Human cytochrome P450 1A1 is a novel target gene of liver X receptor α.
Human cytochrome P450 1A1 is a novel target gene of liver X receptor α.
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人细胞色素 P450 1A1 是肝脏 X 受体 α 的新型靶基因。
DOI：
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发表时间：
2011
影响因子：
2.1
通讯作者：
T. Kamataki
中科院分区：
文献类型：
--
作者：
N. Shibahara;Yuiko Masunaga;S. Iwano;H. Yamazaki;K. Kiyotani;T. Kamataki
细胞色素P450（CYP1A1）参与多环芳烃（PAHs）的代谢活化，并由包括PAHs在内的多种化合物诱导。芳香烃受体（AhR）介导的CYP1A1诱导作用已得到很好的研究，然而，很少有报道以外的因素介导的CYP1A1诱导的机制。在这项研究中，我们研究了肝脏X受体α（LXR α）在诱导CYP1A1中的参与。TO-901317（一种LXR α配体）以剂量依赖性方式诱导CYP1A1 mRNA。使用HepG2细胞进行的荧光素酶报告基因试验表明，TO-901317能够激活CYP1A1基因的启动子，并且位于-452至-467区域的直接重复4（DR 4）基序是通过LXR α诱导CYP1A1所必需的。通过凝胶位移和染色质免疫沉淀试验证实了LXR α与该DR4基序的特异性结合。TO-901317和2，3，7，8-四氯二苯并-p-二恶英（一种典型的AhR配体）共处理HepG2细胞引起CYP1A1 mRNA的协同诱导。因此，我们认为CYP1A1的表达受到LXR α和AhR的调节，这表明暴露于LXR α和AhR配体可以导致个体对CYP1A1代谢激活的环境致癌物的易感性改变。
Cytochrome P450 (CYP) 1A1 is involved in the metabolic activation of polycyclic aromatic hydrocarbons (PAHs) and is induced by several compounds, including PAHs. The induction of CYP1A1 mediated by the aryl hydrocarbon receptor (AhR) has been well investigated; however, little has been reported on the mechanisms of CYP1A1 induction mediated by factors other than AhR. In this study, we investigated the involvement of liver X receptor alpha (LXRα) in the induction of CYP1A1. TO-901317, an LXRα ligand, induced CYP1A1 mRNA in a dose-dependent fashion. Luciferase reporter assays using HepG2 cells showed that TO-901317 was capable of activating the promoter of the CYP1A1 gene and that a direct repeat 4 (DR4) motif located in a region from -452 to -467 was required for the induction of CYP1A1 through LXRα. Specific binding of LXRα to this DR4 motif was confirmed by gel shift and chromatin immunoprecipitation assays. Co-treatment of HepG2 cells with TO-901317 and 2,3,7,8-tetrachlorodibenzo-p-dioxin, a typical AhR ligand, caused the synergistic induction of CYP1A1 mRNA. Thus, we propose that the expression of CYP1A1 is regulated by LXRα as well as by AhR, suggesting that exposure to both LXRα and AhR ligands can result in the alteration of individual susceptibility to environmental carcinogens metabolically activated by CYP1A1.
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3-甲基胆蒽对对甲基胆蒽诱导的肿瘤具有不同易感性的两种同系小鼠品系的动脉粥样硬化的影响。
影响因子：
11.2
作者：
Paigen,B;Holmes,PA;Morrow,A;Mitchell,D
通讯作者：
Mitchell,D
DOI：
10.1074/jbc.m003337200
发表时间：
2000-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
P. Costet;Yi Luo;Nan Wang;A. Tall
通讯作者：
P. Costet;Yi Luo;Nan Wang;A. Tall
培养的大鼠血管平滑肌细胞中细胞色素 P-450IA1 表达的发育调节。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Giachelli,CM;Majesky,MW;Schwartz,SM
通讯作者：
Schwartz,SM
影响因子：
56.9
作者：
Repa, JJ;Turley, SD;Mangelsdorf, DJ
通讯作者：
Mangelsdorf, DJ