Studies on Apoptosis induced by Isoprenoids

类异戊二烯诱导细胞凋亡的研究

• 批准号: 09680611
• 负责人: SAGAMI Hiroshi
• 金额: $ 2.24万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09680611/
• 关键词: isoprenoid; apoptosis; thymus; farnesol; geranylgeraniol; mevalonic acid; compactin; rat; ファルネソ-ル

The ability of various isoprenoid compounds to induce the apoptosis in rat thymocytes was investigated. Farnesol (F OH) and geranylgeraniol (GGOH) acted as apoptotic inducers at the concentration of 25 mu M and 15 mu M, respectively. Next we chemically synthesized farnesyl aldehyde, (FCHO), farnesoic acid (FCOOH), farnesylph osph ate (FP), (R,S)- 2,3- dihydroF OH, (R, S)- 2,3- dihydro- F CHO, (R,S)- 2,3- dihydro-F COQH, (R,S)- 2,3- dihydro- F P, geranylgeranylaldehyde (GGCHO), geranylgeran oicacid (GGCOOH), geranylgeranyl phosphate (GGP), Z,E,E-GGOH, Z,E,E-GGCHO, and E,Z,E-GGOH.As a result, GGOH, GGCHO, and GGGOOH were shown to induce much stronger apoptosis in the organ. The effects of these three compounds on the thymocyte were different from each other in that GGOH directly inhibited phosphatidyl choline (PC) synthesis ; GGCOOH also inhibited the PC synthesis in anindirect manner ; GGCHO partially inhibited the PC synthesis. And, GGOH and GGCOOH were recovered as their original forms but GGCHO was not recovered after at least 30 min incubation, On the analysis of prenylated proteins on SDS-polyacrylamide gel electroph oresis, the radioactivity derived from tritiu m- labeled GGOH, GGP, or geranyl diphosphate was incorporated into 21 -28 k Dproteins with GGP being the better tracer. These results indicate the isoprenoid metabolic pathway is associated with apoptotic phenomena through the action of GGOH and GGCOOH to the PC synthetic pathway and through that of GGGHO to anun known pathway.

研究了不同的异戊二烯类化合物诱导大鼠胸腺细胞凋亡的能力。金合欢醇(F OH)和香叶醇(GGOH)分别在25 mU M和15 mU M浓度下作为细胞凋亡诱导剂。接下来，我们化学合成了金合欢醛、金合欢酸、金合欢酯、(R，S)-2，3-二氢F-OH、(R，S)-2，3-二氢-F-CHO、(R，S)-2，3-二氢-F-COQH、(R，S)-2，3-二氢-F-P、香叶醛、香叶酸、香叶基香叶酸、Z、E、E-GGOH、Z，E、E-GGCHO和E，Z，E-GGOH。和GGGOOH被证明在器官中诱导更强的细胞凋亡。三种化合物对胸腺细胞的作用不同，GGOH直接抑制磷脂酰胆碱(PC)的合成，GGCOOH间接抑制PC的合成，GGCHO部分抑制PC的合成。而GGOH和GGCOOH在孵育至少30min后仍未恢复到原来的形态。在SDS-聚丙烯酰胺凝胶电泳法分析预酯化的蛋白质时，来自氚标记的GGOH、GGP或香叶基二磷酸的放射性被掺入21-28k的DProtein中，GGP是较好的示踪剂。这些结果表明，类异戊二烯代谢途径通过GGOH和GGCOOH作用于PC合成途径和GGGHO作用于Anunn途径而与细胞凋亡现象有关。

项目成果

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T.Kuzuguchi 等人：“人香叶基香叶基二磷酸合成酶：cDNA 克隆和表达”J.Biol.Chem.274。

T.Kuzuguchi et al.: "Human GeranylgeranylDiphosphate Synthatse : cDNA Cloning and Expression" J.Biol.Chem.274. 5855-5894 (1999)

T.Kuzuguchi 等人：“人香叶基香叶基二磷酸合成酶：cDNA 克隆和表达”J.Biol.Chem.274。

T. Ohkura et al.: "A Partial Deficiency of Dehydrodolichol Reduction is a Cause of Carbohydrate Deficient Glycoprotein Syndrome Type I" J. Biol. Chem.272. 6868-6875 (1997)

T. Ohkura 等人：“脱氢多酚还原的部分缺乏是 I 型碳水化合物缺乏糖蛋白综合征的原因”J. Biol。

A. Kikuchi et al.: "Evidence for Covalent Atachment of Diphytanylglyceryl Phosphate to the Cell Surface Glycoprotein of Halobacterium halobium" J. Biol. Chem. in press.

A. Kikuchi 等人：“磷酸二植烷酰甘油酯与盐杆菌细胞表面糖蛋白共价附着的证据”，J. Biol。

T.Ohkura et al.: "A Partial Deficiency of Dehydrodolichol Reduction is a Cause of Carbohydrate Deficient Glycoprotein Syndrome Type l" J.Biol.Chem.272. 6868-6875 (1997)

T.Ohkura 等人：“脱氢多羟基化合物还原的部分缺乏是 I 型碳水化合物缺乏糖蛋白综合征的原因”J.Biol.Chem.272。