Signaling pathways and survival effects of BDNF and NT-3 on cultured cerebellar granule cells

被引：84

作者：

Nonomura, T ^{[1
]}

Kubo, T ^{[1
]}

Oka, T ^{[1
]}

Shimoke, K ^{[1
]}

Yamada, M ^{[1
]}

Enokido, Y ^{[1
]}

Hatanaka, H ^{[1
]}

机构：

[1] OSAKA UNIV,INST PROT RES,DIV PROT BIOSYNTH,SUITA,OSAKA 565,JAPAN

来源：

DEVELOPMENTAL BRAIN RESEARCH | 1996年 / 97卷 / 01期

关键词：

neurotrophin; neuronal death; tyrosine phosphorylation; brain-derived neurotrophic factor; phospholipase C;

D O I：

10.1016/S0165-3806(96)00130-7

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We investigated the signaling pathways exerted by brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in relation to their survival-promoting effects on dissociated cultures of cerebellar granule cells prepared from postnatal 9-day-old rats. Granule neuron survival in culture was supported by BDNF, but not significantly by either nerve growth factor (NGF) or NT-3. BDNF and NT-3 resulted in not only the respective autophosphorylation of the Trk receptors, TrkB or TrkC, but also tyrosine phosphorylation of SHC, a protein involved in controlling p21(ras) activity, and phosphatidylinositol-3' (PI-3') kinase. NGF does not result in TrkA phosphorylation, In parallel, c-Sos was induced within 30 min, in response to BDNF and NT-3. NT-3 induced the phosphorylation of these proteins to a lesser extent than BDNF. BDNF also induced the tyrosine phosphorylation of phospholipase C gamma (PLC gamma), but the NT-3-induced one was not detected. We postulate that no survival promotion by NT-3 is due to lesser level of trkC expression and of the NT-3-induced signaling in the cultured cerebellar granule neurons. Wortmannin, a specific inhibitor of PI-3' inhibited the BDNF effect on neuronal survival. PI-3' kinase-dependent pathways might be involved in the promotion of cerebellar granule cell survival by BDNF.

引用

页码：42 / 50

页数：9

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