Selective inhibition of early-but not late-expressed HIF-1α is neuroprotective in rats after focal ischemic brain damage

Shiu Hwa Yeh, Li Chin Ou, Po Wu Gean, Jan Jong Hung, Wen Chang Chang

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

The expression of hypoxia-inducible factor-1-alpha (HIF-1α) is upregulated in ischemic stroke, but its function is still unclear. In the present study, biphasic expression of HIF-1α was observed during 1-12 h and after 48 h in neurons exposed to ischemic stress in vitro and in vivo. Treating neurons with 2-methoxyestradiol (2ME2) 0.5 h after ischemic stress or pre-silencing HIF-1α with small interfering RNA (siRNA) decreased brain injury, brain edema and number of apoptotic cell, and downregulates Nip-like protein X (Nix) expression. Conversely, applying 2ME2 to neurons 8 h after ischemic stress or silencing the HIF-1α with siRNA 12 h after oxygen-glucose deprivation (OGD) increased neuron damage and decreased vascular endothelial growth factor (VEGF) expression. Taken together, these results demonstrate that HIF-1α induced by ischemia in early and late times leads cellular apoptosis and survival, respectively, and provides a new insight into the divergent roles of HIF-1α expression in neurons after ischemic stroke.

Original languageEnglish
Pages (from-to)249-262
Number of pages14
JournalBrain Pathology
Volume21
Issue number3
DOIs
Publication statusPublished - May 2011
Externally publishedYes

Fingerprint

Hypoxia-Inducible Factor 1
Brain
Neurons
Small Interfering RNA
Stroke
Brain Edema
Brain Injuries
Vascular Endothelial Growth Factor A
Down-Regulation
Ischemia
Cell Count
Apoptosis
Oxygen
Glucose
Proteins

Keywords

  • 2ME2
  • cultured cortical neurons
  • HIF-1
  • MCAO
  • OGD
  • VEGF

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

Selective inhibition of early-but not late-expressed HIF-1α is neuroprotective in rats after focal ischemic brain damage. / Yeh, Shiu Hwa; Ou, Li Chin; Gean, Po Wu; Hung, Jan Jong; Chang, Wen Chang.

In: Brain Pathology, Vol. 21, No. 3, 05.2011, p. 249-262.

Research output: Contribution to journalArticle

Yeh, Shiu Hwa ; Ou, Li Chin ; Gean, Po Wu ; Hung, Jan Jong ; Chang, Wen Chang. / Selective inhibition of early-but not late-expressed HIF-1α is neuroprotective in rats after focal ischemic brain damage. In: Brain Pathology. 2011 ; Vol. 21, No. 3. pp. 249-262.
@article{337a229641e2495681347ede2101c287,
title = "Selective inhibition of early-but not late-expressed HIF-1α is neuroprotective in rats after focal ischemic brain damage",
abstract = "The expression of hypoxia-inducible factor-1-alpha (HIF-1α) is upregulated in ischemic stroke, but its function is still unclear. In the present study, biphasic expression of HIF-1α was observed during 1-12 h and after 48 h in neurons exposed to ischemic stress in vitro and in vivo. Treating neurons with 2-methoxyestradiol (2ME2) 0.5 h after ischemic stress or pre-silencing HIF-1α with small interfering RNA (siRNA) decreased brain injury, brain edema and number of apoptotic cell, and downregulates Nip-like protein X (Nix) expression. Conversely, applying 2ME2 to neurons 8 h after ischemic stress or silencing the HIF-1α with siRNA 12 h after oxygen-glucose deprivation (OGD) increased neuron damage and decreased vascular endothelial growth factor (VEGF) expression. Taken together, these results demonstrate that HIF-1α induced by ischemia in early and late times leads cellular apoptosis and survival, respectively, and provides a new insight into the divergent roles of HIF-1α expression in neurons after ischemic stroke.",
keywords = "2ME2, cultured cortical neurons, HIF-1, MCAO, OGD, VEGF",
author = "Yeh, {Shiu Hwa} and Ou, {Li Chin} and Gean, {Po Wu} and Hung, {Jan Jong} and Chang, {Wen Chang}",
year = "2011",
month = "5",
doi = "10.1111/j.1750-3639.2010.00443.x",
language = "English",
volume = "21",
pages = "249--262",
journal = "Brain Pathology",
issn = "1015-6305",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Selective inhibition of early-but not late-expressed HIF-1α is neuroprotective in rats after focal ischemic brain damage

AU - Yeh, Shiu Hwa

AU - Ou, Li Chin

AU - Gean, Po Wu

AU - Hung, Jan Jong

AU - Chang, Wen Chang

PY - 2011/5

Y1 - 2011/5

N2 - The expression of hypoxia-inducible factor-1-alpha (HIF-1α) is upregulated in ischemic stroke, but its function is still unclear. In the present study, biphasic expression of HIF-1α was observed during 1-12 h and after 48 h in neurons exposed to ischemic stress in vitro and in vivo. Treating neurons with 2-methoxyestradiol (2ME2) 0.5 h after ischemic stress or pre-silencing HIF-1α with small interfering RNA (siRNA) decreased brain injury, brain edema and number of apoptotic cell, and downregulates Nip-like protein X (Nix) expression. Conversely, applying 2ME2 to neurons 8 h after ischemic stress or silencing the HIF-1α with siRNA 12 h after oxygen-glucose deprivation (OGD) increased neuron damage and decreased vascular endothelial growth factor (VEGF) expression. Taken together, these results demonstrate that HIF-1α induced by ischemia in early and late times leads cellular apoptosis and survival, respectively, and provides a new insight into the divergent roles of HIF-1α expression in neurons after ischemic stroke.

AB - The expression of hypoxia-inducible factor-1-alpha (HIF-1α) is upregulated in ischemic stroke, but its function is still unclear. In the present study, biphasic expression of HIF-1α was observed during 1-12 h and after 48 h in neurons exposed to ischemic stress in vitro and in vivo. Treating neurons with 2-methoxyestradiol (2ME2) 0.5 h after ischemic stress or pre-silencing HIF-1α with small interfering RNA (siRNA) decreased brain injury, brain edema and number of apoptotic cell, and downregulates Nip-like protein X (Nix) expression. Conversely, applying 2ME2 to neurons 8 h after ischemic stress or silencing the HIF-1α with siRNA 12 h after oxygen-glucose deprivation (OGD) increased neuron damage and decreased vascular endothelial growth factor (VEGF) expression. Taken together, these results demonstrate that HIF-1α induced by ischemia in early and late times leads cellular apoptosis and survival, respectively, and provides a new insight into the divergent roles of HIF-1α expression in neurons after ischemic stroke.

KW - 2ME2

KW - cultured cortical neurons

KW - HIF-1

KW - MCAO

KW - OGD

KW - VEGF

UR - http://www.scopus.com/inward/record.url?scp=79954594089&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79954594089&partnerID=8YFLogxK

U2 - 10.1111/j.1750-3639.2010.00443.x

DO - 10.1111/j.1750-3639.2010.00443.x

M3 - Article

C2 - 21029239

AN - SCOPUS:79954594089

VL - 21

SP - 249

EP - 262

JO - Brain Pathology

JF - Brain Pathology

SN - 1015-6305

IS - 3

ER -