Abstract
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.
Footnotes
- Received January 7, 2015.
- Accepted May 26, 2015.
This work was supported by the Natural Science Foundation of Zhejiang Province, People’s Republic of China [Grant Y2110105], the International Science and Technology Cooperation Program of China [No. 2014DFG32690], the National Natural Science Foundation of China [Grants 30873152 and 81072536], the Project for Science and Technology of Yunnan Province, China [Grant 2012AE002]. This work was inspired by the international and interdisciplinary environments of the JSPS Asian CORE Program, “Asian Chemical Biology Initiative.”
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- Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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