Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain

Marcelle Bergeron, Jeffrey M. Gidday, Y. Yu Aimee, Gregg L Semenza, Donna M. Ferriero, Frank R. Sharp

Research output: Contribution to journalArticle

Abstract

Hypoxia-inducible factor-1 (HIF-1) is a heterodimer composed of HIF-1α and HIF-1β protein subunits. This transcription factor is essential for the activation of hypoxia-inducible genes like erythropoietin, some glucose transporters, the glycolytic enzymes, and vascular endothelial growth factor. Because HIF-1 activation may promote cell survival in hypoxic tissues, we studied the effect of hypoxic preconditioning on HIF-1 expression in neonatal rat brain. Hypoxic preconditioning (8% O2 for 3 hours), a treatment known to protect the newborn rat brain against hypoxic-ischemic injury, markedly increased HIF-1α and HIF-1β expression. To support the role of HIF-1 in protective preconditioning, we also studied the effect of two other known HIF-1 inducers, cobalt chloride (CoCl2) and desferrioxamine (DFX), on HIF-1 expression and neuroprotection in newborn brain. HIF-1α and HIF-1β protein levels were markedly increased after intraperitoneal injection of CoCl2 (60 mg/kg) and moderately increased after intraperitoneal injection of DFX (200 mg/kg) 1 to 3 hours after the injections. Preconditioning with CoCl2 or DFX 24 hours before hypoxia-ischemia afforded 75 and 56% brain protection, respectively, compared with that in vehicle-injected littermate controls. Thus, HIF-1 activation could contribute to protective brain preconditioning, which could be used in high-risk deliveries and other clinical situations.

Original languageEnglish (US)
Pages (from-to)285-296
Number of pages12
JournalAnnals of Neurology
Volume48
Issue number3
DOIs
StatePublished - 2000

Fingerprint

Hypoxia-Inducible Factor 1
Brain
Deferoxamine
Intraperitoneal Injections
Hypoxia
Facilitative Glucose Transport Proteins
Protein Subunits
Erythropoietin
Vascular Endothelial Growth Factor A

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain. / Bergeron, Marcelle; Gidday, Jeffrey M.; Aimee, Y. Yu; Semenza, Gregg L; Ferriero, Donna M.; Sharp, Frank R.

In: Annals of Neurology, Vol. 48, No. 3, 2000, p. 285-296.

Research output: Contribution to journalArticle

Bergeron, Marcelle ; Gidday, Jeffrey M. ; Aimee, Y. Yu ; Semenza, Gregg L ; Ferriero, Donna M. ; Sharp, Frank R. / Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain. In: Annals of Neurology. 2000 ; Vol. 48, No. 3. pp. 285-296.
@article{4dd87a8998a949f3bcb09c3b87e6210e,
title = "Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain",
abstract = "Hypoxia-inducible factor-1 (HIF-1) is a heterodimer composed of HIF-1α and HIF-1β protein subunits. This transcription factor is essential for the activation of hypoxia-inducible genes like erythropoietin, some glucose transporters, the glycolytic enzymes, and vascular endothelial growth factor. Because HIF-1 activation may promote cell survival in hypoxic tissues, we studied the effect of hypoxic preconditioning on HIF-1 expression in neonatal rat brain. Hypoxic preconditioning (8{\%} O2 for 3 hours), a treatment known to protect the newborn rat brain against hypoxic-ischemic injury, markedly increased HIF-1α and HIF-1β expression. To support the role of HIF-1 in protective preconditioning, we also studied the effect of two other known HIF-1 inducers, cobalt chloride (CoCl2) and desferrioxamine (DFX), on HIF-1 expression and neuroprotection in newborn brain. HIF-1α and HIF-1β protein levels were markedly increased after intraperitoneal injection of CoCl2 (60 mg/kg) and moderately increased after intraperitoneal injection of DFX (200 mg/kg) 1 to 3 hours after the injections. Preconditioning with CoCl2 or DFX 24 hours before hypoxia-ischemia afforded 75 and 56{\%} brain protection, respectively, compared with that in vehicle-injected littermate controls. Thus, HIF-1 activation could contribute to protective brain preconditioning, which could be used in high-risk deliveries and other clinical situations.",
author = "Marcelle Bergeron and Gidday, {Jeffrey M.} and Aimee, {Y. Yu} and Semenza, {Gregg L} and Ferriero, {Donna M.} and Sharp, {Frank R.}",
year = "2000",
doi = "10.1002/1531-8249(200009)48:3<285::AID-ANA2>3.0.CO;2-8",
language = "English (US)",
volume = "48",
pages = "285--296",
journal = "Annals of Neurology",
issn = "0364-5134",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - Role of hypoxia-inducible factor-1 in hypoxia-induced ischemic tolerance in neonatal rat brain

AU - Bergeron, Marcelle

AU - Gidday, Jeffrey M.

AU - Aimee, Y. Yu

AU - Semenza, Gregg L

AU - Ferriero, Donna M.

AU - Sharp, Frank R.

PY - 2000

Y1 - 2000

N2 - Hypoxia-inducible factor-1 (HIF-1) is a heterodimer composed of HIF-1α and HIF-1β protein subunits. This transcription factor is essential for the activation of hypoxia-inducible genes like erythropoietin, some glucose transporters, the glycolytic enzymes, and vascular endothelial growth factor. Because HIF-1 activation may promote cell survival in hypoxic tissues, we studied the effect of hypoxic preconditioning on HIF-1 expression in neonatal rat brain. Hypoxic preconditioning (8% O2 for 3 hours), a treatment known to protect the newborn rat brain against hypoxic-ischemic injury, markedly increased HIF-1α and HIF-1β expression. To support the role of HIF-1 in protective preconditioning, we also studied the effect of two other known HIF-1 inducers, cobalt chloride (CoCl2) and desferrioxamine (DFX), on HIF-1 expression and neuroprotection in newborn brain. HIF-1α and HIF-1β protein levels were markedly increased after intraperitoneal injection of CoCl2 (60 mg/kg) and moderately increased after intraperitoneal injection of DFX (200 mg/kg) 1 to 3 hours after the injections. Preconditioning with CoCl2 or DFX 24 hours before hypoxia-ischemia afforded 75 and 56% brain protection, respectively, compared with that in vehicle-injected littermate controls. Thus, HIF-1 activation could contribute to protective brain preconditioning, which could be used in high-risk deliveries and other clinical situations.

AB - Hypoxia-inducible factor-1 (HIF-1) is a heterodimer composed of HIF-1α and HIF-1β protein subunits. This transcription factor is essential for the activation of hypoxia-inducible genes like erythropoietin, some glucose transporters, the glycolytic enzymes, and vascular endothelial growth factor. Because HIF-1 activation may promote cell survival in hypoxic tissues, we studied the effect of hypoxic preconditioning on HIF-1 expression in neonatal rat brain. Hypoxic preconditioning (8% O2 for 3 hours), a treatment known to protect the newborn rat brain against hypoxic-ischemic injury, markedly increased HIF-1α and HIF-1β expression. To support the role of HIF-1 in protective preconditioning, we also studied the effect of two other known HIF-1 inducers, cobalt chloride (CoCl2) and desferrioxamine (DFX), on HIF-1 expression and neuroprotection in newborn brain. HIF-1α and HIF-1β protein levels were markedly increased after intraperitoneal injection of CoCl2 (60 mg/kg) and moderately increased after intraperitoneal injection of DFX (200 mg/kg) 1 to 3 hours after the injections. Preconditioning with CoCl2 or DFX 24 hours before hypoxia-ischemia afforded 75 and 56% brain protection, respectively, compared with that in vehicle-injected littermate controls. Thus, HIF-1 activation could contribute to protective brain preconditioning, which could be used in high-risk deliveries and other clinical situations.

UR - http://www.scopus.com/inward/record.url?scp=0033839757&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033839757&partnerID=8YFLogxK

U2 - 10.1002/1531-8249(200009)48:3<285::AID-ANA2>3.0.CO;2-8

DO - 10.1002/1531-8249(200009)48:3<285::AID-ANA2>3.0.CO;2-8

M3 - Article

VL - 48

SP - 285

EP - 296

JO - Annals of Neurology

JF - Annals of Neurology

SN - 0364-5134

IS - 3

ER -