Both retinoic-acid-receptor- and retinoid-X-receptor-dependent signalling pathways mediate the induction of the brown-adipose-tissue-uncoupling-protein-1 gene by retinoids
Both retinoic-acid-receptor- and retinoid-X-receptor-dependent signalling pathways mediate the induction of the brown-adipose-tissue-uncoupling-protein-1 gene by retinoids
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DOI：
10.1042/0264-6021:3450091
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发表时间：
2000-01-01
影响因子：
4.1
通讯作者：
Villarroya, F
中科院分区：
文献类型：
--
作者：
Alvarez, R;Checa, M;Villarroya, F
分析了维甲酸（RA）对棕色脂肪解偶联蛋白-1基因（ucp-1）影响的细胞内途径和受体。RA激活ucp-1的转录，并且已知RA受体（RAR）参与该作用。然而，共同转染的维甲酸-X受体（RXR）的表达载体增加的行动，9-顺式RA，但不是全反式RA的影响，在棕色脂肪细胞上的ucp-1启动子。RAR-特异性{p-[（E）-2-（5，6，7，8，-四氢-5，5，8，8-四甲基-2-萘基）-1-丙烯基]苯甲酸}或RXR-特异性[异丙基-（E，E）-（R，S）-11-甲氧基-3，7，11-三甲基十二碳-2，4-二烯酸酯，或甲氧普烯]合成化合物增加UCP-1 mRNA的表达和由ucp-1驱动的氯霉素乙酰转移酶表达载体的活性。1启动子。RXR介导的9-cis RA的作用需要ucp-1中-2469/-2318处的上游增强子区域。在棕色脂肪细胞分化过程中，RXR α和RXR γ mRNA表达与UCP-1 mRNA平行诱导，而三种RAR亚型α、β和γ的mRNA减少。不同RAR和RXR亚型的鼠表达载体的共转染表明RAR α和RAR β以及RXR α是能够介导ucp-1对类维生素A的反应性的主要类维生素A受体亚型。它的结论是维甲酸对ucp-1转录的影响涉及RAR和RXR依赖的信号通路。棕色脂肪组织在体内对类维生素A的反应依赖于RAR和RXR亚型介导ucp-1诱导的能力及其在分化的棕色脂肪细胞中的不同表达的复杂组合。
The intracellular pathways and receptors mediating the effects of retinoic acid (RA) on the brown-fat-uncoupling-protein-1 gene (ucp-1) have been analysed. RA activates transcription of ucp-l and the RA receptor (RAR) is known to be involved in this effect. However, co-transfection of an expression vector for retinoid-X receptor (RXR) increases the action of 9-cis RA but not the effects of all-trans RA on the ucp-1 promoter in brown adipocytes. Either RAR-specific {p-[(E)-2-(5,6,7,8,-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid} or RXR-specific [isopropyl-(E,E)-(R,S)-11-methoxy-3,7,11-trimethyldodeca-2,4-dienoate, or methoprene] synthetic compounds increase the expression of UCP-1 mRNA and the activity of chloramphenicol acetyltransferase expression vectors driven by the ucp-1 promoter. The RXR-mediated action of 9-cis RA requires the upstream enhancer region at - 2469/ - 2318 in ucp-1. During brown-adipocyte differentiation RXR alpha and RXR gamma mRNA expression is induced in parallel with UCP-1 mRNA, whereas the mRNA for the three RAR subtypes, alpha, beta and gamma, decreases. Co-transfection of murine expression vectors for the different RAR and RXR subtypes indicates that RAR alpha and RAR beta as well as RXR alpha are the major retinoid-receptor subtypes capable of mediating the responsiveness of ucp-1 to retinoids. It is concluded that the effects of retinoids on ucp-1 transcription involve both RAR- and RXR-dependent signalling pathways. The responsiveness of brown adipose tissue to retinoids in vivo relies on a complex combination of the capacity of RAR and RXR subtypes to mediate ucp-1 induction and their distinct expression in the differentiated brown adipocyte.