Investigation of nerve growth factor promotor from fungi

真菌神经生长因子启动子的研究

• 批准号: 11672213
• 负责人: OHTA Tomihisa
• 金额: $ 2.18万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11672213/
• 关键词: nerve growth factor; NGF; neurotrophic gactor; Basidiomycetes; PC-12; Sarcodon scabrosus; scabronine; diterpenoid; 子嚢菌; アストロサイトーマ; 菌類

Novel cyathane-type diterpenoids, scabronine A-F, were isolated from the fruit body of the mushroom, Sarcodon scabrosus (Fr.) Karst. The stereostructures of those were elucidated on the basis of the spectroscopic analysis. Among these compounds, scabronines A, B, C and E exhibit inductive activity of the verve growth factor synthesis. Further investigation yielded three more congeners, scabronine G, H and I.When rat pheochromocytoma cells (PC-12) were cultivated with the conditioned medium of human astrocytoma cells (1321Nl) incubated with the new diterpenoids, scabronines A and G, isolated from Sarcodon scabrosus, they changed their morphology and there was neurite outgrowth. The scabronines increased the expression of nIRNA for nerve growth factor (NGF), and the secretion of NGF from 1321Nl cells in a concentration-dependent manner. However, the enhanced neurite outgrowth produced by the conditioned media was slightly inhibited by NGF neutralizing antibody, and the concentration of NGF released in response to the scabronines was insufficient to cause differentiation.In conclusion, the new diterpenoids scabronines A and G potently stimulate the secretion of neurotrophic factors, including NGF.They are useful drugs to clarify the mechanism of synthesis and secretion of neurotrophic factors.

本文报道了一个新的蓝烷型二萜化合物，scabronine A-F，是从蘑菇Sarcodon scabrosus（Fr.）喀斯特根据光谱分析确定了它们的立体结构。在这些化合物中，scabronines A、B、C和E显示出对神经生长因子合成的诱导活性。进一步的研究产生了三个同源物，scabronine G，H和I。当大鼠嗜铬细胞瘤细胞（PC-12）培养的条件培养基的人星形细胞瘤细胞（1321 NI）孵育的新的二萜类化合物，scabronines A和G，分离自Sarcodon scabrosus，它们改变了它们的形态，有神经突生长。结果表明，糙豆碱能浓度依赖性地增加1321 N1细胞神经生长因子（NGF）nIRNA的表达和NGF的分泌。结果表明，新的二萜类化合物scabronines A和G能有效地刺激神经营养因子的分泌，其中包括NGF，它们是阐明神经营养因子合成和分泌机制的有用药物。

项目成果

A.Segawa, Y.Miyaichi, T.Tomimori, F.Kiuchi, T.Ohta: "Studies of Didymocarpus leucocalyx C.B.CLARKE (Gesneriaceae)."Chem.Pharm.Bull.. 47. 1404-1411 (1999)

A.Sekawa、Y.Miyaichi、T.Tomimori、F.Kiuchi、T.Ohta：“Didymocarpus leucocalyx C.B.CLARKE（苦苣苔科）的研究。”Chem.Pharm.Bull.. 47. 1404-1411 (1999)

K.Yoshikawa,T.Ohta 他: "Polyhydroxylated Sterols from the Octocoral Dendronephthya gigantea"J.Nat.Prod.. 63. 670-672 (2000)

K. Yoshikawa, T. Ohta 等人：“来自 Octocoral Dendronephthya gigantea 的多羟基化甾醇” J. Nat. 63. 670-672 (2000)

T.Ohta,K.Uwai 他: "Absolute Stereochemistry of Cicutoxin and Related Toxic Polyacetylenic Alcohols from Cicuta virosa"Tetrahedron. 55. 12087-12098 (1999)

T. Ohta、K. Uwai 等人：“Cicuta virosa 中 Cicuta 毒素和相关有毒聚乙炔醇的绝对立体化学”，Tetrahedron 55。12087-12098 (1999)

K.Yoshikawa, S.Kanekuni, M.Hanahusa, S.Arihara, T.Ohta: "Polyhydroxylated Sterols from the Octocoral Dendronephthya gigantea."J.Nat.Prod.. 63. 670-672 (2000)

K.Yoshikawa、S.Kanekuni、M.Hanahusa、S.Arihara、T.Ohta：“来自 Octocoral Dendronephthya gigantea 的多羟基化甾醇。”J.Nat.Prod.. 63. 670-672 (2000)

A.Segawa,T.Ohta 他: "Studies of Didymocarpus leucocalyx C.B.CLARKE (Gesneriaceae)"Chem.Pharm.Bull. 47. 1404-1411 (1999)

A.Sekawa、T.Ohta 等人：“Didymocarpus leucocalyx C.B.CLARKE（苦苣苔科）的研究”Chem.Pharm.Bull. 47. 1404-1411 (1999)