Neuroprotective effects of erythropoietin against hypoxic injury via modulation of the mitogen-activated protein kinase pathway and apoptosis
- Author(s)
- Ji Eun Jeong; Jae Hyun Park; Chun Soo Kim; Sang Lak Lee; Hai Lee Chung; Woo Taek Kim; Eun JooLee
- Keimyung Author(s)
- Kim, Chun Soo; Park, Jae Hyun; Lee, Sang Lak
- Department
- Dept. of Pediatrics (소아청소년학)
- Journal Title
- Korean Journal of Pediatrics
- Issued Date
- 2017
- Volume
- 60
- Issue
- 6
- Keyword
- Erythropoietin; Apoptosis; Mitogen-activated protein kinases; Brain hypoxia-ischemia; Neuroprotection
- 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.
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