title: Overexpression of BAT3 alleviates prion protein fragment PrP106-126-induced neuronal apoptosis.
abstract: OBJECTIVE
  Prion diseases are a group of infectious neurodegenerative diseases characterized by neuronal death and degeneration. Human leukocyte antigen-B-associated transcript 3 (BAT3) is an important apoptosis regulator. We therefore investigated the interactions between BAT3 and prion protein and the potential role of BAT3 in PrP106-126-induced apoptosis.
  
  
  METHODS
  BAT3 and prion protein were overexpressed in Hela, Neuro2A, or primary neuronal cells by transfection with BAT3-HA or PRNP-EGFP expression plasmids and their relationship studied by immunofluorescence and Western blotting. The effect of BAT3 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
  BAT3 interacted with prion protein and enhanced PrP expression. After PrP106-126 peptide treated, BAT3 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 BAT3, which may be important for the basic regulatory mechanism of neuron survival in prion diseases and associated neurodegenerative diseases in vivo.
authors.affiliation: State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
authors.forename: Zhi-Qi
authors.initials: ZQ
authors.lastname: Song
authors.forename: Li-Feng
authors.initials: LF
authors.lastname: Yang
authors.forename: Yun-Sheng
authors.initials: YS
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Zhu
authors.forename: Xiang-Mei
authors.initials: XM
authors.lastname: Zhou
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Yin
authors.forename: Hong-Qiang
authors.initials: HQ
authors.lastname: Yao
authors.forename: De-Ming
authors.initials: DM
authors.lastname: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D045304:Cytochromes c / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology*; D018621:PrPC Proteins / Q000737:chemistry* / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C484267:Bag6 protein, rat; D010446:Peptide Fragments; D018621:PrPC Proteins; D011506:Proteins; D049452:Green Fluorescent Proteins; D045304:Cytochromes c
keywords: BAT3; Neurodegenerative diseases; Neuronal apoptosis; PrP106-126; Prion diseases