Cyclic phosphatidic acid elicits neurotrophin-like actions in embryonic hippocampal neurons
Cyclic phosphatidic acid elicits neurotrophin-like actions in embryonic hippocampal neurons
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DOI：
10.1046/j.1471-4159.2003.02106.x
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发表时间：
2003-12-01
影响因子：
4.7
通讯作者：
Tigyi, G
中科院分区：
文献类型：
--
作者：
Fujiwara, Y;Sebök, A;Tigyi, G
环磷脂酸（cPA）; 1-酰基-sn-甘油-2，3-环磷酸酯）是生长因子样磷脂介质溶血磷脂酸（LPA）的类似物。由于脑组织是cPA最丰富的来源，我们测试了其对在无血清培养基中培养的16/17天胚胎大鼠海马神经元的影响。纳摩尔浓度的cPA引起的神经营养作用，并促进神经突起的生长，超过了50 ng/mL的神经生长因子（NGF）。百日咳毒素、LPA（1）/LPA（3）受体选择性拮抗剂焦磷酸二辛基甘油、蛋白激酶A（PKI）的肉豆蔻酰化抑制性假底物肽、Wortmannin和PD 98059均能阻断其促轴突生长作用。cPA引起细胞外信号相关激酶（ERK）1/2和Akt的持续激活。艰难梭菌毒素B是一种Rho家族的GTP酶抑制剂，可降低cPA诱导的神经突生长增强。在过表达酪氨酸激酶NGF受体（TrkA）的PC 12细胞的克隆细胞系B5 P细胞中，cPA引起TrkA的转磷酸化。cPA诱导的ERK激活被K252 a和PKI阻断。这些结果表明，cPA模拟的效果，并激活类似的信号通路，神经营养因子NGF在培养的胚胎海马神经元和B5 P细胞。
Cyclic phosphatidic acid (cPA; 1-acyl-sn-glycerol-2,3-cyclic phosphate) is an analog of the growth factor-like phospholipid mediator lysophosphatidic acid (LPA). As brain tissue is the richest source of cPA we tested its effects on hippocampal neurons from day 16/17 embryonic rat cultured in a serum-free medium. Nanomolar concentrations of cPA elicited a neurotrophic effect and promoted neurite outgrowth that exceeded that of 50 ng/mL nerve growth factor (NGF). Pertussis toxin, the LPA(1)/LPA(3) receptor-selective antagonist dioctylglycerol pyrophosphate, the myristoylated inhibitory pseudosubstrate peptide of protein kinase A (PKI), Wortmannin and PD98059 abolished the neurite-promoting effect. cPA elicited a sustained activation of extracellular signal-related kinases (ERK) 1/2 and Akt. Clostridium difficile toxin B, an inhibitor of the Rho family of GTPases, reduced cPA-induced enhancement of neurite outgrowth. In B5P cells, a clonal cell line of PC12 cells overexpressing tyrosine kinase NGF receptor (TrkA), cPA elicited transphosphorylation of TrkA. cPA-elicited ERK activation was blocked by K252a and PKI. These results suggest that cPA mimics the effects of, and activates signaling pathways similar to, the neurotrophin NGF in cultured embryonic hippocampal neurons and B5P cells.