Fenretinide inhibits vitamin A formation from β-carotene and regulates carotenoid levels in mice.
Fenretinide inhibits vitamin A formation from β-carotene and regulates carotenoid levels in mice.
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DOI：
10.1016/j.bbalip.2021.159070
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Amengual J
中科院分区：
文献类型：
--
作者：
Miller AP;Black M;Amengual J
N-[4-羟基苯基]维甲酸，俗称芬维甲酸，是一种对人类健康具有多效性益处的合成类维甲酸，目前用于癌症、囊性纤维化和COVID-19的临床试验。然而，芬维甲酸通过与视黄醇结合蛋白4 （RBP4）相互作用降低血浆维生素A水平，这通常导致可逆性夜盲症患者。细胞培养和体外研究表明，芬维甲酸结合并抑制β-胡萝卜素加氧酶1 （BCO1）的活性，BCO1是内源性维生素A形成的酶。然而，芬维甲酸是否会抑制哺乳动物体内维生素A的合成尚不清楚。本研究的目的是确定芬维甲酸对BCO1的抑制是否会影响喂食β-胡萝卜素的小鼠体内维生素A的形成。结果表明，经芬维甲酸处理10天后，野生型小鼠组织中维生素a含量降低，血浆和几种组织中β-胡萝卜素含量增加2倍（P < 0.01）。这些影响在rbp4缺乏的小鼠中持续存在，并且独立于肠道β-胡萝卜素吸收的变化，这表明芬维甲酸抑制小鼠维生素A的合成。在Bco1 - / -和Bco2 - / -小鼠实验中，我们还发现芬维甲酸通过激活短期维生素A缺乏时的维生素A信号传导调节肠道类胡萝卜素和维生素E的摄取。本研究对芬维甲酸对维生素a、类胡萝卜素和维生素E稳态的影响有了更深入的了解，这对芬维甲酸的药理利用至关重要。
N-[4-hydroxyphenyl]retinamide, commonly known as fenretinide, a synthetic retinoid with pleiotropic benefits for human health, is currently utilized in clinical trials for cancer, cystic fibrosis, and COVID-19. However, fenretinide reduces plasma vitamin A levels by interacting with retinol-binding protein 4 (RBP4), which often results in reversible night blindness in patients. Cell culture and in vitro studies show that fenretinide binds and inhibits the activity of β-carotene oxygenase 1 (BCO1), the enzyme responsible for endogenous vitamin A formation. Whether fenretinide inhibits vitamin A synthesis in mammals, however, remains unknown. The goal of this study was to determine if the inhibition of BCO1 by fenretinide affects vitamin A formation in mice fed β-carotene. Our results show that wild-type mice treated with fenretinide for ten days had a reduction in tissue vitamin A stores accompanied by a two-fold increase in β-carotene in plasma (P < 0.01) and several tissues. These effects persisted in RBP4-deficient mice and were independent of changes in intestinal β-carotene absorption, suggesting that fenretinide inhibits vitamin A synthesis in mice. Using Bco1−/− and Bco2−/− mice we also show that fenretinide regulates intestinal carotenoid and vitamin E uptake by activating vitamin A signaling during short-term vitamin A deficiency. This study provides a deeper understanding of the impact of fenretinide on vitamin A, carotenoid, and vitamin E homeostasis, which is crucial for the pharmacological utilization of this retinoid.
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影响因子：
8.1
作者：
Fenzl A;Kulterer OC;Spirk K;Mitulović G;Marculescu R;Bilban M;Baumgartner-Parzer S;Kautzky-Willer A;Kenner L;Plutzky J;Quadro L;Kiefer FW
通讯作者：
Kiefer FW
影响因子：
7.3
作者：
Cooper JP;Hwang K;Singh H;Wang D;Reynolds CP;Curley RW Jr;Williams SC;Maurer BJ;Kang MH
通讯作者：
Kang MH
影响因子：
4.2
作者：
Grune, Tilman;Lietz, Georg;Biesalski, Hans K.
通讯作者：
Biesalski, Hans K.
DOI：
10.1016/j.biocel.2012.07.026
发表时间：
2012-11-01
影响因子：
4
作者：
Amengual, Jaume;Petrov, Petar;Palou, Andreu
通讯作者：
Palou, Andreu
影响因子：
30.5
作者：
Gundra UM;Girgis NM;Gonzalez MA;San Tang M;Van Der Zande HJP;Lin JD;Ouimet M;Ma LJ;Poles J;Vozhilla N;Fisher EA;Moore KJ;Loke P
通讯作者：
Loke P