Differences in the action and metabolism between retinol and retinoic acid in B lymphocytes
Differences in the action and metabolism between retinol and retinoic acid in B lymphocytes
复制标题
视黄醇和视黄酸在B淋巴细胞中的作用和代谢差异
作者：
Jochen Buck;Andrzej Myc;Annette Garbe;G. Cathomas
我们以前曾报道过活化的B淋巴细胞对视黄醇的依赖性。在这里，我们证实和扩展这些发现，细胞剥夺视黄醇在细胞培养中死亡的几天内，既不显示细胞凋亡的迹象，也没有细胞周期停滞。生理浓度的视黄醇和视黄醛可以阻止细胞死亡，但维甲酸或三种合成的维甲酸类似物不能阻止细胞死亡。为了排除视黄酸如此迅速地降解而逃避检测的可能性，我们测试了其在细胞内和细胞外隔室中的稳定性。与预期相反，我们发现，视黄酸持续时间较长（t1/2 3天），在文化比视黄醇（t1/2 1天）。此外，尽管使用灵敏的示踪标记技术，我们不能检测视黄酸或3，4-二脱氢视黄酸视黄醇代谢产物。然而，视黄醇被转化为几种新的类维生素A，其中一种在没有外部来源的视黄醇的情况下具有维持B细胞生长的能力，支持第二种视黄醇途径的概念。我们还确定了哪些已知的类维生素A结合蛋白在B淋巴母细胞样细胞中表达。根据聚合酶链反应辅助mRNA检测获得的结果，它们转录细胞视黄醇和细胞视黄酸结合蛋白的基因，转录核视黄酸受体、RAR-α、RAR-γ和RXR-α的基因，但不转录RAR-β的基因。我们的研究结果表明，B细胞不合成视黄酸或响应于外源性视黄酸，但在另一方面将视黄醇转化为一种新的生物活性形式的视黄醇，这表明存在第二类视黄酸途径，不同于视黄酸途径。
We have previously reported on the dependency of activated B lymphocytes for retinol. Here we confirm and extend these findings that cells deprived of retinol perish in cell culture within days, displaying neither signs of apoptosis nor of cell cycle arrest. Cell death can be prevented by physiological concentrations of retinol and retinal, but not by retinoic acid or three synthetic retinoic acid analogues. To exclude the possibility that retinoic acid is so rapidly degraded as to escape detection, we have tested its stability in intra- and extracellular compartments. Contrary to expectation, we find that retinoic acid persists for longer (t 1/2 3 d) in cultures than retinol (t 1/2 1 d). Furthermore, despite the use of sensitive trace-labeling techniques, we cannot detect retinoic acid or 3,4-didehydroretinoic acid among retinol metabolites. However, retinol is converted into several new retinoids, one of which has the ability to sustain B cell growth in the absence of an external source of retinol, supporting the notion of a second retinol pathway. We have also determined which of the known retinoid-binding proteins are expressed in B lymphoblastoid cells. According to results obtained with polymerase chain reaction- assisted mRNA detection, they transcribe the genes for cellular retinol- and cellular retinoic acid-binding proteins, for the nuclear retinoic acid receptors, RAR-alpha, -gamma, and RXR-alpha, but not RAR-beta. Our findings that B cells do not synthesize retinoic acid or respond to exogenous retinoic acid on the one hand, but on the other hand convert retinol to a novel bioactive form of retinol, suggest the existence of a second retinoid pathway, distinct from that of retinoic acids.
DOI：
10.1073/pnas.84.16.5645
发表时间：
1987-08-01
影响因子：
11.1
作者：
SHUBEITA, HE;SAMBROOK, JF;MCCORMICK, AM
通讯作者：
MCCORMICK, AM
通过诱导鼠 F9 畸胎癌细胞和人 HL-60 早幼粒细胞白血病细胞的分化来测量一系列新的视黄醛苯甲酸衍生物的结构-活性关系。
影响因子：
11.2
作者：
Strickland,S;Breitman,TR;Frickel,F;Nurrenbach,A;Hadicke,E;Sporn,MB
通讯作者：
Sporn,MB
DOI：
10.1172/jci112565
发表时间：
1986
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Tobler,A;Dawson,MI;Koeffler,HP
通讯作者：
Koeffler,HP