β-Carotene and its cleavage enzyme β-carotene-15,15′-oxygenase (CMOI) affect retinoid metabolism in developing tissues
β-Carotene and its cleavage enzyme β-carotene-15,15′-oxygenase (CMOI) affect retinoid metabolism in developing tissues
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DOI：
10.1096/fj.10-175448
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发表时间：
2011-05-01
期刊：
影响因子：
4.8
通讯作者：
Quadro, Loredana
中科院分区：
文献类型：
--
作者：
Kim, Youn-Kyung;Wassef, Lesley;Quadro, Loredana
哺乳动物胚胎的发育依赖于母体循环的类维生素A（维生素A衍生物）。β -胡萝卜素是人类膳食中主要的维生素原a。β -胡萝卜素-15,15'-加氧酶（CMOI）被认为是体内β -胡萝卜素生成类维甲酸的主要酶。CMOI在胚胎组织中表达，表明β -胡萝卜素在发育过程中局部提供类维生素a。我们在缺乏视黄醇结合蛋白（RBP）的小鼠中进行了CMOI功能丧失的研究，RBP是一种已建立的胚胎维生素A缺乏症（VAD）模型。我们发现，出乎意料的是，在发育组织中缺乏CMOI进一步加剧了VAD的严重程度，从而导致RBP（-/-）小鼠的胚胎畸形。由于β -胡萝卜素不存在于任何小鼠的饮食中，我们揭示了CMOI独立于β -胡萝卜素裂解活性的新作用。我们还首次表明，CMOI通过调节卵磷脂影响视黄醇酯的形成，对类视黄醇酰基转移酶（LRAT）活性施加了额外的功能，至少在发育组织中是这样。最后，我们明确地证明β -胡萝卜素可以作为一种替代维生素A来源，通过CMOI的作用，在发育组织中原位合成类维生素A。金正日,Y.-K。， Wyss， A, Blaner， W. S, Quadro， L. β -胡萝卜素及其裂解酶-胡萝卜素-15,15'-加氧酶（CMOI）影响发育组织的类视黄醇代谢。中国生物医学工程学报，2011,32(2):444 - 444。www.fasebj.org
The mammalian embryo relies on maternal circulating retinoids (vitamin A derivatives) for development. beta-Carotene is the major human dietary provitamin A. beta-Carotene-15,15'-oxygenase (CMOI) has been proposed as the main enzyme generating retinoid from beta-carotene in vivo. CMOI is expressed in embryonic tissues, suggesting that beta-carotene provides retinoids locally during development. We performed loss of CMOI function studies in mice lacking retinol-binding protein (RBP), an established model of embryonic vitamin A deficiency (VAD). We show that, unexpectedly, lack of CMOI in the developing tissues further exacerbates the severity of VAD and thus the embryonic malformations of RBP(-/-) mice. Since beta-carotene was not present in any of the mouse diets, we unveiled a novel action of CMOI independent from its beta-carotene cleavage activity. We also show for the first time that CMOI exerts an additional function on retinoid metabolism by influencing retinyl ester formation via modulation of lecithin: retinol acyltransferase (LRAT) activity, at least in developing tissues. Finally, we demonstrate unequivocally that beta-carotene can serve as an alternative vitamin A source for the in situ synthesis of retinoids in developing tissues by the action of CMOI.-Kim, Y.-K., Wassef, L., Chung, S., Jiang, H., Wyss, A., Blaner, W. S., Quadro, L. beta-Carotene and its cleavage enzyme beta-carotene-15,15'-oxygenase (CMOI) affect retinoid metabolism in developing tissues. FASEB J. 25, 1641-1652 (2011). www.fasebj.org