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Role of PI3-K/Akt pathway and its effect on glial cell line-derived neurotrophic factor in midbrain dopamine cells

Role of PI3-K/Akt pathway and its effect on glial cell line-derived neurotrophic factor in midbrain dopamine cells

作     者:Hong-jun WANG Jun-ping CAO Jing-kao YU Dian-shuai GAO~2 Research Centre of Neurobiology,Xuzhou Medical College,Xuzhou 221002,China 

作者机构:Research Centre of Neurobiology Xuzhou Medical College 

出 版 物:《Acta Pharmacologica Sinica》 (中国药理学报(英文版))

年 卷 期:2007年第28卷第2期

页      面:166-172页

核心收录:

学科分类:1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学] 

基  金:the Education Department Natural Science Research Funds of the Jiangsu Province of China(No 02KJB310211) the National Natural Science Research Funds of China(No 30570564) 

主  题:glial cell line-derived neurotrophic factor phosphatidylinositol 3-kinase/Akt dopa mine cells survival/differentiation 

摘      要:Aim:To explore the intracellular mechanisms underlying the survival/differentia-tion effect of the glial cell line-derived neurotrophic factor(GDNF)on dopamine(DA)***:Midbrain slice culture and primary cell culture wereestablished,and the cultures were divided into 3 groups:control group,GDNFgroup,and the phosphatidylinositol 3-kinase/Akt(PI3-K/Akt)*** the expression of tyrosine hydroxylase(TH)was detected byimmunostaining as well as Western ***:GDNF treatment inducedan increase in the number of TH-immunoreactive(ir)cells and the neurite numberof TH-ir cells,as well as in the level of TH expression in cultures(Number of TH-ir cells in the slice culture:control group,8.76±0.75;GDNF group,18.63±*** of TH-ir cells and neurite number of TH-ir cells in cell culture:controlgroup,3.65±0.88 and 2.49±0.42;GDNF group,6.01±0.43 and 4.89±0.46).Meanwhile,the stimulation of cultured cells with GDNF increased the phosphorylation of Akt,which is a downstream effector of PI3-K/*** effects of GDNF were specifi-cally blocked by the inhibitor of the PI3-K/Akt pathway,wortmannin(Number ofTH-ir cells in slice culture:PI3-K/Akt pathway-inhibited group,6.98±***-ber of TH-ir cells and neurite number of TH-ir cells in cell culture:PI3-K/Aktpathway-inhibited group,3.79±0.62 and 2.50±0.25,respectively).Conclusion:The PI3-K/Akt pathway mediates the survival/differentiation effect of GDNF onDA cells.

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