| First Author | Hyeon JW | Year | 2012 |
| Journal | Biochem Biophys Res Commun | Volume | 424 |
| Issue | 2 | Pages | 214-20 |
| PubMed ID | 22743555 | Mgi Jnum | J:186249 |
| Mgi Id | MGI:5431262 | Doi | 10.1016/j.bbrc.2012.06.056 |
| Citation | Hyeon JW, et al. (2012) The association between prion proteins and Abeta(1-42) oligomers in cytotoxicity and apoptosis. Biochem Biophys Res Commun 424(2):214-20 |
| abstractText | 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 Abeta(1-42) oligomers suggested another role for PrP as a receptor for Abeta(1-42) oligomers, thereby influencing cytotoxicity and apoptosis. Here, the association between PrPC and Abeta(1-42) oligomers was investigated by visualizing protein localization in neuronal cells by immunocytochemistry. Abeta(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 Abeta(1-42) oligomer-mediated apoptosis. In L2-2B1 and HpL 3-4 cells, the difference in the cytotoxicity of Abeta(1-42) oligomers could be clearly distinguished. In addition, Abeta(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 Abeta(1-42) oligomer toxicity, suggesting the importance of the level of PrPC expression in the induction of apoptosis. |
