Proteome-wide muscle protein fractional synthesis rates predict muscle mass gain in response to a selective androgen receptor modulator in rats
| Autor: | Stephen A. Stimpson, Todd W. Shearer, Fritz Kramer, Ying Shen, Marc K. Hellerstein, Chelsea King, Po-yin Anne Wong, Mahalakshmi Shankaran, Alan J. Russell, Philip Stewart Turnbull, William J. Evans, Lisa G. Clifton, Scott M. Turner |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Proteome Anabolism Physiology Ovariectomy Endocrinology Diabetes and Metabolism Muscle Proteins 030209 endocrinology & metabolism Mass Spectrometry Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine medicine Animals Muscle Skeletal Chromatography High Pressure Liquid biology Chemistry Creatine Kinase MM Form Skeletal muscle Organ Size Deuterium Rats 030104 developmental biology Endocrinology medicine.anatomical_structure Selective androgen receptor modulator Receptors Androgen Protein Biosynthesis Androgens Body Composition Ovariectomized rat biology.protein Lean body mass Female Creatine kinase Carbonic anhydrase 3 Pyruvate kinase Chromatography Liquid |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 310:E405-E417 |
| ISSN: | 1522-1555 0193-1849 |
| Popis: | Biomarkers of muscle protein synthesis rate could provide early data demonstrating anabolic efficacy for treating muscle-wasting conditions. Androgenic therapies have been shown to increase muscle mass primarily by increasing the rate of muscle protein synthesis. We hypothesized that the synthesis rate of large numbers of individual muscle proteins could serve as early response biomarkers and potentially treatment-specific signaling for predicting the effect of anabolic treatments on muscle mass. Utilizing selective androgen receptor modulator (SARM) treatment in the ovariectomized (OVX) rat, we applied an unbiased, dynamic proteomics approach to measure the fractional synthesis rates (FSR) of 167–201 individual skeletal muscle proteins in triceps, EDL, and soleus. OVX rats treated with a SARM molecule (GSK212A at 0.1, 0.3, or 1 mg/kg) for 10 or 28 days showed significant, dose-related increases in body weight, lean body mass, and individual triceps but not EDL or soleus weights. Thirty-four out of the 94 proteins measured from the triceps of all rats exhibited a significant, dose-related increase in FSR after 10 days of SARM treatment. For several cytoplasmic proteins, including carbonic anhydrase 3, creatine kinase M-type (CK-M), pyruvate kinase, and aldolase-A, a change in 10-day FSR was strongly correlated ( r2 = 0.90–0.99) to the 28-day change in lean body mass and triceps weight gains, suggesting a noninvasive measurement of SARM effects. In summary, FSR of multiple muscle proteins measured by dynamics of moderate- to high-abundance proteins provides early biomarkers of the anabolic response of skeletal muscle to SARM. |
| Databáze: | OpenAIRE |
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