The role of DNA methylation in catechol-enhanced erythroid differentiation of K562 cells.
The role of DNA methylation in catechol-enhanced erythroid differentiation of K562 cells.
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DOI：
10.1016/j.taap.2012.09.018
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发表时间：
2012-11
影响因子：
3.8
通讯作者：
Xiao-fei Li;Xiaorong Wu;Ming Xue;Yan Wang;Jie-Xie Wang;Yang Li;Suriguga;Guang-Yao Zhang
中科院分区：
文献类型：
--
作者：
Xiao-fei Li;Xiaorong Wu;Ming Xue;Yan Wang;Jie-Xie Wang;Yang Li;Suriguga;Guang-Yao Zhang
儿茶酚是苯在体内的酚类代谢产物之一。儿茶酚也广泛用于制药和化学工业。此外，水果、蔬菜和香烟烟雾中也含有儿茶酚。我们宝贵的研究表明，几种苯代谢物（苯酚、对苯二酚和1,2,4-苯三醇）抑制K562细胞的红系分化。本研究探讨了儿茶酚对K562细胞红系分化的影响。此外，为了研究DNA甲基化在儿茶酚诱导的K562细胞红系分化中的作用，我们利用定量MassARRAY甲基化分析平台分析了红系特异性基因的甲基化水平。联苯胺染色显示儿茶酚暴露增强了血红蛋白诱导的K562细胞中血红蛋白的浓度依赖性和时间依赖性。在儿茶酚处理的K562细胞中，红系特异性基因α-珠蛋白、β-珠蛋白、γ-珠蛋白、红系5-氨基乙酰酸合成酶、红系卟酚胆色素原脱氨酶和转录因子GATA-1基因的mRNA表达呈浓度依赖性增加。儿茶酚暴露导致一些红系特异性基因（包括α-珠蛋白、β-珠蛋白和红系卟啉原脱氨酶基因）的少数CpG位点DNA甲基化水平降低。这些结果表明，儿茶酚至少部分通过上调一些红系相关基因的转录来提高K562细胞的红系分化能力，并提示DNA甲基化的抑制可能参与了一些红系相关基因的上调表达。
Catechol is one of phenolic metabolites of benzene in vivo. Catechol is also widely used in pharmaceutical and chemical industries. In addition, fruits, vegetables and cigarette smoke also contain catechol. Our precious study showed that several benzene metabolites (phenol, hydroquinone, and 1,2,4-benzenetriol) inhibited erythroid differentiation of K562 cells. In present study, the effect of catechol on erythroid differentiation of K562 cells was investigated. Moreover, to address the role of DNA methylation in catechol-induced effect on erythroid differentiation in K562 cells, methylation levels of erythroid-specific genes were analyzed by Quantitative MassARRAY methylation analysis platform. Benzidine staining showed that exposure to catechol enhanced hemin-induced hemoglobin accumulation in K562 cells in concentration- and time-dependent manners. The mRNA expression of erythroid specific genes, including α-globin, β-globin, γ-globin, erythroid 5-aminolevulinate synthase, erythroid porphobilinogen deaminase, and transcription factor GATA-1 genes, showed a significant concentration-dependent increase in catechol-treated K562 cells. The exposure to catechol caused a decrease in DNA methylation levels at a few CpG sites in some erythroid specific genes including α-globin, β-globin and erythroid porphobilinogen deaminase genes. These results indicated that catechol improved erythroid differentiation potency of K562 cells at least partly via up-regulating transcription of some erythroid related genes, and suggested that inhibition of DNA methylation might be involved in up-regulated expression of some erythroid related genes.