PLASMA DELIVERY OF RETINOIC ACID TO TISSUES IN THE RAT
PLASMA DELIVERY OF RETINOIC ACID TO TISSUES IN THE RAT
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DOI：
10.1074/jbc.270.30.17850
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发表时间：
1995-07-28
影响因子：
4.8
通讯作者：
BLANER, WS
中科院分区：
文献类型：
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作者：
KURLANDSKY, SB;GAMBLE, MV;BLANER, WS
全反式维甲酸(RA)激活配体依赖的转录因子，调节维甲酸反应基因的表达。假设全反式维甲酸是通过来自循环的视黄醇的原位氧化在细胞内形成的。然而，循环中含有低水平的全反式视黄醇(约为血浆视黄醇的0.2-0.7%)。我们的研究调查了血浆全反式维甲酸对这种维甲酸组织池的贡献程度，并探索了调节其被组织和细胞摄取的因素。持续给大鼠输注全反式[H-3]RA至稳定状态。根据稳态下全反式[H-3]RA比活性的测定，我们确定全反式RA在脑和肝脏中的优势来自于循环。对于其他六种组织，大约10%-30%的维甲酸来自循环，但胰腺和睾丸来自循环池的很少。在其他研究中，我们发现维甲酸的营养状况影响全反式维甲酸的一次剂量的清除，细胞全反式维甲酸摄取率和细胞内半衰期都不受细胞脂质水平的影响。综上所述，我们的数据表明，血浆全反式维甲酸有助于这种维甲酸的组织池，特定的和生理反应的细胞过程介导其摄取。
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 level 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-[H-3]RA. From measures of specific activities of all-trans [H-3]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.