| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
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.
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