首页> 外文期刊>Life sciences >Inhibition of apolipoprotein A-I gene by the aryl hydrocarbon receptor: A potential mechanism for smoking-associated hypoalphalipoproteinemia
【24h】

Inhibition of apolipoprotein A-I gene by the aryl hydrocarbon receptor: A potential mechanism for smoking-associated hypoalphalipoproteinemia

机译:芳烃受体抑制载脂蛋白A-I基因:吸烟相关的低α脂蛋白血症的潜在机制

获取原文
获取原文并翻译 | 示例
           

摘要

Aims: Smokers have lower plasma concentrations of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I) compared with nonsmokers. To determine the molecular basis of this observation, the effect of activation of the aryl hydrocarbon receptor (AhR) on apo A-I gene expression was examined. Main methods: HepG2 cells were treated with AhR receptor agonists benzo(a)pyrene (BaP) and CAY10465, and AhR receptor antagonist CAY10464 and apo A-I protein, mRNA levels and promoter activity were measured. The effect of nicotine on apo A-I protein secretion was also tested. Using a series or apo A-I gene promoter deletion constructs, a xenobiotic response element (XRE) was identified. Key findings: Treatment of HepG2 cells with the AhR receptor agonists BaP and CAY10465, inhibited apo A-I protein synthesis while nicotine, which does not bind AhR had no effect. Benzo(a)pyrene treatment also suppressed apo A-I mRNA and gene promoter activity. Treatment of HepG2 cells with the AhR receptor antagonist CAY10464 reversed the suppressive effect of BaP on apo A-I gene expression. A putative xenobiotic response element (XRE) was identified between nucleotides - 325 and - 186 (relative to the transcriptional start site, + 1). Significance: These results suggest that the cigarette smoking related environmental contaminant BaP promotes hypoalphalipoproteinemia in part through activation of the hepatic AhR.
机译:目的:与不吸烟者相比,吸烟者的血浆中高密度脂蛋白(HDL)胆固醇和载脂蛋白A-I(apo A-I)浓度较低。为了确定该观察结果的分子基础,研究了芳基烃受体(AhR)活化对载脂蛋白A-I基因表达的影响。主要方法:用AhR受体激动剂苯并(a)py(BaP)和CAY10465处理HepG2细胞,并用AhR受体拮抗剂CAY10464和apo A-I蛋白测定mRNA水平和启动子活性。还测试了尼古丁对载脂蛋白A-1蛋白分泌的影响。使用一系列或载脂蛋白A-I基因启动子缺失构建体,鉴定了异种应答元件(XRE)。关键发现:用AhR受体激动剂BaP和CAY10465处理HepG2细胞可抑制apo A-I蛋白合成,而不结合AhR的烟碱则无作用。苯并(a)treatment处理还抑制了载脂蛋白A-1 mRNA和基因启动子的活性。用AhR受体拮抗剂CAY10464处理HepG2细胞可逆转BaP对apo A-I基因表达的抑制作用。在核苷酸-325和-186(相对于转录起始位点+ 1)之间鉴定出推测的异源生物响应元件(XRE)。意义:这些结果表明,与吸烟有关的环境污染物BaP部分地通过肝AhR的活化而促进低脂蛋白血症。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号