Regulation of the Proapoptotic Factor FOXO1 (FKHR) in Cardiomyocytes by Growth Factors and α1-Adrenergic Agonists
| Autor: | Huy Huynh, James B. Morris, Bronwyn Kenney, Elizabeth A. Woodcock |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
endocrine system
medicine.medical_specialty Heart Ventricles medicine.medical_treatment Cell Culture Techniques Apoptosis Nerve Tissue Proteins FOXO1 Biology Rats Sprague-Dawley Dephosphorylation Phenylephrine Endocrinology Epidermal growth factor Internal medicine medicine Animals Phosphorylation Growth Substances Protein kinase A Protein kinase B Muscle Cells Epidermal Growth Factor Myocardium Growth factor Forkhead Transcription Factors Heart Rats DNA-Binding Proteins Animals Newborn Gene Expression Regulation Cancer research Signal transduction Adrenergic alpha-Agonists hormones hormone substitutes and hormone antagonists |
| Zdroj: | Endocrinology. 146:4370-4376 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2005-0162 |
| Popis: | Apoptotic responses in cardiomyocytes are opposed by the protein kinase Akt (protein kinase B) and thus can be suppressed by a number of growth factors and cytokines. In some cell types, Akt phosphorylates and inactivates members of the forkhead box (FOXO) family of transcription factors that are active in regulating the expression of proapoptotic cytokines and signaling intermediates. In the current study, we investigated the possibility that FOXO1 (FKHR) was expressed, regulated, and functional in cardiomyocytes. Addition of epidermal growth factor (EGF) (10 nm) to neonatal rat cardiomyocytes caused rapid phosphorylation of Akt and slower FOXO1 phosphorylation. In contrast, the α1-adrenergic receptor agonist phenylephrine (50 μm) did not phosphorylate Akt and caused dephosphorylation of FOXO1 acutely and increased FOXO1 expression with chronic exposure. Phenylephrine, but not EGF, caused nuclear translocation of FOXO1, a response that is associated with dephosphorylation. Overexpression of FOXO1 activated transcription of the proapoptotic cytokine, TNFα-related apoptosis-inducing ligand, as indicated by reporter gene activity. This response was enhanced by phenylephrine and inhibited by EGF. FOXO1 is expressed, regulated, and functionally active in cardiomyocytes and thus may contribute to apoptotic responses in heart. |
| Databáze: | OpenAIRE |
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