Inhibition of reactive oxygen species down-regulates protein synthesis in RAW 264.7

Inhibition of reactive oxygen species down-regulates protein synthesis in RAW 264.7
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DOI:
10.1016/j.bbrc.2008.05.036
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发表时间:
2008-07-18
影响因子:
3.1
通讯作者:
Isobe, Ken-ichi
Isobe, Ken-ichi
中科院分区:
生物学4区
文献类型:
--
作者:
Kimura, Kenya;Ito, Sachiko;Isobe, Ken-ichi

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为了检测巨噬细胞的内质网反应,我们用LIPS刺激巨噬细胞系RAW 264.7。我们发现,在相对大量的LIPS刺激的后期,RAW 264.7细胞中真核起始因子eIF 2 α的磷酸化和ATF 4、GADD 34和GADD 153的表达。出乎意料的是,在ROS抑制剂N-乙酰-L-半胱氨酸存在下,LPS快速诱导eIF 2 α的磷酸化和GADD 34表达的诱导。我们测量了LPS刺激的RAW 264.7细胞中细胞质内TNF α的产生。N-乙酰-L-半胱氨酸可显著抑制LPS刺激诱导的TNF α产生。这种抑制发生相对较早,这与早期eIF 2 α磷酸化相关,表明ER应激介导的蛋白质合成关闭。(C)2008年爱思唯尔公司All rights reserved.
In order to examine the endoplasmic reticulum responses in macrophages, we stimulate macrophage cell line RAW 264.7 by LIPS. We found the phosphorylation of eukaryotic initiation factor eIF2 alpha and the expression of ATF4, GADD34, and GADD153 in RAW 264.7 cells in late time by the relatively large amount of LIPS stimulation. Unexpectedly LPS in the presence of ROS inhibitor N-acetyl-L-cysteine rapidly induced phosphorylation of eIF2 alpha and induction of GADD34 expression. We measured intra-cytoplasmic TNF alpha production in LPS stimulated RAW 264.7 cells. TNF alpha production induced by LPS stimulation was greatly suppressed by N-acetyl-L-cysteine. This suppression occurred relatively early, which correlated with early eIF2 alpha, phosphorylation indicating ER stress mediated shutoff of protein synthesis. (C) 2008 Elsevier Inc. All rights reserved.