A novel retinoic acid analogue, 7-hydroxy retinoic acid, isolated from cyanobacteria.
A novel retinoic acid analogue, 7-hydroxy retinoic acid, isolated from cyanobacteria.
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DOI：
10.1016/j.bbagen.2010.11.009
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发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
K. Kaya;F. Shiraishi;H. Uchida;T. Sano
中科院分区：
文献类型：
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作者：
K. Kaya;F. Shiraishi;H. Uchida;T. Sano
反式维甲酸（RA）是一种低分子化合物，来源于维生素A。它通过与视黄酸受体（RAR）结合以各种方式诱导事件，视黄酸受体是动物细胞中的一种核受体。RA及其代谢产物存在于动物组织中。在本文中，我们报告了一种新的RA类似物中发现的蓝藻细胞，描述了其分离的方法，并比较其光稳定性与全反式RA。方法新的A类似物提取铜绿微囊藻和螺旋藻的细胞，并通过高效液相色谱分离。使用酵母双杂交测定方法分析类似物以测量体外RAR激动活性。用液相色谱-质谱/质谱联用技术分析了该RA类似物的化学结构，并对片段进行了分析，结果表明新的RA类似物为7-羟基RA。从3.5 μ g（螺旋藻细胞总RAR激动活性的4.5%）的7-羟基RA的产量是4种异构体的混合物，这是由于顺-反异构化与酮-烯醇互变异构化偶联;当全反式RA的活性设定为1.00时，其相对RAR激动活性为0.49 ± 0.01（n = 3）。结论我们从蓝藻中分离到一种新的RAR激活化合物7-hydroxyRA，一般意义7-hydroxyRA在UV-A下比all-transRA更稳定。
BACKGROUNDAll-trans retinoic acid (RA) is a low-molecular compound derived from vitamin A. It induces events in various ways by binding with the retinoic acid receptor (RAR), a nuclear receptor, in animal cells. RA and its metabolites have been found in animal tissues. In this paper, we report a novel RA analogue found in cyanobacterial cells, describe the method for its isolation, and compare its photo-stability with that of all-trans RA.METHODSThe new A analogue was extracted from cells of Microcystis aeruginosa and Spirulina sp. and fractionated by high-performance liquid chromatography. The analogue was analysed using a yeast two-hybrid assay method to measure in vitro RAR-agonistic activity. Liquid chromatography–mass spectrometry/mass spectrometry analyses was performed to elucidate the chemical structure of this RA analogue.RESULTSThe results of the analysis of the fragments revealed that the novel RA analogue was 7-hydroxy RA. The yields from 3.5μg (4.5% of the total RAR-agonistic activity of Spirulina sp. cells) of 7-hydroxy RA was a mixture of 4 isomers due to cis–trans isomerisation coupled with keto–enol tautomerism; its relative RAR agonistic activity was 0.49±0.01 (n=3) when the activity of all trans RA was set up to 1.00. Under fluorescent light, the mixture of 7-hydroxy RA isomers was more stable than all- trans RA.CONCLUSIONSWe isolated a novel RAR-activating compound, 7-hydroxy RA, from cyanobacteria.GENERAL SIGNIFICANCE7-hydroxy RA is more stable than all-trans RA under UV-A.