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| Subject Categories: Signal Transduction | Cellular Metabolism |
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| The EMBO Journal
(2008) 27, 350–360, doi:10.1038/sj.emboj.7601952 Published online 20 December 2007 |
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| Cooperative control of striated muscle mass and metabolism by MuRF1 and MuRF2 EMBO Open |
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| Christian C Witt1, 3, Stephanie H Witt1, 3, Stefanie Lerche1, Dietmar Labeit1, Walter Back2 and Siegfried Labeit1 |
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1 Institute of Anesthesiology and Intensive Care, Universitätsklinikum Mannheim, Mannheim, Germany 2 Institute of Pathology, Universitätsklinikum Mannheim, Mannheim, Germany To whom correspondence should be addressed Siegfried Labeit, Institute of Anesthesiology and Intensive Care, University Clinic Mannheim, Theodor-Kutzer-Ufer 1-3, Mannheim 68167, Germany. Tel.: +49 621 383 1626; Fax: +49 621 383 1971; E-mail: siegfried.labeit@anaes.ma.uni-heidelberg.de 3 These authors equally contributed to the work Received 2 June 2007; Accepted 15 November 2007; Published online 20 December 2007. |
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| Abstract |
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| The muscle-specific RING finger proteins MuRF1 and MuRF2 have been proposed to regulate protein degradation and gene expression in muscle tissues. We have tested the in vivo roles of MuRF1 and MuRF2 for muscle metabolism by using knockout (KO) mouse models. Single MuRF1 and MuRF2 KO mice are healthy and have normal muscles. Double knockout (dKO) mice obtained by the inactivation of all four MuRF1 and MuRF2 alleles developed extreme cardiac and milder skeletal muscle hypertrophy. Muscle hypertrophy in dKO mice was maintained throughout the murine life span and was associated with chronically activated muscle protein synthesis. During ageing (months 4–18), skeletal muscle mass remained stable, whereas body fat content did not increase in dKO mice as compared with wild-type controls. Other catabolic factors such as MAFbox/atrogin1 were expressed at normal levels and did not respond to or prevent muscle hypertrophy in dKO mice. Thus, combined inhibition of MuRF1/MuRF2 could provide a potent strategy to stimulate striated muscles anabolically and to protect muscles from sarcopenia during ageing. |
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| Keywords: muscle hypertrophy and atrophy, striated muscle, ubiquitin ligases MuRF1 and MuRF2, Z-disks |
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