Phorbol myristate acetate induces neutrophil NADPH-oxidase activity by two separate signal transduction pathways: dependent or independent of phosphatidylinositol 3-kinase
Phorbol myristate acetate induces neutrophil NADPH-oxidase activity by two separate signal transduction pathways: dependent or independent of phosphatidylinositol 3-kinase
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DOI：
10.1002/jlb.67.3.396
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发表时间：
2000-03-01
影响因子：
5.5
通讯作者：
McPhail, LC
中科院分区：
文献类型：
--
作者：
Karlsson, A;Nixon, JB;McPhail, LC
中性粒细胞NADPH氧化酶可被蛋白激酶C（PKC）激动剂如佛波醇肉豆蔻酸酯乙酸酯（PMA）激活，导致超氧阴离子释放。这种超氧化物的释放是独立的磷脂酰肌醇3-激酶（PI 3-激酶），因为抑制剂渥曼青霉素不影响的反应。在这项研究中，PMA也显示出诱导渥曼青霉素敏感的NADPH氧化酶激活，然而，不导致超氧化物的释放，但在细胞内产生的自由基。这表明，两个池的NADPH氧化酶，一个位于质膜和其他在颗粒膜，分别调节和信号转导途径，导致激活这些池不同的PI 3-激酶的参与。两个库的激活依赖于ERK/MAPK激酶（MEK）活性和蛋白磷酸酶1和/或2A。由于抑制剂Go-6850对这两种氧化酶反应的影响不同，因此推测参与这两种信号转导途径的PKC同工酶不同。
The neutrophil NADPH-oxidase can be activated by protein kinase C (PKC) agonists such as phorbol myristate acetate (PMA), resulting in superoxide anion release. This superoxide release is independent of phosphatidylinositol 3-kinase (PI 3-kinase) because the inhibitor wortmannin does not affect the response. In this study, PMA is shown to also induce a wortmannin-sensitive NADPH-oxidase activation, however, not resulting in release of superoxide but in intracellular production of the radical. This indicates that two pools of NADPH-oxidase, one localized in the plasma membrane and the other in the granule membranes, are separately regulated and the signal transduction pathways leading to activation of these pools differ regarding involvement of PI 3-kinase. Activation of both pools was dependent on ERK/MAPK kinase (MEK) activity and protein phosphatase 1 and/or 2A. As the two oxidase responses were differently affected by the inhibitor Go-6850, different PKC isozymes are suggested to take part in the two signal transduction pathways.