Mechanism of transcription of phospholipid glutathione peroxidase

磷脂谷胱甘肽过氧化物酶的转录机制

基本信息

批准号：
10672052
负责人：
NAKAGAWA Yasuhito
金额：
$ 2.43万
依托单位：
Kitasato University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672052/
关键词：
glutathione peroxidase mitochondria infertile genome 過酸化脂質抗酸化酵素

项目摘要

Non-mitochondrial PHGPx was highly expressed in somatic cells such as kidney cells and L929 cells, while the expression of mitochondrial PHGPx was quite low in these cells. Expression of mitochondrial PHGPx was initiated in the 3 weeks development-stage of testis of mice. However, expression of mitochondrial PHGPx was not induced in kidney. Activity of promoter of mitochondrial PHGPx was almost one third of that of total PHGPx. The region of core promoter of mitochondrial PHGPx was the region from -233 to -158 which included SP1 site. While core promoter of non-mitochondrial PHGPx was found in the region from -176 to -56 in which NFY site, CCAAT box and AP2 site.PHGPx was intensely expressed in mitochondria in the mid-piece of human spermatozoa. We found a dramatic decrease in the level of expression of PHGPx in the spermatozoa of some infertile males. These individuals accounted for about 10% of the group of 73 infertile males that we examined. All seven patients with PHGPx-defective spermatozoa were classified as suffering from oligo-asthenozoospermia, a defect in which both the number and the motility of spermatozoa are significantly below normal. Males with PHGPx-defective spermatozoa accounted for 35% of the 27 infertile males with oligo-asthenozoospermia. No defects in expression of PHGPx in spermatozoa were observed in 31 fertile volunteers. Ultrastructual analysis of mitochondria by electron microscopy demonstrated that the morphology of mitochondria in PHGPx-defective spermatozoa was abnormal. The results suggest that failure of the expression of mitochondrial PHGPx in spermatozoa might be one of the causes of oligo-asthenozoospermia in infertile men.

非单位软骨PHGPX在肾细胞和L929细胞等体细胞中高度表达，而这些细胞中线粒体PHGPX的表达非常低。在小鼠睾丸的3周发育阶段开始线粒体PHGPX的表达。但是，线粒体PHGPX的表达未在肾脏中诱导。线粒体PHGPX的启动子的活性几乎是总PHGPX的三分之一。线粒体PHGPX的核心启动子区域是-233至-158区域，其中包括SP1位点。尽管在-176至-56区域发现了非单位角色PHGPX的核心启动子，其中NFY位点，CCAAT盒子和AP2 Site.phgpx在人类精子中间的线粒体中强烈表达。我们发现某些不育男性的精子中PHGPX表达水平急剧下降。这些人约占我们检查的73名不育男性组的10％。所有七名患有PHGPX缺陷精子的患者均被归类为患有寡素 - 甲状腺素的患者，这种缺陷在其中精子的数量和运动性都显着低于正常水平。患有PHGPX缺陷精子的雄性占27个不育男性的35％，占寡素 - 硫代杀菌剂。在31位肥沃的志愿者中，未观察到精子中PHGPX表达的缺陷。通过电子显微镜对线粒体的超结构分析表明，PHGPX缺陷性精子中线粒体的形态异常。结果表明，精子中线粒体PHGPX表达的失败可能是不育男性中寡素 - asthenozoospermia的原因之一。