Tribbles 3 regulates protein turnover in mouse skeletal muscle
| Autor: | Laurie J. Goodyear, Ha-Won Jeong, Abigail McConahay, Jamie L. McClellan, Ran Hee Choi, Michael F. Hirshman, Justin P. Hardee, James A. Carson, Ho-Jin Koh |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Cell signaling Biophysics Muscle Proteins P70-S6 Kinase 1 Cell Cycle Proteins Mice Transgenic Protein degradation Biology Biochemistry Ribosomal Protein S6 Kinases 90-kDa Article 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Muscle Skeletal Molecular Biology Protein kinase B PI3K/AKT/mTOR pathway Mice Knockout SKP Cullin F-Box Protein Ligases Forkhead Box Protein O1 TOR Serine-Threonine Kinases Forkhead Box Protein O3 Protein turnover Skeletal muscle Cell Biology Mice Inbred C57BL Protein catabolism 030104 developmental biology medicine.anatomical_structure Endocrinology Protein Biosynthesis Female Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery |
| Zdroj: | Biochemical and biophysical research communications. 493(3) |
| ISSN: | 1090-2104 |
| Popis: | Skeletal muscle atrophy is associated with a disruption in protein turnover involving increased protein degradation and suppressed protein synthesis. Although it has been well studied that the IGF-1/PI3K/Akt pathway plays an essential role in the regulation of the protein turnover, molecule(s) that triggers the change in protein turnover still remains to be elucidated. TRB3 has been shown to inhibit Akt through direct binding. In this study, we hypothesized that TRB3 in mouse skeletal muscle negatively regulates protein turnover via the disruption of Akt and its downstream molecules. Muscle-specific TRB3 transgenic (TRB3TG) mice had decreased muscle mass and fiber size, resulting in impaired muscle function. We also found that protein synthesis rate and signaling molecules, mTOR and S6K1, were significantly reduced in TRB3TG mice, whereas the protein breakdown pathway was significantly activated. In contrast, TRB3 knockout mice showed increased muscle mass and had an increase in protein synthesis rate, but decreases in FoxOs, atrogin-1, and MuRF-1. These findings indicate that TRB3 regulates protein synthesis and breakdown via the Akt/mTOR/FoxO pathways. |
| Databáze: | OpenAIRE |
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