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 language | English (US) |
|---|---|
| Pages (from-to) | 285-296 |
| Number of pages | 12 |
| Journal | Annals of Neurology |
| Volume | 48 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2000 |
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ASJC Scopus subject areas
- Neuroscience(all)
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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 journal › Article
}
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.
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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 -