Regulation of T-type Cav3.1 channels expression by synthetic glucocorticoid dexamethasone in neonatal cardiac myocytes
| Autor: | Jean-François Renaud, Elodie Gouadon, Yann Ruchon, Laurent Ferron, Fatima BenMohamed, Véronique Capuano |
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| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Patch-Clamp Techniques Molecular Sequence Data Clinical Biochemistry Biology Dexamethasone Calcium Channels T-Type Hormone Antagonists Receptors Glucocorticoid Glucocorticoid receptor Internal medicine medicine Animals Humans Myocyte Myocytes Cardiac Rats Wistar Glucocorticoids Molecular Biology Gene Messenger RNA Base Sequence NF-kappa B Gene Expression Regulation Developmental Cell Biology General Medicine Transfection Nuclear translocation Rats Mifepristone Endocrinology Animals Newborn hormones hormone substitutes and hormone antagonists Glucocorticoid medicine.drug |
| Zdroj: | Molecular and Cellular Biochemistry. 320 |
| ISSN: | 1573-4919 0300-8177 |
| Popis: | The effect of the dexamethasone (Dex) on the regulation of the T-type Ca(2+) channel expressions was investigated in primary cultures of neonatal rat ventricular myocytes. We found that Dex (1 microM) increases the T-type Ca(2+) current (I(CaT)) associated with an increase in Ca(v)3.1 mRNA amount. We isolated the upstream region from Ca(v)3.1 encoding gene and tested the activity of the promoter in transfected ventricular myocytes. We found a minimal Dex-responsive region that displayed putative glucocorticoid receptor (GR) and nuclear factor kappa-B (NFkappaB) targets. The GR selective antagonist, RU38486 (10 microM), nearly turned off the transcriptional activity of Ca(v)3.1 encoding gene, and an NFkappaB inhibitor, pyrrolodine dithiocarbonate (10 microM), completely abolished the Dex-induced mRNA increase. However, Dex-induced GR and NFkappaB synthesis and nuclear translocation were not timely related to Ca(v)3.1 mRNA increase. These results indicate that both GR and NFkappaB were necessary, but not sufficient, to trigger the increase in Ca(v)3.1 mRNA amount. This study showed the relationship between glucocorticoid and T-type channels up-regulation that may be involved in cardiac development and pathology. |
| Databáze: | OpenAIRE |
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