Activation of angiotensin II type I receptor promotes protein kinase C translocation and cell proliferation in human cultured breast epithelial cells
| Autor: | Antonella Muscella, Simona Greco, M. G. Elia, Paola Salvatore, Santo Marsigliante, Carlo Storelli |
|---|---|
| Přispěvatelé: | S., Greco, Muscella, Antonella, Elia, M. G., Salvatore, P., Storelli, Carlo, Marsigliante, Santo |
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
Angiotensin receptor Indoles Thapsigargin Endocrinology Diabetes and Metabolism Carbazoles Losartan Receptor Angiotensin Type 1 Angiotensin Receptor Antagonists chemistry.chemical_compound Endocrinology Internal medicine medicine Humans Staurosporine Breast Calcium Signaling Enzyme Inhibitors Estrenes Protein Kinase C Protein kinase C Analysis of Variance Receptors Angiotensin Angiotensin II receptor type 1 Phospholipase C Chemistry Angiotensin II Biological Transport Epithelial Cells Pyrrolidinones Enzyme Activation Isoenzymes Type C Phospholipases cardiovascular system Female Cell Division hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | Journal of Endocrinology. 174:205-214 |
| ISSN: | 1479-6805 0022-0795 |
| Popis: | The effect of angiotensin II (Ang II) on Ca(2+) signalling in human primary cultured breast epithelial cells was investigated by using fura-2 as the Ca(2+) probe. Ang II (0.1-1000 nM) induced an intracellular free calcium ([Ca(2+)](i)) transient peak which was unchanged by external Ca(2+ )removal. In Ca(2+)-free medium pretreatment with thapsigargin abolished Ang II-induced Ca(2+ )release. Suppression of 1,4,5-inositol trisphosphate formation by U73122, a phospholipase C inhibitor, blocked the Ang II-induced Ca(2+) response. Losartan (DuP753), an inhibitor of Ang II type I receptor (AT1), decreased the [Ca(2+)](i) increase evoked by Ang II, while CGP4221A, an inhibitor of Ang II type II receptor (AT2) did not. AT1 desensitisation was demonstrated with respect to the Ca(2+) response after subsequent exposure of cells to Ang II and also after pretreatment for 25 min with 1000 nM phorbol 12-myristate 13-acetate. Staurosporine, an inhibitor of protein kinases C (PKC), inhibited the AT1 desensitisation. Epithelial breast cells expressed PKC-alpha, -beta1, -delta and -zeta isozymes, and Ang II provoked translocation from the cytosol to the membranes of PKC-alpha, -beta1, and -delta (but not -zeta). Ang II was also able to stimulate cell proliferation in a dose-dependent manner; this effect was blocked by Go 6976, a specific inhibitor of PKC-alpha and -beta1, the Ca(2+)-dependent isozymes. The main conclusion of this study is that the the Ang II signalling mechanism in breast epithelial cells is based on the elevation of [Ca(2+)](i )released from intracellular stores through AT1 activation. In addition, Ang II stimulates cell proliferation by the activation of PKC isozymes. |
| Databáze: | OpenAIRE |
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