IGF-1 protects against Aβ25-35-induced neuronal cell death via inhibition of PUMA expression and Bax activation.
Amyloid-β-peptide (Aβ) 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 Aβ 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 Aβ-induced neurotoxicity via inhibition of PUMA expression and Bax activation. We found that IGF-1 could activate Akt, which in turn inhibited Aβ-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 Aβ. 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 Aβ-induced apoptosis.
Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China; Department of Anti-Aging, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China; Anti-Aging Monitoring Laboratory, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China.
Xunyao
X
Hou
Department of Hematology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China.
Yan
Y
Jin
Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China; Department of Anti-Aging, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China; Anti-Aging Monitoring Laboratory, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China.
Jian
J
Chen
Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China; Department of Anti-Aging, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China; Anti-Aging Monitoring Laboratory, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China.
Yan
Y
Hong
Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China; Department of Anti-Aging, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China; Anti-Aging Monitoring Laboratory, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China.
Dingzhen
D
Luo
Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China; Department of Anti-Aging, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China; Anti-Aging Monitoring Laboratory, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China.
Qingqing
Q
Yin
Department of Senile Neurology, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China; Department of Anti-Aging, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China; Anti-Aging Monitoring Laboratory, Provincial Hospital Affiliated to Shandong University, 324#, Jing Wu Road, Jinan, 250021, China. Electronic address: xuepingliu2002@sina.com.
Xueping
X
Liu
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D016923:Cell Death; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; C438378:BBC3 protein, human; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; C074636:amyloid beta-protein (25-35); D051028:bcl-2-Associated X Protein; D007334:Insulin-Like Growth Factor I
AD; Akt; Aβ; Bax; IGF-1; PUMA