Dehydroepiandrosterone Stimulates Endothelial Proliferation and Angiogenesis through Extracellular Signal-Regulated Kinase 1/2-Mediated Mechanisms
| Autor: | Laurie L. Homan, Lingling Yang, Dongmin Liu, Yiqiang Wang, Mary Iruthayanathan, Yao Wang, Joseph S. Dillon |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Receptors Steroid Endothelium Angiogenesis Dehydroepiandrosterone Neovascularization Physiologic GTP-Binding Protein alpha Subunits Gi-Go Biology Article Endocrinology Cell Movement Cell surface receptor Internal medicine medicine polycyclic compounds Animals Humans Aorta Cells Cultured Cell Proliferation Mitogen-Activated Protein Kinase 1 Mitogen-Activated Protein Kinase 3 Enzyme Activation Endothelial stem cell Chorioallantoic membrane medicine.anatomical_structure Cattle Endothelium Vascular Signal transduction human activities hormones hormone substitutes and hormone antagonists Signal Transduction |
| Popis: | Dehydroepiandrosterone (DHEA) activates a plasma membrane receptor on vascular endothelial cells and phosphorylates ERK 1/2. We hypothesize that ERK1/2-dependent vascular endothelial proliferation underlies part of the beneficial vascular effect of DHEA. DHEA (0.1–10 nm) activated ERK1/2 in bovine aortic endothelial cells (BAECs) by 15 min, causing nuclear translocation of phosphorylated ERK1/2 and phosphorylation of nuclear p90 ribosomal S6 kinase. ERK1/2 phosphorylation was dependent on plasma membrane-initiated activation of Gi/o proteins and the upstream MAPK kinase because the effect was seen with albumin-conjugated DHEA and was blocked by pertussis toxin or PD098059. A 15-min incubation of BAECs with 1 nm DHEA (or albumin-conjugated DHEA) increased endothelial proliferation by 30% at 24 h. This effect was not altered by inhibition of estrogen or androgen receptors or nitric oxide production. There was a similar effect of DHEA to increase endothelial migration. DHEA also increased the formation of primitive capillary tubes of BAECs in vitro in solubilized basement membrane. These rapid DHEA-induced effects were reversed by the inhibition of either Gi/o-proteins or ERK1/2. Additionally, DHEA enhanced angiogenesis in vivo in a chick embryo chorioallantoic membrane assay. These findings indicate that exposure to DHEA, at concentrations found in human blood, causes vascular endothelial proliferation by a plasma membrane-initiated activity that is Gi/o and ERK1/2 dependent. These data, along with previous findings, define an important vascular endothelial cell signaling pathway that is activated by DHEA and suggest that this steroid may play a role in vascular function. |
| Databáze: | OpenAIRE |
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