Myostatin Regulates Cardiomyocyte Growth Through Modulation of Akt Signaling
| Autor: | Godfrina McKoy, Takashi Matsui, Mikhail S. Novikov, Ling Li, Gavin Brooks, Anthony Rosenzweig, Noboru Ashida, Michael R. Morissette, Shi-Yin Foo, Stuart A. Cook, Marielle Scherrer-Crosbie |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Physiology Myostatin p38 Mitogen-Activated Protein Kinases Article Muscle hypertrophy Rats Sprague-Dawley Mice Phenylephrine Downregulation and upregulation Transforming Growth Factor beta Internal medicine Genetic model medicine Animals Myocytes Cardiac Phosphorylation Protein kinase B Cells Cultured Mice Knockout biology Myocardium Transforming growth factor beta musculoskeletal system Rats Endocrinology biology.protein Signal transduction Cardiology and Cardiovascular Medicine Adrenergic alpha-Agonists Proto-Oncogene Proteins c-akt Cell Division Signal Transduction medicine.drug |
| Zdroj: | Circulation Research. 99:15-24 |
| ISSN: | 1524-4571 0009-7330 |
| Popis: | Myostatin is a highly conserved, potent negative regulator of skeletal muscle hypertrophy in many species, from rodents to humans, although its mechanisms of action are incompletely understood. Transcript profiling of hearts from a genetic model of cardiac hypertrophy revealed dramatic upregulation of myostatin, not previously recognized to play a role in the heart. Here we show that myostatin abrogates the cardiomyocyte growth response to phenylephrine in vitro through inhibition of p38 and the serine-threonine kinase Akt, a critical determinant of cell size in many species from drosophila to mammals. Evaluation of male myostatin-null mice revealed that their cardiomyocytes and hearts overall were slightly smaller at baseline than littermate controls but exhibited more exuberant growth in response to chronic phenylephrine infusion. The increased cardiac growth in myostatin-null mice corresponded with increased p38 phosphorylation and Akt activation in vivo after phenylephrine treatment. Together, these data demonstrate that myostatin is dynamically regulated in the heart and acts more broadly than previously appreciated to regulate growth of multiple types of striated muscle. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|