Extracellular Signal-regulated Kinase 1/2 is Involved in the Activation of NADPH Oxidase Induced by FMLP Receptor but not by Complement Receptor 3 in Rat Neutrophils

Extracellular Signal-regulated Kinase 1/2 is Involved in the Activation of NADPH Oxidase Induced by FMLP Receptor but not by Complement Receptor 3 in Rat Neutrophils
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细胞外信号调节激酶 1/2 参与大鼠中性粒细胞中由 FMLP 受体而非补体受体 3 诱导的 NADPH 氧化酶的激活

DOI:
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发表时间:
2003
影响因子:
3.3
通讯作者:
M. Kuwabara
M. Kuwabara
中科院分区:
生物学3区
文献类型:
--
作者:
K. Waki;O. Inanami;T. Yamamori;M. Kuwabara

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本实验旨在阐明细胞外信号调节激酶ERK1/2在大鼠腹膜中性粒细胞NADPH氧化酶依赖的O2-产生中的作用。当中性粒细胞暴露于N-甲酰-甲硫基-亮氨酰-苯丙氨酸(FMLP)刺激N-甲酰肽受体时,不仅观察到O2-的产生,而且观察到ERK1/2的激活。在fMLP刺激的中性粒细胞中,NADPH氧化酶组分p47Phox也发生了从胞浆到膜的移位。ERK1/2激酶抑制剂U0126可抑制fMLP诱导的O2-的产生和p47Phox的易位。而用调理酵母多糖(OZ)刺激中性粒细胞补体受体3时,ERK1/2的激活程度弱于fMLP。在这种情况下,U0126对O2-的产生没有抑制作用,对p47Phox的转位有轻微的抑制作用。只有PKC抑制剂GF109203X对臭氧诱导的中性粒细胞产生O2-有较大的抑制作用。本研究表明,ERK1/2信号通路中存在受体依赖性,导致NADPH氧化酶的激活。
This experiment was performed to clarify the role of extracellular signal-regulated kinase, ERK1/2, in NADPH oxidase-dependent O2- production in rat peritoneal neutrophils. When neutrophils were exposed to N-formyl-methionyl-leucyl-phenylalanine (fMLP) to stimulate an N-formyl peptide receptor, not only the production of O2- but also the activation of ERK1/2 was observed. The translocation of an NADPH oxidase component, p47phox, from cytosol to membrane also occurred in neutrophils stimulated with fMLP. U0126, an ERK1/2 kinase inhibitor, inhibited both the production of O2- and the translocation of p47phox elicited by fMLP. On the other hand, when complement receptor 3 of neutrophils was stimulated with opsonized zymosan (OZ), weaker activation of ERK1/2 than that by fMLP was observed. In this case, U0126 showed no inhibition against the production of O2- and slight inhibition against the translocation of p47phox. Large inhibition against the OZ-induced production of O2- was only observed in neutrophils treated with GF109203X, a PKC inhibitor. The present study indicates that receptor dependence exists in the ERK1/2 signaling pathway leading to the activation of NADPH oxidase.
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