SILAC analysis of oxidative stress-mediated proteins in human pneumocytes: New role for treacle
SILAC analysis of oxidative stress-mediated proteins in human pneumocytes: New role for treacle
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DOI：
10.1002/pmic.201000020
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发表时间：
2010-06-01
期刊：
影响因子：
3.4
通讯作者：
Merali, Salim
中科院分区：
文献类型：
--
作者：
Duan, Xunbao;Kelsen, Steve G.;Merali, Salim
为了更好地理解肺氧化应激反应，我们使用“氨基酸稳定同位素标记”检测了暴露于H2 O2的A549肺细胞。“我们鉴定了466种细胞质蛋白和387种核蛋白; H2 O2暴露在31种蛋白中产生了>=两倍的差异，所有这些蛋白都是下调的。以前没有报道过氧化应激反应蛋白，尽管它们具有共同的功能。其中一个反应者，糖浆，与p53有关，这是一种重要的氧化应激反应。Treacher Collins-Franceschetti综合征可由糖蜜突变引起，并且不足被认为引起p53增加而导致综合征。然而，这里的结果表明，p53和糖蜜反应H2 O2是独立的：糖蜜仍然抑制p53恢复后，糖蜜减少的阈值远高于p53的诱导和糖蜜抑制短干扰RNA不修改p53的反应。糖蜜抗氧化活性的证据包括减少被驱动的蛋白酶体降解独立的mRNA，典型的氧化剂吸收蛋白，和增加的敏感性H2 O2随之短干扰RNA抑制。这里的数据显示氧化应激和糖蜜减少之间的联系，表明糖蜜不控制p53，提供证据的糖蜜氧化防御作用，支持氧化应激在Treacher Collins-Franceschetti综合征中发挥作用的假设，并提高糖蜜在肺中发挥抗氧化作用的可能性。
To better understand lung oxidant stress responses, we examined A549 lung cells exposed to H2O2 using "stable isotope labeling by amino acids." We identified 466 cytosolic and 387 nuclear proteins; H2O2 exposure produced >= twofold differences in 31, all were down-regulations. None were previously reported as oxidant stress response proteins, although they share common functions. One of the responders, treacle, was linked to p53, an important oxidative stress response. The Treacher Collins-Franceschetti syndrome can result from treacle mutation and insufficiency was suggested to cause increased p53 leading to the syndrome. However, results here indicate p53 and treacle responses to H2O2 are independent: treacle remains suppressed after p53 recovery; the threshold for treacle reduction is well above that for p53 induction; and treacle suppression by short interfering RNA does not modify the p53 response. Evidence of treacle antioxidant activity include reduction being driven by proteasome degradation independently of mRNA, typical for oxidant-absorbing proteins, and increased sensitivity to H2O2 consequent to short interfering RNA suppression. Data here show a link between oxidative stress and treacle reduction, demonstrate that treacle does not control p53, provide evidence of a treacle oxidant defense role, support the hypothesis that oxidant stress plays a role in the Treacher Collins-Franceschetti syndrome, and raise the possibility that treacle plays an anti-oxidant role in lungs.