Nox4 and Nox2 NADPH oxidases mediate distinct cellular redox signaling responses to agonist stimulation
Nox4 and Nox2 NADPH oxidases mediate distinct cellular redox signaling responses to agonist stimulation
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DOI：
10.1161/atvbaha.108.164277
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发表时间：
2008-07-01
影响因子：
8.7
通讯作者：
Shah, Ajay M.
中科院分区：
文献类型：
--
作者：
Anilkumar, Narayana;Weber, Roberta;Shah, Ajay M.
目的：NADPH氧化酶亚型Nox 2和Nox 4在许多细胞类型中共表达，并参与激动剂刺激的氧化还原敏感性信号转导。我们比较了参与Nox 2与Nox 4在氧化还原敏感性蛋白激酶激活激动剂stimulation.Methods和Results-We转染HEK 293细胞与Nox 2或Nox 4和比较活性氧的生产和激活促分裂原活化蛋白激酶（MAPKs），Akt，和GSK 3 β急性激动剂刺激后。Nox 4过表达显著增加基础ROS生成，而在Nox 2过表达细胞中，血管紧张素II和肿瘤坏死因子（TNF）α引起的ROS生成增强。Nox 4过表达诱导ERK 1/2和JNK的基础活化，而Nox 2转染的细胞显示p38 MAPK活化的适度增加。血管紧张素II或TNF α处理后，Nox 2转染细胞中JNK活化增强，但Nox 4转染细胞中未增强，而胰岛素特异性增强Nox 4过表达细胞中p38 MAPK、Akt和GSK 3 β的磷酸化，特异性增强Nox 2过表达细胞中JNK的磷酸化。和胰岛素并调节不同蛋白激酶的活化。
Objectives-The NADPH oxidase isoforms Nox2 and Nox4 are coexpressed in many cell types and are implicated in agonist-stimulated redox-sensitive signal transduction. We compared the involvement of Nox2 versus Nox4 in redox-sensitive protein kinase activation after agonist stimulation.Methods and Results-We transfected HEK293 cells with Nox2 or Nox4 and compared ROS production and activation of mitogen activated protein kinases (MAPKs), Akt, and GSK3 beta after acute agonist stimulation. Nox4 overexpression substantially increased basal ROS generation whereas ROS generation in response to angiotensin II and tumor necrosis factor (TNF)alpha was enhanced in Nox2-overexpressing cells. Nox4 overexpression induced basal activation of ERK1/2 and JNK whereas Nox2-transfected cells showed a modest increase in p38MAPK activation. After angiotensin II or TNF alpha treatment, JNK activation was augmented in Nox2 but not Nox4-transfected cells, whereas insulin augmented phosphorylation of p38MAPK, Akt, and GSK3 beta specifically in Nox4-overexpressing cells and JNK specifically in Nox2-overexpressing cells.Conclusions-These data indicate that Nox2 and Nox4 exhibit distinctive patterns of acute activation by angiotensin II, TNF alpha, and insulin and regulate the activation of distinct protein kinases.