Tumor necrosis factor a activates the phosphorylation of ERK, SAPK/JNK, and p38 kinase in primary cultures of neurons
Tumor necrosis factor a activates the phosphorylation of ERK, SAPK/JNK, and p38 kinase in primary cultures of neurons
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DOI：
10.1023/a:1011086426652
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发表时间：
2001-02-01
影响因子：
4.4
通讯作者：
Zalc, B
中科院分区：
文献类型：
--
作者：
Barbin, G;Roisin, MP;Zalc, B
新出现的数据表明，炎症细胞因子TNF α对脑损伤具有神经保护作用。为了更好地理解TNFa对神经元的作用机制，我们研究了各种MAP激酶的可能激活。神经元暴露于TNFa触发MAP激酶家族的三个成员的快速磷酸化，即细胞外信号调节激酶（ERK1/2），应激激活蛋白激酶/JUN n末端激酶（SAPWJNK）和p38激酶；这种激活以相同的时间过程发生，并且是短暂的。化合物PD 98059是MAP激酶MEK1/2的特异性抑制剂，可特异性阻止TNF α诱导的ERK1/2活化。ERK1/2的激活也被黄原衍生物D609特异性抑制，D609是磷酸肌苷磷脂酶C的特异性抑制剂，这表明神经元中的TNF α信号通路与酸性鞘磷脂酶有关。
Emerging data indicate that the inflammatory cytokine TNF alpha exerts a neuroprotective effect against brain injury. To better understand the mechanism of action of TNFa on neurons we have investigated the possible activation of various MAP kinases. Exposure of neurons to TNFa triggered the rapid phosphorylation of three members of the MAP kinase family, i.e., extracellular signal-regulated kinase (ERK1/2), stress-activated protein kinase/JUN N-terminal kinase (SAPWJNK) and the p38 kinase; this activation occured with the same time course and was transient. The TNF alpha -induced activation of ERK1/2, was specifically prevented by compound PD 98059 a specific inhibitor of the MAP kinase kinase MEK1/2. Activation of ERK1/2 was also specifically inhibited by the xanthogenic derivative D609, a specific inhibitor of phosphoinositide phospholipase C suggesting that TNF alpha signaling in neurons involved the acidic sphingomyelinase.