Neuroprotective effects of erythropoietin against hypoxic injury via modulation of the mitogen-activated protein kinase pathway and apoptosis / 소아과
Korean Journal of Pediatrics
;
: 181-188, 2017.
Artigo
em Inglês
| WPRIM
| ID: wpr-121492
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.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosforilação
/
Fosfotransferases
/
Proteínas Quinases
/
Western Blotting
/
Astrócitos
/
Mortalidade
/
Eritropoetina
/
Apoptose
/
Fármacos Neuroprotetores
/
Hipóxia-Isquemia Encefálica
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Korean Journal of Pediatrics
Ano de publicação:
2017
Tipo de documento:
Artigo
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