H3K9me3参与调节高糖诱导大鼠胸主动脉平滑肌细胞增殖  

H3K9me3 is involved in Proliferation of Rat Thoracic Aortic Smooth Muscle Cells induced by High Glucose

作　　者：李婷婷[1] 陈明云[1] 李梅芳[1] 陆俊茜[1] 李连喜[1] 

机构地区：[1]上海交通大学附属第六人民医院内分泌代谢科,上海200233

出　　处：《现代生物医学进展》2016年第25期4801-4804,共4页Progress in Modern Biomedicine

基　　金：国家自然科学基金面上项目(81170759)

摘　　要：目的:研究H3K9me3在高糖诱导大鼠胸主动脉平滑肌A7r5细胞增殖中的作用,并初步探讨其可能的作用机制。方法:应用MTT法检测高糖刺激下不同浓度的H3K9甲基转移酶SUV39H1特异性抑制剂Chaetocin(0、10、25、50、75、100 nmol/L)和50nmol/L H3K9甲基转移酶SUV39H1特异性抑制剂Chaetocin在不同时间点(24、48、72 h和5 d)对细胞增殖的影响。应用Western bolt法观察50 nmol/L H3K9甲基转移酶SUV39H1特异性抑制剂Chaetocin在高糖浓度下干预A7r5细胞72 h后,对H3K9me3和p53表达的影响。结果:Chaetocin可显著抑制高糖诱导下A7r5细胞的增殖,且抑制作用呈浓度和时间依赖性。与正常糖相比,Chaetocin可显著下调A7r5细胞在高糖诱导下表达增多的H3K9me3,同时显著上调在高糖诱导下表达减少的p53(P<0.05)。结论:高糖可通过H3K9me3下调p53的表达促进大鼠胸主动脉平滑肌A7r5细胞的增殖,H3K9甲基转移酶SUV39H1特异性抑制剂Chaetocin可抑制上述过程,为减少糖尿病大血管并发症提供了治疗的新思路。Objective： To explore the effects of H3K9me3 on rat thoracic aortic smooth muscle A7r5 cell proliferation induced by high glucose, and to study its underlying mechanism. Methods： Under the high glucose condition, MTT assays were applied to observe the effects of different concentrations of H3K9 methyltransferase SUV39H1 specific inhibitor Chaetocin（0, 10, 25, 50, 75, 100 nmol/L）and 50 nmol/L Chaetocin at different time points（24, 48, 72 h, 5 d）on rat thoracic aortic muscle A7r5 cell proliferation, respectively.Western bolt was used to explore the protein expression of H3K9me3 and p53 after 50 nmol/L Chaetocin incubating A7r5 cells for 72 h.Results： Chaetocin can significantly suppressed A7r5 cell proliferation induced by high glucose in a concentration- and time- dependent manner. Compared with normal concentration of glucose, Chaetocin significantly inhibited the up-regulated expression of H3K9me3 and increased the down-regulated expression of p53 induced by high glucose in A7r5 cells（P〈0.05）. Conclusions： Down-regulated p53 can enhance the proliferation of rat thoracic aortic muscle cell induced by high glucose via H3K9me3, while H3K9 methyltransferase inhibitor Chaetocin can suppressed this process, which provides a new insight for the treatment of diabetic macroangiopathy.

关 键 词：组蛋白修饰 大鼠胸主动脉平滑肌A7r5细胞 细胞增殖 P53 

分 类 号：R-33[医药卫生] R587.2