Desmin Knock-Out Cardiomyopathy: A Heart on the Verge of Metabolic Crisis
| العنوان: | Desmin Knock-Out Cardiomyopathy: A Heart on the Verge of Metabolic Crisis |
|---|---|
| المؤلفون: | Barbara Elsnicova, Daniela Hornikova, Veronika Tibenska, David Kolar, Tereza Tlapakova, Benjamin Schmid, Markus Mallek, Britta Eggers, Ursula Schlötzer-Schrehardt, Viktoriya Peeva, Carolin Berwanger, Bettina Eberhard, Hacer Durmuş, Dorothea Schultheis, Christian Holtzhausen, Karin Schork, Katrin Marcus, Jens Jordan, Thomas Lücke, Peter F. M. van der Ven, Rolf Schröder, Christoph S. Clemen, Jitka M. Zurmanova |
| المصدر: | International Journal of Molecular Sciences; Volume 23; Issue 19; Pages: 12020 International Journal of Molecular Sciences [online] 23(19), nestránkováno. (2022) |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Proteomics, Creatine Kinase, Mitochondrial Form, desmin, desminopathy, cardiomyopathy, mitochondriopathy, desmin knock-out metabolism, glucose, fatty acid, amino acid, creatine kinase, mitochondria, Oxidative Phosphorylation, Catalysis, Desmin, Inorganic Chemistry, Mice, Hexokinase, Animals, Citrates, ddc:610, Amino Acids, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy, Mice, Knockout, Glucose Transporter Type 1, Myocardium, Fatty Acids, Organic Chemistry, General Medicine, Computer Science Applications, Glucose, Cardiomyopathies |
| الوصف: | Desmin mutations cause familial and sporadic cardiomyopathies. In addition to perturbing the contractile apparatus, both desmin deficiency and mutated desmin negatively impact mitochondria. Impaired myocardial metabolism secondary to mitochondrial defects could conceivably exacerbate cardiac contractile dysfunction. We performed metabolic myocardial phenotyping in left ventricular cardiac muscle tissue in desmin knock-out mice. Our analyses revealed decreased mitochondrial number, ultrastructural mitochondrial defects, and impaired mitochondria-related metabolic pathways including fatty acid transport, activation, and catabolism. Glucose transporter 1 and hexokinase-1 expression and hexokinase activity were increased. While mitochondrial creatine kinase expression was reduced, fetal creatine kinase expression was increased. Proteomic analysis revealed reduced expression of proteins involved in electron transport mainly of complexes I and II, oxidative phosphorylation, citrate cycle, beta-oxidation including auxiliary pathways, amino acid catabolism, and redox reactions and oxidative stress. Thus, desmin deficiency elicits a secondary cardiac mitochondriopathy with severely impaired oxidative phosphorylation and fatty and amino acid metabolism. Increased glucose utilization and fetal creatine kinase upregulation likely portray attempts to maintain myocardial energy supply. It may be prudent to avoid medications worsening mitochondrial function and other metabolic stressors. Therapeutic interventions for mitochondriopathies might also improve the metabolic condition in desmin deficient hearts. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d19ad60d1d81ab8fb4764ce8cf6e21b7Test https://opus4.kobv.de/opus4-fau/frontdoor/index/index/docId/20790Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d19ad60d1d81ab8fb4764ce8cf6e21b7 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |