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KMID : 0624620090420070444
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BMB Reports
2009 Volume.42 No. 7 p.444 ~ p.449
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Cytosolic prion protein induces apoptosis in human neuronal cell SH-SY5Y via mitochondrial disruption pathway
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Wang Xin
Dong Chen-Fang
Shi Qi
Shi Song
Wang Gui-Rong
Xu Kun
An Run
Chen Jian-Ming
Jiang Hui-Ying
Tian Chan
Gao Chen
Han Jun
Dong Xiao-Ping
Zhao Yu-Jun
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Abstract
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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.
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KEYWORD
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Apoptosis, CytoPrP, Cytotoxicity, Prion, Proteasome
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