The Selective Estrogen Receptor Modulator Raloxifene Regulates Arginine-Vasopressin Gene Expression in Human Female Neuroblastoma Cells Through G Protein-Coupled Estrogen Receptor and ERK Signaling
| Autor: | Samar Ghorbanpoor, Daniela Grassi, Luis M. Garcia-Segura, Isabel Ruiz-Palmero, Estefania Acaz-Fonseca |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
MAPK/ERK pathway
Selective Estrogen Receptor Modulators Vasopressin medicine.medical_specialty medicine.drug_class MAP Kinase Signaling System Blotting Western Pharmacology Receptors G-Protein-Coupled Neuroblastoma Endocrinology Internal medicine Cell Line Tumor medicine Humans Raloxifene Pyrroles RNA Messenger Phosphorylation Extracellular Signal-Regulated MAP Kinases Protein kinase C Protein Kinase C Kinase Chemistry Reverse Transcriptase Polymerase Chain Reaction Arginine Vasopressin Gene Expression Regulation Neoplastic Receptors Estrogen Selective estrogen receptor modulator Estrogen Raloxifene Hydrochloride Quinazolines Female RNA Interference GPER medicine.drug |
| Zdroj: | Endocrinology. 156(10) |
| ISSN: | 1945-7170 |
| Popis: | The selective estrogen receptor modulator raloxifene reduces blood pressure in hypertensive postmenopausal women. In the present study we have explored whether raloxifene regulates gene expression of arginine vasopressin (AVP), which is involved in the pathogenesis of hypertension. The effect of raloxifene was assessed in human female SH-SY5Y neuroblastoma cells, which have been recently identified as a suitable cellular model to study the estrogenic regulation of AVP. Raloxifene, within a concentration ranging from 10−10M to 10−6M, decreased the mRNA levels of AVP in SH-SY5Y cells with maximal effect at 10−7M. This effect of raloxifene was imitated by an agonist (±)-1-[(3aR*,4S*,9bS*)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl]-ethanone of G protein-coupled estrogen receptor-1 (GPER) and blocked by an antagonist (3aS*,4R*,9bR*)-4-(6-bromo-1,3-benzodioxol-5-yl)-3a,4,5,9b-3H-cyclopenta[c]quinoline of GPER and by GPER silencing. Raloxifene induced a time-dependent increase in the level of phosphorylated ERK1 and ERK2, by a mechanism blocked by the GPER antagonist. The treatment of SH-SY5Y cells with either a MAPK/ERK kinase 1/2-specific inhibitor (1,4-diamino-2, 3-dicyano-1,4-bis(2-aminophenylthio)butadine) or a protein kinase C inhibitor (sotrastaurin) blocked the effects of raloxifene on the phosphorylation of ERK1/2 and the regulation of AVP mRNA levels. These results reveal a mechanism mediating the regulation of AVP expression by raloxifene, involving the activation of GPER, which in turn activates protein kinase C, MAPK/ERK kinase, and ERK. The regulation of AVP by raloxifene and GPER may have implications for the treatment of blood hypertension. |
| Databáze: | OpenAIRE |
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