Erythropoietin prevents PC12 cells from beta-amyloid-induced apoptosis via PI3K？Akt pathway

The protective effect of Epo was studied in differentiated PC12 cells treated with Abeta. The viability of the cells, the apoptosis of the cells and the level of Bax, Bcl-2, cleaved caspase-3 and cleaved PARP expression were detected by MTT, Hoechst 33258 staining and Western blotting respectively.20 μM Abeta (25-35) could induce a decreased viability and a increased apoptosis in PC12 cell in a time-dependent manner. However, 20 μM Abeta (35-25) had no effect on cell viability and apoptosis. Western blot analysis also showed that Abeta(25-35) treatment could decrease the expression of Bcl-2 (P < 0.05) and increase the expression of Bax (P < 0.05), Cleaved casapase-3 (P < 0.05), and Cleaved PARP (P < 0.05). The pretreatment of Epo could effectively reverse all the above changes induced by Abeta(25-35) (P < 0.05). Furthermore, the protective effect of Epo could be blocked by PI3K inhibitor LY294002 (P < 0.05).Epo prevented cell injuries in PC12 cells exposed to the Abeta(25-35) and this effect may depend on the PI3K？Akt pathway. Our study provided an important evidence for the potential application of Epo in the therapy of Alzheimer's disease.Apoptosis is a particular type of programmed cell death controlled by precise intrinsic genetic programme in order to regulate cell population. Among the mechanisms of cell death, apoptosis has been proposed to explain the cell loss observed in many neurodegenerative disorders including Alzheimer's disease (AD) [1-3]. AD is a neurodegenerative disorder of the central nervous system (CNS), which correlate with the appearance of neurofibrillary tangles (NFTs) and senile plaques (SPs) [4]. The major component of SPs is beta-amyloid peptide (Abeta), which is believed to be the most probable cause of AD [3,5]. Many studies have shown that Abeta can directly induce neuronal death via apoptosis [2,6,7].Erythropoietin (Epo) was originally characterized as the principal regulator of erythropoiesis [8]. Many experimental studies have shown