Molecular mechanism of apoptosis of reproductive cells and fertilization
生殖细胞凋亡和受精的分子机制
基本信息
- 批准号:14571542
- 负责人:
- 金额:$ 2.24万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2002
- 资助国家:日本
- 起止时间:2002 至 2003
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
1) To understand the molecular mechanisms leading to ovarian follicular atresia in MRL/lpr mouse, we examined the apoptotic signalling pathway. The results indicated that MRL/+ murine oocytes and MRL/lpr is through the Fas receptor followed by the activation of caspase-3. In contrast, we found that the aberrant expression and dysfunction of the mutant Fas receptor in MRL/lpr murine oocytes caused by insertion of the early transposable element into the Fas gene were associated with an inability to activate the caspase cascade (especially caspase-3) and to induce nuclear DNA fragmentation. These findings indicate that the induction of apoptosis in MRL/lpr murine oocytes did not occur in the presence of a defective Fas receptor lacking the death domain to trigger the caspase cascade, suggesting a failure to induce ovarian follicular atresia.2) Six apoptosis-inducing nucleosides (AINs) released into cell culture media of 57.DR-NS (the CD57^+HLA-DR-<bright> natural suppressor cell line deri … More ved from human decidual tissue) were isolated by the combination of physicochemical procedures. Subsequently, we demonstrated that AINs could induce apoptosis 'in human leukemia Molt4 and carcinoma BeWo/GCIY cells but not human fibroblast WI-38 cells. The AINs also induced apoptosis in human prostate cancer PC3 cells, estrogen-non-responsive human breast carcinoma MDA-MB-435 cells, and human gastric carcinoma cells. Apoptosis was characterized by DNA strand breaks and activation of the caspase cascade, especially caspase-3. The administration of AINs into tumor bearing SCID mice culminated in suppression of tumor growth due to apoptosis of tumor cells.3) By using sugar probes, we found several proteins in boar sperm lysate which bind to oligosaccharide probes. One of them was a homologue of ADAM4 based on the analysis of partial amino acid sequence. We cloned its cDNA, and produced its recombinant protein in a secreted form in yeast. Functional analysis indicated that the protein has an adhesion activity to integrin, suggesting its role in fertilization. Less
1)为了了解导致MRL/lpr小鼠卵巢卵泡闭锁的分子机制,我们研究了凋亡信号通路。结果表明,MRL/+小鼠卵母细胞和MRL/lpr是通过Fas受体后caspase-3的激活。与此相反,我们发现,在MRL/lpr小鼠卵母细胞的突变型Fas受体的早期转座因子插入到Fas基因的异常表达和功能障碍与不能激活caspase级联反应(特别是caspase-3),并诱导核DNA片段。这些发现表明,在缺乏触发caspase级联反应的死亡结构域的缺陷型Fas受体存在的情况下,MRL/lpr小鼠卵母细胞中的凋亡诱导并不发生,这表明诱导卵巢卵泡闭锁失败。2)将六种凋亡诱导核苷(AIN)释放到57.DR-NS(CD 57 ^+ HLA-DR-天然抑制细胞系,来自于CD 57 ^+HLA-DR-天然抑制细胞系,来自于CD 57 ^+HLA-DR-天然抑制细胞系,来自于CD 57 ^+HLA-DR-<bright>天然抑制细胞系,来自于CD 57 ^+HLA-DR-天然抑制细胞系。 ...更多信息 VED来自人蜕膜组织)通过物理化学方法的组合分离。随后,我们证明AINs可以诱导人白血病Molt 4和癌BeWo/GCIY细胞凋亡,但不能诱导人成纤维细胞WI-38细胞凋亡。AINs还诱导人前列腺癌PC 3细胞、雌激素非应答性人乳腺癌MDA-MB-435细胞和人胃癌细胞的凋亡。细胞凋亡的特点是DNA链断裂和激活的caspase级联反应,特别是caspase-3。将AIN给予荷瘤SCID小鼠,由于肿瘤细胞的凋亡,肿瘤生长受到抑制。3)通过使用糖探针,我们在猪精子裂解物中发现了几种与寡糖探针结合的蛋白质。其中一个经部分氨基酸序列分析为ADAM 4的同源物。我们克隆了它的cDNA,并在酵母中以分泌形式产生了它的重组蛋白。功能分析表明,该蛋白具有粘附活性的整合素,表明其在受精中的作用。少
项目成果
期刊论文数量(41)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mori, T.: "Human malignant cell death by apoptosis-inducing nucleosides from the decidua derived CD57^+HLA-DR^<bright> natural suppressor cell line"J.Reprod.Immunol.. 53. 289-303 (2002)
Mori, T.:“来自蜕膜来源的 CD57^ HLA-DR^<bright> 天然抑制细胞系的凋亡诱导核苷引起的人类恶性细胞死亡”J.Reprod.Immunol.. 53. 289-303 (2002)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Mori, T.: "Human malignant cell death by apoptosis-inducing nucleosides from the decidua derived CD57^+HLA-DR^<bright> natural suppressor cell line"J Reprod Immunol.. 53. 289-303 (2002)
Mori, T.:“来自蜕膜来源的 CD57^ HLA-DR^<bright> 天然抑制细胞系的凋亡诱导核苷引起的人类恶性细胞死亡”J Reprod Nutrition.. 53. 289-303 (2002)
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- 影响因子:0
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- 通讯作者:
Jin, A.: "Therapeutic effects of novel anti-tumor reagent, apoptosis inducing nucleotides from CD57^+HLA-DR^<bright> natural suppressor cell line on human gastric carcinoma-bearing SCID mice"Int.J.Oncol. 24(in press). (2004)
Jin, A.:“新型抗肿瘤试剂、CD57^HLA-DR^<bright>天然抑制细胞系的凋亡诱导核苷酸对人胃癌荷瘤 SCID 小鼠的治疗效果”Int.J.Oncol。
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- 影响因子:0
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Asano, M: "Impaired selectin ligand biosynthesis and reduced inflammatory responses in β-1,4-galactosyltransferase-I-deficient mice"Blood. 102・5. 1678-1685 (2003)
Asano, M:“β-1,4-半乳糖基转移酶-I 缺陷型小鼠的选择蛋白配体生物合成受损并减少炎症反应”Blood 102・5 (2003)。
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- 影响因子:0
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Mori, T., et al.: "Human malignant cell death by apoptosis-inducing nucleosides from the decidua derived CD57^+HLA-DR^<bright> natural suppressor cell line"J. Reprod. Immunol.. 53. 289-303 (2002)
Mori, T. 等人:“来自蜕膜来源的 CD57^ HLA-DR^<bright> 天然抑制细胞系的凋亡诱导核苷导致人类恶性细胞死亡”J.
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TAKASAKI Seiichi其他文献
TAKASAKI Seiichi的其他文献
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{{ truncateString('TAKASAKI Seiichi', 18)}}的其他基金
Analysis of sperm proteins involved in mammalian fertilization
哺乳动物受精过程中精子蛋白的分析
- 批准号:
17590240 - 财政年份:2005
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Analysis of sperm carbohydrate recognition molecules involved in fertilization
参与受精的精子碳水化合物识别分子分析
- 批准号:
12680604 - 财政年份:2000
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Analysis of carbohydrate recognition mechanism in fertilization
受精过程中碳水化合物识别机制分析
- 批准号:
10680578 - 财政年份:1998
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Cell and molecular biology of enzymes involved in branch formation of mucin-type sugar chains
参与粘蛋白型糖链分支形成的酶的细胞和分子生物学
- 批准号:
07458150 - 财政年份:1995
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Analysis of structure and function of sugar chains included in Fc receptor
Fc受体中糖链的结构和功能分析
- 批准号:
02808025 - 财政年份:1990
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
Role of sugar chain in the induction of Fc receptor-mediated phagocytosis by macrophages
糖链在诱导巨噬细胞 Fc 受体介导的吞噬作用中的作用
- 批准号:
62580109 - 财政年份:1987
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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