Study on Activated Prenylated Derivertives-Containing Liposomes Controllable for Switching of Cell Cycle

含活化异戊二烯衍生物的可控细胞周期转换脂质体的研究

• 批准号: 11670123
• 负责人: YASUDA Tatsuji
• 金额: $ 1.79万
• 依托单位: OKAYAMA 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-11670123/
• 关键词: Cell cycle; liposome; cholesterol synthesis; small G protein; geranylgeranyl pyrophosphate synthase; gene cloning; ゲラニルゲレニルピロリン酸合成酵素; イソプレノイド; HMG-GoA還元酵素阻害剤; アポトーシス; GTP結合タンパク質Rho

The major purpose of the present study is to clarify the biological significance of prenylation of proteins associated with intracellular transduction and the mechanism on prenylation.To analysis on the roles of isopenoide compounds, as an intermediated metabollite of the cholesterol synthesis pathway, we developed a novel method to incorporate those intermediates-encapslated liposomes into cells rested by inhibiting HMG-CoA reductase, as a rate-limiting enzyme in the cholesterol synthesis pathway. This method provided the observation that geranylgeranyl pyrophosphate (GGPP), one of isoprenoid compounds, has a role on hormone-dependent DNA synthesis in thyroid cells and results in regulating those cell cycle. It was also observed that GGPP is a critical compound for cortical nuerons to protect cell death.We also cloned cDNA of GGPP synthase by detecting a function assay of genes for lipid metabolism enzymes, using E.coli.

本研究的主要目的是阐明与细胞内转导相关的蛋白质异戊烯化的生物学意义以及异戊烯化的机制。为了分析异戊烯化合物作为胆固醇合成途径的中间代谢物的作用，我们开发了一种新方法，将这些中间体封装的脂质体掺入通过抑制HMG-CoA而休息的细胞中。 还原酶，作为胆固醇合成途径中的限速酶。该方法观察到类异戊二烯化合物之一香叶基香叶基焦磷酸 (GGPP) 对甲状腺细胞中激素依赖性 DNA 合成具有作用，并导致调节这些细胞周期。还观察到GGPP是皮质神经元保护细胞死亡的关键化合物。我们还通过使用大肠杆菌检测脂质代谢酶基因的功能分析克隆了GGPP合酶的cDNA。

项目成果

Sadahira Y,Yasuda T, 他: "Impaired splenic erythropoiesis in phlebotomized mice injected with CL2M DP-liposome : an experimental model for studying the role of stromal macrophages in erythropoiesis."J Leukoc Biol.. 68(4). 464-470 (2000)

Sadahira Y、Yasuda T 等人：“注射 CL2M DP 脂质体的静脉切开小鼠脾脏红细胞生成受损：研究基质巨噬细胞在红细胞生成中的作用的实验模型。”J Leukoc Biol.. 68(4)。 470 (2000)

Kunitomi M,Yasuda T, 他: "Selective inhibition of hepatoma cells using diphtheria a toxin A under the control of the promoter/enhancer region of the human alpha-fetoprotein gene."Jpn J Cancer Res.. 91(3). 343-350 (2000)

Kunitomi M、Yasuda T 等人：“在人甲胎蛋白基因的启动子/增强子区域的控制下，使用白喉毒素 A 选择性抑制肝癌细胞。”Jpn J Cancer Res.. 91(3)。 343- 350 (2000)

Idani, H., Yasuda, T., et al.: "Intra-tumoral injection of doxorubicin (adriamycin) encapsulated in liposome inhibits tumor growth, prolongs survival time and is not associated with local or systemic side effects."Int.J.Cancer. 88. 645-651 (2000)

Idani, H.、Yasuda, T. 等人：“肿瘤内注射封装在脂质体中的阿霉素（阿霉素）可抑制肿瘤生长，延长生存时间，并且与局部或全身副作用无关。”Int.J.

Sadahira Y,Yasuda T, 他: "Impaired splenic erythropoiesis in phlebotomized mice injected with CL2MDP-liposome : an experimental model for studying the role of stromal macrophages in erythropoiesis."J Leukoc Biol.. 68(4). 464-470 (2000)

Sadahira Y、Yasuda T 等人：“注射 CL2MDP 脂质体的静脉切开小鼠脾脏红细胞生成受损：研究基质巨噬细胞在红细胞生成中的作用的实验模型。J Leukoc Biol.. 464-470。” (2000)

Nishimura, M., Yasuda, T., et al.: "Collagen secretion and growth of mesangial cells require geranylgeranyl-pyrophosphate.."Kidney International. 55. 520-528 (1999)

Nishimura, M.、Yasuda, T. 等人：“胶原蛋白分泌和系膜细胞生长需要香叶基香叶基焦磷酸盐。”肾脏国际。