Mechanism of phorbol myristate acetate-induced lymphotoxin production by a human T cell hybridoma.
Mechanism of phorbol myristate acetate-induced lymphotoxin production by a human T cell hybridoma.
复制标题
佛波醇肉豆蔻酸酯乙酸酯诱导人 T 细胞杂交瘤产生淋巴毒素的机制。
DOI：
10.1093/oxfordjournals.jbchem.a134790
复制
发表时间：
1984
影响因子：
2.7
通讯作者：
T. Osawa
中科院分区：
文献类型：
--
作者：
Y. Kobayashi;M. Asada;T. Osawa
多种羟基自由基清除剂可显著抑制人T细胞杂杂瘤AC5-8诱导的肉豆蔻酸磷酯（PMA）诱导的淋巴毒素（LT）的产生。其中，四甲基脲（TMU）是最有效的清除剂，并且发现必须在添加PMA后2小时内添加TMU才能抑制LT的产生。与此事实一致，可溶性NADPH依赖的O2形成酶(s)被PMA激活了数倍。PMA还诱导DNA链断裂，这一过程被TMU显著抑制。正如预期的那样，adp -核糖基转移酶（ADPRT）被PMA激活，这是众所周知的需要DNA链断裂才能产生酶活性的酶。此外，ADPRT的特异性抑制剂，即3-氨基苯甲酰胺和烟酰胺，可以抑制pma诱导的LT产生。综上所述，这三个连续的事件，即可溶性NADPH依赖性O2形成酶的激活、DNA链断裂和ADPRT的激活，可能是AC5-8诱导pma诱导的LT产生所必需的。
Various hydroxyl radical scavengers markedly inhibited phorbol myristate acetate (PMA)-induced lymphotoxin (LT) production by a human T cell hybridoma, AC5-8. Among those we tested, tetramethylurea (TMU) was the most potent scavenger, and it was revealed that TMU must be added before 2 h have elapsed after PMA addition in order for LT production to be inhibited. In concordance with this fact, soluble NADPH dependent O2- forming enzyme(s) were activated several fold by PMA. PMA also induced DNA strand breaks, a process markedly inhibited by TMU. As expected, ADP-ribosyl transferase (ADPRT), which is well known to require DNA strand breaks for its enzymatic activity, was activated by PMA treatment. In addition, specific inhibitors for ADPRT, namely 3-amino-benzamide and nicotinamide, inhibited PMA-induced LT production. Taken together, these three successive events, activation of soluble NADPH dependent O2- forming enzyme(s), DNA strand breaks and activation of ADPRT, may be required for PMA-induced LT production by AC5-8.