title: Involvement of phospholipase C-γ in the pro-survival role of glial cell             line-derived neurotrophic factor in developing motoneurons in rat spinal cords.
abstract: The glial cell line-derived neurotrophic factor (GDNF) has been proven to be the most powerful neurotrophic factor in neuronal development. However, it remains uncertain as to which intracellular signaling pathway interacting with GDNF is invovlved in motoneuron (MN) development. In this study, we investigated whether phosphoinositide phospholipase C-γ (PLC-γ) is involved in GDNF-promoted MN development. The primary spinal MNs from 12- to 14-day-old embryos of Sprague-Dawley rats were cultured and survival was sustained by GDNF. A specific inhibitor of PLC-γ, 1-[6-((17b-3-methoxyestra-1,3,5(10)-trien-17-yl) amino)hexyl]-1H-pyrrole-2,5-dione (U73122), was used to block the pro-survival effect of GDNF. Our results showed that MN-like cells appeared at 72 h after initial implantation and were sustained for a period of up to seven days under GDNF treatment. These cultured MNs expressed neuron-specific enolase, SMI-32, 75-kDa low-affinity neurotrophic receptor and choline acetyltransferase. The survival rate of the cultured MNs at 24 h was significantly lower in the GDNF + U73122-treated group (31.87±2.17%), compared either with that of the GDNF- (81.38±1.13%) or GDNF + DMSO (79.39±1.22%)-treated groups. The present data suggest that PLC-γ may be one of the intracellular signals that play a role in the survival-promoting effects of GDNF in developing spinal MNs.
authors: Zhong Shan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.
authors: Rao
authors: R
authors: Fu
authors: Li-Qing
authors: LQ
authors: Wang
authors: Guo-Liang
authors: GL
authors: Chu
authors: Li-Hua
authors: LH
authors: Zhou
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004622:Embryo, Mammalian / Q000187:drug effects*; D004963:Estrenes / Q000494:pharmacology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology*; D009046:Motor Neurons / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology* / Q000378:metabolism
chemical_list: D004963:Estrenes; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D010726:Phosphodiesterase Inhibitors; D011760:Pyrrolidinones; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C068313:Ngfr protein, rat; D002795:Choline O-Acetyltransferase; D051966:Phospholipase C gamma; D010751:Phosphopyruvate Hydratase