Effect of gender on NADPH-oxidase activity, expression, and function in the cerebral circulation - Role of estrogen
Effect of gender on NADPH-oxidase activity, expression, and function in the cerebral circulation - Role of estrogen
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DOI：
10.1161/strokeaha.106.477406
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发表时间：
2007-07-01
期刊：
影响因子：
8.3
通讯作者：
Sobey, Christopher G.
中科院分区：
文献类型：
--
作者：
Miller, Alyson A.;Drummond, Grant R.;Sobey, Christopher G.
背景和目的-这项研究测试是否NADPH氧化酶的活性，表达和功能的影响，血管紧张度的性别在大鼠脑circulation.Methods -NADPH刺激的超氧化物的产生大脑（基底[ BA];大脑中）动脉从男性和女性Sprague-Dawley大鼠使用光泽精增强化学发光和dihydroethidium的影响，以及这种差异是否是雌激素依赖。蛋白质表达的Nox 1，Nor 2，Nox 4，超氧化物歧化酶1（SOD 1），SOD 2，和SOD 3使用蛋白质印迹法测定。在肌电描记器中评估BA对NADPH的血管反应。一些雌性大鼠卵巢切除和治疗与车辆（二甲基亚砜）或17 β-estradiol.Results -NADPH刺激的超氧化物的生产BA和大脑中动脉从男性约2倍大于女性的血管。NADPH氧化酶抑制剂diphenyleneiodonium几乎完全抑制了超氧化物的产生。Nox 1和Nox 4在BA中的蛋白表达在雄性中也高于雌性（分别为2.4倍和2.8倍），而Nox 2、SOD 1、SOD 2和SOD 3的表达在性别之间没有差异。NADPH对雄性大鼠BA的舒张作用强于雌性大鼠（P < 0.05）。过氧化氢清除剂，过氧化氢酶，取消这些NADPH诱导的松弛。用溶剂处理的卵巢切除大鼠中，由BA引起的NADPH刺激的超氧化物产生量是完整雌性大鼠的3倍。用17 β-雌二醇治疗卵巢切除大鼠可减少超氧化物的产生（P < 0.05）。17 β-雌二醇处理组的NADPH诱导的BA舒张作用小于对照组（P < 0.05）。结论雌性大鼠脑动脉中NADPH氧化酶活性和功能较低。这些性别差异是雌激素依赖性的，并与较低的Nox 1和Nox 4表达有关。
Background and Purpose - This study tested whether NADPH-oxidase activity, expression, and functional effects on vascular tone are influenced by gender in the rat cerebral circulation and whether such differences are estrogen-dependent.Methods - NADPH-stimulated superoxide production by cerebral (basilar [ BA]; middle cerebral) arteries from male and female Sprague-Dawley rats was measured using lucigenin-enhanced chemiluminescence and dihydroethidium. Protein expression of Nox1, Nor2,Nox4, superoxide dismutase 1 (SOD1), SOD2, and SOD3 was measured using Western blotting. Vascular responses of BA to NADPH were assessed in a myograph. Some female rats were ovariectomized and treated with either vehicle (dimethyl sulfoxide) or 17 beta-estradiol.Results - NADPH-stimulated superoxide production by BA and middle cerebral arteries from males was approximately 2-fold greater than vessels from females. Superoxide production was virtually abolished by the NADPH-oxidase inhibitor, diphenyleneiodonium. Protein expression of Nox1 and Nox4 in BA was also higher in males than in females (2.4- and 2.8-fold, respectively), whereas Nox2, SOD1, SOD2, and SOD3 expression did not differ between genders. NADPH induced greater vasorelaxant effects in BA from males versus females (P < 0.05). The hydrogen peroxide scavenger, catalase, abolished these NADPH- induced relaxations. NADPH- stimulated superoxide production by BA from ovariectomized rats treated with vehicle was 3-fold greater than levels in intact females. Treatment of ovariectomized rats with 17 beta-estradiol decreased superoxide production (P < 0.05). NADPH- induced relaxations of BA were smaller in 17 beta-estradiol-treated than in vehicle-treated ovariectomized rats (P < 0.05).Conclusions - NADPH- oxidase activity and function are lower in cerebral arteries of female rats. These gender differences are estrogen-dependent and are associated with lower Nox1 and Nox4 expression.