丁酸钠上调白血病K562细胞CYP1A1和1B1基因的表达(英文)  

Sodium butyrate upregulates expression of CYP1A1 and 1B1 genes in human leukemia K562 cells

作　　者：汉丽萍[1] 倪秀珍[1] 高立宏[1] 范亚军[1] 莫金钢[1] 

机构地区：[1]长春师范学院生命科学学院,吉林长春130032

出　　处：《中国现代医学杂志》2013年第21期1-7,共7页China Journal of Modern Medicine

基　　金：National Natural Science Foundation of China(No:31050015);Foundation of Jilin Education Department for Science and Technology Research in the"11th 5-year"Plan(No:2007174)

摘　　要：目的研究丁酸钠(NaB)在诱导白血病K562细胞分化过程中,对细胞色素CYP1A1/1B1基因转录的作用及作用机制。因为与肿瘤发生发展密切相关,细胞色素P450(sCYPs)已经成为最有潜力的抗肿瘤药物的靶标。对于白血病细胞中这些基因表达机制的研究将有助于揭示它们在造血过程以及血液肿瘤发生中的作用。方法丁酸钠诱导K562细胞分化,RT-PCR检测CYP1A1/1B1转录水平的变化,染色质免疫沉淀(ChIP)分析乙酰化组蛋白H3和组蛋白乙酰转移酶p300与CYP1A1/1B1启动子的结合情况。结果丁酸钠在诱导白血病K562细胞分化过程中,促进了组蛋白乙酰转移酶p300与启动子区域的结合、升高了CYP1A1/1B1基因启动子组蛋白H3乙酰化修饰水平、上调了CYP1A1/1B1基因的转录。结论组蛋白乙酰化修饰和组蛋白乙酰转移酶p300参与了丁酸钠诱导的白血病K562细胞CYP1A1/1B1基因的转录。[Objective] To investigate the alterations of CYP1A1/1B1 transcription in sodium butyrate （NaB）-in- duced differentiated human leukemia K562 cells, and the mechanism by which NaB affects CYP1A1/1B1 transcrip- tion. Since cytochrome P450s （CYPs） appeared to play important roles in tumor development and progression, they have been becoming most potential targets in cancer drug development. A more detailed understanding about the ex- pression of these genes in leukemia cells will potentially clarify their roles during hematogenesis and in the etiology of human hematopoietic malignancy. [Methods] K562 cells were induced to differentiate using NaB, RT-PCR as- says were performed to detect the transcription levels of CYPIA1/1B1, and chromatin immunoprecipitation （CHIP） assays were performed to detect the associations of acetylated histone H3 and histone acetyltransferase p300 with CYP1A1/1B1 promoters. [Results] NaB facilitated histone acetyltransferase p300 association with CYPIA1/1B1 pro- moters, increased the acetylation level of histone H3 at these promoters, and up-regulated both CYP1A1 and 1B1 transcription in K562 cells. [ Conclusion] Histone acetylation and p300 are involved in transcription regulation of CYPIA1/1B1 in K562 cells.

关 键 词：CYP1A1 1B1 丁酸钠 转录 诱导分化 K562细胞 

分 类 号：R34[医药卫生—基础医学]