The Nuclear Receptor, Nor-1, Induces the Physiological Responses Associated With Exercise
| Autor: | Shu-Ching M. Wang, Zewen K. Tuong, Emily Shao, Joel M. Goode, Tae Gyu Oh, George E.O. Muscat, Michael A. Pearen |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Muscle tissue Receptors Steroid medicine.medical_specialty Transgene Neovascularization Physiologic Mice Transgenic Nerve Tissue Proteins mTORC1 Mechanistic Target of Rapamycin Complex 1 Biology Models Biological Cell Line Muscle hypertrophy 03 medical and health sciences 0302 clinical medicine Endocrinology Physical Conditioning Animal Internal medicine Autophagy medicine Animals RNA Messenger Muscle Skeletal Molecular Biology Original Research Sirolimus Receptors Thyroid Hormone Calcineurin Autophagosomes Skeletal muscle Hypertrophy General Medicine DNA-Binding Proteins Mice Inbred C57BL Phenotype 030104 developmental biology medicine.anatomical_structure Autophagy Protein 5 Calcium Signal transduction Lysosomes Microtubule-Associated Proteins 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Molecular Endocrinology. 30:660-676 |
| ISSN: | 1944-9917 0888-8809 |
| Popis: | Skeletal muscle remodels metabolic capacity, contractile and exercise phenotype in response to physiological demands. This adaptive remodeling response to physical activity can ameliorate/prevent diseases associated with poor diet and lifestyle. Our previous work demonstrated that skeletal muscle-specific transgenic expression of the neuron-derived orphan nuclear receptor, Nor-1 drives muscle reprogramming, improves exercise endurance, and oxidative metabolism. The current manuscript investigates the association between exercise, Nor-1 expression and the role of Nor-1 in adaptive remodeling. We demonstrate that Nor-1 expression is induced by exercise and is dependent on calcium/calcineurin signaling (in vitro and in vivo). Analysis of fatigue-resistant transgenic mice that express Nor-1 in skeletal muscle revealed increased hypertrophy and vascularization of muscle tissue. Moreover, we demonstrate that transgenic Nor-1 expression is associated with increased intracellular recycling, ie, autophagy, involving 1) increased expression of light chain 3A or LC3A-II, autophagy protein 5, and autophagy protein 12 in quadriceps femoris muscle extracts from Tg-Nor-1 (relative to Wild-type (WT) littermates); 2) decreased p62 expression indicative of increased autophagolysosome assembly; and 3) decreased mammalian target of rapamycin complex 1 activity. Transfection of LC3A-GFP-RFP chimeric plasmid demonstrated that autophagolysosome formation was significantly increased by Nor-1 expression. Furthermore, we demonstrated a single bout of exercise induced LC3A-II expression in skeletal muscle from C57BL/6 WT mice. This study, when combined with our previous studies, demonstrates that Nor-1 expression drives multiple physiological changes/pathways that are critical to the beneficial responses of muscle to exercise and provides insights into potential pharmacological manipulation of muscle reprogramming for the treatment of lifestyle induced chronic diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|