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Neuroprotective effects of erythropoietin against hypoxic injury via modulation of the mitogen-activated protein kinase pathway and apoptosis

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Author(s)
Ji Eun JeongJae Hyun ParkChun Soo KimSang Lak LeeHai Lee ChungWoo Taek KimEun JooLee
Keimyung Author(s)
Kim, Chun SooPark, Jae HyunLee, Sang Lak
Department
Dept. of Pediatrics (소아청소년학)
Journal Title
Korean Journal of Pediatrics
Issued Date
2017
Volume
60
Issue
6
Keyword
ErythropoietinApoptosisMitogen-activated protein kinasesBrain hypoxia-ischemiaNeuroprotection
Abstract
Purpose: Hypoxic-ischemic encephalopathy is a significant cause of neonatal morbidity and mortality.
Erythropoietin (EPO) is emerging as a therapeutic candidate for neuroprotection. Therefore, this study
was designed to determine the neuroprotective role of recombinant human EPO (rHuEPO) and the
possible mechanisms by which mitogen-activated protein kinase (MAPK) signaling pathway including
extracellular signal-regulated kinase (ERK1/2), JNK, and p38 MAPK is modulated in cultured cortical
neuronal cells and astrocytes.
Methods: Primary neuronal cells and astrocytes were prepared from cortices of ICR mouse embryos
and divided into the normoxic, hypoxia (H), and hypoxia-pretreated with EPO (H+EPO) groups. The
phosphorylation of MAPK pathway was quantified using western blot, and the apoptosis was assessed
by caspase-3 measurement and terminal deoxynucleotidyl transferase dUTP nick end labeling assay.
Results: All MAPK pathway signals were activated by hypoxia in the neuronal cells and astrocytes
(P<0.05). In the neuronal cells, phosphorylation of ERK-1/-2 and apoptosis were significantly decreased
in the H+EPO group at 15 hours after hypoxia (P<0.05). In the astrocytes, phosphorylation of ERK-1/-2,
p38 MAPK, and apoptosis was reduced in the H+EPO group at 15 hours after hypoxia (P<0.05).
Conclusion: Pretreatment with rHuEPO exerts neuroprotective effects against hypoxic injury reducing
apoptosis by caspase-dependent mechanisms. Pathologic, persistent ERK activation after hypoxic injury
may be attenuateed by pretreatment with EPO supporting that EPO may regulate apoptosis by affecting
ERK pathways.
Keimyung Author(s)(Kor)
김천수
박재현
이상락
Publisher
School of Medicine
Citation
Ji Eun Jeong et al. (2017). Neuroprotective effects of erythropoietin against hypoxic injury via modulation of the mitogen-activated protein kinase pathway and apoptosis. Korean Journal of Pediatrics, 60(6), 181–188. doi: 10.3345/kjp.2017.60.6.181
Type
Article
ISSN
1738-1061
DOI
10.3345/kjp.2017.60.6.181
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/32511
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Pediatrics (소아청소년학)
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