Beta(2)-adrenergic receptor regulates cardiac fibroblast autophagy and collagen degradation
| Autor: | Hernan E. Lara, Rodrigo Troncoso, Guillermo Díaz-Araya, Sergio Lavandero, Miguel Copaja, Constanza Carrillo, Jose Miguel Vicencio, Pablo Aránguiz-Urroz, Jimena Canales |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Agonist
Male LC3 macroautophagy lysosome autophagy LAMP1 medicine.medical_specialty Adrenergic receptor Cardiac fibrosis medicine.drug_class Adrenergic beta-Antagonists Blotting Western Adrenergic Stimulation Biology Tritium Propanolamines Rats Sprague-Dawley chemistry.chemical_compound Norepinephrine Radioligand Assay Microscopy Electron Transmission Beta adrenergic receptor Catecholamine isoproterenol norepinephrine propanolol salbutamol ICI-118 551 dihydroalprenolol Internal medicine medicine Autophagy Animals Receptor Molecular Biology Cells Cultured Heart failure cardiac fibrosis remodeling Dose-Response Relationship Drug Adenine Myocardium Isoproterenol Adrenergic beta-Agonists Fibroblasts medicine.disease Cell biology Rats Endocrinology chemistry Dihydroalprenolol Molecular Medicine Collagen Receptors Adrenergic beta-2 |
| Zdroj: | BIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE Artículos CONICYT CONICYT Chile instacron:CONICYT Biochimica et Biophysica Acta |
| Popis: | Autophagy is a physiological degradative process key to cell survival during nutrient deprivation, cell differentiation and development. It plays a major role in the turnover of damaged macromolecules and organelles, and it has been involved in the pathogenesis of different cardiovascular diseases. Activation of the adrenergic system is commonly associated with cardiac fibrosis and remodeling, and cardiac fibroblasts are key players in these processes. Whether adrenergic stimulation modulates cardiac fibroblast autophagy remains unexplored. In the present study, we aimed at this question and evaluated the effects of b(2)-adrenergic stimulation upon autophagy. Cultured adult rat cardiac fibroblasts were treated with agonists or antagonists of beta-adrenergic receptors (b-AR), and autophagy was assessed by electron microscopy, GFP-LC3 subcellular distribution, and immunowesternblot of endogenous LC3. The predominant expression of b(2)-ARs was determined and characterized by radioligand binding assays using [(3)H]dihydroalprenolol. Both, isoproterenol and norepinephrine (non-selective b-AR agonists), as well as salbutamol (selective b(2)-AR agonist) increased autophagic flux, and these effects were blocked by propanolol (b-AR antagonist), ICI-118,551 (selective b(2)-AR antagonist), 3-methyladenine but not by atenolol (selective b(1)-AR antagonist). The increase in autophagy was correlated with an enhanced degradation of collagen, and this effect was abrogated by the inhibition of autophagic flux. Overall, our data suggest that b(2)-adrenergic stimulation triggers autophagy in cardiac fibroblasts, and that this response could contribute to reduce the deleterious effects of high adrenergic stimulation upon cardiac fibrosis. |
| Databáze: | OpenAIRE |
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