1. Evidence of oxidative stress-induced BNIP3 expression in amyloid beta neurotoxicity
- Author
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Zhang, Surong, Zhang, Zhengfeng, Sandhu, Garry, Ma, Xiuli, Yang, Xuefen, Geiger, Jonathan D., and Kong, Jiming
- Subjects
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OXIDATIVE stress , *AMYLOID beta-protein , *MACROMOLECULES , *CELL death - 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]
- Published
- 2007
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