Estrogen, Heat Shock Proteins, and NFκB in Human Vascular Endothelium
| Autor: | Sanjiv Gupta, Anne A Knowlton, Karyn L. Hamilton, Fiona N. Mbai |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty Endothelium medicine.drug_class Electrophoretic Mobility Shift Assay HSP72 Heat-Shock Proteins Regulatory Sequences Nucleic Acid Biology Transfection Binding Competitive Heat Shock Transcription Factors Internal medicine Heat shock protein Consensus Sequence medicine Humans Transcription factor Heat-Shock Proteins Estradiol Estrogen Antagonists NF-kappa B Endothelial Cells Hypoxia (medical) Coronary Vessels Cytoprotection Cell Hypoxia DNA-Binding Proteins Heat shock factor Tamoxifen Endocrinology medicine.anatomical_structure Gene Expression Regulation Estrogen Female Endothelium Vascular medicine.symptom Cardiology and Cardiovascular Medicine hormones hormone substitutes and hormone antagonists Transcription Factors medicine.drug |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 24:1628-1633 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.0000137188.76195.fb |
| Popis: | We hypothesized that estrogen would increase HSP72 in human coronary artery endothelial cells (HCAEC), and that these would be more sensitive to estrogen than our previous observations in myocytes.HCAEC were treated with 17beta-estradiol or tamoxifen, ranging from physiological to pharmacological(1 nM to 10 micromol/L) for either 24 hours (early) or 7 days (chronic). HSP expression was assessed by Western blots. Both early and chronic 17beta-estradiol and tamoxifen increased HSP72. Electromobility shift assays (EMSA) showed activation of HSF-1 with early, but not chronic, 17beta-estradiol. 17beta-Estradiol activated NFkappaB within 10 minutes, and the ER-alpha selective inhibitor, ICI 182 780, abolished this effect. Transcription factor decoys containing the heat shock element blocked HSP72 induction. Estrogen pretreatment decreased lactate dehydrogenase release with hypoxia. This protective effect persisted despite blockade of HSF-1 by decoys. However, an NF-kappaB decoy prevented the increase in HSP72 and abolished the estrogen-associated protection during hypoxia.17beta-Estradiol upregulates HSP72 early and chronically via different mechanisms in HCAEC, and provides cytoprotection during hypoxia, independent of HSP72 induction. NF-kappaB mediates the early increase in HSP72, suggesting that estrogen activates NF-kappaB via a nongenomic, receptor-dependent mechanism, and this leads to activation of HSF-1. Activation of NF-kappaB was critical for estrogen-associated protection. Further studies are needed to elucidate the involved signaling pathways. We hypothesized that estrogen would increase HSP72 in human coronary artery endothelial cells (HCAEC). Both early and chronic treatment increased HSP72. EMSA showed activation of HSF-1 with early, but not chronic, 17beta-estradiol. Transcription factor decoys blocked estrogen-related HSP72 induction. Estrogen decreased LDH release with hypoxia. An NF-kappaB decoy blocked the HSP72 increase and estrogen-associated protection. |
| Databáze: | OpenAIRE |
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