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

Acta Pharmacologica Sinica 2007年第2期28卷 166-172页

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 Research Centre of Neurobiology Xuzhou Medical College

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.

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

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Role of PI3-K/Akt pathway and its effect on glial cell line-derived neurotrophic factor in midbrain dopamine cells1

Role of PI3-K/Akt pathway and its effect on glial cell line-...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

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

＜正＞Aim:To explore the intracellular mechanisms underlying the survival/differentiation effect of the glial cell linederived neurotrophic factor（GDNF） on dopamine（DA） ***:Midbrain slice culture and primary cell culture were established,and the cultures were divided into 3 groups:control group,GDNF group,and the phosphatidylinositol 3- kinase/Akt（PI3-K/Akt） pathway-inhibited *** the expression of tyrosine hydroxylase（TH） was detected by immunostaining as well as Western ***:GDNF treatment induced an increase in the number of TH-immunoreactive （ir） cells and the neurite number of TH-ir cells,as well as in the level of TH expression in cultures（Number of Thir 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:control group,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 specifically blocked by the inhibitor of the PI3-K/Akt pathway,wortmannin（Number of TH- ir cells in slice culture:PI3-K/Akt pathway-inhibited group,6.98±*** of TH-ir cells and neurite number of TH-ir cells in cell culture:PI3-K/Akt pathway-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 on DA cells.

关键词： glial cell line-derived neurotrophic factor phospha t i dyl inosi tol 3 -ki na se/Ak t dopamine cells survival/differentiation

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