Korean J Phys Anthropol.  2005 Dec;18(4):291-301.

Effects of Recombinant EPO on Death of Cortical Neuron in Chronic Hypoxia

• Kim HJ
• Baek JG
• Yang JS
• Kang KY
• Kim KR
• Kim H

Abstract

Chronic hypoxia has been associated with change in neurovascular behavior, mediated, in part, by erythropoietin (EPO). EPO, a hematopoietic growth factor, could act as a neurotrophic factor. In the present study, we investigated the characteristics of EPO and erythropoietin receptor (EPOR) expressions by cortical neuron in vivo and in vitro and tested the hypothesis that EPO serves protective functions under chronic hypoxia. E18, P5 and P7 mice for 3 days and primary cultured neurons for 6 days were incubated in hypoxic conditions consisted of a mixture of 10% O2, 5% CO2, 85% N2. To study expressions of EPO, EPOR, caspases, pAKT, pERK, and PARP, immunohistochemical stainning and western blotting were carried out. In addition to expressing EPO and EPOR under normoxic conditions, neurons increased their expression of EPO and EPOR under hypoxia. The effects of recombinant EPO appeared to be mediated via the phosphatidylinositol (PI) 3- kinase-AKT pathway, correlated directly with activation of caspase 3. Also recombinant EPO decreased expression of caspase 8, but not caspase 9. Finally, recombinant EPO decreased apoptosis of cultured neurons as evaluated by expression of PARP. These data support a role for EPO in maintenance of cortical neuron under chronic hypoxia.

Keyword

Chronic hypoxia; Neuronal cell death; Recombinant EPO; EPOR

MeSH Terms

Animals
Anoxia*
Apoptosis
Blotting, Western
Caspase 3
Caspase 8
Caspase 9
Caspases
Erythropoietin
Mice
Neurons*
Phosphatidylinositols
Receptors, Erythropoietin
Caspase 3
Caspase 8
Caspase 9
Caspases
Erythropoietin
Phosphatidylinositols
Receptors, Erythropoietin