Abstract
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 α 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.
| Original language | English |
|---|---|
| Pages (from-to) | 433-440 |
| Number of pages | 8 |
| Journal | Neuroscience |
| Volume | 126 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 28-06-2004 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
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Protective effect of vitamin E against focal brain ischemia and neuronal death through induction of target genes of hypoxia-inducible factor-1. / Zhang, B.; Tanaka, J.; Yang, L.; Yang, L.; Sakanaka, M.; Hata, R.; Maeda, N.; Mitsuda, N.
In: Neuroscience, Vol. 126, No. 2, 28.06.2004, p. 433-440.Research output: Contribution to journal › Article
TY - JOUR
T1 - Protective effect of vitamin E against focal brain ischemia and neuronal death through induction of target genes of hypoxia-inducible factor-1
AU - Zhang, B.
AU - Tanaka, J.
AU - Yang, L.
AU - Yang, L.
AU - Sakanaka, M.
AU - Hata, R.
AU - Maeda, N.
AU - Mitsuda, N.
PY - 2004/6/28
Y1 - 2004/6/28
N2 - 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 α 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.
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 α 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.
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U2 - 10.1016/j.neuroscience.2004.03.057
DO - 10.1016/j.neuroscience.2004.03.057
M3 - Article
VL - 126
SP - 433
EP - 440
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
IS - 2
ER -