FK506 potentiates NGF-induced neurite outgrowth via the Ras/Raf/MAP kinase pathway
FK506 potentiates NGF-induced neurite outgrowth via the Ras/Raf/MAP kinase pathway
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DOI：
10.1038/sj.bjp.0705522
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发表时间：
2003-11-01
影响因子：
7.3
通讯作者：
Matsuoka, N
中科院分区：
文献类型：
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作者：
Price, RD;Yamaji, T;Matsuoka, N
1神经生长因子（NGF）和神经营养因子家族的其他成员对于外周和中枢神经系统内神经元的存活和分化至关重要。2在几种实验模型中，亲神经素配体（包括FK 506）可增强NGF诱导的神经突生长，尽管这种增强的机制尚不清楚。3因此，我们使用各种信号分子的特异性药理学抑制剂检测了哪些信号通路参与FK 506增强SH-SY 5 Y神经母细胞瘤细胞中的神经突生长。4 Ras抑制剂（洛伐他汀）、Raf（GW 5074）或MAP激酶（PD 98059和U 0126）阻断FK 506活性，磷脂酶C（U 73122）和磷脂酰肌醇30激酶的抑制剂也是如此（LY 294002）.5蛋白激酶C抑制剂（Go 6983和Ro 31 -8220）轻微但显著地抑制神经突生长，而p38 MAPK（SB 203580）或c-Jun N-末端激酶（SP 600125）的抑制剂则无影响。6这些数据表明，FK 506通过磷脂酶C和磷脂酰肌醇30激酶下游的Ras/Raf/MAP激酶信号通路促进神经突生长。
1 Nerve growth factor (NGF) and other members of the neurotrophin family are critical for the survival and differentiation of neurons within the peripheral and central nervous systems.2 Neurophilin ligands, including FK506, potentiate NGF-induced neurite outgrowth in several experimental models, although the mechanism of this potentiation is unclear.3 Therefore, we tested which signaling pathways were involved in FK506-potentiated neurite outgrowth in SH-SY5Y neuroblastoma cells using specific pharmacological inhibitors of various signaling molecules.4 Inhibitors of Ras (lovastatin), Raf (GW5074), or MAP kinase (PD98059 and U0126) blocked FK506 activity, as did inhibitors of phospholipase C (U73122) and phosphatidylinositol 30 kinase (LY294002).5 Protein kinase C inhibitors (Go6983 and Ro31-8220) slightly but significantly inhibited neurite outgrowth, whereas inhibitors of p38 MAPK (SB203580) or c-Jun N-terminal kinase (SP600125) had no effect.6 These data suggest that FK506 potentiates neurite outgrowth through the Ras/Raf/MAP kinase signaling pathway downstream of phospholipase C and phosphatidylinositol 30 kinase.