Glioma cell proliferation mechanism regarding the signal transduction system in vivo.

胶质瘤细胞增殖机制与体内信号转导系统有关。

• 批准号: 02454337
• 负责人: UEDA Satoshi
• 金额: $ 4.42万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454337/
• 关键词: Signal transduction; Cell proliferation; Phosphoinositide turnover; Phospholipase C; Diacylglycerol; Protein Kinase C; PDGF; EGF; グリオ-マ; 細胞内情報伝達; 1,2ー[ ^<11>C]ジアシルグリセロ-ル; Protein kinase C

1. The major advance in cell biology in recent has been the clarification of a series of intracellular signaling pathways that link to the cell surface receptors. One of the most extensively studied signaling pathways is the phospholipase C dependent hydrolysis of membrane phosphoinositides to form inositol polyphosphate and diacylglycerols. We studied the tumor signal transduction mechanism regarding tumor proliferation and we found the metabolic difference in phospholipid turnover between the CNS and the glioma. Carbon-11-labeled 1, 2-diacylglycerol(DAG) uptake was observed in rat brain and transplanted rat glioma (C_6 glioma) using in vivo autoradiographic technique. Marked DAG uptake was shown in the transplanted cells, suggesting that phospholipid turnover in the glioma was prompted than the CNS. Chromatographic studies also showed the difference in the metabolic fraction, in which glioma cells simultaneously produced radioactive phosphatidylcholine (PC) and phosphatidylethanolamine (PE) accompanied with phosphatidic acids (PA), phosphatidylinositols(PI) and phosphoinositides(PIP and PIP_2). This suggest specific feature of the tumor signal transduction system represented by the dissociation of PI-PKC (protein kinase C) system.2. In our studies with using growth factors, we found the fact that the many responses were observed in the tumor signal transduction in each stimulation. There was obvious difference in the response between PDGF and EGF. Platelet derived growth factor predominantly activated PC-PLD(phospholipase D) system, suggesting the PI-PKC dissociation, based on analogy to TPA. We conclude that the tumor signal transduction should be regulated by "dual phospholipid turnover system", i. e. PI-PCL and PC-PLD, positioned in te higher signaling hierarchy.

1.近年来细胞生物学的主要进展是阐明了一系列与细胞表面受体相关的细胞内信号通路。最广泛研究的信号传导途径之一是膜磷酸肌醇的磷脂酶C依赖性水解以形成肌醇多磷酸盐和二酰基甘油。我们研究了肿瘤增殖的信号转导机制，发现CNS和胶质瘤之间磷脂代谢的差异。用放射自显影技术观察了大鼠脑和移植性胶质瘤（C_6胶质瘤）对~（11）C标记的1，2-二酰甘油（DAG）的摄取。在移植的细胞中显示出显著的DAG摄取，表明胶质瘤中的磷脂周转比CNS中的磷脂周转更快。色谱分析结果表明，胶质瘤细胞代谢组分的差异主要表现为同时产生放射性磷脂酰胆碱（PC）和磷脂酰乙醇胺（PE），以及磷脂酸（PA）、磷脂酰肌醇（PI）和磷脂酰肌醇（PIP和PIP_2）。这提示了以PI-PKC（蛋白激酶C）系统解离为代表的肿瘤信号转导系统的特异性.在我们使用生长因子的研究中，我们发现在每种刺激中，在肿瘤信号转导中观察到许多反应。PDGF和EGF的反应有明显差异。血小板源性生长因子主要激活磷脂酶D（phospholipase D，PC-PLD）系统，与TPA类似，提示PI-PKC解离。我们认为肿瘤信号转导受“双磷脂周转系统”的调控。e. PI-PCL和PC-PLD，定位于更高的信令层次。

项目成果

今堀 良夫、上田 聖 著: "ポジトロンCTによる細胞内情報伝達系測定法の開発と高次脳機能イメ-ジング" 177 (1992)放射線医学総合研究所 館野之男編著 実業公報社"ポジトロン核医学の将来展望"164ー176,1992.,

今堀义雄、上田清：“利用正电子CT和高级脑功能成像的细胞内信息转导系统测量方法的开发”177（1992）国立放射线科学研究所，馆野幸雄、实行编，《正电子核医学》未来展望” 164-176, 1992.,

Yoshio Imahori,Ryou Fujii,Satoshi Ueda,Yoshio Ohmori,and Keigo Matsumoto:"Rapid Incorporation of Carbonー11ーlabeledー1,2ーdiacylgycerol into the Cell Membrane Phospholipids." FEBS letter,. (1992)

Yoshio Imahori、Ryou Fujii、Satoshi Ueda、Yoshio Ohmori 和 Keigo Matsumoto：“将碳－11 标记的－1,2-二酰基甘油快速掺入细胞膜 FEBS 信中”（1992 年）。

Yoshio Ohmori,Yoshio Imahori,Satoshi Ueda,Ryou Fujii,Tatsuo Ido,and Hisamitsu Nakahashi:"Protein kinase C Imaging using Carbon-11-Labeled Phorbol Esters;12-Deoxyphorbol 13-Isobutyrate-20-〔1-^<11>C〕Butyrate as the potential Ligand." The Journal Nnclar Medi

Yoshio Ohmori、Yoshio Imahori、Satoshi Ueda、Ryou Fujii、Tatsuo Ido 和 Hisamitsu Nakahashi：“使用碳 11 标记的佛波酯进行蛋白质激酶 C 成像；12-脱氧佛波醇 13-异丁酸酯-20-〔1-^<11>C” 〕丁酸盐作为潜在的配体。”《Nnclar Medi 杂志》

Yoshio Imahori,Ryou Fujii,Satoshi Ueda,Tatsuo Ido,Hoyoku Nishino,Yoshihiko Moriyama,Y.Lucas Yamamoto,and Hisamitsu Nakahashi:"No CarrierAdded Carbonー11ーLabele snー1,2ーand snー1,3ーDiacylーglycerols by [^<11>C]propyl Ketene Method." The Journal Nuclear Medicin

Yoshio Imahori、Ryou Fujii、Satoshi Ueda、Tatsuo Ido、Hoyoku Nishino、Yoshihiko Moriyama、Y.Lucas Yamamoto 和 Hisamitsu Nakahashi：“无载体添加碳－11－Labele sn－1,2－和 sn－1,3－Diacy－通过[^11C]丙基乙烯酮法制备甘油。”《核医学杂志》

Yoshio Imahori,Ryou Fujii,Satoshi Ueda,Yoshio Ohmori,and Keigo Matsumoto:"Rapid Incorporation of Carbon-11-labeled-1,2-diacylglycerol into the Cell Membrane Phospholipids." FFBS letter,1992.

Yoshio Imahori、Ryou Fujii、Satoshi Ueda、Yoshio Ohmori 和 Keigo Matsumoto：“将碳 11 标记的 1,2-二酰基甘油快速掺入细胞膜磷脂中。”