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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.

非线粒体PHGPx在肾细胞和L929细胞中高表达，而线粒体PHGPx在这些细胞中低表达。小鼠睾丸线粒体PHGPx在3周发育期开始表达。而线粒体PHGPx在肾脏中的表达不受诱导。线粒体PHGPx启动子活性约为总PHGPx启动子活性的三分之一。线粒体PHGPx核心启动子区域在-233~-158之间，含有SP1酶切位点。而非线粒体PHGPx的核心启动子位于NFY位点、CCAAT盒和AP2位点的-176~-56之间，在人精子中段线粒体中高表达。我们发现，在一些不育男性的精子中，PHGPx的表达水平急剧下降。在我们检查的73名不育男性中，这些人约占10%。所有7名PHGPx缺陷精子患者都被归类为少弱精子症，这种缺陷的精子数量和活力都明显低于正常。在27例患有少弱精子症的不育男性中，携带PHGPx缺陷精子的男性占35%。在31名有生育能力的志愿者中，没有观察到PHGPx在精子中的表达缺陷。电子显微镜下的线粒体超微结构分析表明，PHGPx缺陷精子的线粒体形态异常。提示精子线粒体PHGPx表达障碍可能是导致少弱精子症的原因之一。