Persistent activation of c-Jun N-terminal kinase 1 (JNK1) in gamma radiation-induced apoptosis
Persistent activation of c-Jun N-terminal kinase 1 (JNK1) in gamma radiation-induced apoptosis
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DOI：
10.1074/jbc.271.2.631
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发表时间：
1996-01-12
影响因子：
4.8
通讯作者：
Tan, TH
中科院分区：
文献类型：
--
作者：
Chen, YR;Meyer, CF;Tan, TH
c-Jun N-末端激酶（JNK）被各种刺激激活，包括UV光、白细胞介素-1、肿瘤坏死因子-α（TNF-α）和CD 28共刺激。由TNF-α（一种强凋亡诱导剂）诱导JNK，意味着JNK在程序性细胞死亡的调节中可能起作用。目前的研究表明，致死剂量的γ辐射（GR）诱导JNK活性在Jurkat T细胞凋亡的早期阶段。我们证明，JNK 1被激活的T细胞活化信号，抗CD 28单克隆抗体加佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA），或骨化诱导处理，GR，然而，诱导模式是不同的，在CD 28信号加PMA引起的快速和短暂的JNK 1激活，GR诱导延迟和持久的JNK 1激活。这意味着JNK 1在辐射细胞中具有独特的调节机制和特异性功能。核和胞浆JNK 1活性同时增加，在辐射的细胞没有明显的蛋白质水平的变化。GR诱导JNK 1活化的能力与DNA断裂的能力相关，外周血淋巴细胞对GR的JNK 1诱导作用比Jurkat细胞更敏感。JNK 1对GR的反应性表明JNK 1参与了凋亡过程的启动。
The c-Jun N-terminal kinases (JNK) are activated by various stimuli, including UV light, interleukin-1, tumor necrosis factor-alpha (TNF-alpha), and CD28 costimulation. Induction of JNK by TNF-alpha, a strong apoptosis inducer, implies a possible role of JNK in the regulation of programmed cell death. Present studies show that lethal doses of gamma radiation (GR) induced JNK activities at the early phase of apoptosis in Jurkat T-cells. We demonstrate that JNK1 was activated by either the T-cell activation signals, anti-CD28 monoclonal antibody plus phorbol 12-myristate 13-acetate (PMA), or the apoptosis-inducing treatment, GR; however, the induction patterns were different, In contrast to the rapid and transient JNK1 activation caused by CD28 signaling plus PMA, GR induced a delayed and persistent JNK1 activation. This implies a distinct regulatory mechanism and specific function of JNK1 in irradiated cells. The nuclear and cytosolic JNK1 activities were simultaneously increased in the irradiated cells without an evident change in the protein levels. The abilities of GR to induce JNK1 activation and DNA fragmentation were correlated, Peripheral blood lymphocytes were more sensitive to GR than Jurkat cells in JNK1 induction. The responsiveness of JNK1 to GR suggests the involvement of JNK1 in the initiation of the apoptosis process.