17β-Estradiol and steady-state concentrations of H2O2: antiapoptotic effect in endometrial cells from patients with endometriosis
17β-Estradiol and steady-state concentrations of H2O2: antiapoptotic effect in endometrial cells from patients with endometriosis
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DOI：
10.1016/j.freeradbiomed.2013.01.034
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发表时间：
2013-07-01
影响因子：
7.4
通讯作者：
da Silva, Ismael D. C. G.
中科院分区：
文献类型：
--
作者：
Andrade, Sheila S.;Azevedo, Aline de C.;da Silva, Ismael D. C. G.
过氧化氢（H2 O2）水平的增加可以启动保护性反应，以限制或修复氧化损伤。然而，H2 O2信号也微调对控制细胞分裂、分化和增殖的生长因子和细胞因子的响应。由于17 β-雌二醇（E-2）在这些过程中也发挥着重要作用，并且被认为是子宫内膜异位症发生和进展的主要危险因素，因此本研究评估了E-2是否对子宫内膜细胞的氧化应激具有抗凋亡作用。与稳态H2 O2水平（[H2 O2]ss）相结合。从18例子宫内膜异位症和非子宫内膜异位症妇女的在位子宫内膜中制备子宫内膜基质细胞，以产生原代细胞。这些细胞用E-2刺激20小时，暴露于[H2 O2]ss，并检查细胞活力、增殖和凋亡。子宫内膜异位症患者的子宫内膜细胞在高浓度H2 O2下可维持120 min的稳态。当它们用E-2预处理并暴露于[H_2O_2]ss时，与对照细胞相比，观察到凋亡水平降低（p < 0.01）。子宫内膜异位症患者的子宫内膜细胞同时受到E-2和[H2 O2]ss的刺激，ERK磷酸化水平升高。这些发现表明，H2 O2是一种下调子宫内膜细胞凋亡的信号分子，支持子宫内膜异位症，尽管是一种良性疾病，但与癌症有一些共同的特征，如过氧化氢酶水平降低。这些结果将E-2对[H2 O2]ss的影响与子宫内膜异位症的抗凋亡和进展联系起来。(C)2013 Elsevier Inc. All rights reserved.
Increased levels of hydrogen peroxide (H2O2) can initiate protective responses to limit or repair oxidative damage. However, H2O2 signals also fine-tune responses to growth factors and cytokines controlling cell division, differentiation, and proliferation. Because 17 beta-estradiol (E-2) also plays important roles in these processes, and is considered a major risk factor in the development and progression of endometriosis, this study evaluated whether E-2 has an antiapoptotic effect on oxidative stress in endometrial cells in combination with steady-state H2O2 levels ([H2O2]ss). Endometrial stromal cells were prepared from the eutopic endometrium of 18 women with and without endometriosis to produce primary cells. These cells were stimulated with E-2 for 20 h, exposed to [H2O2]ss, and examined for cell viability, proliferation, and apoptosis. The endometrial cells from women with endometriosis maintained the steady state for 120 min at high H2O2 concentrations. When they were pretreated with E-2 and exposed to [H2O2]ss, a decrease in apoptosis level was observed compared to the control cells (p < 0.01). The endometrial cells from patients with endometriosis subjected to both E-2 and [H2O2]ss showed increased ERK phosphorylation. These findings suggested that H2O2 is a signaling molecule that downregulates apoptosis in endometrial cells, supporting the fact that endometriosis, albeit a benign disease, shares some features with cancer such as decreased catalase levels. These results link the E-2 effects on [H2O2]ss to resistance to apoptosis and progression of endometriosis. (C) 2013 Elsevier Inc. All rights reserved.