Gender Disparity in Susceptibility to Oxidative Stress and Apoptosis Induced by Autoantibodies Specific to RLIP76 in Vascular Cells
Gender Disparity in Susceptibility to Oxidative Stress and Apoptosis Induced by Autoantibodies Specific to RLIP76 in Vascular Cells
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DOI：
10.1089/ars.2011.3942
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发表时间：
2011-12-01
影响因子：
6.6
通讯作者：
Malorni, Walter
中科院分区：
文献类型：
--
作者：
Matarrese, Paola;Colasanti, Tania;Malorni, Walter
目的：Ral 结合蛋白 1 (RLIP76) 是一种细胞表面蛋白，可催化还原型谷胱甘肽 (GSH) 缀合物从细胞中挤出。我们最近证明，患有以血管功能障碍为特征的免疫介导疾病的患者中存在 RLIP76 (aaRLIP76) 血清抗体。这项工作的目的是分析性别在此问题中可能的影响，研究 aaRLIP76 对雄性和雌性大鼠血管平滑肌细胞和人内皮细胞的影响。结果：我们观察到，在 aaRLIP76 处理后，与雄性细胞相比，雌性血管细胞在 H2O2 和 O-2（中心点）产生、4-羟基-t-2,3-壬烯醛和 GSH 水平、C-Jun NH2 激酶信号激活和细胞凋亡方面对细胞内氧化还原平衡紊乱的敏感性显着更高。有趣的是，在轻度氧化应激（H2O2 30μm，持续30分钟）下，这些与性别相关的差异变得更加明显。在培养基中存在性激素的情况下进行的实验清楚地表明，雌激素可以显着增加雌性细胞对 aaRLIP76 影响的敏感性，而雄性细胞似乎不受影响。创新：这些结果为以血管功能障碍为特征的自身免疫性疾病的性别依赖性致病机制开辟了新的视角。结论：总而言之，这些结果表明，aaRLIP76 对 RLIP76 的损伤可能在女性血管细胞的损伤中发挥作用，有助于免疫介导的血管疾病的性别相关发病机制。抗氧化剂。氧化还原信号。 15、2825-2836。
Aim: Ral-binding protein 1 (RLIP76) is a cell surface protein that catalyzes the extrusion from the cell of reduced glutathione (GSH) conjugates. We recently demonstrated the presence of serum antibodies to RLIP76 (aaRLIP76) in patients with immune-mediated diseases characterized by vascular dysfunction. The aim of this work was to analyze the possible implication of gender in this issue, investigating the effects of aaRLIP76 in rat vascular smooth muscle cells and human endothelial cells from males and females. Results: We observed that, after aaRLIP76 treatment, vascular cells from females showed a significantly higher susceptibility to the disturbance of intracellular redox balance, in terms of H2O2 and O-2(center dot) production, 4-hydroxy-t-2,3-nonenal and GSH levels, C-Jun NH2 kinase signaling activation, and apoptosis in comparison with cells from males. Interestingly, under mild oxidative stress (H2O2 30 mu m for 30 min), these sex-associated differences became significantly more pronounced. Experiments carried out in the presence of sex hormones in the culture medium clearly suggested that estrogens could significantly increase the susceptibility of cells from females to the effects of aaRLIP76, whereas cells from males appeared unaffected. Innovation: These results open a new perspective in the gender-dependent pathogenic mechanisms of autoimmune diseases characterized by vascular dysfunction. Conclusions: Altogether these results suggest that the impairment of RLIP76 by aaRLIP76 can play a role in the damage of vascular cells from females, contributing to the gender-associated pathogenesis of immune-mediated vascular diseases. Antioxid. Redox Signal. 15, 2825-2836.