title: The association between prion proteins and Aβ₁₋₄₂ oligomers in cytotoxicity and apoptosis.
abstract: Misfolding of prion protein (PrP to PrPSc) can cause neurodegenerative prion diseases. As a glycosylphosphatidylinositol (GPI)-anchored membrane protein, the normal form of PrP (PrPC) can function as a receptor for ligands in the extracellular space. PrPC was suggested to be involved in memory, synaptic neuronal communication, and anti-oxidation as a neuroprotective agent. The recently identified interaction between PrPC and Aβ(1-42) oligomers suggested another role for PrP as a receptor for Aβ(1-42) oligomers, thereby influencing cytotoxicity and apoptosis. Here, the association between PrPC and Aβ(1-42) oligomers was investigated by visualizing protein localization in neuronal cells by immunocytochemistry. Aβ(1-42) oligomer-induced cytotoxicity was tested in respective expressions of PrPC by using mouse neuroblastoma-2a (N2a) cells, the prion protein overexpressed cells (L2-2B1), and a Prnp-null mouse hippocampal cell line (HpL 3-4). Moreover, apoptotic proteins such as caspase-8 were used to assess the effect of PrPC on Aβ(1-42) oligomer-mediated apoptosis. In L2-2B1 and HpL 3-4 cells, the difference in the cytotoxicity of Aβ(1-42) oligomers could be clearly distinguished. In addition, Aβ(1-42) oligomers induced mitochondria dysfunction, reactive oxygen species (ROS) generation, and calcium influx PrPC-dependently. Apoptosis, related to mitochondria dysfunction, was further investigated to determine the cytotoxic pathway; the results suggest that PrPC could be involved in both the intrinsic and extrinsic apoptotic pathways. Finally, cells with abundant PrPC expression seemed to be more susceptible to Aβ(1-42) oligomer toxicity, suggesting the importance of the level of PrPC expression in the induction of apoptosis.
authors: Division of Zoonoses, Center for Immunology & Pathology, National Institutes of Health, Korea Centers for Disease Control & Prevention, Osong Health Technology Administration Complex, 187 Osongsaengmyeong2-ro, Gangoe-myeon, Cheongwon-gun, Chungcheongbuk-do 363-951, Republic of Korea.
authors: Jae Wook
authors: JW
authors: Hyeon
authors: Su Yeon
authors: SY
authors: Kim
authors: Jun Sun
authors: JS
authors: Park
authors: Bo Yeong
authors: BY
authors: Choi
authors: Sol Moe
authors: SM
authors: Lee
authors: Young Ran
authors: YR
authors: Ju
authors: Seong Soo A
authors: SS
authors: An
authors: Chi-Kyeong
authors: CK
authors: Kim
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity; D018621:PrPC Proteins / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D018621:PrPC Proteins; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); D053181:Caspase 8; D002118:Calcium