PMID- 15207361
OWN - NLM
STAT- MEDLINE
DCOM- 20040824
LR  - 20161124
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 126
IP  - 2
DP  - 2004
TI  - Protective effect of vitamin E against focal brain ischemia and neuronal death 
      through induction of target genes of hypoxia-inducible factor-1.
PG  - 433-40
AB  - Vitamin E has been shown to have protective effects against cerebral ischemia, 
      possibly due to its anti-oxidant effects. However, its non-anti-oxidant, 
      intracellular molecular mechanism remains elusive. For in vivo experiments in 
      rats, orally administered vitamin E significantly reduced not only the brain 
      infarct volume but also space navigation disability after permanent middle 
      cerebral artery (MCA) occlusion. The level of anti-oxidant after MCA occlusion 
      was significantly increased specifically in the ipsilateral brain tissues of 
      vitamin E-treated rats. For in vitro experiments, posttreatment with vitamin E 
      protected primary cultured neurons from nitric oxide-induced insult. Vitamin E 
      induced the expression of the alpha subunit of hypoxia-inducible factor-1 (HIF-1) 
      and its target genes, including vascular endothelial growth factor (VEGF) and 
      heme oxygenase-1. The hypoxia response element on the VEGF promoter was 
      responsible for this vitamin E-induced transcriptional activation of VEGF gene. 
      Taken together, these results suggest that cerebral infarction increased the 
      permeability of vitamin E across the blood-brain barrier, and this increased 
      vitamin E in brain tissue elicited neuroprotective effects not only through 
      scavenging oxidants, as are previously well reported, but also by transactivating 
      HIF-1-dependent genes, which results in protection of brains from ischemic 
      insults.
CI  - Copyright 2004 IBRO
FAU - Zhang, B
AU  - Zhang B
AD  - Department of Physiology, School of Medicine, Ehime University, Shitsukawa, 
      Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan.
FAU - Tanaka, J
AU  - Tanaka J
FAU - Yang, L
AU  - Yang L
FAU - Yang, L
AU  - Yang L
FAU - Sakanaka, M
AU  - Sakanaka M
FAU - Hata, R
AU  - Hata R
FAU - Maeda, N
AU  - Maeda N
FAU - Mitsuda, N
AU  - Mitsuda N
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Antioxidants)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, rat)
RN  - 1406-18-4 (Vitamin E)
RN  - EC 1.13.- (Oxygenases)
RN  - EC 1.14.14.18 (Heme Oxygenase (Decyclizing))
RN  - EC 1.14.14.18 (Hmox1 protein, rat)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Brain Ischemia/genetics/metabolism/*prevention & control
MH  - Cell Death/drug effects/physiology
MH  - DNA-Binding Proteins/*biosynthesis/genetics
MH  - Dose-Response Relationship, Drug
MH  - Escape Reaction/drug effects/physiology
MH  - Heat-Shock Proteins/*biosynthesis/genetics
MH  - Heme Oxygenase (Decyclizing)
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Male
MH  - Neurons/drug effects/metabolism
MH  - Neuroprotective Agents/pharmacology/therapeutic use
MH  - Nuclear Proteins/*biosynthesis/genetics
MH  - *Oxygenases
MH  - Rats
MH  - Rats, Inbred SHR
MH  - *Transcription Factors
MH  - Vascular Endothelial Growth Factor A/*biosynthesis/genetics
MH  - Vitamin E/pharmacology/*therapeutic use
EDAT- 2004/06/23 05:00
MHDA- 2004/08/25 05:00
CRDT- 2004/06/23 05:00
PHST- 2004/03/22 00:00 [accepted]
PHST- 2004/06/23 05:00 [pubmed]
PHST- 2004/08/25 05:00 [medline]
PHST- 2004/06/23 05:00 [entrez]
AID - S0306452204002246 [pii]
AID - 10.1016/j.neuroscience.2004.03.057 [doi]
PST - ppublish
SO  - Neuroscience. 2004;126(2):433-40. doi: 10.1016/j.neuroscience.2004.03.057.