Department of Biochemistry and Molecular Biology, University of Debrecen, 4032 Debrecen, Hungary.
Departamento de Química Orgánica, Universidade de Vigo, Faculdad de Química, 36310 Vigo, Spain.
Nutrients. 2019 Sep 4;11(9):2084. doi: 10.3390/nu11092084.
Carotenoids can be metabolized to various apo-carotenoids and retinoids. Apo-15´-carotenoic acid (retinoic acid, RA) is a potent activator of the retinoic acid receptor (RAR) in its all-- (ATRA) and 9- (9CRA) forms. In this study we show firstly, that apo-14´-carotenoic acid (A14CA), besides retinoic acids, is present endogenously and with increased levels in the human organism after carrot juice supplementation rich in β-carotene. All--A14C (ATA14CA) is just a moderate activator of RAR-transactivation in reporter cell lines but can potently activate retinoic acid response element (RARE)-mediated signalling in DR5/RARE-reporter mice and potently increase retinoid-reporter target gene expression in ATA14CA-supplemented mice and treated MM6 cells. Further metabolism to all--13,14-dihydroretinoic acid (ATDHRA) may be the key for its potent effects on retinoid target gene activation in ATA14CA-treated MM6 cells and in liver of supplemented mice. We conclude that besides RAs, there are alternative ways to activate RAR-response pathways in the mammalian organism. ATA14CA alone and in combination with its metabolite ATDHRA may be an alternative pathway for potent RAR-mediated signalling.
类胡萝卜素可以代谢为各种脱辅基类胡萝卜素和视黄醛。脱辅基-15'-视黄酸（视黄酸，RA）是其全-（ATRA）和 9-（9CRA）形式的视黄酸受体（RAR）的有效激活剂。在这项研究中，我们首先表明，除了视黄酸之外，脱辅基-14'-视黄酸（A14CA）在人体组织中也内源性存在，并且在富含β-胡萝卜素的胡萝卜汁补充后水平升高。全- A14C（ATA14CA）仅适度激活报告细胞系中的 RAR 转录激活，但可有效激活 DR5/RARE-报告基因小鼠中的视黄酸反应元件（RARE）介导的信号传导，并可有效增加 ATA14CA 补充小鼠和经处理的 MM6 细胞中的视黄酸报告基因表达。进一步代谢为全-13,14-二氢视黄酸（ATDHRA）可能是其在 ATA14CA 处理的 MM6 细胞和补充小鼠肝脏中对视黄酸靶基因激活产生有效作用的关键。我们得出结论，除了视黄醛之外，哺乳动物体内还有其他激活 RAR 反应途径的方法。ATA14CA 单独及其代谢物 ATDHRA 可能是 RAR 介导的信号转导的有效替代途径。
