화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.423, No.4, 850-856, 2012
Both estrogen receptor subtypes, ER alpha and ER beta, prevent aldosterone-induced oxidative stress in VSMC via increased NADPH bioavailability
Activation of vascular mineralocorticoid (MR) or estrogen receptors (ER) exerts opposing effects on vascular remodeling. As we have previously shown, activation of either estrogen receptor subtype, ER alpha or ER beta, is fully sufficient to attenuate vascular remodeling in aldosterone salt-treated rats. To further elucidate the underlying mechanism(s) we tested the hypothesis that ER and MR activation might differentially modulate vascular reactive oxygen species (ROS) generation. In support of this concept, aldosterone increased ROS generation in vascular smooth muscle cells as determined by quantitative dihydroethidium fluorescence microscopy. Co-treatment with the selective ER alpha agonist 16 alpha-LE2, the selective Er beta agonist 8 beta-VE2 or the non-selective ER agonist 17 beta-estradiol (E2) significantly reduced aldosterone-induced ROS generation. The pure ER antagonist ICI 182,780 completely blocked these salutary effects of E2, 16 alpha-LE2 and 8 beta-VE2. Activation of ER alpha or ER beta fully blocked the reduction of intracellular nicotinamide adenine dinucleotide phosphate (NADPH) levels observed in aldosterone treated vascular smooth muscle cells. Intracellular NADPH levels were closely associated with expression and activity of the NADPH generating enzyme glucose-6-phosphate dehydrogenase. In conclusion, estrogens attenuate the detrimental vascular effects of excessive MR activation at least in part by preventing the depletion of intracellular NADPH levels. (C) 2012 Elsevier Inc. All rights reserved.