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Open AccessArticle

Neuritogenic Monoglyceride Derived from the Constituent of a Marine Fish for Activating the PI3K/ERK/CREB Signalling Pathways in PC12 Cells

College of Pharmaceutical Sciences, Zhejiang University, Yu Hang Tang Road 866, Hangzhou 310058, China
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Int. J. Mol. Sci. 2013, 14(12), 24200-24210; https://doi.org/10.3390/ijms141224200
Received: 16 September 2013 / Revised: 20 November 2013 / Accepted: 20 November 2013 / Published: 12 December 2013
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
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. View Full-Text
Keywords: 1-O-(myristoyl) glycerol; neuritogenic activity; Ilisha elongate; PC12 cells; 1-O-(stearoyl) glycerol; ERK 1-O-(myristoyl) glycerol; neuritogenic activity; Ilisha elongate; PC12 cells; 1-O-(stearoyl) glycerol; ERK
MDPI and ACS Style

Yang, W.; Luo, Y.; Tang, R.; Zhang, H.; Ye, Y.; Xiang, L.; Qi, J. Neuritogenic Monoglyceride Derived from the Constituent of a Marine Fish for Activating the PI3K/ERK/CREB Signalling Pathways in PC12 Cells. Int. J. Mol. Sci. 2013, 14, 24200-24210.

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