Kurlandsky S B, Gamble M V, Ramakrishnan R, Blaner W S
Institute of Human Nutrition, Columbia University, New York, New York 10032, USA.
J Biol Chem. 1995 Jul 28;270(30):17850-7. doi: 10.1074/jbc.270.30.17850.
All-trans-retinoic acid (RA) activates ligand-dependent transcription factors that regulate retinoid-responsive gene expression. It is assumed that all-trans-RA is formed within cells through in situ oxidation of retinol derived from the circulation. However, the circulation contains low levels of all-trans-RA (approximately 0.2-0.7% of that of plasma retinol). Our studies investigated the extent to which plasma all-trans-RA contributes to tissue pools of this retinoid and explored factors responsible for regulating its uptake by tissues and cells. Rats were continuously infused, to steady state, with all-trans-[3H]RA. From measures of specific activities of all-trans-[3H]RA at steady state, we determined that the preponderance of all-trans-RA in brain and liver was derived from the circulation. For six other tissues, approximately 10-30% of the retinoid was derived from the circulation, but pancreas and testis derived very little from the circulating pool. In other studies, we showed that retinoid nutritional status influences clearance of a bolus dose of all-trans-RA and that neither the rate of cellular all-trans-RA uptake nor its intracellular half-life is influenced by cellular lipid levels. Taken together, our data indicate that plasma all-trans-RA contributes to tissue pools of this retinoid and that specific and physiologically responsive cellular processes mediate its uptake.
全反式维甲酸（RA）可激活依赖配体的转录因子，这些转录因子可调节维甲酸反应性基因的表达。据推测，全反式维甲酸是通过循环中视黄醇的原位氧化在细胞内形成的。然而，循环中全反式维甲酸的水平较低（约为血浆视黄醇水平的0.2 - 0.7%）。我们的研究调查了血浆全反式维甲酸对该类维生素A组织库的贡献程度，并探讨了负责调节其被组织和细胞摄取的因素。给大鼠持续输注全反式[³H]RA直至稳态。通过测定稳态下全反式[³H]RA的比活性，我们确定脑和肝脏中全反式维甲酸的主要来源是循环。对于其他六种组织，约10 - 30%的类维生素A来源于循环，但胰腺和睾丸从循环库中的摄取量很少。在其他研究中，我们表明类维生素A的营养状况会影响一次大剂量全反式维甲酸的清除，并且细胞全反式维甲酸的摄取速率及其细胞内半衰期均不受细胞脂质水平的影响。综上所述，我们的数据表明血浆全反式维甲酸对该类维生素A的组织库有贡献，并且特定的和生理反应性的细胞过程介导了其摄取。
