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Overexpression of tau proteins antagonizes amyloid-beta-potentiated apoptosis through mitochondria-caspase-3 pathway in N2a cells.
- Source :
-
Journal of Alzheimer's disease : JAD [J Alzheimers Dis] 2010; Vol. 20 (1), pp. 145-57. - Publication Year :
- 2010
-
Abstract
- It has been a puzzle why the tangle-bearing neurons in Alzheimer's disease (AD) brain do not die preferentially of apoptosis even though they are actually challenged by multiple proapoptotic factors. Recently, we have reported that phosphorylation of tau can antagonize apoptosis induced by exogenous apoptotic inducers. Amyloid-beta (Abeta), a recognized endogenous proapoptotic factor, is significantly increased in the AD brains, however, it is not known whether tau could abate the Abeta-potentiated apoptosis. Here, we observed that the cells bearing high level of Abeta were more vulnerable than the controls to H2O2-induced apoptosis, and this effect of Abeta was associated with decrease of Bcl-2, elevation of Bax and cytosolic cytochrome-c, as well as activation of caspase-3, suggesting that Abeta could potentiate the oxidant-induced cell apoptosis with involvement of mitochondria-caspase-3 pathway. More importantly, we also found that expression of tau that became hyperphosphorylated could reduce the Abeta-potentiated apoptosis with simultaneous preservation of Bcl-2 and suppression of Bax, cytosolic cytochrome-c, and caspase-3 activity, implying that overexpression of tau that became hyperphosphorylated can attenuate the Abeta-potentiated cell apoptosis through mitochondria-caspase-3 pathway. These findings provide an explanation of the chronic nature of neurodegeneration of neurons with neurofibrillary pathology of abnormal hyperphosphorylated tau in AD and related tauopathies.
- Subjects :
- Analysis of Variance
Animals
Apoptosis physiology
Cell Line, Tumor
Cell Survival drug effects
Cytochromes c metabolism
Dose-Response Relationship, Drug
Drug Synergism
Enzyme-Linked Immunosorbent Assay methods
Green Fluorescent Proteins genetics
Humans
Hydrogen Peroxide pharmacology
Mice
Neuroblastoma
Peptide Fragments pharmacology
Transfection methods
tau Proteins genetics
Amyloid beta-Peptides pharmacology
Apoptosis drug effects
Caspase 3 metabolism
Signal Transduction drug effects
tau Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1875-8908
- Volume :
- 20
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of Alzheimer's disease : JAD
- Publication Type :
- Academic Journal
- Accession number :
- 20164595
- Full Text :
- https://doi.org/10.3233/JAD-2010-1351