Schaefer András, Kósa Ferenc, Bittorf Thomas, Magócsi Mária, Rosche Anette, Ramirez-Chávez Yoandra, Marotzki Stefan, Marquardt Hans
Institute of Toxicology, Hamburg University Medical School and Department of Environmental Medicine and Toxicology, Umweltmedizin Hamburg e.V., Vogt-Kölln-Strasse 30, 22527 Hamburg, Germany.
Cell Signal. 2004 Feb;16(2):223-34. doi: 10.1016/j.cellsig.2003.07.001.
The effect of erythropoietin (Epo) on the expression of mitogen-activated protein kinase (MAPK) target genes egr-1 and c-fos was investigated in Epo-responsive murine erythroblastic cell line ELM-I-1. Epo induced a transient rise in egr-1 mRNA without a similar effect on c-fos expression. The induction of egr-1 correlated with a rapid ERK1/2 phosphorylation and was prevented with MEK1/2 inhibitors PD 98059 and UO126. The p38 inhibitor SB 203580 enhanced ERK1/2 phosphorylation and egr-1 mRNA levels. Longer incubations of ELM-I-1 cells with Epo revealed a second later phase of increase in egr-1 expression which was also prevented by MEK1/2 inhibitors, whereas SB 203580 had a stimulatory effect. In contrast, the beta-globin mRNA production was enhanced in the presence of PD 98059 and UO126 and reduced by SB 203580. The results suggest a regulatory role of egr-1 expression in Epo signal transduction and provide pharmacological evidence for the negative modulation of differentiation-specific gene expression by the ERK1/2 pathway in murine erythroleukemia cells.
在对促红细胞生成素（Epo）有反应的小鼠成红细胞系ELM-I-1中，研究了促红细胞生成素（Epo）对丝裂原活化蛋白激酶（MAPK）靶基因egr-1和c-fos表达的影响。Epo诱导egr-1 mRNA短暂升高，但对c-fos表达无类似影响。egr-1的诱导与ERK1/2的快速磷酸化相关，并被MEK1/2抑制剂PD 98059和UO126所抑制。p38抑制剂SB 203580增强了ERK1/2磷酸化和egr-1 mRNA水平。用Epo对ELM-I-1细胞进行更长时间的孵育，发现egr-1表达增加的第二个较晚阶段，MEK1/2抑制剂也可阻止该阶段，而SB 203580具有刺激作用。相反，在存在PD 98059和UO126的情况下，β-珠蛋白mRNA的产生增加，而SB 203580则使其减少。结果表明egr-1表达在Epo信号转导中具有调节作用，并为ERK1/2途径对小鼠红白血病细胞中分化特异性基因表达的负调控提供了药理学证据。
