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P3‐302: Tau overexpression depressed apoptosis by inhibiting P53 and cytochrome C
Author(s) -
Li Honglian
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1871
Subject(s) - apoptosis , cytochrome c , tau protein , microbiology and biotechnology , caspase , phosphorylation , chemistry , biology , programmed cell death , biochemistry , alzheimer's disease , medicine , disease
Background: Formation of tau inclusions in the brain neurons is one of the hallmarks of Alzheimer’s disease (AD) and related tauopathies. In our previous study, we showed that cells overexpressing tau exhibited marked resistance to apoptosis induced by various apoptotic stimuli (PNAS 2007, 104: 3591-3596). But it is little known how the tau inclusions-bearing neurons not dying of apoptosis but rather degeneration regulate the apoptotic factors, such as P53 and cytochrome C. Methods: we utilized mouse neuroblastoma N2a cells (N2a/wt) and stably expressing wild-type tau (N2a/tau) to study the level of phosphorylated tau, apoptotic rate and the alterations of the related proteins. Results: We found that cells overexpressing tau protein are more resistant to apoptosis induced by apoptotic inducers. The anti-apoptotic effect of tau overexpression involves depression of P53, arrest of cytochrome C release from mitochondrial and inhibition of caspases-9/-3 activity. Inverse staining pattern of hyperphosphorylated tau and activated caspase-3 or fragmented nuclei was observed in cells overexpressing tau. Further studies demonstrated that tau overexpression decreases phosphorylated -catenin, increases -catenin and nuclear translocation of -catenin. Knock down of -catenin antagonized the antiapoptotic effect of tau. Conclusions: These findings reveal an antiapoptotic function of tau which involves P53-mediated pathway and stabilization of -catenin.