2000 Fiscal Year Final Research Report Summary
Mechanism of transcription of phospholipid glutathione peroxidase
| Project/Area Number |
10672052
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kitasato University |
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Principal Investigator |
NAKAGAWA Yasuhito Kitasato University, School of Pharmaceutical Science, Professor, 薬学部, 教授 (00119603)
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| Co-Investigator(Kenkyū-buntansha) |
IMAI Hirotaka Kitasato University, School of Pharmaceutical Science, 薬学部, 講師 (50255361)
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| Project Period (FY) |
1999 – 2000
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| Keywords | glutathione peroxidase / mitochondria / infertile / genome |
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| Research Abstract |
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.
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[Publications] Imai, H., Suzuki, K., Ishizaka, K., Ichinose, S., Oshima, H., Okayasu, I., Emoto, K., Umeda, M.and Nakagawa, Y.: "Failure of the the Expression of Phospholipid Hydroperoxide Glutathione Peroxidase in the Spermatozoa of Human Infaile Males"Biology of Reproduction. 64. 674-683 (2001)
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