Ritter S J, Smith J E
Nutrition Department, Pennsylvania State University, University Park 16802-6504, USA.
Biochim Biophys Acta. 1996 Jun 4;1290(2):157-64. doi: 10.1016/0304-4165(96)00015-3.
N-(4-Hydroxyphenyl)retinamide (HPR; Fenretinide), a synthetic retinoid possessing antitumor activity, depresses plasma retinol and retinol-binding protein (RBP) concentrations. In study 1, the ability of retinol or HPR to induce RBP secretion from the livers of vitamin A-deficient rats was compared. A large apoRBP pool accumulated in the liver rough microsomes of these rats. Following retinol repletion, 80% of the accumulated RBP was rapidly secreted into the plasma. In contrast, HPR treatment only induced two-thirds of the RBP secretion observed with retinol. Prior colchicine treatment caused a large RBP accumulation in the Golgi-enriched fraction following retinol repletion. HPR plus colchicine treatment produced significantly less accumulation of RBP in the Golgi-enriched fraction than did retinol. In study 2, HPR treatment of vitamin A-adequate rats caused RBP to accumulate in the liver rough microsomes. When vitamin A-adequate rats were treated with colchicine, the concentration of RBP in the Golgi-enriched fraction increased 2.9-fold. However, significantly less RBP accumulated in the Golgi following HPR treatment. These studies demonstrate that HPR will induce liver RBP secretion, but to a lesser degree than retinol. Further, more RBP remained in the rough microsomes of HPR treated, vitamin A-adequate rats, indicating that HPR depressed the amount of RBP secreted.
N-(4-羟基苯基)视黄酰胺(HPR;芬维A胺)是一种具有抗肿瘤活性的合成类视黄醇,可降低血浆视黄醇和视黄醇结合蛋白(RBP)的浓度。在研究1中,比较了视黄醇或HPR诱导维生素A缺乏大鼠肝脏分泌RBP的能力。这些大鼠肝脏粗面微粒体中积累了大量的脱辅基RBP池。视黄醇补充后,80%积累的RBP迅速分泌到血浆中。相比之下,HPR处理仅诱导了视黄醇处理时观察到的RBP分泌量的三分之二。预先进行秋水仙碱处理会导致视黄醇补充后高尔基体富集部分出现大量RBP积累。与视黄醇相比,HPR加秋水仙碱处理在高尔基体富集部分产生的RBP积累明显更少。在研究2中,对维生素A充足的大鼠进行HPR处理导致RBP在肝脏粗面微粒体中积累。当对维生素A充足的大鼠用秋水仙碱处理时,高尔基体富集部分的RBP浓度增加了2.9倍。然而,HPR处理后高尔基体中积累的RBP明显更少。这些研究表明,HPR会诱导肝脏RBP分泌,但程度低于视黄醇。此外,在接受HPR处理的维生素A充足的大鼠的粗面微粒体中保留了更多的RBP,这表明HPR降低了分泌的RBP量。