Molecular mechanism ofapoptosis in target organs of sex steroid hormones

性类固醇激素靶器官凋亡的分子机制

• 批准号: 12670220
• 负责人: TERADA Nobuyuki
• 金额: $ 2.18万
• 依托单位: HYOGO COLLEGE OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670220/
• 关键词: apoptosis; androgen; estrogen; Fas; Fas ligand; VDAC; mouse; cytochrome C; 子宮; 精嚢; 前立腺; 精巣上体; 凝固腺

1.We examined the effect of castration on apoptosis in the epithelia of the mouse seminal vesicle and epididymis, and found the followings. (1) Castration induces apoptosis in the epithelia of these organs from birth to adulthood. (2) The extent of apoptosis is lower at the slowly growing stage of these organs than at their rapidly growing stage thereafter.2.By the experiments with mutant mice deficient in Fas or Fas ligand, we have shown that the Fas- Fas ligand system plays little role in castration-induced apoptosis in the mouse seminal vesicle, epididymis, prostate and coagulating gland.3.We have shown that apoptosis in the mouse uterine epithelium after estrogen deprivation correlates to release of cytochrome C in mitochondria into cytoplasm, activation of caspase-3, the ratio of Bak or Bax/Bcl-2 or Bcl-xL and the amount of voltage dependent anion channel (VDAC) in the mitochondria. These results suggest the followings. (1) Mitochondria play an important role in estrogen deprivation-induced apoptosis in the uterine epithelium. (2) This apoptotic process is regulated by proteins of the Bcl-2 family. (3) The increase in VDAC enhances the sensitivity of cells to apoptosis since VDAC is thought to be a channel, through which cytochrome C moves from mitochondria to cytoplasm.

1.研究了去势对小鼠精囊和附睾上皮细胞凋亡的影响。(1)去势可诱导这些器官从出生到成年期的上皮细胞的凋亡。2.通过Fas或Fas配体缺陷突变小鼠的实验，我们发现Fas-Fas配体系统在去势诱导的小鼠精囊、附睾腺、前列腺和凝固腺的凋亡中作用不大。3.我们发现雌激素剥夺后小鼠子宫上皮细胞的凋亡与线粒体中细胞色素C释放到细胞质、caspase-3的激活、Bak或Bax/Bcl2或Bclxl的比值以及线粒体中电压依赖性阴离子通道(VDAC)的数量有关。这些结果说明了以下几点。(1)线粒体在雌激素缺乏诱导子宫上皮细胞凋亡中起重要作用。(2)这一凋亡过程受Bcl2家族蛋白的调控。(3)VDAC的增加增强了细胞对凋亡的敏感性，因为VDAC被认为是细胞色素C从线粒体进入细胞质的通道。

项目成果

Takagi-Morishita Y,: "Castration induces apoptosis in the mouse epididymis during postnatal development"Endocrine Journal. 49-1. 75-84 (2002)

Takagi-Morishita Y，：“去势在产后发育过程中诱导小鼠附睾细胞凋亡”内分泌杂志。

SugiharaA.,: "Castration induces apoptosis in the male accessory sex organs of Fas-deficient Ipr and Fas ligand-deficient gld mutant mice"InVivo. 15-5. 385-390 (2001)

SugiharaA.，：“去势诱导 Fas 缺陷 Ipr 和 Fas 配体缺陷 gld 突变小鼠的雄性副性器官凋亡”体内。

Sugihara A., Terada N., et al.: "Castration induces apoptosis in the male accessory sex organs of Fas-deficient Ipr and Fas ligand-deficient gid mutant mice"In Vivo. 15・5. 385-390 (2001)

Sugihara A., Terada N., et al.：“去势诱导 Fas 缺陷 Ipr 和 Fas 配体缺陷 gid 突变小鼠的雄性副性器官凋亡”In Vivo 15·5 (2001)。

Sugihara A., Terada N., et al.: "Castration induces apoptosis in the male accessory sex organs of Fas-deficient lpr and Fas ligand-deficient gld mutant mice"In Vivo. 15・5. 385-390 (2001)

Sugihara A., Terada N., et al.：“去势诱导 Fas 缺陷 lpr 和 Fas 配体缺陷 gld 突变小鼠的雄性副性器官凋亡”In Vivo 15·5 (2001)。

Sugihara A.: "Castration induces apoptosis in the male accessory sex organs of Fas-deficient lpr and Fas ligand-deficient gld mutant mice"in vivo. (in press). (2001)

Sugihara A.：“去势会诱导 Fas 缺陷 lpr 和 Fas 配体缺陷 gld 突变小鼠的雄性副性器官凋亡”体内。