TY - JOUR
T1 - Estrogen and β-amyloid toxicity
T2 - Role of integrin and PI3-K
AU - Bozzo, Chiarella
AU - Graziola, Francesca
AU - Chiocchetti, Annalisa
AU - Canonico, Pier Luigi
N1 - Funding Information:
This work was supported by grants from University of Piemonte Orientale “A. Avogadro” to C.B and P.L.C. and from Fondazione Cavalieri Ottolenghi to C.B.
PY - 2010/10
Y1 - 2010/10
N2 - Β-Amyloid peptide (ΒAP) induces apoptosis and down-regulation of Α1Β1 integrin in neuronal cells, indicating a relationship between ΒAP neurotoxicity and modulation of integrin expression. Estrogen may play a role in protecting women from Alzheimer Disease (AD). It is here reported that both 17Α-estradiol (17βE2) and its non-estrogenic stereoisomer 17Α-estradiol (17ΑE2) rescue neuronal cells from βAP-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 17βE2 protection against βAP-induced apoptosis. 17βE2 up-regulates α1β1 integrin expression and completely abolishes βAP-induced α1β1 down-regulation. Inadequate cell cycle control may contribute to neuronal death in AD βAP induces RA-SK-N-BE cells to enter cell cycle, which remains incomplete. 17αE2 induces βAP-treated cells to complete cell cycle. Our data suggest that estrogen protects from βAP neurotoxicity by restoring integrin expression and cell cycle control.
AB - Β-Amyloid peptide (ΒAP) induces apoptosis and down-regulation of Α1Β1 integrin in neuronal cells, indicating a relationship between ΒAP neurotoxicity and modulation of integrin expression. Estrogen may play a role in protecting women from Alzheimer Disease (AD). It is here reported that both 17Α-estradiol (17βE2) and its non-estrogenic stereoisomer 17Α-estradiol (17ΑE2) rescue neuronal cells from βAP-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 17βE2 protection against βAP-induced apoptosis. 17βE2 up-regulates α1β1 integrin expression and completely abolishes βAP-induced α1β1 down-regulation. Inadequate cell cycle control may contribute to neuronal death in AD βAP induces RA-SK-N-BE cells to enter cell cycle, which remains incomplete. 17αE2 induces βAP-treated cells to complete cell cycle. Our data suggest that estrogen protects from βAP neurotoxicity by restoring integrin expression and cell cycle control.
KW - Alzheimer Disease
KW - Anoikis
KW - Apoptosis
KW - Cell cycle
KW - Human neuroblastoma cell line
KW - Neurodegeneration
UR - https://www.scopus.com/pages/publications/77955768159
U2 - 10.1016/j.mcn.2010.05.012
DO - 10.1016/j.mcn.2010.05.012
M3 - Article
SN - 1044-7431
VL - 45
SP - 85
EP - 91
JO - Molecular and Cellular Neurosciences
JF - Molecular and Cellular Neurosciences
IS - 2
ER -
