Role of PHGPx on the embryogenesis and sperm maturation

PHGPx 对胚胎发生和精子成熟的作用

• 批准号: 16590059
• 负责人: NAKAGAWA Yasuhito
• 金额: $ 2.3万
• 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: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590059/
• 关键词: testis; apoptosis; glutathione peroxidase; embryo; 胚発生; トランスジェニックマウス; グルタチオペルオキシダーゼ; 精子形成; ethane dimethane sulfonate

Condition of primary culture of fertilized ovum was established to realized the mechanism of embryonic lethal of knockout mouse of PHGPx (GPx4). Inner cell mass (ICM) and prominent expression of PHGPx were formed during 3days culture of wild type of embryo. On the other hand, growth of ICM was significantly suppressed in PHGPx-KO embryo and was disappeared during 7 days culture. We prepared PHGPx-hetero mouse which were introduced exogeous PHGPx gene. KO-PHGPx mouse was rescued by the introduction of PHGPx gene.Low expression of PHGPx in sperm caused severe infertility of male. EDS induced infertility of mouse by the injury of testis. Injury of testis was more prominent in hetero mouse whose expression of PHGPx was almost half as compare to wild type of mouse.

为了解PHGPx（GPx 4）基因敲除小鼠胚胎致死机理，建立了受精卵原代培养条件。野生型胚胎在培养3d时形成内细胞团（ICM），PHGPx的表达明显增强。另一方面，在PHGPx-KO胚胎中ICM的生长受到显著抑制，并且在培养7天期间消失。我们制备了PHGPx-异源小鼠，导入外源PHGPx基因。通过导入PHGPx基因拯救了KO-PHGPx小鼠，PHGPx在精子中的低表达导致了严重的雄性不育。EDS通过损伤睾丸导致小鼠不育。异源小鼠睾丸损伤较明显，PHGPx表达量较野生型小鼠减少近一半。

项目成果

Up-regulation of phospholipid hydroperoxide glutathione peroxidase in rat casein-induced polymorphonuclear neutrophiils.

大鼠酪蛋白诱导的多形核中性粒细胞中磷脂氢过氧化物谷胱甘肽过氧化物酶的上调。

• 发表时间: 2005
• 期刊: Biochem. J. 389
• 作者: Hattori H;Imai H;Hanamoto A;Furuhama K;Nakagawa Y
• 通讯作者: Nakagawa Y

Involvement of hydro peroxide in mitochondria in the induction of apoptosis by EPA

线粒体中过氧化氢参与 EPA 诱导细胞凋亡

• 发表时间: 2005
• 期刊: Free Radical Res. 39
• 作者: Hiroyuki;Watanabe;et. al.;Hattori H.;吉岡 麻也;Otsu K.;Koumura T.
• 通讯作者: Koumura T.

Induction of phospholipid hydroperoxide glutathione peroxidase in human polymorphonuclear neutrophills and HL60 cells stimulated with TNF-α.

在用 TNF-α 刺激的人多形核中性粒细胞和 HL60 细胞中诱导磷脂氢过氧化物谷胱甘肽过氧化物酶。

• 发表时间: 2005
• 期刊: Biochemical and Biophysical Research Communications 337
• 作者: Hattori H;Imai H;Furuhama K;Sato O;Nakagawa Y
• 通讯作者: Nakagawa Y

Biological significance of lipid hydroperoxidase and its reducing enzyme, phospholipid hydroperoxide glutathione peroxidase in mammalian cells

脂质氢过氧化物酶及其还原酶磷脂氢过氧化物谷胱甘肽过氧化物酶在哺乳动物细胞中的生物学意义

• 发表时间: 2004
• 期刊: YAKUGAKU ZASSH 124(12)
• 作者: Hirokazu;Takagi;Nakagawa Y;渡邉 廣行;Imai H
• 通讯作者: Imai H

Initiation of apoptotic signal by the peroxidation of cardiolipin of mitochondria

• DOI: 10.1196/annals.1293.018
• 发表时间: 2004-01-01
• 期刊: MITOCHONDRIAL PATHOGENESIS: FROM GENES AND APOPTOSIS TO AGING AND DISEASE
• 作者: Nakagawa, Y