Afzal-Ahmed Iram, Mann Giovanni E, Shennan Andrew H, Poston Lucilla, Naftalin Richard J
Cardiovascular Division, School of Medicine, King's College London, 150 Stamford Street, London SE1 9NH, UK.
Free Radic Biol Med. 2007 Jun 15;42(12):1781-90. doi: 10.1016/j.freeradbiomed.2007.02.032. Epub 2007 Mar 12.
Inactivation of glucose-6-phosphate dehydrogenase (G6PD) may contribute to vascular dysfunction in preeclampsia, and oxidative stress has been implicated in the pathogenesis of this disease. We have compared the susceptibility of erythrocytes and human umbilical vein endothelial cells (HUVEC) to oxidative stress in women with normotensive or preeclamptic pregnancies. The redox status of erythrocytes was also correlated with neutrophil-mediated superoxide (O(2)(.-)) production in women recruited to the "Vitamins in Preeclampsia" (VIP) trial. Erythrocytes and HUVEC from women with preeclampsia demonstrated impaired redox regulation and diminished response to glucose, detectable at 14-20 weeks gestation prior to onset of the clinical disease. Hexokinase and G6PD activities were decreased in erythrocytes and G6PD activity was decreased in HUVEC from preeclamptic pregnancies. Phorbol-ester-stimulated O(2)(.-) was enhanced in preeclamptic neutrophils. Impaired redox regulation in erythrocytes and HUVEC in preeclampsia may be due to diminished hexokinase and G6PD activities resulting from increased release of reactive oxygen species from activated neutrophils. Our findings provide the first evidence that decreased G6PD activity in preeclampsia is associated with impaired redox regulation in erythrocytes and fetal endothelial cells. The deficiency in G6PD in preeclampsia potentially accounts for the lack of protection against oxidative stress afforded by antioxidant vitamin C/E supplementation in the VIP trial.
葡萄糖-6-磷酸脱氢酶（G6PD）的失活可能导致子痫前期的血管功能障碍，并且氧化应激被认为与该疾病的发病机制有关。我们比较了血压正常或子痫前期孕妇的红细胞和人脐静脉内皮细胞（HUVEC）对氧化应激的敏感性。在“子痫前期维生素”（VIP）试验招募的女性中，红细胞的氧化还原状态也与中性粒细胞介导的超氧化物（O(2)(.-)）生成相关。子痫前期女性的红细胞和HUVEC表现出氧化还原调节受损以及对葡萄糖的反应减弱，在临床疾病发作前的妊娠14 - 20周即可检测到。子痫前期妊娠的红细胞中己糖激酶和G6PD活性降低，HUVEC中G6PD活性降低。子痫前期中性粒细胞中佛波酯刺激的O(2)(.-)增强。子痫前期红细胞和HUVEC中氧化还原调节受损可能是由于活化的中性粒细胞释放的活性氧增加导致己糖激酶和G6PD活性降低。我们的研究结果首次证明，子痫前期G6PD活性降低与红细胞和胎儿内皮细胞氧化还原调节受损有关。子痫前期G6PD缺乏可能是VIP试验中抗氧化维生素C/E补充未能提供抗氧化应激保护的原因。
