JNK (c-Jun NH2-terminal Kinase) Is a Target for Antioxidants in T Lymphocytes*
JNK (c-Jun NH2-terminal Kinase) Is a Target for Antioxidants in T Lymphocytes*
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JNK（c-Jun NH2 末端激酶）是 T 淋巴细胞中抗氧化剂的靶标*
DOI：
10.1074/jbc.271.42.26335
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
J. Redondo
中科院分区：
文献类型：
--
作者：
P. G. Arco;S. Martinez;V. Calvo;A. Armesilla;J. Redondo
AP-1已被证明是一种氧化还原敏感的转录因子，可以被氧化剂和抗氧化剂刺激激活。然而，抗氧化剂激活AP-1的机制在很大程度上是未知的。在这项研究中，我们表明，结构无关的抗氧化剂吡咯烷二硫代氨基甲酸酯（PDTC），丁基羟基茴香醚，和N乙酰半胱氨酸激活JNK（c-Jun NH 2-末端激酶）在Jurkat T细胞。这种激活与佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）和Ca 2+离子载体介导的或与抗T细胞受体-CD 3复合物和CD 28抗体共刺激产生的激活有很大不同。经典的T细胞刺激激活JNK是短暂的，而PDTC和丁基羟基茴香醚（但不是N-乙酰半胱氨酸）介导的持续。JNK激活的动力学与c-jun的表达相关，PMA加离子载体刺激后c-jun的表达是短暂的，PDTC刺激后c-jun的表达延长，PDTC也短暂诱导c-fos的表达。此外，JNK激活PMA加离子载体是敏感的信号通路，包括Ca 2+，蛋白激酶C，酪氨酸磷酸化，未能抑制PDTC介导的激活抑制剂。ras和raf的反式显性负表达载体的转染，连同AP-1依赖的报告结构，以及使用抗ERK（细胞外信号调节激酶）抗体的Western印迹分析，表明Ras/Raf/ERK途径似乎不介导抗氧化剂的作用。然而，PDTC和PMA（两种对AP-1活化有协同作用的药物）的联合治疗导致ERK-2的持续磷酸化。总之，我们的研究结果确定JNK作为抗氧化剂的目标，可以调节氧化剂和抗氧化剂条件下的差异。
AP-1 has been shown to behave as a redox-sensitive transcription factor that can be activated by both oxidant and antioxidant stimuli. However, the mechanisms involved in the activation of AP-1 by antioxidants are largely unknown. In this study we show that the structurally unrelated antioxidant agents pyrrolidine dithiocarbamate (PDTC), butylated hydroxyanisole, and Nacetylcysteine activated JNK (c-Jun NH2-terminal kinase) in Jurkat T cells. This activation differed substantially from that mediated by phorbol 12-myristate 13-acetate (PMA) and Ca2+ ionophore or produced by costimulation with antibodies against the T cell receptor-CD3 complex and to CD28. The activation of JNK by classical T cell stimuli was transient, whereas that mediated by PDTC and butylated hydroxyanisole (but not N-acetylcysteine) was sustained. The kinetics of JNK activation correlated with the expression of c-jun which was transient after stimulation with PMA plus ionophore and prolonged in response to PDTC, which also transiently induced c-fos. In addition, JNK activation by PMA plus ionophore was sensitive to inhibitors of signaling pathways involving Ca2+, protein kinase C, and tyrosine phosphorylation, which failed to inhibit the activation mediated by PDTC. Transfection of trans-dominant negative expression vectors of ras and raf, together with AP-1-dependent reporter constructs, as well as Western blot analysis using anti-ERK (extracellular signal-regulated kinase) antibodies, indicated that the Ras/Raf/ERK pathway did not appear to mediate the effect of the antioxidant. However, the combined treatment with PDTC and PMA, two agents that synergize on AP-1 activation, resulted in the persistent phosphorylation of ERK-2. In conclusion, our results identify JNK as a target of antioxidant agents which can be regulated differentially under oxidant and antioxidant conditions.
DOI：
10.1073/pnas.87.24.9943
发表时间：
1990-12-01
影响因子：
11.1
作者：
STAAL, FJT;ROEDERER, M;HERZENBERG, LA
通讯作者：
HERZENBERG, LA