机构：[1]Department of Neurology, Second Affiliated Hospital of Soochow University, and Institute of Neuroscience, Soochow University, 1055 Sanxiang Road, Suzhou 215004, Jiangsu Province, China[2]Department of Neurology, First People’s Hospital of Xuzhou, Xuzhou 221002, China[3]Soochow University Affiliated Children’s Hospital, Suzhou 215003, China[4]Department of Neurology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China[5]Department of Anatomy, Nantong Medical College, Nantong 226001, China
The aim of this study was to determine the mechanism by which erythropoietin (EPO) suppressed 6-hydroxydopamine (6-OHDA)-induced apoptosis. Our results showed that 6-OHDA remarkably decreased phosphorylation of glycogen synthase kinase 3 beta (GSK3 beta) as well as enhanced the level of Bax in the mitochondria. Besides, 6-OHDA decreased the mitochondrial expression of Bcl-2 without altering the cytoplasmic expression of Bcl-2. In line with these results, 6-OHDA treatment enhanced the apoptosis and caspase 3 activity in PC12 cells. These findings indicated that mitochondrial dysfunction was involved in the neurotoxicity of 6-OHDA and GSK3 beta might act upstream of Bax/Bcl-2 and the caspase 3 pathways in 6-OHDA-treated PC12 cells. Furthermore, EPO reduced 6-OHDA-induced growth inhibition. Western blot exhibited that GSK3 beta inhibitor 4-benzyl-2-methyl-1, 2,4-thiadiazolidine-3, 5-dione (TDZD8) and EPO not only increased the phosphorylation of GSK3 beta but also inhibited the mitochondrial translocation of Bax. In agreement with these results, EPO and TDZD8 obviously increased the mitochondrial expression of Bcl-2. Finally, TDZD-8 and EPO significantly suppressed the enhanced apoptosis and activity of caspase 3 induced by 6-OHDA. Taken together, GSK3 beta-mediated mitochondrial cell death pathway is involved in the neuroprotective effect of EPO against 6-OHDA-induced apoptosis.
基金：
a research grant from
the National Natural Science Foundation of China (No. 30870869).
第一作者机构：[1]Department of Neurology, Second Affiliated Hospital of Soochow University, and Institute of Neuroscience, Soochow University, 1055 Sanxiang Road, Suzhou 215004, Jiangsu Province, China[2]Department of Neurology, First People’s Hospital of Xuzhou, Xuzhou 221002, China
通讯作者：
通讯机构：[1]Department of Neurology, Second Affiliated Hospital of Soochow University, and Institute of Neuroscience, Soochow University, 1055 Sanxiang Road, Suzhou 215004, Jiangsu Province, China
推荐引用方式(GB/T 7714)：
Xu-Hua Ge,Guo-Ji Zhu,De-Qin Geng,et al.Erythropoietin attenuates 6-hydroxydopamine-induced apoptosis via glycogen synthase kinase 3 beta-mediated mitochondrial translocation of Bax in PC12 cells[J].NEUROLOGICAL SCIENCES.2012,33(6):1249-56.doi:10.1007/s10072-012-0959-3.
APA：
Xu-Hua Ge,Guo-Ji Zhu,De-Qin Geng,Zhi-Jun Zhang&Chun-Feng Liu.(2012).Erythropoietin attenuates 6-hydroxydopamine-induced apoptosis via glycogen synthase kinase 3 beta-mediated mitochondrial translocation of Bax in PC12 cells.NEUROLOGICAL SCIENCES,33,(6)
MLA：
Xu-Hua Ge,et al."Erythropoietin attenuates 6-hydroxydopamine-induced apoptosis via glycogen synthase kinase 3 beta-mediated mitochondrial translocation of Bax in PC12 cells".NEUROLOGICAL SCIENCES 33..6(2012):1249-56
