Mitogen-activated protein kinase pathway mediates hyperoxia-induced apoptosis in cultured macrophage cells
Mitogen-activated protein kinase pathway mediates hyperoxia-induced apoptosis in cultured macrophage cells
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DOI：
10.1152/ajplung.1999.277.3.l589
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发表时间：
1999-09-01
影响因子：
4.9
通讯作者：
Choi, AMK
中科院分区：
文献类型：
--
作者：
Petrache, I;Choi, ME;Choi, AMK
我们以前已经证明，小鼠的肺可以表现出增加的程序性细胞死亡或凋亡后，体内高氧暴露。在这份报告中，我们表明，高氧暴露在体外培养的小鼠巨噬细胞（RAW 264.7）的DNA梯状，末端脱氧核苷酸转移酶dUTP缺口末端标记，和核小体分析评估也可以诱导细胞凋亡。为了进一步描述高氧诱导RAW 264.7巨噬细胞凋亡的信号通路，我们首先表明，高氧可以激活丝裂原活化蛋白激酶（MAPK）通路，细胞外信号调节激酶（ERK）p42/p44，在时间依赖性的方式通过蛋白质印迹分析ERK 1/ERK 2磷酸化的增加进行评估。c-Jun NH 2-末端激酶/应激活化蛋白激酶和p38 MAPK均未被高氧激活。通过DNA梯状和核小体ELISA评估，分别通过PD-98059（MAPK激酶的选择性抑制剂）和ERK显性阴性突变体对ERK p42/p44 MAPK通路进行化学或遗传抑制，可减弱高氧诱导的细胞凋亡。总之，我们的数据表明，高氧可以诱导培养的小鼠巨噬细胞的细胞凋亡和MAPK途径介导的高氧诱导的细胞凋亡。
We have previously demonstrated that the lungs of mice can exhibit increased programmed cell death or apoptosis after hyperoxic exposure in vivo. In this report, we show that hyperoxic exposure in vitro can also induce apoptosis in cultured murine macrophage cells (RAW 264.7) as assessed by DNA-laddering, terminal deoxynucleotidyltransferase dUTP nick end-labeling, and nucleosomal assays. To further delineate the signaling pathway of hyperoxia-induced apoptosis in RAW 264.7 macrophages, we first show that hyperoxia can activate the mitogen-activated protein kinase (MAPK) pathway, the extracellular signal-regulated kinases (ERKs) p42/p44, in a time-dependent manner as assessed by increased phosphorylation of ERK1/ERK2 by Western blot analyses. Neither the c-Jun NH2-terminal kinase/stress-activated protein kinase nor the p38 MAPK was activated by hyperoxia in these cells. Chemical or genetic inhibition of the ERK p42/p44 MAPK pathway by PD-98059, a selective inhibitor of MAPK kinase, and dominant negative mutants of ERK, respectively, attenuated hyperoxia-induced apoptosis as assessed by DNA laddering and nucleosomal ELISAs. Taken together, our data suggest that hyperoxia can induce apoptosis in cultured murine macrophages and that the MAPK pathway mediates hyperoxia-induced apoptosis.