Involvement of β₁ integrin in βAP-induced apoptosis in human neuroblastoma cells

Integrin-mediated cell adhesion is required for cell survival and differentiation. Recently, integrins have been proposed as a target for β-amyloid peptide (βAP) neurotoxicity. We report here that treatment with βAP (1-42) or with the active βAP 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°, fibronectin, or laminin, βAP toxicity was severely reduced. This protective effect seems to be mediated by integrins, because preincubation of neuroblastoma cells with antibodies directed against β₁ and α₁ integrin subunits greatly enhanced βAP-induced apoptosis. In addition, treatment with βAP induced a strong reduction of β₁ and α₁ integrin subunits expressed in plasma membrane, which occurred 3 h after treatment, before the appearance of the apoptotic morphology. The rapid downregulation of the α₁β₁ integrin was almost completely recovered 15-24 h after βAP treatment and was not prevented by cycloheximide. In conclusion, our data indicate a relationship between βAP neurotoxicity and modulation of α₁β₁ integrin expression, and support the hypothesis that aberrant integrin function may play a significant role in βAP-mediated neurotoxicity.