An analysis of retinoic acid-induced gene expression and metabolism in AB1 embryonic stem cells
An analysis of retinoic acid-induced gene expression and metabolism in AB1 embryonic stem cells
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DOI：
10.1074/jbc.271.25.14971
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发表时间：
1996-06-21
影响因子：
4.8
通讯作者：
Gudas, LJ
中科院分区：
文献类型：
--
作者：
Chen, AC;Gudas, LJ
小鼠胚胎干细胞如AB 1细胞系在视黄酸（RA）存在下经历分化成胚外上皮细胞类型。这导致基因如Hoxa-1、Hoxb-1、层粘连蛋白、胶原IV（α 1）、组织纤溶酶原激活物、RAR β和CRABPI II的激活。CRABPI基因以不寻常的方式调节; CRABPI信息和蛋白水平在低浓度的RA下被诱导，但诱导在较高浓度下被减弱。AB 1细胞从培养基中迅速摄取RA，并且向培养基中加入低浓度的外源性RA导致非常高的细胞内RA浓度。例如，在5 nM [H-3]RA中培养的AB 1干细胞在第一个小时内具有1-2 μ M的内部[H-3]RA浓度。AB_1细胞也能将[H-3]RA代谢为极性更强的RA衍生物。RA在未暴露于RA的AB_1细胞中的半衰期约为2-2.5小时，而在1 μ M外源性RA中培养2-3天的细胞中的半衰期为40-45分钟。因此，代谢RA的酶被RA诱导或激活。此外，引发某些生物学反应所需的RA局部浓度可能高于先前认为的。
Murine embryonic stem cells such as the AB1 cell line undergo differentiation in the presence of retinoic acid (RA) into an extraembryonic epithelial cell type. This results in the activation of genes such as Hoxa-1, Hoxb-1, laminin, collagen IV(alpha 1), tissue plasminogen activator, RAR beta, and CRABPII, The CRABPI gene is regulated in an unusual fashion; CRABPI message and protein levels are induced at low concentrations of RA, but induction is diminished at higher concentrations. AB1 cells take up RA rapidly from the medium, and the addition of low, exogenous concentrations of RA to the culture medium results in very high intracellular RA concentrations, For example, AB1 stem cells cultured in 5 nM [H-3]RA have an internal [H-3]RA concentration of 1-2 mu M within the first hour. AB1 cells also metabolize [H-3]RA to more polar RA derivatives, The half-life of RA in AB1 cells not previously exposed to RA is about 2-2.5 h versus 40-45 min in cells cultured for 2-3 days in 1 mu M exogenous RA. Thus, the enzyme(s) which metabolize RA are induced or activated by RA, Furthermore, the local concentration of RA required to elicit some biological responses may be higher than previously thought.