Role of glial cell derived neurotrophic factor in the protective effect of smilagenin on rat mesencephalic dopaminergic neurons damaged by MPP+

被引：23

作者：

Zhang, Yongfang ^{[1
]}

Xia, Zongqin ^{[1
]}

Hu, Yaer ^{[1
]}

Orsi, Antonia ^{[2
]}

Rees, Daryl ^{[2
]}

机构：

[1] Shanghai Jiao Tong Univ, Sch Med, Shanghai 200025, Peoples R China

[2] Phytopharm Co, Godmanchester, Cambs, England

来源：

FEBS LETTERS | 2008年 / 582卷 / 06期

基金：

中国国家自然科学基金;

关键词：

smilagenin; glial cell derived neurotrophic factor; GDNF receptor; dopaminergic neuron; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; tyrosine hydroxylase;

D O I：

10.1016/j.febslet.2008.02.039

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Tyrosine hydroxylase immunohistochemical analysis revealed that in cultured mesencephalic dopaminergic neurons smilagenin (SMI), added prior to 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPP+), protected against the drop of neuron number and neurite outgrowth length caused by MPP+. Addition of anti-GDNF and/or anti-GFR alpha 1 functional antibodies to the medium prior to SMI, eliminated mostly, though incompletely, the action of SMI. The expression of glial cell derived neurotrophic factor (GDNF) mRNA, but not GDNF receptor alphal (GFR alpha 1) or receptor tyrosine kinase mRNA in MPP+ intoxicated neurons was markedly elevated as early as 2 h after the addition of SMI with a peak at 24-48 h. Therefore, an important route of the protective action of SMI on dopaminergic neurons is to stimulate intrinsic GDNF expression. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

引用

页码：956 / 960

页数：5

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