Analysis of high dysmorphogenic activity of Ro 13-6307, a tetramethylated tetralin analog of retinoic acid.
Analysis of high dysmorphogenic activity of Ro 13-6307, a tetramethylated tetralin analog of retinoic acid.
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Ro 13-6307（一种视黄酸四甲基化四氢萘类似物）的高变形活性分析。
DOI：
10.1002/tera.1420450608
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Penner,JD
中科院分区：
文献类型：
--
作者：
Kochhar,DM;Penner,JD
某些合成的类维生素A在致畸效力方面与维甲酸（RA）差异很大，比RA有效或多或少。据推测，类维生素A的效力可能取决于其与细胞结合组分（核视黄酸受体或细胞质结合蛋白）的相互作用的性质，以及在类维生素A是哺乳动物致畸剂的情况下，取决于决定其对胚胎可及性的因素。为了研究影响效力的一些因素，我们使用了一种新的合成类维生素A Ro 13 - 6307，其结构与RA不同，在其侧链中插入了一个芳香环，沿着天然环己烯基环的宝石二甲基修饰。妊娠ICR小鼠在妊娠第11天接受单次经口给药（0、1或10 mg/kg），并在第17天监测由此产生的致畸结果。通过将肢芽间充质细胞的高密度培养物暴露于一系列浓度（0.3 ng/ml-3 μg/ml）的Ro 13 - 6307并对软骨形成抑制进行评分，获得对细胞分化的直接影响。通过HPLC测定母体给予Ro 13 - 6307后到达胚胎的浓度，以定量口服给药后4 h内的类似物。我们发现，这种类维生素A在诱导致畸和抑制软骨形成方面的活性是RA的40倍，但其在受影响胚胎中的浓度仅为在类似方案中使用等效剂量的RA后所达到的浓度的一小部分。由于Ro 13 - 6307的形态发生活性不成比例地超过其在小鼠胚胎中的水平，因此可能涉及受体或其他结合蛋白或两者的强制性介导。© 1992 Wiley利斯公司
Certain synthetic retinoids differ widely from retinoic acid (RA) in teratogenic potency, being much more or much less effective than RA. It is assumed that the potency of a retinoid may depend on the nature of its interaction with cellular binding components (nuclear retinoic acid receptors or cytoplasmic binding proteins) and, as in the case of retinoids that are mammalian teratogens, on factors that determine its accessibility to the embryo. To investigate some of the factors that contribute to potency, we used a new synthetic retinoid Ro 13‐6307 that differs in structure from RA in having an aromatic ring inserted in its side chain along with gem dimethyl modification of the natural cyclohexenyl ring. Pregnant ICR mice were given a single oral dose (0, 1, or 10 mg/kg) on day 11 of gestation, and the resultant teratogenic outcome was monitored on day 17. Direct effects on cell differentiation were obtained by exposing high density cultures of limb bud mesenchymal cells to a range of concentrations (0.3 ng/ml‐3 μg/ml) of Ro 13‐6307 and scoring for chondrogenic suppression. Concentrations reaching the embryo after maternal administration of Ro 13‐6307 were measured by HPLC to quantify the analog for a period of 4 h after administration of the oral dose. We found that this retinoid was 40‐fold as active as RA in both inducing teratogenesis and suppressing chondrogenesis, yet its concentration in the affected embryo was only a fraction of that achieved after an equivalent dose of RA was employed in a similar protocol. Since the morphogenetic activity of Ro 13‐6307 is disproportionately in excess of its levels in the mouse embryo, obligatory mediation by the receptors or by other binding proteins, or both, is likely involved. © 1992 Wiley‐Liss, Inc.
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影响因子：
64.8
作者：
BRAND, N;PETKOVICH, M;DEJEAN, A
通讯作者：
DEJEAN, A
新合成类视黄醇对肢体模式的重新特异性及其与细胞视黄酸结合蛋白的相互作用。
DOI：
10.1111/j.1432-0436.1991.tb00220.x
发表时间：
1991
期刊：
Differentiation; research in biological diversity
影响因子：
--
作者：
M. Maden;D. Summerbell;J. Maignan;M. Darmon;B. Shroot
通讯作者：
B. Shroot
影响因子：
3.8
作者：
D. Kochhar;J. Penner;M. Satre
通讯作者：
D. Kochhar;J. Penner;M. Satre
影响因子：
11.4
作者：
ZELENT, A;MENDELSOHN, C;CHAMBON, P
通讯作者：
CHAMBON, P
类维生素A与胎儿细胞视黄酸结合蛋白（CRABP）的结合亲和力与其在仓鼠中的致畸效力相关。
影响因子：
5.8
作者：
Howard,WB;Sharma,RP;Willhite,CC;Dawson,MI
通讯作者：
Dawson,MI