PMID- 17274962
OWN - NLM
STAT- MEDLINE
DCOM- 20070521
LR  - 20141120
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1138
DP  - 2007 Mar 23
TI  - Evidence of oxidative stress-induced BNIP3 expression in amyloid beta 
      neurotoxicity.
PG  - 221-30
AB  - The formation of Abeta 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 Abeta-induced oxidative stress are known to cause oxidative 
      damage to macromolecules. However, the molecular mechanisms by which 
      Abeta-induced oxidative stress leads to neuronal cell death are not fully 
      understood. Here we show that Abeta-induced oxidative stress activates the 
      pro-death gene BNIP3. Abeta treatment results in mitochondrial dysfunction, 
      accumulation of reactive oxygen species, and subsequent expression of BNIP3 in 
      rat primary cortical neurons. Pretreatment with antioxidants abolished 
      Abeta-induced BNIP3 expression and attenuated cell death, demonstrating the role 
      of oxidative stress in BNIP3 induction. Abeta-induced BNIP3 expression may be 
      mediated by hypoxia-inducible factor-1 (HIF-1) because Abeta-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 Abeta-induced 
      neuronal death. Together, these results suggest a potential pathological role of 
      BNIP3 in the etiology of AD.
FAU - Zhang, Surong
AU  - Zhang S
AD  - Department of Human Anatomy and Cell Science, University of Manitoba Faculty of 
      Medicine, 730 William Avenue, Winnipeg, Manitoba, Canada R3E 0W3.
FAU - Zhang, Zhengfeng
AU  - Zhang Z
FAU - Sandhu, Garry
AU  - Sandhu G
FAU - Ma, Xiuli
AU  - Ma X
FAU - Yang, Xuefen
AU  - Yang X
FAU - Geiger, Jonathan D
AU  - Geiger JD
FAU - Kong, Jiming
AU  - Kong J
LA  - eng
GR  - P20RR017699/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070108
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (BNIP3 protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Membrane Proteins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Neurotoxins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (amyloid beta-protein (25-35))
SB  - IM
MH  - Amyloid beta-Peptides/*pharmacology
MH  - Animals
MH  - Cell Death
MH  - Cells, Cultured
MH  - Cerebral Cortex/drug effects/*metabolism
MH  - Embryo, Mammalian
MH  - Female
MH  - Hypoxia-Inducible Factor 1/metabolism
MH  - Membrane Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - Mitochondria/metabolism
MH  - Mitochondrial Proteins
MH  - Neurons/drug effects
MH  - Neurotoxicity Syndromes/*metabolism/physiopathology
MH  - Neurotoxins/*pharmacology
MH  - *Oxidative Stress
MH  - Peptide Fragments/*pharmacology
MH  - Proto-Oncogene Proteins/antagonists & inhibitors/genetics/*metabolism
MH  - RNA Interference
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2007/02/06 09:00
MHDA- 2007/05/22 09:00
CRDT- 2007/02/06 09:00
PHST- 2006/06/23 00:00 [received]
PHST- 2006/12/25 00:00 [revised]
PHST- 2006/12/27 00:00 [accepted]
PHST- 2007/02/06 09:00 [pubmed]
PHST- 2007/05/22 09:00 [medline]
PHST- 2007/02/06 09:00 [entrez]
AID - S0006-8993(06)03736-X [pii]
AID - 10.1016/j.brainres.2006.12.086 [doi]
PST - ppublish
SO  - Brain Res. 2007 Mar 23;1138:221-30. doi: 10.1016/j.brainres.2006.12.086. Epub 
      2007 Jan 8.