Lewczuk P, Hasselblatt M, Kamrowski-Kruck H, Heyer A, Unzicker C, Sirén A L, Ehrenreich H
Department of Neurology, George-August-University, Goettingen, Germany.
Neuroreport. 2000 Nov 9;11(16):3485-8. doi: 10.1097/00001756-200011090-00017.
The potential of erythropoietin (EPO) to reduce hypoxia-induced cell death has been investigated in 5-day-old primary cultures of rat postnatal hippocampal neurons. Application of EPO (100 pM) at the start of hypoxia resulted in a significant reduction of neuronal death (33.0 +/- 7.5% in cells incubated with EPO vs 56.75 +/- 7.3% in non-treated cells; n = 4, p < 0.021). Similiar results were obtained upon application of cycloheximide (CHX; 1 microM) simultaneously with hypoxia (34.75 +/- 5.6% vs 56.75 +/- 7.3% with and without CHX, respectively, n = 4, p < 0.035), indicating that hypoxia-induced neuronal death is an active, protein synthesis-dependent process. Both, EPO and EPO receptor (EPOR) were found to be expressed after hypoxia in hippocampal neurons in vitro and in vivo. These results demonstrate for the first time that EPO can reverse hypoxia-induced neuronal death when applied simultaneously with the hypoxic stimulus.
在出生5天的大鼠海马神经元原代培养物中，研究了促红细胞生成素（EPO）减少缺氧诱导的细胞死亡的潜力。在缺氧开始时应用EPO（100 pM）可显著减少神经元死亡（与未处理细胞的56.75 +/- 7.3%相比，用EPO孵育的细胞中为33.0 +/- 7.5%；n = 4，p < 0.021）。在与缺氧同时应用放线菌酮（CHX；1 microM）时也获得了类似的结果（分别为34.75 +/- 5.6%和56.75 +/- 7.3%，有和没有CHX；n = 4，p < 0.035），表明缺氧诱导的神经元死亡是一个活跃的、蛋白质合成依赖性过程。在体外和体内的海马神经元缺氧后，均发现EPO和EPO受体（EPOR）表达。这些结果首次证明，当与缺氧刺激同时应用时，EPO可以逆转缺氧诱导的神经元死亡。
