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Effects of Recombinant EPO on Death of Cortical Neuron inChronic Hypoxia

김호정 1 백진기 2 양성준 2 강기영 2 김강련 2 Hyun Kim 3

1관동대학교
2한양대학교
3부산대학교

Candidate

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.

Citation status

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