Neuritogenic monoglyceride derived from the constituent of a marine fish for activating the PI3K/ERK/CREB signalling pathways in PC12 cells.
Neuritogenic monoglyceride derived from the constituent of a marine fish for activating the PI3K/ERK/CREB signalling pathways in PC12 cells.
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源自海鱼成分的神经源性单甘油酯，用于激活 PC12 细胞中的 PI3K/ERK/CREB 信号通路
DOI：
10.3390/ijms141224200
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发表时间：
2013-12-12
影响因子：
5.6
通讯作者：
Qi J
中科院分区：
文献类型：
--
作者：
Yang W;Luo Y;Tang R;Zhang H;Ye Y;Xiang L;Qi J
利用PC 12细胞生物测定系统从长牡蛎头中分离得到一种促神经生的单甘酯1-O-肉豆蔻酰甘油（MG），并利用光谱方法对其化学结构进行了鉴定。MG在10 μM浓度下可诱导42%的PC 12细胞突起生长。为了研究MG的构效关系，设计并合成了一系列单甘酯。生物活性测定结果表明，烷基链的长度起着关键作用的单甘酯的神经元活性。还研究了连接丙二醇和烷基链的基团。一个酯键，而不是一个氨基，被认为是最佳的神经活性。因此，10 μM的1-O-（硬脂酰）甘油（SG）可诱导PC 12细胞57%的神经突生长，被确定为神经突生成活性的先导化合物。然后，我们研究的作用机制SG诱导的神经突起生长的PC 12细胞上使用蛋白质特异性抑制剂和蛋白质印迹分析。丝裂原活化激酶/ERK激酶（MEK）抑制剂U 0126和磷脂酰肌醇-3激酶（PI 3 K）抑制剂LY 294002显着减少神经突生长。同时，SG在蛋白水平上增加CREB的磷酸化。因此，SG诱导的轴突发生活性依赖于PC 12细胞中细胞外调节蛋白激酶（ERK）、cAMP反应元件结合蛋白（CREB）和PI 3 K信号通路的激活。
A neuritogenic monoglyceride, 1-O-(myristoyl) glycerol (MG), was isolated from the head of Ilisha elongate using a PC12 cell bioassay system, and its chemical structure was elucidated using spectroscopic methods. MG significantly induced 42% of the neurite outgrowth of PC12 cells at a concentration of 10 μM. To study the structure-activity relationships of MG, a series of monoglycerides was designed and synthesised. Bioassay results indicated that the alkyl chain length plays a key role in the neuritogenic activity of the monoglycerides. The groups that link the propane-1,2-diol and alkyl chain were also investigated. An ester linkage, rather than an amido one, was found to be optimal for neuritogenic activity. Therefore, 1-O-(stearoyl) glycerol (SG), which induces 57% of the neurite outgrowth of PC12 cells at 10 μM, was determined to be a lead compound for neuritogenic activity. We then investigated the mechanism of action of neurite outgrowth induced by SG on PC12 cells using protein specific inhibitors and Western blot analysis. The mitogen-activated kinase/ERK kinase (MEK) inhibitor U0126 and the phosphatidylinositol-3 kinase (PI3K) inhibitor LY294002 significantly decreased neurite outgrowth. At the same time, SG increased phosphorylation of CREB in protein level. Thus, SG-induced neuritogenic activity depends on the activation of the extracellular-regulated protein kinase (ERK), cAMP responsive element-binding protein (CREB) and PI3K signalling pathways in PC12 cells.
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影响因子：
3.5
作者：
Qi, JH;Ojika, M;Sakagami, Y
通讯作者：
Sakagami, Y
影响因子：
--
作者：
Batovska, DI;Tsubota, S;Ubukata, M
通讯作者：
Ubukata, M
影响因子：
2.1
作者：
Qi, JH;Ojika, M;Sakagami, Y
通讯作者：
Sakagami, Y
影响因子：
1.9
作者：
Zhang, Jie;Takita, Toru
通讯作者：
Takita, Toru
影响因子：
64.5
作者：
COWLEY, S;PATERSON, H;MARSHALL, CJ
通讯作者：
MARSHALL, CJ