COX-2 inhibitor reduces skeletal muscle hypertrophy in mice
| Autor: | Margaret L. Novak, Thomas J. McLoughlin, Sierra M. Smith, Troy A. Hornberger, Kunal Balu Sukhija, Timothy J. Koh, William Billich |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Time Factors Physiology Muscle Proteins Inflammation Biology Muscle hypertrophy Mice Muscular Diseases Physiology (medical) Internal medicine medicine Myocyte Animals Insulin-Like Growth Factor I Phosphorylation Muscle Skeletal Protein kinase B Nitrobenzenes Cell Proliferation Sulfonamides SKP Cullin F-Box Protein Ligases Cyclooxygenase 2 Inhibitors Cell growth Macrophages TOR Serine-Threonine Kinases Skeletal muscle Ribosomal Protein S6 Kinases 70-kDa Hypertrophy Urokinase-Type Plasminogen Activator Mice Inbred C57BL Disease Models Animal Phosphotransferases (Alcohol Group Acceptor) Endocrinology medicine.anatomical_structure Cyclooxygenase 2 Exercise and Respiratory Physiology Plantaris muscle medicine.symptom Carrier Proteins Proto-Oncogene Proteins c-akt |
| Zdroj: | American journal of physiology. Regulatory, integrative and comparative physiology. 296(4) |
| ISSN: | 0363-6119 |
| Popis: | Anti-inflammatory strategies are often used to reduce muscle pain and soreness that can result from high-intensity muscular activity. However, studies indicate that components of the acute inflammatory response may be required for muscle repair and growth. The hypothesis of this study was that cyclooxygenase (COX)-2 activity is required for compensatory hypertrophy of skeletal muscle. We used the synergist ablation model of skeletal muscle hypertrophy, along with the specific COX-2 inhibitor NS-398, to investigate the role of COX-2 in overload-induced muscle growth in mice. COX-2 was expressed in plantaris muscles during compensatory hypertrophy and was localized mainly in or near muscle cell nuclei. Treatment with NS-398 blunted the increases in mass and protein content in overloaded muscles compared with vehicle-treated controls. Additionally, the COX-2 inhibitor decreased activity of the urokinase type plasminogen activator, macrophage accumulation, and cell proliferation, all of which are required for hypertrophy after synergist ablation. Expression of insulin-like growth factor-1 and phosphorylation of Akt, mammalian target of rapamycin, and p70S6K were increased following synergist ablation, but were not affected by NS-398. Additionally, expression of atrogin-1 was reduced during hypertrophy, but was also not affected by NS-398. These results demonstrate that COX-2 activity is required for skeletal muscle hypertrophy, possibly through facilitation of extracellular protease activity, macrophage accumulation, and cell proliferation. |
| Databáze: | OpenAIRE |
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