Protective effect of erythropoietin on beta-amyloid-induced PC12 cell death through antioxidant mechanisms.
Erythropoietin (EPO), a haematopoietic growth factor has been reported to display neuroprotective properties in different animal models. In the present study, we investigated the neuroprotective effects of EPO on Abeta(25-35)-induced neuronal toxicity and its potential mechanisms in PC12 cells. Abeta(25-35) significantly reduced cell viability and increased the number of apoptotic-like cells. In addition, increased ROS production and decreased mitochondrial membrane potential were also found after Abeta(25-35) exposure. All of these phenotypes induced by Abeta(25-35) were markedly reversed by EPO. Pretreatment with EPO prior to Abeta(25-35) exposure significantly elevated cell viability, reduced Abeta(25-35)-induced apoptosis, decreased ROS production, and stabilized mitochondrial membrane potential. Furthermore, EPO also attenuated the downstream cascade following ROS, including Bcl-2/Bax, and caspase-3 activation. Our results suggest that EPO holds potential for neuroprotection and therefore, may be promising for the treatment of Alzheimer's disease.
Li
Gang
G
Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
Ma
Rong
R
Huang
Chengfang
C
Tang
Qiang
Q
Fu
Qin
Q
Liu
Hui
H
Hu
Benrong
B
Xiang
Jizhou
J
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); D051028:bcl-2-Associated X Protein; D004921:Erythropoietin; D053148:Caspase 3