Studies on Apoptosis induced by Isoprenoids

本文研究了几种类异戊二烯化合物诱导大鼠胸腺细胞凋亡的能力。法尼醇（F OH）和香叶基香叶醇（GGOH）分别在25 μ M和15 μ M的浓度下作为凋亡诱导剂。接下来，我们化学合成了法呢基醛（FCHO）、法呢酸（FCOOH）、法呢基磷酸酯（FP）、（R，S）-2，3-二氢-FOH、（R，S）-2，3-二氢-FCHO、（R，S）-2，3-二氢-FCOQH、（R，S）-2，3-二氢-FNP、香叶基香叶基醛（GGCHO）、香叶基香叶酸（GGCOOH）、香叶基香叶基磷酸酯（GGP）、Z，E，E-GGOH、Z，E，结果显示，GGOH、GGCHO和GGGOOH在器官中诱导强得多的凋亡。这三种化合物对胸腺细胞的作用不同，GGOH直接抑制PC合成，GGCOOH也间接抑制PC合成，GGCHO部分抑制PC合成。在SDS-聚丙烯酰胺凝胶电泳上分析异戊二烯化的蛋白质时，氚标记的GGOH、GGP或二磷酸香叶酯的放射性掺入到21 - 28 KD蛋白质中，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对PC合成途径的作用以及GGGHO对未知途径的作用与凋亡现象有关。

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.