Metabolism of retinoic acid and retinol during differentiation of F9 embryonal carcinoma cells.
Metabolism of retinoic acid and retinol during differentiation of F9 embryonal carcinoma cells.
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F9胚胎癌细胞分化过程中视黄酸和视黄醇的代谢。
DOI：
10.1073/pnas.82.14.4658
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发表时间：
1985
影响因子：
11.1
通讯作者：
Napoli,JL
中科院分区：
文献类型：
--
作者：
Williams,JB;Napoli,JL
视黄醇和视黄酸的剂量-反应曲线，获得促进分化的F9小鼠胚胎癌细胞与层粘连蛋白，分化的F9细胞的产物的酶联免疫吸附测定。视黄酸在1.3 nM时产生半最大响应，在约30 nM时产生最大响应;视黄醇的效力为1/175。最大分化需要48小时的视黄酸连续曝光，而视黄醇需要72小时的曝光。视黄酸转化为极性代谢产物的半衰期为3.5小时;通过用视黄酸预处理F9细胞加速代谢。氧化代谢抑制剂酮康唑降低了视黄酸代谢速率，并降低了产生半最大反应所需的视黄酸浓度。不变的视黄酸是唯一的化合物分离的F9细胞与视黄酸孵育的细胞核。视黄醇的半衰期比视黄酸长约5倍，获得更高的细胞浓度，并被F9细胞转化为视黄酸。这些数据表明，视黄酸本身指导F9细胞的分化，并可能介导由视黄醇诱导的分化。
Retinol and retinoic acid dose-response curves were obtained for promotion of the differentiation of F9 murine embryonal carcinoma cells with an enzyme-linked immunoadsorbent assay for laminin, a product of differentiated F9 cells. Retinoic acid produced a half-maximum response at 1.3 nM and a maximum response at about 30 nM; retinol was 1/175th as potent. Maximum differentiation required 48 hr of continuous exposure to retinoic acid, whereas retinol required 72 hr of exposure. The half-time of retinoic acid conversion into polar metabolites was 3.5 hr; metabolism was accelerated by pretreating F9 cells with retinoic acid. An inhibitor of oxidative metabolism, ketoconazole, decreased the rate of retinoic acid metabolism and decreased the concentration of retinoic acid required to produce a half-maximum response. Unchanged retinoic acid was the sole compound isolated from nuclei of F9 cells incubated with retinoic acid. Retinol had a half-life approximately 5-fold longer than retinoic acid, attained greater cell concentrations, and was converted into retinoic acid by F9 cells. These data indicate that retinoic acid itself directs the differentiation of F9 cells and may mediate differentiation induced by retinol.