Hydrogen peroxide-induced liver cell necrosis is dependent on AP-1 activation.
Hydrogen peroxide-induced liver cell necrosis is dependent on AP-1 activation.
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DOI：
10.1152/ajpgi.1997.273.4.g795
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发表时间：
1997-10
期刊：
影响因子：
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通讯作者：
Yang Xu;C. Bradham;D. Brenner;M. Czaja
中科院分区：
文献类型：
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作者：
Yang Xu;C. Bradham;D. Brenner;M. Czaja
为了确定参与细胞凋亡的细胞内信号事件是否也可能介导坏死，我们在氧化应激诱导的细胞坏死肝癌细胞模型中研究了转录因子AP-1的作用。通过光镜、荧光染色和DNA片段缺失检测，h2o2处理人肝癌细胞系HuH-7可引起剂量依赖性坏死。h2o2处理导致c- fos和c- jun mRNA水平、jun核激酶活性和AP-1 DNA结合增加。用AP-1驱动的荧光素酶报告基因测定的AP-1转录活性也增加。为了确定AP-1激活是否有助于h2o2诱导的细胞坏死，我们用反义c- jun表达载体稳定转染了HuH-7细胞。表达反义c- jun的细胞在h2o2暴露后AP-1激活水平降低，存活率显著提高。这些数据表明，AP-1激活发生在氧化诱导的细胞坏死过程中，并有助于细胞死亡。因此，坏死并不总是一个被动的过程，它可能涉及细胞内信号通路的激活，类似于介导细胞凋亡的信号通路。
To determine whether intracellular signaling events involved in apoptosis may also mediate necrosis, the role of the transcription factor AP-1 was investigated in a hepatoma cell model of cellular necrosis induced by oxidant stress. Treatment of the human hepatoma cell line HuH-7 with H2O2caused dose-dependent necrosis as determined by light microscopy, fluorescent staining, and an absence of DNA fragmentation. H2O2treatment led to increases in c- fosand c- jun mRNA levels, Jun nuclear kinase activity, and AP-1 DNA binding. AP-1 transcriptional activity measured with an AP-1-driven luciferase reporter gene was also increased. To determine whether this AP-1 activation contributed to H2O2-induced cell necrosis, HuH-7 cells were stably transfected with an antisense c- jun expression vector. Cells expressing antisense c- jun had decreased levels of AP-1 activation and significantly increased survival after H2O2exposure. These data indicate that AP-1 activation occurs during oxidant-induced cell necrosis and contributes to cell death. Necrosis is therefore not always a passive process but may involve the activation of intracellular signaling pathways similar to those that mediate apoptosis.