Project/Area Number |
11470344
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Obstetrics and gynecology
|
Research Institution | The University of Tokyo |
Principal Investigator |
MORI Tsuneatsu Institute of Medical Science, The University of Tokyo, Associate Professor, 医科学研究所, 助教授 (40012760)
|
Co-Investigator(Kenkyū-buntansha) |
TAKASAKI Seiichi Institute of Medical Science, The University of Tokyo, Associate Professor, 医科学研究所, 助教授 (80112093)
|
Project Period (FY) |
1999 – 2001
|
Project Status |
Completed (Fiscal Year 2001)
|
Budget Amount *help |
¥7,800,000 (Direct Cost: ¥7,800,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥3,200,000 (Direct Cost: ¥3,200,000)
|
Keywords | Soern / Egg / Fas / FasL system / Apoptosis / CD5γHLA-DR* NS cell / Apoptosis-inducing nucleosides / DNA strand break / Caspase-3 / FasL系 / CD57^+HLA-DR^<bright>NS細胞 / DNA strand break / 精巣 / 卵巣 / 受精 / 胎盤脱落膜 / Fas-FasL / Apoptosis Inducing Nucleoside |
Research Abstract |
The ovarian follicular arresia is one of typical phenomenoes in programmed cell death. We have recently demonstrated that the definite expression of Fas was found in ovarian oocytes, ovarilated eggs and grandosa cells in maturated follicle, while, Fas legend (L) was restrictedly expressed in grandosa cells under the * regulation of gonadotropins. Therefore, we concluded that Fas -FasL system display a primary role to promote ovarian atresia through apoptosis, most likely depending on local gonadotropin levels in the ovary. In marine tests, we have revended that Fas is expressed in testicular germ cells and FasL is expressed in sertoli cells indicating their molecular interactions during the spermatogenesis. Based on the analysis of all or partial sugar structurer os porcine or marine zona pellucida (ZP), we found that marine or porine sperm bound to β-Galactose rather than α-Galactose residue and/or Le^x residue on egg ZP. We are now cloning the gene of β-Galactose binding protein from
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porcine tests. We have further confirmed the expression and function of CD4/p56* complex on marine egg plasma membrane corresponding to the presence of MHC class 11 molecule at the posteriox region of sprm. The decidua-derived CD57-HLA-DR* natural suppressor (57.DR-NS) cell line relenses a series of active factors into the culture to generate the apoptosis of human malignant cells and trophoblast cells. Actually, 57-DR-NS cell line generated the apoptosis in human * (Molt4/K562) and gastric / esophageal / prostatix or chorionic carcinoma (GCIY / T.Tn / PC-3 /BeWo) cells but not in a human diploid normal (W1-38) cells. The chemical structures of the active factors were determined as a series of modified nucleasides. They could generate the apoptotic cell death of Molt4/K562 and GCIY/T.Tn/PC-3/BeWo malignant cells following by DNA strand breaks and caspase-3 activation, but not that of WI-38 normal cells at all. The administration of them into GCIY/Molt4 tumor bearing SCID mice resulted in the drastic suppression of turnor growth followed by the decrease in tunor size due to the occurrence of apoptosis in * tissues. Less
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