Expression of MuRF1 or MuRF2 is essential for the induction of skeletal muscle atrophy and dysfunction in a murine pulmonary hypertension model
Abstract Background Pulmonary hypertension leads to right ventricular heart failure and ultimately to cardiac cachexia. Cardiac cachexia induces skeletal muscles atrophy and contractile dysfunction. MAFbx and MuRF1 are two key proteins that have been implicated in chronic muscle atrophy of several w...
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| Format: | Article |
| Language: | English |
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BMC
2020-04-01
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| Series: | Skeletal Muscle |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13395-020-00229-2 |
| _version_ | 1818904229973065728 |
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| author | Thanh Nguyen T. Scott Bowen Antje Augstein Antje Schauer Alexander Gasch Axel Linke Siegfried Labeit Volker Adams |
| author_facet | Thanh Nguyen T. Scott Bowen Antje Augstein Antje Schauer Alexander Gasch Axel Linke Siegfried Labeit Volker Adams |
| author_sort | Thanh Nguyen |
| collection | DOAJ |
| description | Abstract Background Pulmonary hypertension leads to right ventricular heart failure and ultimately to cardiac cachexia. Cardiac cachexia induces skeletal muscles atrophy and contractile dysfunction. MAFbx and MuRF1 are two key proteins that have been implicated in chronic muscle atrophy of several wasting states. Methods Monocrotaline (MCT) was injected over eight weeks into mice to establish pulmonary hypertension as a murine model for cardiac cachexia. The effects on skeletal muscle atrophy, myofiber force, and selected muscle proteins were evaluated in wild-type (WT), MuRF1, and MuRF2-KO mice by determining muscle weights, in vitro muscle force and enzyme activities in soleus and tibialis anterior (TA) muscle. Results In WT, MCT treatment induced wasting of soleus and TA mass, loss of myofiber force, and depletion of citrate synthase (CS), creatine kinase (CK), and malate dehydrogenase (MDH) (all key metabolic enzymes). This suggests that the murine MCT model is useful to mimic peripheral myopathies as found in human cardiac cachexia. In MuRF1 and MuRF2-KO mice, soleus and TA muscles were protected from atrophy, contractile dysfunction, while metabolic enzymes were not lowered in MuRF1 or MuRF2-KO mice. Furthermore, MuRF2 expression was lower in MuRF1KO mice when compared to C57BL/6 mice. Conclusions In addition to MuRF1, inactivation of MuRF2 also provides a potent protection from peripheral myopathy in cardiac cachexia. The protection of metabolic enzymes in both MuRF1KO and MuRF2KO mice as well as the dependence of MuRF2 expression on MuRF1 suggests intimate relationships between MuRF1 and MuRF2 during muscle atrophy signaling. |
| first_indexed | 2024-12-19T21:04:08Z |
| format | Article |
| id | doaj.art-8999eed3249244529adcbce514dc50b8 |
| institution | Directory Open Access Journal |
| issn | 2044-5040 |
| language | English |
| last_indexed | 2024-12-19T21:04:08Z |
| publishDate | 2020-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Skeletal Muscle |
| spelling | doaj.art-8999eed3249244529adcbce514dc50b82022-12-21T20:05:42ZengBMCSkeletal Muscle2044-50402020-04-0110111010.1186/s13395-020-00229-2Expression of MuRF1 or MuRF2 is essential for the induction of skeletal muscle atrophy and dysfunction in a murine pulmonary hypertension modelThanh Nguyen0T. Scott Bowen1Antje Augstein2Antje Schauer3Alexander Gasch4Axel Linke5Siegfried Labeit6Volker Adams7University Clinic of Cardiology, Heart Center LeipzigSchool of Biomedical Sciences, University of LeedsLaboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center DresdenLaboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center DresdenMedical Faculty Mannheim, University of HeidelbergLaboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center DresdenMedical Faculty Mannheim, University of HeidelbergLaboratory of Molecular and Experimental Cardiology, TU Dresden, Heart Center DresdenAbstract Background Pulmonary hypertension leads to right ventricular heart failure and ultimately to cardiac cachexia. Cardiac cachexia induces skeletal muscles atrophy and contractile dysfunction. MAFbx and MuRF1 are two key proteins that have been implicated in chronic muscle atrophy of several wasting states. Methods Monocrotaline (MCT) was injected over eight weeks into mice to establish pulmonary hypertension as a murine model for cardiac cachexia. The effects on skeletal muscle atrophy, myofiber force, and selected muscle proteins were evaluated in wild-type (WT), MuRF1, and MuRF2-KO mice by determining muscle weights, in vitro muscle force and enzyme activities in soleus and tibialis anterior (TA) muscle. Results In WT, MCT treatment induced wasting of soleus and TA mass, loss of myofiber force, and depletion of citrate synthase (CS), creatine kinase (CK), and malate dehydrogenase (MDH) (all key metabolic enzymes). This suggests that the murine MCT model is useful to mimic peripheral myopathies as found in human cardiac cachexia. In MuRF1 and MuRF2-KO mice, soleus and TA muscles were protected from atrophy, contractile dysfunction, while metabolic enzymes were not lowered in MuRF1 or MuRF2-KO mice. Furthermore, MuRF2 expression was lower in MuRF1KO mice when compared to C57BL/6 mice. Conclusions In addition to MuRF1, inactivation of MuRF2 also provides a potent protection from peripheral myopathy in cardiac cachexia. The protection of metabolic enzymes in both MuRF1KO and MuRF2KO mice as well as the dependence of MuRF2 expression on MuRF1 suggests intimate relationships between MuRF1 and MuRF2 during muscle atrophy signaling.http://link.springer.com/article/10.1186/s13395-020-00229-2Cardiac cachexiaPulmonary hypertensionMuscle atrophyMyofibrillar proteinsMuRF1 and MuRF2Muscle energy metabolism |
| spellingShingle | Thanh Nguyen T. Scott Bowen Antje Augstein Antje Schauer Alexander Gasch Axel Linke Siegfried Labeit Volker Adams Expression of MuRF1 or MuRF2 is essential for the induction of skeletal muscle atrophy and dysfunction in a murine pulmonary hypertension model Skeletal Muscle Cardiac cachexia Pulmonary hypertension Muscle atrophy Myofibrillar proteins MuRF1 and MuRF2 Muscle energy metabolism |
| title | Expression of MuRF1 or MuRF2 is essential for the induction of skeletal muscle atrophy and dysfunction in a murine pulmonary hypertension model |
| title_full | Expression of MuRF1 or MuRF2 is essential for the induction of skeletal muscle atrophy and dysfunction in a murine pulmonary hypertension model |
| title_fullStr | Expression of MuRF1 or MuRF2 is essential for the induction of skeletal muscle atrophy and dysfunction in a murine pulmonary hypertension model |
| title_full_unstemmed | Expression of MuRF1 or MuRF2 is essential for the induction of skeletal muscle atrophy and dysfunction in a murine pulmonary hypertension model |
| title_short | Expression of MuRF1 or MuRF2 is essential for the induction of skeletal muscle atrophy and dysfunction in a murine pulmonary hypertension model |
| title_sort | expression of murf1 or murf2 is essential for the induction of skeletal muscle atrophy and dysfunction in a murine pulmonary hypertension model |
| topic | Cardiac cachexia Pulmonary hypertension Muscle atrophy Myofibrillar proteins MuRF1 and MuRF2 Muscle energy metabolism |
| url | http://link.springer.com/article/10.1186/s13395-020-00229-2 |
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