Estrogen and beta-amyloid toxicity: role of integrin and PI3-K
| Autor: | Annalisa Chiocchetti, Chiarella Bozzo, Pier Luigi Canonico, Francesca Graziola |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
MAPK/ERK pathway
medicine.drug_class Integrin Estrogen receptor Down-Regulation Apoptosis Biology Integrin alpha1beta1 Cellular and Molecular Neuroscience Phosphatidylinositol 3-Kinases Cell Line Tumor medicine Humans Molecular Biology Protein kinase B Phosphoinositide-3 Kinase Inhibitors Neurons Amyloid beta-Peptides Estradiol Kinase Cell Biology Cell cycle Protein-Tyrosine Kinases Cell biology Up-Regulation Receptors Estrogen Estrogen Cytoprotection biology.protein Mitogen-Activated Protein Kinases Tyrosine kinase |
| Zdroj: | Molecular and cellular neurosciences. 45(2) |
| ISSN: | 1095-9327 |
| Popis: | Beta-amyloid peptide (betaAP) induces apoptosis and down-regulation of alpha(1)beta(1) integrin in neuronal cells, indicating a relationship between betaAP neurotoxicity and modulation of integrin expression. Estrogen may play a role in protecting women from Alzheimer Disease (AD). It is here reported that both 17beta-estradiol (17betaE(2)) and its non-estrogenic stereoisomer 17alpha-estradiol (17alphaE(2)) rescue neuronal cells from betaAP-induced apoptosis. As cellular model, the human neuroblastoma cell line SK-N-BE was used, which responds to retinoic acid by growth arrest and differentiation toward the neuronal phenotype (RA-SK-N-BE). Estrogen receptor antagonist does not hinder estrogen protection. Inhibition of phosphatidylinositol 3-kinase (PI3-K), but not of tyrosine kinases or mitogen-activated protein kinases (MAPK) blocks 17betaE(2) protection against betaAP-induced apoptosis. 17betaE(2) up-regulates alpha(1)beta(1) integrin expression and completely abolishes betaAP-induced alpha(1)beta(1) down-regulation. Inadequate cell cycle control may contribute to neuronal death in AD. betaAP induces RA-SK-N-BE cells to enter cell cycle, which remains incomplete. 17betaE(2) induces betaAP-treated cells to complete cell cycle. Our data suggest that estrogen protects from betaAP neurotoxicity by restoring integrin expression and cell cycle control. |
| Databáze: | OpenAIRE |
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