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The role of reactive oxygen species as bioactive substances in the regulation of luteal function

活性氧作为生物活性物质在黄体功能调节中的作用

基本信息

批准号：
20591918
负责人：
SUGINO Norihiro
金额：
$ 3万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2010
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591918/
关键词：
生殖医学黄体プロゲステロン PGF2α 活性酸素黄体退縮

项目摘要

This study was undertaken to investigate how prostaglandin F2α(PGF2α) increases PGF2αsynthesis and cyclooxygenase-2 (COX-2) expression in the corpus luteum in pseudopregnant rats. We further investigated the molecular mechanism by which PGF2αstimulates COX-2 expression. PGF2α (3 mg/kg) or phosphate buffer as a control was injected subcutaneously on day 7 of pseudopregnancy. COX-2 mRNA expression and PGF2αconcentrations in the corpus luteum were measured 2 h, 6 h, and 24 h after PGF2αinjection. PGF2αsignificantly increased COX-2 mRNA expression at 2 h and luteal PGF2αconcentrations at 24 h. PGF2αsignificantly decreased serum progesterone levels at all of the times studied. Simultaneous administration of a selective COX-2 inhibitor (NS-398, 10 mg/kg) completely abolished the increase in luteal PGF2αconcentrations induced by PGF2α. PGF2αincreased NF-κB p65 protein expression in the nucleus of luteal cells 30 min after PGF2αinjection, and electrophoretic mobility shift assay revealed that PGF2αincreased binding activities of NF-κB to the NF-κB consensus sequence of the COX-2 gene promoter. Simultaneous administration of both superoxide dismutase (SOD) and catalase to scavenge reactive oxygen species (ROS) inhibited the increases of nuclear NF-κB p65 protein expression, lipid peroxide levels, and COX-2 mRNA expression induced by PGF2α. In conclusion, PGF2αstimulates COX-2 mRNA expression and PGF2αsynthesis through NF-κB activation via ROS in the corpus luteum of pseudopregnant rats.

本研究旨在探讨前列腺素F2受体(Prostaglandin F2α，α)对假孕大鼠黄体组织中PGF2α合成和环氧合酶-2(COX-2)表达的影响。我们进一步研究了前列腺素F2α刺激COX-2表达的分子机制。假孕第7天皮下注射前列腺素F2α(3 mg/kg)或磷酸盐缓冲液作为对照。分别于注射前列腺素F2α后2、6、24 h检测黄体组织环氧合酶-2mRNA的表达及α浓度。PgF2α在2 h可显著增加COX-2mRNA的表达，在24 h可显著增加黄体中PgF 2α的浓度，而PgF 2α可显著降低血清孕酮水平。同时给予选择性COX-2抑制剂(NS-398，10 mg/kg)，可完全消除由PGF_2αα引起的黄体PGF_2α浓度升高。注射pGF2α后30min，黄体细胞核内NF-κB p65蛋白表达增加，凝胶迁移率改变分析显示，pGF2α增加了NF-αB与COX-2基因启动子的NF-κB共同序列的结合活性。同时给予超氧化物歧化酶和过氧化氢酶清除活性氧可抑制PgF2P65蛋白表达、脂质过氧化水平和COX-2mR NA表达的增加。κB p65蛋白表达、脂质过氧化水平和COX-2mR NA表达均可被抑制。结论：PGF_2α通过ROS激活假孕大鼠黄体组织中的核因子-αB，促进COX-2mRNA表达和PGF_2κ合成。