Active G protein–coupled receptors (GPCR), matrix metalloproteinases 2/9 (MMP2/9), heparin-binding epidermal growth factor (hbEGF), epidermal growth factor receptor (EGFR), erbB2, and insulin-like growth factor 1 receptor (IGF-1R) are necessary for trenbolone acetate–induced alterations in protein turnover rate of fused bovine satellite cell cultures1
Autor: | Michael E White, William R Dayton, E. Kamanga-Sollo, Kara J Thornton |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
TGF alpha Satellite Cells Skeletal Muscle medicine.medical_treatment Biology Protein degradation Receptor IGF Type 1 Receptors G-Protein-Coupled 03 medical and health sciences Insulin-like growth factor Anabolic Agents Growth factor receptor Epidermal growth factor Genetics medicine Animals Humans Growth factor receptor inhibitor ERBB3 Cells Cultured 0402 animal and dairy science Protein turnover 04 agricultural and veterinary sciences General Medicine Genes erbB-2 040201 dairy & animal science Matrix Metalloproteinases Cell biology ErbB Receptors Fibroblast Growth Factors 030104 developmental biology Gene Expression Regulation Biochemistry Cattle Animal Science and Zoology Trenbolone Acetate Food Science |
Zdroj: | Journal of Animal Science. 94:2332-2343 |
ISSN: | 1525-3163 0021-8812 |
Popis: | Trenbolone acetate (TBA), a testosterone analog, increases protein synthesis and decreases protein degradation in fused bovine satellite cell (BSC) cultures. However, the mechanism through which TBA alters these processes remains unknown. Recent studies indicate that androgens improve rate and extent of muscle growth through a nongenomic mechanism involving G protein-coupled receptors (GPCR), matrix metalloproteinases (MMP), heparin-binding epidermal growth factor (hbEGF), the epidermal growth factor receptor (EGFR), erbB2, and the insulin-like growth factor-1 receptor (IGF-1R). We hypothesized that TBA activates GPCR, resulting in activation of MMP2/9 that releases hbEGF, which activates the EGFR and/or erbB2. To determine whether the proposed nongenomic pathway is involved in TBA-mediated alterations in protein turnover, fused BSC cultures were treated with TBA in the presence or absence of inhibitors for GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R, and resultant protein synthesis and degradation rates were analyzed. Assays were replicated at least 9 times for each inhibitor experiment utilizing BSC cultures obtained from at least 3 different steers that had no previous exposure to steroid compounds. As expected, fused BSC cultures treated with 10 n TBA exhibited increased (0.05) protein synthesis rates and decreased (0.05) protein degradation rates when compared to control cultures. Treatment of fused BSC cultures with 10 n TBA in the presence of inhibitors for GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R suppressed (0.05) TBA-mediated increases in protein synthesis rate. Alternatively, inhibition of GPCR, MMP2/9, hbEGF, EGFR, erbB2, or IGF-1R in the presence of 10 n TBA each had no (0.05) effect on TBA-mediated decreases in protein degradation. However, inhibition of both EGFR and erbB2 in the presence of 10 n TBA resulted in decreased (0.05) ability of TBA to decrease protein degradation rate. Additionally, fused BSC cultures treated with 10 n TBA exhibit increased (0.05) pAKT protein levels. These data indicate the TBA-mediated increases in protein synthesis likely involve GPCR, MMP2/9, hbEGF, EGFR, erbB2, and IGF-1R. However, the mechanism through which TBA mediates changes in protein degradation is different and appears to involve only the EGFR and erbB2. Furthermore, it appears the protein kinase B pathway is involved in TBA's effects on fused BSC cultures. |
Databáze: | OpenAIRE |
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