Helicobacter pylori and mitogen-activated protein kinases mediate activator protein-1 (AP-1) subcomponent protein expression and DNA-binding activity in gastric epithelial cells.
Helicobacter pylori and mitogen-activated protein kinases mediate activator protein-1 (AP-1) subcomponent protein expression and DNA-binding activity in gastric epithelial cells.
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DOI：
10.1111/j.1574-695x.2008.00439.x
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发表时间：
2008-08
影响因子：
--
通讯作者：
Goldberg JB
中科院分区：
文献类型：
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作者：
Ding SZ;Olekhnovich IN;Cover TL;Peek RM Jr;Smith MF Jr;Goldberg JB
新的证据表明激活蛋白 (AP)-1 在调节各种细胞功能中发挥着关键作用。本研究的目的是研究幽门螺杆菌和丝裂原激活蛋白激酶 (MAPK) 对胃上皮细胞中 AP-1 亚成分表达和 AP-1 DNA 结合活性的影响。我们发现，幽门螺杆菌感染导致 c-Jun、JunB、JunD、Fra-1 和 c-Fos 蛋白的表达呈时间和剂量依赖性增加，这些蛋白构成了 AGS 和 MKN45 细胞中主要的 AP-1 DNA 结合蛋白，而 Fra-2 和 FosB 的表达水平保持不变。幽门螺杆菌感染和 MAPK 抑制改变了 AP-1 亚组分蛋白表达和 AP-1 DNA 结合活性，但没有改变总体亚组分组成。幽门螺杆菌的不同临床分离株表现出不同的诱导 AP-1 DNA 结合的能力。 cagA、cagPAI 或 vacA 以及不可磷酸化的 CagA 突变体 (cagAEPISA) 的突变显示幽门螺杆菌诱导的 AP-1 DNA 结合活性较低，而幽门螺杆菌鞭毛的突变则没有影响。 ERK、p38 和 JNK 各自选择性调节 AP-1 亚组分表达和 DNA 结合活性。这些结果让我们更深入地了解幽门螺杆菌和 MAPK 如何调节胃上皮细胞中的 AP-1 亚成分，从而改变下游靶基因的表达并影响细胞功能。
Emerging evidence has suggested a critical role for activator protein (AP)-1 in regulating various cellular functions. The goal of this study was to investigate the effects of H. pylori and mitogen-activated protein kinases (MAPKs) on AP-1 subcomponents expression and AP-1 DNA binding activity in gastric epithelial cells. We found that H. pylori infection resulted in a time- and dose-dependent increase in the expression of the proteins c-Jun, JunB, JunD, Fra-1, and c-Fos, which make up the major AP-1 DNA binding proteins in AGS and MKN45 cells, while the expression levels of Fra-2 and FosB remained unchanged. H. pylori infection and MAPK inhibition altered AP-1 subcomponent protein expression and AP-1 DNA-binding activity, but did not change the overall subcomponent composition. Different clinical isolates of H. pylori showed various abilities to induce AP-1 DNA binding. Mutation of cagA, cagPAI, or vacA, and the nonphosphorylateable CagA mutant (cagAEPISA) showed less H. pylori-induced AP-1 DNA binding activity, while mutation of the H. pylori flagella had no effect. ERK, p38, and JNK each selectively regulated AP-1 subcomponent expression and DNA binding activity. These results provide more insight into how H. pylori and MAPK modulate AP-1 subcomponents in gastric epithelial cells to alter the expression of downstream target genes and affect cellular functions.