Identification of AMP N1-oxide in royal jelly as a component neurotrophic toward cultured rat pheochromocytoma PC12 cells.
An extract of royal jelly (RJ) induced processes from cultured rat pheochromocytoma PC12 cells. Active components were isolated, and identified as adenosine monophosphate (AMP) and AMP N1-oxide. AMP N1-oxide was more than 20 times as active as AMP, judging from the minimal concentration to elicit activity. AMP N1-oxide was thought to be responsible for about half of the process-forming activity of whole RJ. Chemically-synthesized AMP N1-oxide was active similarly to the molecule purified from RJ, confirming AMP N1-oxide as the active entity. AMP N1-oxide also suppressed proliferation of PC12 cells and stimulated expression of neurofilament M, a specific protein of mature neurons, demonstrating the stimulatory activity of AMP N1-oxide to induce neuronal differentiation of PC12 cells. Pharmacological experiments suggested that AMP N1-oxide actions are mediated by adenyl cyclase-coupled adenosine receptors, including A2A. Thus AMP N1-oxide is a key molecule that characterizes RJ, and is not found in natural products other than RJ.
Hattori
Noriko
N
Laboratory of Molecular Biology, Gifu Pharmaceutical University, Gifu, Japan.
Nomoto
Hiroshi
H
Mishima
Satoshi
S
Inagaki
Shinsuke
S
Goto
Masashi
M
Sako
Magoichi
M
Furukawa
Shoei
S
D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape; D002852:Chromatography, Ion Exchange; D005227:Fatty Acids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D010087:Oxides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D016716:PC12 Cells; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D000099219:Royal Jelly
D000249:Adenosine Monophosphate; D005227:Fatty Acids; D010087:Oxides; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D000099219:Royal Jelly; C511284:AMP N1-oxide