Identification of AMP N1-oxide in royal jelly as a component neurotrophic toward cultured rat pheochromocytoma PC12 cells

Identification of AMP N1-oxide in royal jelly as a component neurotrophic toward cultured rat pheochromocytoma PC12 cells
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DOI:
10.1271/bbb.70.897
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发表时间:
2006-04-01
影响因子:
1.6
通讯作者:
Furukawa, S
Furukawa, S
中科院分区:
工程技术4区
文献类型:
--
作者:
Hattori, N;Nomoto, H;Furukawa, S

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蜂王浆 (RJ) 提取物诱导培养的大鼠嗜铬细胞瘤 PC12 细胞的生长过程。分离出活性成分,并鉴定为单磷酸腺苷 (AMP) 和 AMP NI-氧化物。从引发活性的最低浓度来看,AMP N-1-氧化物的活性是 AMP 的 20 倍以上。 AMP N-1-氧化物被认为负责整个 RJ 大约一半的过程形成活性。化学合成的 AMP NI-氧化物的活性与从 RJ 中纯化的分子类似,证实 AMP N-1-氧化物是活性实体。 AMP N-1-氧化物还抑制 PC12 细胞的增殖并刺激神经丝 M(成熟神经元的一种特定蛋白)的表达,证明 AMP N-1-氧化物具有诱导 PC12 细胞神经元分化的刺激活性。药理学实验表明,AMP N-1-氧化物的作用是由腺苷酸环化酶偶联的腺苷受体(包括 A(2A))介导的。因此,AMP N-1-氧化物是表征 RJ 的关键分子,并且在除 RJ 之外的天然产物中未发现。
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 NI-oxide. AMP N-1-oxide was more than 20 times as active as AMP, judging from the minimal concentration to elicit activity. AMP N-1-oxide was thought to be responsible for about half of the process-forming activity of whole RJ. Chemically-synthesized AMP NI-oxide was active similarly to the molecule purified from RJ, confirming AMP N-1-oxide as the active entity. AMP N-1-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 N-1-oxide to induce neuronal differentiation of PC12 cells. Pharmacological experiments suggested that AMP N-1-oxide actions are mediated by adenyl cyclase-coupled adenosine receptors, including A(2A). Thus AMP N-1-oxide is a key molecule that characterizes RJ, and is not found in natural products other than RJ.