STUDY ON THE MECHANISM OF INTERFERENCE OF 3,4,3',4'-TETRACHLOROBIPHENYL WITH THE PLASMA RETINOL-BINDING PROTEINS IN RODENTS
STUDY ON THE MECHANISM OF INTERFERENCE OF 3,4,3',4'-TETRACHLOROBIPHENYL WITH THE PLASMA RETINOL-BINDING PROTEINS IN RODENTS
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DOI：
10.1016/0009-2797(88)90017-8
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发表时间：
1988-01-01
影响因子：
5.1
通讯作者：
VANDENBERG, KJ
中科院分区：
文献类型：
--
作者：
BROUWER, A;BLANER, WS;VANDENBERG, KJ
采用放射免疫化学方法对暴露鼠和对照鼠的循环和肝脏视黄醇结合蛋白（RBP）和甲状腺转甲素（TTR）含量进行分析，探讨了3,4,3”，4”-四氯联苯（TCB）对鼠血浆视黄醇降低的作用机制。暴露于TCB后第4天，C57BL/Rij小鼠血浆RBP浓度显著降低（50%），DBA/2小鼠血浆RBP浓度在第4天和第8天显著降低（37-41%），Sprague-Dawley大鼠血浆RBP浓度在第2天显著降低（58%）。这些减少与暴露于TCB后血浆视黄醇减少的时间过程相似。tcb处理的动物肝脏RBP浓度有所升高，尤其是C57BL/Rij小鼠和Sprague-Dawley大鼠。然而，正如在维生素A缺乏大鼠中分析的那样，TCB治疗并没有阻断肝脏RBP进入循环的释放。此外，tcb治疗大鼠血浆TTR含量在正常范围内。通过荧光偏振分析，RBP-TTR复合物的解离常数明显增加（从0.5倍）。10-7 M-1到2.4倍。10-7 M-1)存在从TCB治疗大鼠血浆中分离的TCB代谢物。此外，用TCB代谢物处理TTR后，RBP在TTR分子上的估计结合位点数量减少（从2.8个减少到1.7个）。这些数据支持了一种假设，即在与TTR结合的TCB代谢物存在的情况下，TCB降低血浆视黄醇可能是由于RBP-TTR复合物的减弱。
The mechanism of plasma retinol reduction in rodents by 3,4,3'',4''-tetrachlorobiphenyl (TCB) was investigated by radioimmunochemical analysis of the amounts of circulating and hepatic retinol-binding protein (RBP) and transthyretin (TTR) in exposed and control animals. Plasma RBP concentrations were markedly reduced in C57BL/Rij mice (50%) at 4 days, in DBA/2 mice (37-41%) at 4 and 8 days, and in Sprague-Dawley rats (58%) at 2 days after exposure to TCB. These reductions paralled the time course of reduction of plasma retinol after exposure to TCB. Hepatic RBP concentrations were somewhat increased in TCB-treated animals, especially in the C57BL/Rij mouse and Sprague-Dawley rat. However, the release of hepatic RBP into the circulation was not blocked by TCB treatment, as analysed in vitamin A deficient rats. In addition, the amount of plasma TTR was in the normal range in TCB-treated rats. The dissociation constants of the RBP-TTR complex as analysed by polarization of fluorescence appeared to be significantly increased (from 0.5 .times. 10-7 M-1 to 2.4 .times. 10-7 M-1) in the presence of a TCB metabolite, isolated from plasma of TCB-treated rats. In addition, the estimated number of binding sites for RBP on the TTR molecule was reduced (from 2.8 to 1.7 sites) upon treatment of TTR with the TCB metabolite. These data support the hypothesis that plasma retinol reduction by TCB might result from a weakening of the RBP-TTR complex, in the presence of the TCB metabolite bound to the TTR.