In vitro and in vivo activation of extracellular signal-regulated kinases by coal dusts and quartz
In vitro and in vivo activation of extracellular signal-regulated kinases by coal dusts and quartz
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DOI：
10.1006/taap.2002.9500
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发表时间：
2002-10-01
影响因子：
3.8
通讯作者：
Mossman, BT
中科院分区：
文献类型：
--
作者：
Albrecht, C;Borm, PJA;Mossman, BT
肺泡II型上皮细胞是吸入超负荷浓度的难溶性颗粒（PSP）后发展成癌的主要前体细胞，但导致这些细胞中初始增殖事件的机制尚不清楚。在这里的研究中，细胞周期动力学，丝裂原活化蛋白激酶（MAPK）信号转导事件，激活蛋白-1家族成员的基因表达进行了研究，在小鼠肺泡II型上皮细胞（C10）或大鼠体内暴露后，几个煤矿粉尘（CMD）的高或低石英含量。与使用未暴露的C10细胞或暴露于非致病性颗粒玻璃珠的细胞的结果相反，流式细胞术显示在添加DQ 12石英或CMD后亚二倍体细胞和S期细胞的数量增加。使用核糖核酸酶保护试验，增加的mRNA水平的fos和jun家族成员看到响应DQ 12石英和CMD与高石英含量。Western印迹分析显示，细胞外信号调节激酶（ERK）12的磷酸化水平在DQ 12和CMD暴露的细胞中增加。使用羟基自由基清除剂四甲基硫脲阻断了DQ 12和CMD进入S期以及ERK的磷酸化。CMD暴露大鼠肺切片的免疫组化显示上皮细胞中磷酸化ERK的慢性激活，支持PSP在体内肺上皮增殖中此信号级联的可能作用。(C)2002 Elsevier Science（美国）。
Alveolar type II epithelial cells are the main precursor cells that develop into carcinomas after inhalation of poorly soluble particles (PSP) at overload concentrations, but the mechanisms leading to initial proliferative events in these cells are unclear. In studies here, cell cycle kinetics, mitogen-activated protein kinase (MAPK) signaling events, and gene expression of activator protein-1 family members were investigated in murine alveolar type II epithelial cells (C10) or rats in vivo after exposure to several coal mine dusts (CMDs) of high or low quartz content. In contrast to results using unexposed C10 cells or cells exposed to the nonpathogenic particle glass beads, flow cytometry showed increased numbers of hypodiploid cells and cells in S phase after addition of DQ12 quartz or CMDs. Using a ribonuclease protection assay, increased mRNA levels of fos and jun family members were seen in response to DQ12 quartz and CMD with high quartz content. Increased phosphorylation of extracellular signal regulated kinases (ERKs)1/2 occurred in DQ12- and CMD-exposed cells by Western blot analysis. The use of the hydroxyl radical scavenger tetramethylthiourea blocked S-phase entry by DQ12 and CMDs as well as the phosphorylation of ERKs. Immunohistochemistry on lung sections of CMD-exposed rats showed chronic activation of phosphorylated ERKs in epithelial cells, supporting the possible role of this signal cascade in proliferation of pulmonary epithelium by PSP in vivo. (C) 2002 Elsevier Science (USA).