山东医药2018，Vol.58Issue(24)：22-25,4.DOI:10.3969/j.issn.1002-266X.2018.24.006
泡沫细胞DNA甲基化及其对脂代谢基因SREBP1表达的影响
DNA methylation of foam cells and its effect on SREBP1 expression
摘要
Abstract
Objective To investigate the DNA methylation of foam cells and its regulation effect on the lipid metabo-lism gene sterol regulatory element-binding protein-1 ( SREBP1) expression.Methods Human monocytic cells THP-1 were stimulated with Ox-LDL to form THP-1 foam cell models.DNA methyltransferase 1 (DNMT1), DNMT3A, DNMT3B mRNA expression in THP-1 monocytes and THP-1 foam cells were detected by real-time PCR.The result showed that DN-MT1 mRNA expression level was significant lower in the THP-1 foam cells than in the THP-1 monocytes (P＜0.05), and no significant difference was found in DNMT3A and DNMT3B expression between the foam cells and monocytes (both P＞0.05).We subsequently selected the DNMT1 gene for transfection.The foam cells were randomly divided into three groups.The control group was cultured routinely.The empty vector group was transfected with the empty control plasmid , and the DNMT1 group was transfected with the DNMT1 plasmid.The results showed that the relative expression of DNMT 1 protein in the DNMT1 group was higher than that in the other two groups , indicating the transfection was successful.The methylation status of SREBP1 promoter was detected by mass spectrometry , and the expression of SREBP1 mRNA and pro-tein was detected by RT-qPCR and Western blotting.Results Compared with the control group and the empty vector group, the hypermethylation of the promoter of No.22 CG locus of CpG island in the promoter region of SREBP-1 gene was observed in the DNMT1 group, while no methylation of the other 28 CG loci was observed.The relative expression of SREBP1 mRNA and SREBP1 protein in the DNMT1 group was lower than that in other two groups (all P＜0.05).Con-clusion Abnormal alteration of DNMT1 takes part in the formation of foam cells , and the up-regulation of DNMT1 could inhibit the expression of SREBP1, which suggests that DNMT expression alteration might contribute to the hypermethylation of lipid-metabolism gene and play important role in the formation of foam cells.关键词
动脉粥样硬化/DNA甲基转移酶/泡沫细胞/胆固醇调节元件结合蛋白1Key words
atherosclerosis/DNA methyltransferases/foam cells/sterol regulatory element-binding protein-1分类
医药卫生引用本文复制引用
李显东,陈平英,谢华强,彭春艳,张吉才..泡沫细胞DNA甲基化及其对脂代谢基因SREBP1表达的影响[J].山东医药,2018,58(24):22-25,4.基金项目
国家自然科学基金资助项目(81600358) . （81600358）
