Calcineurin mediates the angiotensin II-induced aldosterone synthesis in the adrenal glands by up-regulation of transcription of the CYP11B2 gene
| Autor: | Jin Zhang, Toshiyuki Yamashiro, Hideaki Kuge, Koichi Honke |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Aldosterone synthase
medicine.medical_specialty Transcription Genetic Calcineurin Inhibitors Biology Biochemistry Gene Expression Regulation Enzymologic Cell Line chemistry.chemical_compound Genes Reporter Internal medicine Adrenal Glands medicine Animals Cytochrome P-450 CYP11B2 Humans Luciferase RNA Messenger Enzyme Inhibitors Molecular Biology Aldosterone Adrenal gland Angiotensin II Calcineurin General Medicine Molecular biology Rats Up-Regulation Enzyme Activation medicine.anatomical_structure Endocrinology chemistry Zona glomerulosa biology.protein Signal transduction |
| Zdroj: | Journal of biochemistry. 148(1) |
| ISSN: | 1756-2651 |
| Popis: | Aldosterone synthesis in the zona glomerulosa of the adrenal gland is catalysed by aldosterone synthase (CYP11B2). The CYP11B2 expression is induced by angiotensin II (Ang II), mediated by increase of intracellular Ca 2+ level. Since calcineurin (CN) is an important mediator activated by Ca 2+ , we investigated the issue of whether CN is involved in the Ang II-induced CYP11B2 expression in human adrenocortical H295R cells. First, CN inhibitors, cyclosporine A (CysA) and tacrolimus (FK506) inhibited the Ang II-induced elevation of CYP11B2 mRNA level. Second, enforced expression of a constitutively active CN increased the CYP11B2 mRNA level. Third, depletion of CN by siRNA technique blocked the Ang II-induced elevation of CYP11B2 mRNA level. Fourth, in reporter assays using a luciferase gene connected to a 5′-flanking region (from −134 to +43 bp) of the hCYP11B2 gene, both CysA and FK506 inhibited the Ang II-mediated up-regulation of luciferase activity. Finally, activation of CN in living H295R cells following the Ang II treatment was confirmed using a fluorescence resonance energy transfer-based sensor. Taken together, we conclude that CN mediates the Ang II-induced aldosterone synthesis through up-regulation of the CYP11B2 transcription. |
| Databáze: | OpenAIRE |
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