BINDING OF A METABOLITE OF 3,4,3',4'-TETRACHLOROBIPHENYL TO TRANSTHYRETIN REDUCES SERUM VITAMIN-A TRANSPORT BY INHIBITING THE FORMATION OF THE PROTEIN COMPLEX CARRYING BOTH RETINOL AND THYROXINE
BINDING OF A METABOLITE OF 3,4,3',4'-TETRACHLOROBIPHENYL TO TRANSTHYRETIN REDUCES SERUM VITAMIN-A TRANSPORT BY INHIBITING THE FORMATION OF THE PROTEIN COMPLEX CARRYING BOTH RETINOL AND THYROXINE
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DOI：
10.1016/0041-008x(86)90337-6
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发表时间：
1986-09-30
影响因子：
3.8
通讯作者：
VANDENBERG, KJ
中科院分区：
文献类型：
--
作者：
BROUWER, A;VANDENBERG, KJ
本文从维生素A血浆转运蛋白系统水平探讨了多氯联苯降低血清维生素A的机制。[3 H]视黄醇标记的血清蛋白的聚丙烯酰胺凝胶电泳（PAGE）分析表明，视黄醇与两种蛋白，被确定为视黄醇结合蛋白（RBP）和RBP与甲状腺素运载蛋白（TTR）复合物的协会。血清中[3 H]视黄醇放射性的量以及与结合蛋白相关的标记物被3，4，3“，4”-四氯联苯（TCB）强烈降低。使用放射性标记的TCB，研究了TCB与视黄醇结合蛋白的可能相互作用。通过PAGE分析血浆蛋白，发现存在4个3 H-TCB标记峰，主要的峰与脂蛋白和TTR相关。在RBP或RBP-TTR复合物所在的凝胶区域未发现3 H-TCB放射性。与TTR相关的放射性化合物的HPLC分析显示存在TCB的代谢物，而不是母体化合物。这些数据表明TCB的代谢物与TTR的直接相互作用导致抑制携带视黄醇和甲状腺素的血清转运蛋白复合物的形成。提出了一个模型，它可以解释某些特征的毒性病理学病变中观察到的物种接触多氯联苯和相关化合物（TCDD，多溴联苯等）。
The mechanism of serum vitamin A reduction by polychlorinated biphenyls was studied at the level of the plasma transport protein system for vitamin A. Analysis of [3H]retinol-labeled serum proteins by polyacrylamide gel electrophoresis (PAGE) showed association of retinol with two proteins that were identified as retinol binding protein (RBP) and the RBP complex with transthyretin (TTR). The amount of [3H] retinol radioactivity in the serum as well as the label associated with the binding proteins was strongly reduced by 3,4,3'',4''-tetrachlorobiphenyl (TCB). A possible interaction of TCB with the retinol binding proteins was investigated, using radiolabeled TCB. Analysis of the plasma proteins by PAGE revealed the presence of four peaks of 3H-TCB label, the major ones being associated with lipoproteins and TTR. No 3H-TCB radioactivity was found in the region of the gel where RBP or the RBP-TTR complex was located. HPLC analysis of the radioactive compound associated with TTR showed the presence of a metabolite of TCB, rather than the parent compound. These data indicate a direct interaction of a metabolite of TCB with TTR leading to an inhibition of formation of the serum transport protein complex carrying both retinol and thyroxin. A model is proposed, which may explain certain characteristic toxicopathological lesions observed in species exposed to polychlorinated biphenyls and related compounds (TCDD, PBBs, etc.).