Kwon Min-Soo, Kim Mi-Hee, Kim Seon-Hee, Park Ki-Dae, Yoo Si-Hyung, Oh Il-Ung, Pak Suenie, Seo Young-Jun
Neurol Res. 2014 Mar;36(3):215-23. doi: 10.1179/1743132813Y.0000000284.
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.
尽管促红细胞生成素（EPO）是一种神经营养细胞因子，因其在神经系统发育、维持、保护和修复中的作用而被广泛认可，但关于EPO对中枢神经系统胶质细胞影响的报道却很少。在本研究中，我们研究了EPO对C6胶质瘤细胞（C6细胞）的抗炎和抗凋亡作用。当用脂多糖/肿瘤坏死因子-α混合物处理时，促红细胞生成素并未减弱炎症反应，如亚硝酸盐产生、诱导型一氧化氮合酶基因表达和促炎细胞因子。然而，EPO通过对星形孢菌素刺激发挥细胞保护作用来提高C6细胞活力。促红细胞生成素在30分钟时增加瞬时Akt表达，并随着时间的推移诱导ERK1/2和p38表达逐渐升高。用特异性磷脂酰肌醇-3激酶（PI3K）、磷酸化ERK1/2或磷酸化p38抑制剂预处理后，EPO的细胞保护作用也显著减弱。总之，这些结果表明，EPO可能通过直接的细胞保护活性而非抗炎作用发挥其细胞保护功能。此外，PI3K/Akt和丝裂原活化蛋白激酶（MAPK）途径可能负责细胞抵抗细胞毒性的存活。
