PHYTOL METABOLITES ARE DIETARY FACTORS THAT ACTIVATE THE NUCLEAR RECEPTOR RXR

工作总结：RXR是一种核受体， 通过与许多其他细胞配对，在细胞信号转导中发挥核心作用 感受器。以前，9-顺式维甲酸是从氯仿中提取的 依赖RXR的牛血清提取物的研究 转录活性。材料的质谱学分析 活性组分指向饱和的二萜酸，它 诱导依赖RXR转录的浓度在4 还有呢。尽管其效力是植酸的200倍， 9cRA在等量的萃取物中检测不到，不能 出现的浓度可以解释活动的原因。 合成了另一种植醇代谢物植酸，并对其进行了表征。 刺激RXR的效力和疗效与植物药相似 酸。这些代谢物特别取代[~3H]-9cRA。 RXR，K1值为4um，表明它们的转录 这些效应是通过直接受体相互作用来实现的。植酸脂 代谢物是令人信服的生理效应物， 因为它们的RXR结合亲和力和激活势匹配 他们的微摩尔循环浓度。考虑到他们的独家 饮食来源，这些叶绿素代谢物可能代表必需的 协调细胞新陈代谢的营养物质 依赖RXR的信号通路。这一假设正在被 通过比较饲养在植物中的大鼠的生长情况来测试 缺酸日粮与饲喂补充饲料的动物群 加了植酸。综上所述，这些发现引导我们提出 植物酚代谢物可能是连接 动物的饮食状态与多种内分泌和内分泌 通过核受体RXR的信号通路。

Summary of Work: RXR is a nuclear receptor which plays a central role in cell signalling by pairing with a host of other receptors. Previously, 9-cis-retinoic acid was from chloroform extracts of bovine serum by following RXR-dependent transcriptional activity. Mass spectrometric analyses of material in active fractions pointed to the saturated diterpenoid acid, which induced RXR-dependent transcription at concentrations between 4 and 64 uM. Although 200 times more potent than phytanic acid, 9cRA was undetectable in equivalent amounts of extract and cannot be present at a concentration that could account for the activity. Phytenic acid, another phytol metabolite, was synthesized and stimulated RXR with a potency and efficacy similar to phytanic acid. These metabolites specifically displaced [3H]-9cRA from RXR with k1 values of 4 uM, indicating that their transcriptional effects are mediated by direct receptor interactions. Phytol metabolites are compelling candidates for physiological effectors, because their RXR binding affinities and activation potencies match their micromolar circulating concentrations. Given their exclusive dietary origin, these chlorophyll metabolites may represent essential nutrients that coordinate cellular metabolism through RXR-dependent signalling pathways. This hypothesis is being tested by comparing the growth of rats raised on phytanic acid-deficient diets with groups of animals fed diets supplemented with phytanic acid. In summary, these findings lead us to propose that phytol metabolites may be nutritional signals linking the animal's dietary state with a variety of endocrine and intracrine signalling pathways through the nuclear receptor RXR.