Modulation of antioxidant enzyme expression and function by estrogen
Modulation of antioxidant enzyme expression and function by estrogen
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DOI：
10.1161/01.res.0000082334.17947.11
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发表时间：
2003-07-25
影响因子：
20.1
通讯作者：
Nickenig, G
中科院分区：
文献类型：
--
作者：
Strehlow, K;Rotter, S;Nickenig, G
氧化应激在动脉粥样硬化的发病机制中起着关键作用，自由基清除酶的活性和表达可以有效地影响氧化应激。雌激素的血管保护作用可能与抗氧化特性有关。因此，研究了17 β-雌二醇对活性氧和自由基清除酶产生的影响。17 β-雌二醇减少血管平滑肌细胞中血管紧张素II诱导的自由基产生（DCF荧光激光显微镜）。17 β-雌二醇时间和浓度依赖性上调锰（MnSOD）和细胞外超氧化物歧化酶（ecSOD）的表达（北方和西方印迹法）和酶活性（光度测定）。核连续实验表明，17 β-雌二醇增加MnSOD和ecSOD的转录速率。MnSOD mRNA的半衰期不受影响，而ecSOD mRNA的稳定雌激素。铜锌超氧化物歧化酶，谷胱甘肽过氧化物酶，过氧化氢酶没有受到雌激素的影响。雌激素缺乏在卵巢切除小鼠诱导下调ecSOD和MnSOD的表达，这与血管自由基的产生增加，并防止雌激素替代或治疗与PEG-SOD。在人类中，增加雌激素水平导致循环单核细胞中ecSOD和MnSOD表达增强。雌激素至少在一定程度上通过刺激MnSOD和ecSOD的表达和活性来发挥抗氧化作用，这可能有助于其血管保护作用。
Oxidative stress plays a pivotal role in the pathogenesis of atherosclerosis and can be effectively influenced by radical scavenging enzyme activity and expression. The vasoprotective effects of estrogens may be related to antioxidative properties. Therefore, effects of 17beta-estradiol on production of reactive oxygen species and radical scavenging enzymes were investigated. 17beta-estradiol diminished angiotensin II-induced free radical production in vascular smooth muscle cells (DCF fluorescence laser microscopy). 17beta-estradiol time- and concentration-dependently upregulated manganese (MnSOD) and extracellular superoxide dismutase (ecSOD) expression (Northern and Western blotting) and enzyme activity (photometric assay). Nuclear run-on assays demonstrated that 17beta-estradiol increases MnSOD and ecSOD transcription rate. Half-life of MnSOD mRNA was not influenced, whereas ecSOD mRNA was stabilized by estrogen. Copper-zinc SOD, glutathione-peroxidase, and catalase were not affected by estrogen. Estrogen deficiency in ovariectomized mice induced a downregulation of ecSOD and MnSOD expression, which was associated with increased production of vascular free radicals and prevented by estrogen replacement or treatment with PEG-SOD. In humans, increased estrogen levels led to enhanced ecSOD and MnSOD expression in circulating monocytes. Estrogen acts antioxidative at least to some extent via stimulation of MnSOD and ecSOD expression and activity, which may contribute to its vasoprotective effects.