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  • Title: Involvement of beta(1) integrin in betaAP-induced apoptosis in human neuroblastoma cells.
    Author: Bozzo C, Lombardi G, Santoro C, Canonico PL.
    Journal: Mol Cell Neurosci; 2004 Jan; 25(1):1-8. PubMed ID: 14962735.
    Abstract:
    Integrin-mediated cell adhesion is required for cell survival and differentiation. Recently, integrins have been proposed as a target for beta-amyloid peptide (betaAP) neurotoxicity. We report here that treatment with betaAP (1-42) or with the active betaAP fragment (25-35) induced a great deal of apoptosis in SK-N-BE and SH-SY5Y cell lines. In the presence of either collagen I degrees, fibronectin, or laminin, betaAP toxicity was severely reduced. This protective effect seems to be mediated by integrins, because preincubation of neuroblastoma cells with antibodies directed against beta(1) and alpha(1) integrin subunits greatly enhanced betaAP-induced apoptosis. In addition, treatment with betaAP induced a strong reduction of beta(1) and alpha(1) integrin subunits expressed in plasma membrane, which occurred 3 h after treatment, before the appearance of the apoptotic morphology. The rapid downregulation of the alpha(1)beta(1) integrin was almost completely recovered 15-24 h after betaAP treatment and was not prevented by cycloheximide. In conclusion, our data indicate a relationship between betaAP neurotoxicity and modulation of alpha(1)beta(1) integrin expression, and support the hypothesis that aberrant integrin function may play a significant role in betaAP-mediated neurotoxicity.
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