Calò Lorenzo A, Zaghetto Francesca, Pagnin Elisa, Davis Paul A, De Mozzi Paola, Sartorato Paola, Martire Giuseppe, Fiore Cristina, Armanini Decio
Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padua, Padua 35100, Italy.
J Clin Endocrinol Metab. 2004 Apr;89(4):1973-6. doi: 10.1210/jc.2003-031545.
Aldosterone excess can produce heart and kidney fibrosis, which seem to be related to a direct effect of aldosterone at the level of specific receptors. We report a direct, mineralocorticoid-mediated effect on the protein expression of two markers of oxidative stress after incubation of mononuclear leukocytes with 1 x 10(-8) M aldosterone (p22(phox)/beta-actin = 1.38 +/- 0.05 and PAI-1/beta-actin = 1.80 +/- 0.05). The same effect was also found with 3 x 10(-5) M glycyrrhetinic acid, the principal constituent of licorice root (p22(phox)/beta-actin = 1.37 +/- 0.97 and PAI-1/beta-actin = 1.80 +/- 0.04). The effect of both aldosterone and glycyrrhetinic acid is blocked by incubation with added 1 x 10(-6) M of receptor-antagonist canrenone. Canrenone alone did not show any effect. PAI-1 related protein was also found using 4 x 10(-9) M aldosterone. Incubations with 1 x 10(-9) M for 3 hours as well as 1 x 10(-8) M aldosterone for 5, 10, and 20 minutes were ineffective for both proteins. These data support the previous finding of an involvement of mononuclear leukocytes in the pathogenesis of the oxidative stress induced by hyperaldosteronism. In addition, the results confirm our previous data on a direct effect of glycyrrhetinic acid at the level of mineralocorticoid receptors.
醛固酮过量可导致心脏和肾脏纤维化，这似乎与醛固酮在特定受体水平的直接作用有关。我们报告了单核白细胞与1×10⁻⁸ M醛固酮孵育后，盐皮质激素介导的对两种氧化应激标志物蛋白表达的直接影响（p22(phox)/β-肌动蛋白 = 1.38 ± 0.05，纤溶酶原激活物抑制剂-1/β-肌动蛋白 = 1.80 ± 0.05）。用3×10⁻⁵ M甘草次酸（甘草根的主要成分）也发现了相同的效果（p22(phox)/β-肌动蛋白 = 1.37 ± 0.97，纤溶酶原激活物抑制剂-1/β-肌动蛋白 = 1.80 ± 0.04）。醛固酮和甘草次酸的作用都可通过加入1×10⁻⁶ M受体拮抗剂坎利酮孵育来阻断。单独的坎利酮未显示任何作用。使用4×10⁻⁹ M醛固酮也发现了纤溶酶原激活物抑制剂-1相关蛋白。用1×10⁻⁹ M孵育3小时以及用1×10⁻⁸ M醛固酮孵育5、10和20分钟对这两种蛋白均无效。这些数据支持了先前关于单核白细胞参与高醛固酮血症诱导的氧化应激发病机制的发现。此外，结果证实了我们先前关于甘草次酸在盐皮质激素受体水平直接作用的数据。
