title: p75(NTR) activation of NF-kappaB 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-kappaB 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-kappaB 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-kappaB SN50 reduced the activation of NF-kappaB and attenuated the apoptotic effect by PrP106-126. This study offers a possible interpretation that NF-kappaB signaling pathway was activated by the interaction of PrP106-126 with p75(NTR), and NF-kappaB activity showed the pro-apoptotic effect in PrP106-126-induced apoptosis in N2a cells. Involvement of NF-kappaB signaling pathway in p75(NTR)-mediated apoptosis may partially account for the PrP106-126-induced neurotoxicity in N2a cells.
authors.affiliation: National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Bai
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Jianmin
authors.initials: J
authors.lastname: Yang
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Yin
authors.forename: Deming
authors.initials: D
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020134:Catalytic Domain / Q000502:physiology; D045744:Cell Line, Tumor; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity*; D010455:Peptides / Q000494:pharmacology; D018620:PrPSc Proteins / Q000378:metabolism; D017096:Prion Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D011328:Prions / Q000378:metabolism / Q000633:toxicity*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000906:Antibodies; D016328:NF-kappa B; D010446:Peptide Fragments; D010455:Peptides; D018620:PrPSc Proteins; D011328:Prions; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; C118258:SN50 peptide; C517634:Ngfr protein, mouse; C082632:prion protein (106-126)