Reactive oxygen species generated by thiol-modifying phenylarsine oxide stimulate the expression of protein L-isoaspartyl methyltransferase
Reactive oxygen species generated by thiol-modifying phenylarsine oxide stimulate the expression of protein L-isoaspartyl methyltransferase
复制标题
DOI：
10.1016/j.bbrc.2008.04.009
复制
发表时间：
2008-06-27
影响因子：
3.1
通讯作者：
Desrosiers, Richard R.
中科院分区：
文献类型：
--
作者：
Fanelus, Irvens;Desrosiers, Richard R.
修复酶蛋白l -异天冬氨酸甲基转移酶（PIMT）的表达已被报道在大脑中发挥重要作用。然而，对于脑内氧化蛋白损伤后PIMT表达的调控却知之甚少。苯larsin oxide （PAO）是一种砷化合物，通过与邻近的半胱氨酸残基形成二硫键来改变蛋白质。在这里，我们报道PAO在U-87人类星形胶质瘤细胞中迅速上调PIMT。我们还证实PAO对PIMT的上调是通过与邻近半胱氨酸的反应介导的。此外，我们发现PAO诱导PIMT依赖于活性氧（ROS）的形成。关键是，抗氧化剂n -乙酰- l-半胱氨酸和NADPH氧化酶抑制剂二苯二氯铵均能抑制PAO的ROS形成和PIMT诱导。重要的是，siRNA下调PIMT显著增强了pao诱导的ROS。综上所述，这些结果强调了PIMT的表达受ROS调控，并可能主要作为抗氧化酶。(C) 2008爱思唯尔公司版权所有。
Expression of the repair enzyme protein L-isoaspartyl methyltransferase (PIMT) has been reported to play important roles in brain. However, little is known about the regulation of PIMT expression following protein damage by oxidation in brain. Phenylarsine oxide (PAO) is an arsenical compound that alters proteins by forming disulfide bond with vicinal cysteinyl residues. Here we report that PIMT was rapidly up-regulated by PAO in U-87 human astroglioma cells. We also confirmed that PIMT up-regulation by PAO was mediated by the reaction with vicinal cysteines. Furthermore, we showed that PIMT induction by PAO was dependent on formation of reactive oxygen species (ROS). Crucially, both ROS formation and PIMT induction by PAO were inhibited by antioxidant N-acetyl-L-cysteine and NADPH oxidase inhibitor diphenyleneiodonium chloride. Importantly, down-regulation of PIMT by siRNA strikingly enhanced PAO-induced ROS. Together, these results highlight that PIMT expression is regulated by ROS and could primarily act as an antioxidant enzyme. (C) 2008 Elsevier Inc. All rights reserved.