title: Cytosolic prion protein induces apoptosis in human neuronal cell SH-SY5Y via mitochondrial disruption pathway.
abstract: Different neurodegenerative disorders like prion disease, is caused by protein misfolding conformers. Reverse-transfected cytosolic prion protein (PrP) and PrP expressed in the cytosol have been shown to be neurotoxic. To investigate the possible mechanism of neurotoxicity due to accumulation of PrP in cytosol, a PrP mutant lacking the signal and GPI (CytoPrP) was introduced into the SH-SY5Y cell. MTT and trypan blue assays indicated that the viability of cells expressing CytoPrP was remarkably reduced after treatment of MG-132. Obvious apoptosis phenomena were detected in the cells accumulated with CytoPrP, including loss of mitochondrial transmembrane potential, increase of caspase-3 activity, more annexin V/PI-double positive-stained cells and reduced Bcl-2 level. Moreover, DNA fragmentation and TUNEL assays also revealed clear evidences of late apoptosis in the cells accumulated CytoPrP. These data suggest that the accumulation of CytoPrP in cytoplasm may trigger cell apoptosis, in which mitochondrial relative apoptosis pathway seems to play critical role.
authors: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Ying-Xin Rd 100, Beijing 100052, China.
authors: Xin
authors: X
authors: Wang
authors: Chen-Fang
authors: CF
authors: Dong
authors: Qi
authors: Q
authors: Shi
authors: Song
authors: S
authors: Shi
authors: Gui-Rong
authors: GR
authors: Wang
authors: Yan-Jun
authors: YJ
authors: Lei
authors: Kun
authors: K
authors: Xu
authors: Run
authors: R
authors: An
authors: Jian-Ming
authors: JM
authors: Chen
authors: Hui-Ying
authors: HY
authors: Jiang
authors: Chan
authors: C
authors: Tian
authors: Chen
authors: C
authors: Gao
authors: Yu-Jun
authors: YJ
authors: Zhao
authors: Jun
authors: J
authors: Han
authors: Xiao-Ping
authors: XP
authors: Dong
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011328:Prions / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014162:Transfection
chemical_list: D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D011328:Prions; D019253:Proto-Oncogene Proteins c-bcl-2; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde