AMP <i>N</i><sub>1</sub>‐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
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説明
<jats:p>Earlier we identified adenosine monophosphate (AMP) <jats:italic>N</jats:italic><jats:sub>1</jats:sub>‐oxide as a unique compound of royal jelly (RJ) that induces neurite outgrowth (neuritegenesis) from cultured rat pheochromocytoma PC12 cells via the adenosine A<jats:sub>2A</jats:sub> receptor. Now, we found that AMP <jats:italic>N</jats:italic><jats:sub>1</jats:sub>‐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 <jats:italic>N</jats:italic><jats:sub>1</jats:sub>‐oxide‐induced neuritegenesis, whereas that of protein kinase A (PKA) by a selective inhibitor, KT5720, significantly reduced neurite outgrowth. AMP <jats:italic>N</jats:italic><jats:sub>1</jats:sub>‐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 <jats:italic>N</jats:italic><jats:sub>1</jats:sub>‐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 <jats:italic>N</jats:italic><jats:sub>1</jats:sub>‐oxide elicited neuronal differentiation of PC12 cells, as evidenced by generation of neurites, and inhibited cell growth through adenosine A<jats:sub>2A</jats:sub> receptor‐mediated PKA signaling, which may be responsible for characteristic actions of RJ.</jats:p>
収録刊行物
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- Evidence-Based Complementary and Alternative Medicine
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Evidence-Based Complementary and Alternative Medicine 7 (1), 63-68, 2007-08-20
Wiley