Activation of phosphatidylinositol 3-kinase, but not extracellular-regulated kinases, is necessary to mediate brain-derived neurotrophic factor-induced motoneuron survival

被引:114
作者
Dolcet, X
Egea, J
Soler, RM
Martin-Zanca, D
Comella, JX
机构
[1] Univ Lleida, Fac Med, Dept Ciencies Med Basiques, Grp Neurobiol Mol, E-25198 Lleida, Spain
[2] Univ Salamanca, CSIC, Inst Microbiol Bioquim, E-37008 Salamanca, Spain
关键词
motoneuron; survival; neurotrophin; phosphatidylinositol; 3-kinase;
D O I
10.1046/j.1471-4159.1999.0730521.x
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
Chick embryo spinal cord motoneurons develop a trophic response to some neurotrophins when they are maintained in culture in the presence of muscle extract. Thus, after 2 days in culture, brain-derived neurotrophic factor (BDNF) promotes motoneuron survival. In the present study we have analyzed the intracellular pathways that may be involved in the BDNF-induced motoneuron survival. We have observed that BDNF activated the extracellular-regulated kinase (ERK) mitogen-activated protein (MAP) kinase and the phosphatidylinositol (PI) 3-kinase pathways. To examine the contribution of these pathways to the survival effect triggered by BDNF, we used PD 98059, a specific inhibitor of MAP kinase kinase, and LY 294002, a selective inhibitor of PI 3-kinase, PD 98059, at doses that significantly reduced the phosphorylation of ERKs, did not show any prominent effect on neuronal survival, However, LY 294002 at doses that inhibited the phosphorylation of AM, a downstream element of the PI 3-kinase, completely abolished the motoneuron survival effects of BDNF, Moreover, cell death triggered by tY 294002 treatment exhibited features similar to those observed after muscle extract deprivation. Our results suggest that the PI 3-kinase pathway plays an important role in the survival effect triggered by BDNF on motoneurons, whereas activation of the ERK MAP kinase pathway is not relevant.
引用
收藏
页码:521 / 531
页数:11
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