دورية أكاديمية
Intracellular sodium elevation reprograms cardiac metabolism.
| العنوان: | Intracellular sodium elevation reprograms cardiac metabolism. |
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| المؤلفون: | Aksentijević, D, Karlstaedt, A, Basalay, MV, O'Brien, BA, Sanchez-Tatay, D, Eminaga, S, Thakker, A, Tennant, DA, Fuller, W, Eykyn, TR, Taegtmeyer, H, Shattock, MJ |
| سنة النشر: | 2020 |
| المجموعة: | Queen Mary University of London: Queen Mary Research Online (QMRO) |
| مصطلحات موضوعية: | Animals, Cellular Reprogramming, Cytoplasm, Disease Models, Animal, Energy Metabolism, Gene Knock-In Techniques, Heart, Heart Failure, Hypertrophy, Isolated Heart Preparation, Male, Metabolic Diseases, Mice, Inbred C57BL, Knockout, Mitochondria, Myocardium, Rats, Wistar, Sodium, Sodium-Calcium Exchanger, Thiazepines |
| الوصف: | Intracellular Na elevation in the heart is a hallmark of pathologies where both acute and chronic metabolic remodelling occurs. Here, we assess whether acute (75 μM ouabain 100 nM blebbistatin) or chronic myocardial Nai load (PLM3SA mouse) are causally linked to metabolic remodelling and whether the failing heart shares a common Na-mediated metabolic 'fingerprint'. Control (PLMWT), transgenic (PLM3SA), ouabain-treated and hypertrophied Langendorff-perfused mouse hearts are studied by 23Na, 31P, 13C NMR followed by 1H-NMR metabolomic profiling. Elevated Nai leads to common adaptive metabolic alterations preceding energetic impairment: a switch from fatty acid to carbohydrate metabolism and changes in steady-state metabolite concentrations (glycolytic, anaplerotic, Krebs cycle intermediates). Inhibition of mitochondrial Na/Ca exchanger by CGP37157 ameliorates the metabolic changes. In silico modelling indicates altered metabolic fluxes (Krebs cycle, fatty acid, carbohydrate, amino acid metabolism). Prevention of Nai overload or inhibition of Na/Camito may be a new approach to ameliorate metabolic dysregulation in heart failure. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 4337 - ? |
| اللغة: | English |
| العلاقة: | Nat Commun; https://qmro.qmul.ac.uk/xmlui/handle/123456789/65715Test |
| DOI: | 10.1038/s41467-020-18160-x |
| الإتاحة: | https://doi.org/10.1038/s41467-020-18160-xTest https://qmro.qmul.ac.uk/xmlui/handle/123456789/65715Test |
| حقوق: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0Test/. ; © 2020 The Author(s) |
| رقم الانضمام: | edsbas.617B5F76 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-020-18160-x |
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