P75 NTR activation of NF-κB is involved in PrP106-126-induced apoptosis in mouse neuroblastoma cells

Abstract

Neuronal death is a pathological hallmark of prion diseases. Synthetic prion peptide PrP106-126 can convert PrP C into protease-resistant aggregates, which can cause neurotoxicity in vivo and in vitro. Various cell surface proteins can participate in the infection process of prions. p75 NTR can interact with PrP106-126 and has a neurotoxic effect on neurons. However, for p75 NTR lacking intrinsic catalytic activity domain in cytoplasm, p75 NTR -associated signaling molecular and the signaling events in cytoplasm in p75 NTR-mediated apoptosis responding to PrP106-126 remain still unknown. Thus p75 NTR -associated NF-κB signaling pathway was investigated in this study. Herein PrP106-126-induced apoptosis in mouse neuroblastoma cell line N2a, PrP106-126 significantly up-regulated p75 NTR expression on mRNA and protein levels. For the first time we found that PrP106-126 induced activation of NF-κB by Western blot assay, and blocking the interaction of p75 NTR with PrP106-126 by p75 NTR polyclonal antibody sc-6189 or pretreatment with inhibitor NF-κB SN50 reduced the activation of NF-κB and attenuated the apoptotic effect by PrP106-126. This study offers a possible interpretation that NF-κB signaling pathway was activated by the interaction of PrP106-126 with p75 NTR, and NF-κB activity showed the pro-apoptotic effect in PrP106-126-induced apoptosis in N2a cells. Involvement of NF-κB signaling pathway in p75 NTR-mediated apoptosis may partially account for the PrP106-126-induced neurotoxicity in N2a cells.