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首页> 外文期刊>The European Journal of Neuroscience >Role of retinoids in the CNS: differential expression of retinoid binding proteins and receptors and evidence for presence of retinoic acid.
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Role of retinoids in the CNS: differential expression of retinoid binding proteins and receptors and evidence for presence of retinoic acid.

机译:维甲酸在中枢神经系统中的作用:维甲酸结合蛋白和受体的差异表达以及视黄酸的存在证据。

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摘要

Retinoic acid (RA), a retinoid metabolite, acts as a gene regulator via ligand-activated transcription factors, known as retinoic acid receptors (RARs) and retinoid X receptors (RXRs), both existing in three different subtypes, alpha, beta and gamma. In the intracellular regulation of retinoids, four binding proteins have been implicated: cellular retinol binding protein (CRBP) types I and II and cellular retinoic acid binding protein (CRABP) types I and II. We have used in situ hybridization to localize mRNA species encoding CRBP- and CRABP I and II as well as all the different nuclear receptors in the developing and adult rat and mouse central nervous system (CNS), an assay to investigate the possible presence of RA, and immunohistochemistry to also analyse CRBP I- and CRABP immunoreactivity (IR). RXRbeta is found in most areas while RARalpha and -beta and RXRalpha and -gamma show much more restricted patterns of expression. RARalpha is found in cortex and hippocampus and RARbeta and RXRgamma are both highly expressed in the dopamine-innervated areas caudate/putamen, nucleus accumbens and olfactory tubercle. RARgamma could not be detected in any part of the CNS. Using an in vitro reporter assay, we found high levels of RA in the developing striatum. The caudate/putamen of the developing brain showed strong CRBP I-IR in a compartmentalized manner, while at the same time containing many evenly distributed CRABP I-IR neurons. The CRBP I- and CRABP I-IR patterns were closely paralleled by the presence of the corresponding transcripts. The specific expression pattern of retinoid-binding proteins and nuclear retinoid receptors as well as the presence of RA in striatum suggests that retinoids are important in many brain structures and emphasizes a role for retinoids in gene regulatory events in postnatal and adult striatum.
机译:维甲酸(RA)是一种类维生素A代谢产物,通过配体激活的转录因子(称为维甲酸受体(RAR)和类维生素X受体(RXR))充当基因调节剂,两者均以三种不同的亚型(α,β和γ)存在。在类维生素A的细胞内调节中,涉及到四种结合蛋白:I和II型细胞视黄醇结合蛋白(CRBP)和I和II型细胞视黄酸结合蛋白(CRABP)。我们已经使用原位杂交技术来定位编码CRBP-和CRABP I和II以及发育中和成年大鼠和小鼠中枢神经系统(CNS)中所有不同核受体的mRNA种类,该方法旨在研究RA的可能存在,以及免疫组织化学分析CRBP I和CRABP免疫反应性(IR)。在大多数地区都发现了RXRbeta,而RARalpha和-beta以及RXRalpha和-gamma显示出更多受限制的表达模式。 RARalpha在皮层和海马中发现,RARbeta和RXRgamma都在多巴胺神经支配区的尾状/壳状,伏隔核和嗅结节中高表达。在CNS的任何部分均未检测到RARgamma。使用体外报告基因检测,我们发现发育中的纹状体中RA水平较高。发育中的大脑的尾状/丘脑以分隔的方式显示出较强的CRBP I-IR,同时包含许多均匀分布的CRABP I-IR神经元。 CRBP I-和CRABP I-IR模式与相应转录本的存在紧密平行。类视黄醇结合蛋白和核类视黄醇受体的特定表达模式以及纹状体中RA的存在表明类视黄醇在许多脑结构中很重要,并强调类视黄醇在产后和成年纹状体的基因调控事件中的作用。

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