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- W2078014268 abstract "Neurofibrillary tangles (NFTs) in the brain neurons is one of the pathological hallmarks of Alzheimer's disease (AD) and related tauopathies. It is little known why the NFTs-bearing neurons do not die of apoptosis but rather degeneration even though they are constantly exposed to viarious apoptotic stimuli in the brains of patients with AD and related tauopathies. To reveal the effect of tau protein on the anti-apoptosis of NFTs-bearing neurons and the mechanisms. Neuroblastoma 2a (N2a) cells were transiently transfected with tau or its vector as a control, and treated with staurosporine, an apoptosis inducer, after transfection for 48 hours. Apoptosis was assayed using an Annexin V- Propidium Iodide (PI) staining kit by following the manufacture's procedure and apoptotic rate was automatically quantified by flow cytometry with the standardized program of the instrument. Double- or triple-labeling immunofluorescence showed the staining pattern of overexpressed EGFP-tau or hyperphosphorylated tau and activated caspase-3 or fragmented nuclei. Western blotting was used to observed the related proteins level. Here we report that cells overexpressing tau protein are more resistant to apoptosis induced by staurosporine. Inverse staining pattern of overexpressed EGFP-tau or hyperphosphorylated tau and activated caspase-3 or fragmented nuclei was observed in cells overexpressing tau, suggesting that tau's anti-apoptotic effect involves its hyperphosphorylation. Furthermore, tau overexpression decreases the phosphorylation of p53 at Ser33 site and p53 level, arrests release of cytochrome C from mitochondrial and inhibits activity of caspases-9/-3. In addition, tau overexpression decreases phosphorylated β-catenin, increases β-catenin and nuclear translocation of β-catenin. Knock down of β-catenin antagonized the antiapoptotic effect of tau. These findings together reveal an anti-apoptotic function of tau which involves hyperphosphorylation of tau, p53-mediated pathway and stabilization of β-catenin." @default.
- W2078014268 created "2016-06-24" @default.
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- W2078014268 date "2008-07-01" @default.
- W2078014268 modified "2023-09-27" @default.
- W2078014268 title "P2-156: Tau overexpression inhibits apoptosis induced by staurosporine and the underlying mechanisms" @default.
- W2078014268 doi "https://doi.org/10.1016/j.jalz.2008.05.1230" @default.
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