IGF-1 protects against A beta(25-35)-induced neuronal cell death via inhibition of PUMA expression and Bax activation
作者
Hou, XY;Jin, Y;Chen, J;Hong, Y;Luo, DZ;Yin, QQ;Liu, XP
作者单位
[Hou, Xunyao; Chen, Jian; Hong, Yan; Luo, Dingzhen; Yin, Qingqing; Liu, Xueping] Shandong Univ, Prov Hosp Affiliated, Dept Senile Neurol, 324 Jing Wu Rd, Jinan 250021, Peoples R China.;-;[Hou, Xunyao; Chen, Jian; Hong, Yan; Luo, Dingzhen; Yin, Qingqing; Liu, Xueping] Shandong Univ, Prov Hosp Affiliated, Dept Antiaging, 324 Jing Wu Rd, Jinan 250021, Peoples R China.;-;[Hou, Xunyao; Chen, Jian; Hong, Yan; Luo, Dingzhen; Yin, Qingqing; Liu, Xueping] Shandong Univ, Prov Hosp Affiliated, Antiaging Monitoring Lab, 324 Jing Wu Rd, Jinan 250021, Peoples R China.;-;Shandong Univ, Prov Hosp Affiliated, Dept Hematol, 324 Jing Wu Rd, Jinan 250021, Peoples R China.
摘要
Amyloid-p-peptide (A beta) is considered to be the toxic species in AD and causes cell death in the affected areas of patient's brain. Insulin-like growth factor 1 (IGF-1) has been reported to attenuate A beta toxicity in neuronal cells. However, the molecular mechanisms involved in the neuroprotective function of IGF-1 remain largely unknown. In the present study, we for the first time demonstrated that IGF-1 protects against A beta-induced neurotoxicity via inhibition of PUMA expression and Bax activation. We found that IGF-1 could activate Akt, which in turn inhibited A beta-induced FOXO3a nuclear translocation and thus decreased the binding ability of FOXO3a to PUMA promoter, leading to decreased PUMA expression. In addition, IGF-1 inhibited the translocation of Bax to the mitochondria induced by A beta. Notably, addition of wortmannin, a specific inhibitor of PI3K, significantly abolished the neuroprotective effect of IGF-1, suggesting that IGF-1 exerts its anti-apoptotic effect depend on PI3K activity. Our findings may provide new insights into molecular mechanisms mediated by IGF-1 in cell survival against A beta-induced apoptosis. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
关键词
FACTOR-I PREVENTS; ALZHEIMERS-DISEASE; HIPPOCAMPAL-NEURONS; APOPTOSIS; INSULIN; PATHWAY; BIM; FOXO3A
基本信息
