Overexpression of BAT 3 Alleviates Prion Protein Fragment PrP106‐126‐Induced Neuronal Apoptosis

摘要

Summary Backgrounds and aims Prion diseases are a group of infectious neurodegenerative diseases characterized by neuronal death and degeneration. Human leukocyte antigen‐B‐associated transcript 3 ( BAT 3) is an important apoptosis regulator. We therefore investigated the interactions between BAT 3 and prion protein and the potential role of BAT 3 in PrP106‐126‐induced apoptosis. Methods BAT 3 and prion protein were overexpressed in Hela, Neuro2A, or primary neuronal cells by transfection with BAT 3‐ HA or PRNP ‐ EGFP expression plasmids and their relationship studied by immunofluorescence and Western blotting. The effect of BAT 3 on PrP106‐126‐induced cytotoxicity and apoptosis was detected by the CCK ‐8 assay and terminal‐deoxynucleotidyl transferase‐mediated nick end labeling ( TUNEL ) assay. The expression of cytochrome c and Bcl‐2 was examined by Western blotting. Results BAT 3 interacted with prion protein and enhanced PrP expression. After PrP106‐126 peptide treated, BAT 3 was transported from the nucleus to cytoplasm, increased cell viability, and protected neurons from PrP106‐126‐induced apoptosis through stabilizing the level of Bcl‐2 protein and inhibiting the release of cytochrome c to cytoplasm. Conclusions Our present data showed a novel molecular mechanism of PrP106‐126‐induced apoptotic process regulation through the overexpression of BAT 3, which may be important for the basic regulatory mechanism of neuron survival in prion diseases and associated neurodegenerative diseases in vivo .