RT Journal Article
SR Electronic
T1 Neuritogenic Activity of Tetradecyl 2,3-Dihydroxybenzoate Is Mediated through the Insulin-Like Growth Factor 1 Receptor/Phosphatidylinositol 3 Kinase/Mitogen-Activated Protein Kinase Signaling Pathway
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 326
OP 334
DO 10.1124/mol.115.097758
VO 88
IS 2
A1 Ruiqi Tang
A1 Lijuan Gao
A1 Makoto Kawatani
A1 Jianzhong Chen
A1 Xueli Cao
A1 Hiroyuki Osada
A1 Lan Xiang
A1 Jianhua Qi
YR 2015
UL http://molpharm.aspetjournals.org/content/88/2/326.abstract
AB Tetradecyl 2,3-dihydroxybenzoate (ABG-001) is a lead compound derived from neuritogenic gentisides. In the present study, we investigated the mechanism by which ABG-001 induces neurite outgrowth in a rat adrenal pheochromocytoma cell line (PC12). Inhibitors of insulin-like growth factor 1 (IGF-1) receptor, phosphatidylinositol 3-kinase (PI3K), and extracellular signal-regulated kinase (ERK) 1/2 significantly decreased ABG-001–induced neurite outgrowth. Western blot analysis revealed that ABG-001 significantly induced phosphorylation of IGF-1 receptor, protein kinase B (Akt), ERK, and cAMP responsive element-binding protein (CREB). These effects were markedly reduced by addition of the corresponding inhibitors. We also found that ABG-001–induced neurite outgrowth was reduced by protein kinase C inhibitor as well as small-interfering RNA against the IGF-1 receptor. Furthermore, like ABG-001, IGF-1 also induced neurite outgrowth of PC12 cells, and low-dose nerve growth factor augmented the observed effects of ABG-001 on neurite outgrowth. These results suggest that ABG-001 targets the IGF-1 receptor and activates PI3K, mitogen-activated protein kinase, and their downstream signaling cascades to induce neurite outgrowth.