Evidence of oxidative stress-induced BNIP3 expression in amyloid beta neurotoxicity

Surong Zhang, Zhengfeng Zhang, Garry Sandhu, Xiuli Ma, Xuefen Yang, Jonathan D. Geiger, Jiming Kong

Research output: Contribution to journalArticle

29 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)221-230
Number of pages10
JournalBrain Research
Volume1138
Issue number1
DOIs
StatePublished - Mar 23 2007

Fingerprint

Amyloid
Hypoxia-Inducible Factor 1
Oxidative Stress
Cell Death
Amyloid Plaques
RNA Interference
Reactive Oxygen Species
Antioxidants
Neurons
Genes

Keywords

  • Alzheimer's disease
  • Amyloid beta
  • BNIP3
  • Mitochondria
  • Neuron
  • Oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Evidence of oxidative stress-induced BNIP3 expression in amyloid beta neurotoxicity. / Zhang, Surong; Zhang, Zhengfeng; Sandhu, Garry; Ma, Xiuli; Yang, Xuefen; Geiger, Jonathan D.; Kong, Jiming.

In: Brain Research, Vol. 1138, No. 1, 23.03.2007, p. 221-230.

Research output: Contribution to journalArticle

Zhang, Surong ; Zhang, Zhengfeng ; Sandhu, Garry ; Ma, Xiuli ; Yang, Xuefen ; Geiger, Jonathan D. ; Kong, Jiming. / Evidence of oxidative stress-induced BNIP3 expression in amyloid beta neurotoxicity. In: Brain Research. 2007 ; Vol. 1138, No. 1. pp. 221-230.
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