视黄酸及其合成类似物可不同程度地激活视黄酸受体依赖性转录。
Retinoic acid and synthetic analogs differentially activate retinoic acid receptor dependent transcription.
作者信息
Aström A, Pettersson U, Krust A, Chambon P, Voorhees J J
机构信息
Department of Dermatology, University of Michigan, Ann Arbor 48109.
出版信息
Biochem Biophys Res Commun. 1990 Nov 30;173(1):339-45. doi: 10.1016/s0006-291x(05)81062-9.
We have developed an assay where the potency of retinoids in retinoic acid receptor (RAR) mediated transcriptional activation can be rapidly evaluated. In this assay hRAR-alpha, hRAR-beta and hRAR-gamma were expressed in CV-1 cells together with a reporter gene containing a retinoic acid responsive element (TRE3-tk-CAT). Concentrations required to obtain half-maximum induction (ED50) of CAT-activity were determined for several retinoids, e.g., all-trans-retinoic acid (RA), 13-cis-retinoic acid (13-cis-RA), arotinoid acid (TTNPB) and m-carboxy-arotinoid acid (m-carboxy-TTNPB, an inactive arotinoid analog). The ED50 values for RA decreased in the order of RAR-alpha (24 nM) greater than RAR-beta (4.0 nM) greater than RAR-gamma (1.3 nM), while the ED50 values for TTNPB and 13-cis-RA decreased in the order of RAR-alpha (6.5 nM, 190 nM) greater than RAR-gamma (2.3 nM, 140 nM) greater than RAR-beta (0.6 nM, 43 nM), respectively. No significant inductions were obtained when cells were treated with m-carboxy-TTNPB, even at 10 microM concentrations. The fold induction of CAT-activity for all compounds tested decreased in the order of RAR-alpha greater than RAR-beta greater than RAR-gamma.
我们开发了一种检测方法，可快速评估维甲酸受体（RAR）介导的转录激活中类视黄醇的效力。在该检测方法中，hRAR-α、hRAR-β和hRAR-γ在CV-1细胞中与含有视黄酸反应元件（TRE3-tk-CAT）的报告基因一起表达。测定了几种类视黄醇（如全反式维甲酸（RA）、13-顺式维甲酸（13-cis-RA）、芳维甲酸（TTNPB）和间羧基芳维甲酸（m-羧基-TTNPB，一种无活性的芳维甲酸类似物））诱导CAT活性达到半最大值（ED50）所需的浓度。RA的ED50值按RAR-α（24 nM）＞RAR-β（4.0 nM）＞RAR-γ（1.3 nM）的顺序降低，而TTNPB和13-顺式RA的ED50值分别按RAR-α（6.5 nM，190 nM）＞RAR-γ（2.3 nM，140 nM）＞RAR-β（0.6 nM，43 nM）的顺序降低。用m-羧基-TTNPB处理细胞时，即使在10 μM浓度下也未获得显著诱导。所有测试化合物的CAT活性诱导倍数按RAR-α＞RAR-β＞RAR-γ的顺序降低。
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