Identification of the C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol synthesis in HepG2 cells
作者：
Sun, Shaowei;Wen, Juan;Qiu, Fei;Yin, Yufang;Xu, Guina;...
期刊：
Biochemical and Biophysical Research Communications,2016年480(1):139-145 ISSN：0006-291X
通讯作者：
Chen, Jianxiong;Tuo, Qinhui
（庹勤慧） 作者机构：
[Xu, Guina; Sun, Shaowei; Wen, Juan; Xiong, Guozuo; Li, Tianping; Zhang, Caiping] Univ South China, Inst Pharm & Pharmacol, Sch Life Sci & Technol, Hengyang 421001, Hunan, Peoples R China.;[Nie, Juan; Tuo, Qinhui; Chen, Jianxiong; Sun, Shaowei; Qiu, Fei; Chen, JX; Liao, Duangfang] Hunan Univ Chinese Med, Sch Med, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.;[Yin, Yufang] Southern Illinois Univ, Dept Pharmacol, Sch Med, Springfield, IL 62702 USA.;[Chen, Jianxiong] Univ Mississippi, Med Ctr, Dept Pharmacol & Toxicol, Jackson, MS 39216 USA.
通讯机构：
[Chen, JX; Tuo, QH] H;Hunan Univ Chinese Med, Sch Med, 300 Xueshi Rd, Changsha 410208, Hunan, Peoples R China.
关键词：
Fas death domain-associated protein;Androgen receptor;SCAP;SREBP;Cholesterol
摘要：
Daxx is a highly conserved nuclear transcriptional factor, which has been implicated in many nuclear processes including transcription and cell cycle regulation. Our previous study demonstrated Daxx also plays a role in regulation of intracellular cholesterol content. Daxx contains several domains that are essential for interaction with a growing number of proteins. To delineate the underlying mechanism of hypocholesterolemic activity of Daxx, we constructed a set of plasmids which can be used to overexpress different fragments of Daxx and transfected to HepG2 cells. We found that the C- terminal region Daxx626–740 clearly reduced intracellular cholesterol levels and inhibited the expression of SREBPs and SCAP. In GST pull-down experiments and Double immunofluorescence assays, Daxx626–740 was demonstrated to bind directly to androgen receptor (AR). Our findings suggest that the interaction of Daxx626-740 and AR abolishes the AR-mediated activation of SCAP/SREBPs pathway, which suppresses the de novo cholesterol synthesis. Thus, C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol content in HepG2 cells. © 2016 Elsevier Inc.
语种：
英文
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竹节参皂苷IVa甲酯对血管紧张素II诱导的血管平滑肌细胞增殖影响及机制研究
作者：
杨冬梅
（杨冬梅）;聂娟
（聂娟）;孙四玉;邱飞;刘杨;...
期刊：
中国临床药理学与治疗学,2016年21(8):873-877 ISSN：1009-2501
作者机构：
湖南中医药大学药理教研室, 湖南, 长沙, 410208;湖南中医药大学医学院血管生物学实验室, 湖南, 长沙, 410208;湖南中医药大学中药民族药物创新与发展实验室, 湖南, 长沙, 410208;南华大学第二附属医院普外科, 湖南, 衡阳, 421001;[聂娟] 湖南中医药大学医学院血管生物学实验室, 湖南, 长沙, 410208
关键词：
竹节参皂苷IVa甲酯;血管平滑肌细胞;增殖;作用机制
摘要：
目的:探讨竹节参皂苷IVa甲酯(chikusetsu saponin iva methyl,CSIM)对血管紧张素II(angiotensin,Ang-II)刺激的血管平滑肌细胞(vascular smooth muscle cells,VSMCs)增殖的影响及机制研究。方法:以大鼠血管平滑肌细胞为实验对象,建立Ang-II刺激的VSMCs增殖模型。MTT法检测CSIM对VSMCs的毒性; CCK-8法、BrdU法检测CSIM对VSMCs增殖的影响,划痕实验检测 CSIM对VSMCs迁移力的影响,免疫蛋白印迹法检测PTEN、NF-κB蛋白表达水平。结果: 3 μmol /L的CSIM可显著抑制Ang-II诱导的 VSMCs增殖(P < 0. 05)与迁移(P < 0. 05),并伴随着PTEN蛋白的明显上调(P < 0. 05)及NF-κB蛋白表达的显著性降低(P < 0. 05) 。结论: CSIM抑制Ang-II诱导的VSMCs增殖与迁移,其机制可能与上调PTEN蛋白,降低NF-κB蛋白表达有关。
语种：
中文
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