Department of Molecular Medicine-Biological Chemistry, University of Padua, Viale G. Colombo 3, 35131 Padua, Italy.
J Clin Endocrinol Metab. 2013 Jun;98(6):2494-501. doi: 10.1210/jc.2012-3571. Epub 2013 Mar 28.
Aldosterone (Aldo) effects include NADPH oxidase activation involved in Aldo-related oxidative stress. Red blood cells (RBCs) are particularly sensitive to oxidative assault, and both the formation of high molecular weight aggregates (HMWAs) and the diamide-induced Tyr phosphorylation (Tyr-P) level of membrane band 3 can be used to monitor their redox status.
The Aldo-related alterations in erythrocytes were evaluated by comparing in vitro evidence.
This was a multicenter comparative study.
The study included 12 patients affected by primary aldosteronism (PA) and 6 healthy control subjects (HCs), whose RBCs were compared with those of patients with PA. For in vitro experiments, RBCs from HCs were incubated with increasing Aldo concentrations.
The Tyr-P level, band 3 HMWA formation, and autologous IgG binding were evaluated.
In patients with PA, both Tyr-P levels and band 3 HMWAs were higher than those in HCs. RBCs from HCs were treated with increasing Aldo concentrations in both platelet-poor plasma (PPP) and charcoal-stripped (CS)-PPP. Results showed that Aldo had dose- and time-dependent effects on band 3 Tyr-P and HMWA formation in CS-PPP more than in PPP. These effects were almost completely prevented by canrenone or cortisol. Aldo-related membrane alterations led to increased autologous IgG binding.
Erythrocytes from patients with PA show oxidative-like stress evidenced by increased HMWA content and diamide-induced band 3 Tyr-P level. Aldo effects are mediated by the mineralocorticoid receptor, as suggested by the inhibitory effects of canrenone, an antagonist of Aldo. In CS-PPP, in which Aldo induces remarkable membrane alterations leading to IgG binding, Aldo may be responsible for premature RBC removal from circulation.
醛固酮(Aldo)的作用包括参与醛固酮相关氧化应激的 NADPH 氧化酶激活。红细胞(RBC)对氧化攻击特别敏感,高分子量聚集物(HMWAs)的形成和膜带 3 的二酰胺诱导的酪氨酸磷酸化(Tyr-P)水平均可用于监测其氧化还原状态。
通过比较体外证据评估红细胞中的 Aldo 相关变化。
这是一项多中心比较研究。
该研究包括 12 例原发性醛固酮增多症(PA)患者和 6 例健康对照者(HCs),比较了他们的 RBC。对于体外实验,将 HCs 的 RBC 与 PA 患者的 RBC 一起孵育,用递增浓度的 Aldo 处理。
评估 Tyr-P 水平、带 3 HMWAs 形成和自身 IgG 结合。
PA 患者的 Tyr-P 水平和带 3 HMWAs 均高于 HCs。在血小板贫乏血浆(PPP)和活性炭处理的(CS)-PPP 中,用递增浓度的 Aldo 处理来自 HCs 的 RBC。结果表明,Aldo 在 CS-PPP 中对带 3 Tyr-P 和 HMWAs 形成具有剂量和时间依赖性的影响,而在 PPP 中则不然。这些作用几乎完全被坎利酮或皮质醇所预防。Aldo 相关的膜改变导致自身 IgG 结合增加。
PA 患者的 RBC 显示出氧化样应激,表现为 HMWAs 含量增加和二酰胺诱导的带 3 Tyr-P 水平升高。Aldo 作用是通过盐皮质激素受体介导的,如 Aldo 拮抗剂坎利酮的抑制作用所表明的那样。在 CS-PPP 中,Aldo 可诱导显著的膜改变导致 IgG 结合,Aldo 可能导致 RBC 从循环中过早清除。