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Title 

EPO receptor-mediated ERK kinase and NF-κB activation in erythropoietin-promoted differentiation of astrocytes

Authors 

S M LeeN T H NgaM H ParkK S KimK J ChoD C MoonH Y KimDo Young YoonJ T Hong

Publisher 

Elsevier

Issue Date 

2004

Citation 

Biochemical and Biophysical Research Communications, vol. 320, no. 4, pp. 1087-1095

Keywords 

astrocytesdifferentiationEPOEPO receptorERKNF-κBerythropoietinerythropoietin receptorglial fibrillary acidic proteinimmunoglobulin enhancer binding protein

Abstract 

Erythropoietin (EPO), a hematopoietic factor, is also required for normal brain development, and its receptor is localized in brain. Therefore, it is possible that EPO could act as a neurotropic factor inducing differentiation of neurons. In the present study, we investigated whether EPO can promote differentiation of neuronal stem cells into astrocytes. In primary culture of cortical neuronal stem cells isolated from post neonatal (Day 1) rat brain, EPO dose (0.1-10U/ml) dependently promoted initiation of morphological differentiation of astrocyte and expression of an astrocyte marker protein, glial fibrillary acidic protein (GFAP). Expression of EPO receptor was also increased during morphological differentiation of astrocytes. EPO-induced increased morphological differentiation of astrocytes and GFAP expression were reduced by treatment with anti-EPO and EPO receptor antibodies. Since our previous study showed that activation of MAPK family and transcription factors is differentially involved in neuronal cell differentiation, we further determined the activation of MAP kinase family and NF-κB during morphological differentiation of astrocytes. Concomitant with the progression of the morphological differentiation of astrocytes, ERK2 but not JNK1 and p38 MAPK as well as NF-κB were activated. However, in the presence of PD98,059, an inhibitor of ERK, and salicylic acid, an NF-κB inhibitor, the EPO-induced morphological differentiation of astrocytes and expression of FGAP and EPO receptor were reduced. Conversely, treatment with anti-EPO and EPO receptor antibodies also reduced EPO-induced ERK2 and NF-κB activation. These data demonstrate that EPO can promote differentiation of neuronal stem cells into astrocytes in an EPO receptor dependent manner, and this effect may be associated with the activation of ERK kinase and NF-κB pathway.

ISSN 

0006-291X

Link 

http://dx.doi.org/10.1016/j.bbrc.2004.06.060

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2017-04-19


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