Hypoxic induction of human visfatin gene is directly mediated by hypoxia-inducible factor-1

Hypoxic induction of human visfatin gene is directly mediated by hypoxia-inducible factor-1
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DOI:
10.1016/j.febslet.2006.06.052
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发表时间:
2006-07-24
期刊:
影响因子:
3.5
通讯作者:
Bae, Moon-Kyoung
Bae, Moon-Kyoung
中科院分区:
生物学3区
文献类型:
--
作者:
Bae, Soo-Kyung;Kim, Su-Ryun;Bae, Moon-Kyoung

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内脂素最初被鉴定为早期B细胞的生长因子,最近被称为脂肪因子。在这里,我们报告缺氧诱导MCF 7乳腺癌细胞内脂素mRNA和蛋白水平。我们还证明内脂素基因的诱导受缺氧诱导因子-1 α(HIF-1 α)的调控。此外,人内脂素基因的5 '侧翼启动子区含有两个功能性HIF应答元件(HRE),激活内脂素的表达。内脂素启动子中这些HRE的突变消除了内脂素启动子在缺氧下驱动的荧光素酶报告基因的激活。综上所述,我们的研究结果表明,visfatin是一个新的缺氧诱导基因,其表达是通过HIF-1与其启动子区的HRE位点的相互作用刺激。(c)2006年欧洲生物化学学会联合会。Elsevier B. V.出版,保留所有权利。
Visfatin has been originally identified as a growth factor for early stage B cells and recently known as an adipokine. Here, we report that hypoxia induces the visfatin mRNA and protein levels in MCF7 breast cancer cells. We also demonstrate that induction of visfatin gene is regulated by hypoxia-inducible factor-1 alpha (HIF-1 alpha). Moreover, 5 '-flanking promoter region of human visfatin gene contains two functional HIF responsive elements (HREs), activating the expression of visfatin. Mutation of these HREs in the visfatin promoter abrogates activation of a luciferase reporter gene driven by visfatin promoter under hypoxia. Taken together, our results demonstrate that visfatin is a new hypoxia-inducible gene of which expression is stimulated through the interaction of HIF-1 with HRE sites in its promoter region. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.