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Evidence of oxidative stress-induced BNIP3 expression in amyloid beta neurotoxicity
- Source :
-
Brain Research . Mar2007, Vol. 1138, p221-230. 10p. - Publication Year :
- 2007
-
Abstract
- Abstract: The formation of Aβ and its subsequent deposition in senile plaques are considered to be initial events that lead to a cascade of pathological changes in AD. Mediators of Aβ-induced oxidative stress are known to cause oxidative damage to macromolecules. However, the molecular mechanisms by which Aβ-induced oxidative stress leads to neuronal cell death are not fully understood. Here we show that Aβ-induced oxidative stress activates the pro-death gene BNIP3. Aβ treatment results in mitochondrial dysfunction, accumulation of reactive oxygen species, and subsequent expression of BNIP3 in rat primary cortical neurons. Pretreatment with antioxidants abolished Aβ-induced BNIP3 expression and attenuated cell death, demonstrating the role of oxidative stress in BNIP3 induction. Aβ-induced BNIP3 expression may be mediated by hypoxia-inducible factor-1 (HIF-1) because Aβ-treatment induced accumulation and nuclear translocation of HIF-1 and knock-down of HIF-1 by RNAi inhibited BNIP3 expression. Finally, knockdown of BNIP3 reduced Aβ-induced neuronal death. Together, these results suggest a potential pathological role of BNIP3 in the etiology of AD. [Copyright &y& Elsevier]
- Subjects :
- *OXIDATIVE stress
*AMYLOID beta-protein
*MACROMOLECULES
*CELL death
Subjects
Details
- Language :
- English
- ISSN :
- 00068993
- Volume :
- 1138
- Database :
- Academic Search Index
- Journal :
- Brain Research
- Publication Type :
- Academic Journal
- Accession number :
- 24191861
- Full Text :
- https://doi.org/10.1016/j.brainres.2006.12.086