phosphatase 1, Atrial Fibrillation, Sinus rhythm, Phosphorylation, Endoplasmic Reticulum Chaperone BiP, Heat-Shock Proteins, Aged, 80 and over, Ejection fraction, medicine.diagnostic_test, Atrial fibrillation, Middle Aged, Endoplasmic Reticulum Stress, Isoenzymes, Female, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, Heart Ventricles, Adrenergic beta-Antagonists, macromolecular substances, Biology, Transfection, 03 medical and health sciences, Western blot, Physiology (medical), Internal medicine, medicine, Humans, Heart Atria, Aged, Heart Failure, Myocardium, Stroke Volume, Protein phosphatase 1, medicine.disease, HEK293 Cells, 030104 developmental biology, Endocrinology, Case-Control Studies, Heart failure, Unfolded protein response |
| الوصف: | 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. |
| تدمد: | 1435-1803 0300-8428 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::78868f14a38122e74f003039bb57b26eTest https://doi.org/10.1007/s00395-017-0635-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....78868f14a38122e74f003039bb57b26e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14351803 03008428 |
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