title: Erythropoietin exerts cell protective effect by activating PI3K/Akt and MAPK pathways in C6 Cells.
abstract: Even though erythropoietin (EPO) is a neurotropic cytokine that is recognized widely for its role in the development, maintenance, protection, and repair of the nervous system, there are few reports concerning EPO-mediated influences on the glial cells in the central nervous system. In this study, we investigated anti-inflammatory and anti-apoptotic effects of EPO on C6 glioma cells (C6 cells). Erythropoietin did not attenuate inflammatory response, such as nitrite production, iNOS gene expression, and pro-inflammatory cytokines when LPS/TNF-alpha mixture was treated. However, EPO increased C6 cell viability by exerting cell protective effect against staurosporine stimulation. Erythropoietin increased the transient Akt expression at 30 minutes and induced the gradual elevation of ERK1/2 and p38 expression as time progressed. The cell protective effect of EPO was also significantly attenuated with pretreatment of specific PI3K, pERK1/2, or pP38 inhibitor. In summary, these results suggest that EPO may exert its cell protective functions via the direct cell protective activity rather than via its anti-inflammatory effect. Moreover, the PI3K/Akt and mitogen activated protein kinase (MAPK) pathways may be responsible for cell survival against cytotoxicity.
authors: Min-Soo
authors: MS
authors: Kwon
authors: Mi-Hee
authors: MH
authors: Kim
authors: Seon-Hee
authors: SH
authors: Kim
authors: Ki-Dae
authors: KD
authors: Park
authors: Si-Hyung
authors: SH
authors: Yoo
authors: Il-Ung
authors: IU
authors: Oh
authors: Suenie
authors: S
authors: Pak
authors: Young-Jun
authors: YJ
authors: Seo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival; D004921:Erythropoietin / Q000378:metabolism / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D004921:Erythropoietin; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: Anti-inflammation,; C6 cells,; Cell protection,; Erythropoietin,; Signal pathway