Cirp protects against tumor necrosis factor-α-induced apoptosis via activation of extracellular signal-regulated kinase
Cirp protects against tumor necrosis factor-α-induced apoptosis via activation of extracellular signal-regulated kinase
复制标题
DOI：
10.1016/j.bbamcr.2006.02.007
复制
发表时间：
2006-03-01
影响因子：
5.1
通讯作者：
Fujita, Jun
中科院分区：
文献类型：
--
作者：
Sakurai, Toshiharu;Itoh, Katsuhiko;Fujita, Jun
亚低温对脑损伤和心脏骤停患者有保护作用。为了阐明这些影响的分子机制，我们分析了低温培养（32℃）和冷诱导rna结合蛋白（Cirp）表达对体外细胞凋亡的影响。在肿瘤坏死因子(TNF)- α和环己亚胺处理的EALB/3T3细胞中，温度从37℃降至32℃时，Cirp表达增加，细胞凋亡受到抑制。caspase-8的激活被抑制，磷酸化的细胞外信号调节激酶（ERK）水平升高。在37℃和32℃下，Cirp转导到Cirp缺陷小鼠成纤维细胞中，磷酸化的ERK水平升高，tnf α诱导的细胞凋亡受到抑制。ERK特异性抑制剂PD98059降低了Cirp的细胞保护作用以及低培养温度下的细胞保护作用。这些数据表明，亚低温保护细胞免受tnf - α诱导的凋亡，至少部分是通过诱导Cirp，而Cirp通过激活ERK途径保护细胞。(c) 2006 Elsevier B.V.版权所有
Mild hypothermia shows protective effects on patients with brain damage and cardiac arrest. To elucidate the molecular mechanisms underlying these effects, we analyzed the effects of low culture temperature (32 degrees C) and cold-inducible RNA-binding protein (Cirp) expression on apoptosis in vitro. In EALB/3T3 cells treated with tumor necrosis factor (TNF)-alpha and cycloheximide, the down-shift in temperature from 37 degrees C to 32 degrees C increased the expression of Cirp and suppressed the apoptosis. Activation of caspase-8 was suppressed, and the level of phosphorylated extracellular signal-regulated kinase (ERK) was increased. Transduction of Cirp into the Cirp-deficient mouse fibroblasts increased the level of phosphorylated ERK and suppressed the TNF-alpha-induced apoptosis both at 37 degrees C and 32 degrees C. The ERK-specific inhibitor PD98059 decreased the cytoprotective effect of Cirp as well as that of low culture temperature. These data suggest that mild hypothermia protects cells from TNF-alpha-induced apoptosis, at least partly, via induction of Cirp, and that Cirp protects cells by activating the ERK pathway. (c) 2006 Elsevier B.V. All rights reserved.