AMP N1-Oxide, a Unique Compound of Royal Jelly, Induces Neurite Outgrowth from PC12 Vells via Signaling by Protein Kinase A Independent of that by Mitogen-Activated Protein Kinase. Issue 1 (2010)

• Record Type: Journal Article
• Authors: Hattori, Noriko; Nomoto, Hiroshi; Fukumitsu, Hidefumi; Mishima, Satoshi; Furukawa, Shoei
• Is Part Of: Evidence-based complementary and alternative medicine. Volume 7:Issue 1(2010)
• Page Start: 63
• Page End: 68
• Publication Date: 2010
• Subjects: adenosine A2A receptor -- 5-bromodeoxy uridine -- neuronal differentiation -- neurotrophic factor; Alternative medicine -- Periodicals; 615.505
• DOI: 10.1093/ecam/nem146
• Languages: English
• ISSNs: 1741-427X

Abstract

Abstract : Earlier we identified adenosine monophosphate (AMP) N 1 -oxide as a unique compound of royal jelly (RJ) that induces neurite outgrowth (neuritegenesis) from cultured rat pheochromocytoma PC12 cells via the adenosine A2A receptor. Now, we found that AMP N 1 -oxide stimulated the phosphorylation of not only mitogen-activated protein kinase (MAPK) but also that of cAMP/calcium-response element-binding protein (CREB) in a dose-dependent manner. Inhibition of MAPK activation by a MEK inhibitor, PD98059, did not influence the AMP N 1 -oxide-induced neuritegenesis, whereas that of protein kinase A (PKA) by a selective inhibitor, KT5720, significantly reduced neurite outgrowth. AMP N 1 -oxide also had the activity of suppressing the growth of PC12 cells, which correlated well with the neurite outgrowth-promoting activity. KT5720 restored the growth of AMP N 1 -oxide-treated PC12 cells. It is well known that nerve growth factor suppresses proliferation of PC12 cells before causing stimulation of neuronal differentiation. Thus, AMP N 1 -oxide elicited neuronal differentiation of PC12 cells, as evidenced by generation of neurites, and inhibited cell growth through adenosine A2A receptor-mediated PKA signaling, which may be responsible for characteristic actions of RJ.