A NOVEL REGULATORY PATHWAY OF BROWN FAT THERMOGENESIS - RETINOIC ACID IS A TRANSCRIPTIONAL ACTIVATOR OF THE MITOCHONDRIAL UNCOUPLING PROTEIN GENE
A NOVEL REGULATORY PATHWAY OF BROWN FAT THERMOGENESIS - RETINOIC ACID IS A TRANSCRIPTIONAL ACTIVATOR OF THE MITOCHONDRIAL UNCOUPLING PROTEIN GENE
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DOI：
10.1074/jbc.270.10.5666
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发表时间：
1995-03-10
影响因子：
4.8
通讯作者：
VILLARROYA, F
中科院分区：
文献类型：
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作者：
ALVAREZ, R;DEANDRES, J;VILLARROYA, F
线粒体解偶联蛋白（UCP）负责棕色脂肪的产热功能，是棕色脂肪细胞类型的分子标记。视黄酸（RA）使培养的棕色脂肪细胞中UCP mRNA水平增加数倍，这种诱导作用不依赖于肾上腺素能途径或蛋白质合成。RA刺激ucp基因的表达，无论棕色脂肪细胞分化的阶段。在瞬时转染实验中，RA诱导由大鼠ucp基因5 '-非编码区的4.5个酶驱动的氯霉素乙酰转移酶载体的表达，并且RA受体表达载体的共转染增强了RA的作用。维甲酸受体α比维甲酸X受体更有效地促进RA作用，而两者的混合物是最有效的。ucp基因中的RA反应区位于-2469/-2318处，包含三个维甲酸反应元件的共有半位点的基序（在-2357和-2330之间）。这个27碱基对序列特异性结合纯化的视黄酸受体α以及来自棕色脂肪细胞核的相关蛋白质。总之，一种新的潜在的棕色脂肪发育和产热功能的调节途径已被确认为确定RA作为一个转录激活因子的ucp基因。
The mitochondrial uncoupling protein (UCP) is responsible for the thermogenic function of brown fat, and it is a molecular marker of the brown adipocyte cell type. Retinoic acid (RA) increased UCP mRNA levels severalfold in brown adipocytes differentiated in culture, This induction was independent of adrenergic pathways or protein synthesis. RA stimulated ucp gene expression regardless of the stage of brown adipocyte differentiation. In transient transfection experiments RA induced the expression of chloramphenicol acetyltransferase vectors driven by 4.5 kilobases of the 5'-noncoding region of the rat ucp gene, and co-transfection of expression vectors for RA receptors enhanced the action of RA. Retinoic acid receptor alpha was more effective than retinoid X receptor in promoting RA action, whereas a mixture of the two was the most effective. The RA-responsive region in the ucp gene was located at -2469/-2318 and contains three motifs (between -2357 and -2330) of the consensus half sites characteristic of retinoic acid response elements. This 27-base pair sequence specifically binds purified retinoic acid receptor alpha as well as related proteins from brown fat nuclei. In conclusion, a novel potential regulatory pathway of brown fat development and thermogenic function has been recognized by identifying RA as a transcriptional activator of the ucp gene.