Mechanism of transcription of phospholipid glutathione peroxidase

非线粒体PHGPx在体细胞如肾细胞和L929细胞中高表达，而线粒体PHGPx在这些细胞中表达很低。线粒体PHGPx的表达始于小鼠睾丸发育的3周。然而，线粒体PHGPx的表达在肾脏中没有被诱导。线粒体PHGPx启动子活性约为总PHGPx启动子活性的1/3。线粒体PHGPx核心启动子区为-233 ~-158区域，包括SP1位点。而非线粒体型PHGPx基因的核心启动子位于NFY位点、CCAAT box和AP 2位点之间的-176 ~-56区域，在人精子中段线粒体中有较强的表达。我们发现一个显着的下降，PHGPx的表达水平在一些不育男性的精子。这些人占我们检查的73名不育男性中的10%。所有7例PHGPx缺陷型精子患者均被归类为患有少弱精子症，这是一种精子数量和活力均明显低于正常的缺陷。PHGPx缺陷精子占27例少弱精子症不育男性的35%。31例正常生育者精子PHGPx表达无异常。电镜下线粒体超微结构分析表明，PHGPx缺陷精子线粒体形态异常。结果提示，精子线粒体PHGPx表达缺失可能是导致少弱精子症的原因之一。

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.